Neurophysiology
The brain is the hardest-working organ in the body. A typical brain weighs about 3 pounds (Chan et al., 2009), consists of about 2% of body weight, but uses 20% of its energy and oxygen (Raichle & Gusnard, 2002). This biological activity results in electrical fields that are measurable from the scalp. Action potential animation © vasara/Shutterstock.com.
The brain uses a sophisticated communication and command-and-control system that monitors and manages interactions between roughly 86 billion neurons, each with 5,000-10,000 synaptic connections, for as many as 500 trillion synapses in adults (Breedlove & Watson, 2023).
An electroencephalograph (EEG) monitors brainwave activity at various frequencies, from DC shifts (slow cortical potentials) to fast potentials exceeding 50 Hz. The EEG records the excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) propagated by the apical dendrites of large pyramidal cells arranged in thousands of cortical columns. Local field potentials, the aggregate effect of interconnected neuron firing and modulation by glial cells, regulate neuron excitability and firing. Action potential animation © NIMEDIA/Shutterstock.com.
Neuroplasticity, the remodeling of neurons and neural networks with experience, is responsible for learning and memory and makes neurofeedback training possible.
This unit addresses II. Basic Neurophysiology and Neuroanatomy - A. Neurophysiology.
This unit covers the Bioelectric Origin and Functional Correlates of EEG, Definition of ERPs and SCPs, and Neuroplasticity.
Please click on the podcast icon below to hear a full-length lecture.
We can divide neurons into sensory, motor, and interneurons. Glial cells like astrocytes and microglia. Glial cells like astrocytes and microglia work in partnership with neurons.
Sensory neurons are specialized for sensory intake. They are called afferent because they transmit sensory information towards the central nervous system (brain and spinal cord). Sensory neuron graphic © TimeLineArtist/Shutterstock.com.
Motor neurons convey commands to glands, muscles, and other neurons. They are called efferent because they convey information towards the periphery. Motor and sensory neuron graphic © iso-form llc/Shutterstock.com.
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Interneurons provide the integration required for decisions, learning and memory, perception, planning, and movement. They have short processes, analyze incoming information, and distribute their analysis with other neurons in their network. Interneurons are entirely confined to the central nervous system, account for many of its neurons, and comprise most of the brain (Breedlove & Watson, 2023).
Local interneurons analyze small amounts of information provided by neighboring neurons. Relay interneurons connect networks of local interneurons from separate regions to enable diverse functions like perception, learning, and memory, and executive functions like planning (Carlson & Birkett, 2021). Neuron graphic © Aldona Griskeviciene/Shutterstock.com.
Reflex arc graphic © SANDIP NEOGI/Shutterstock.com.
The cell body or soma contains the machinery for the neuron’s life processes. It receives and integrates EPSPs and IPSPs, small graded positive and negative changes in membrane potential generated by axons. The cell body of a typical neuron is 20 μm in diameter, and its spherical nucleus, which contains chromosomes comprised of DNA, is 5-10 μm across. The cell body is the primarily location where neurons manufacture proteins (like enzymes, receptors, and ion channels) and peptides (neurotransmitters like oxytocin). There is increasing evidence of distributed protein manufacturing via local mRNA translation (Nagano & Araki, 2021). Check out the Khan Academy YouTube video, Anatomy of a Neuron. Cell body graphic © MattL_Images/Shutterstock.com.
Mitochondria power diverse processes throughout neurons like opening ion channels, conducting action potentials, releasing and returning neurotransmitters, and transporting proteins. They are responsible for EEG signal strength since they fuel postsynaptic potentials. Mitochondria are orange in the graphic below © Corona Borealis Studio/Shutterstock.com.
Imagine you're peering into the microscopic world of the brain, where tiny cellular powerhouses called mitochondria are orchestrating an intricate biological symphony. While you might have heard mitochondria described simply as cellular energy factories, their role in the brain is far more fascinating and complex. These remarkable organelles are actually master multitaskers, performing a diverse array of functions that keep our neurons firing and our minds sharp. Their involvement in cellular respiration, calcium homeostasis, and reactive oxygen species (ROS) management makes them integral to the brain's demanding physiological environment (Fischer et al., 2020).
At their most fundamental level, mitochondria are indeed energy producers, generating the ATP that neurons desperately need to function. Think of neurons as particularly demanding cells - they're constantly sending electrical signals, releasing neurotransmitters, and rebuilding connections. This requires an enormous amount of energy, which is why mitochondria cluster at synapses (the communication points between neurons) like miniature power plants, ensuring there's always enough fuel for crucial processes like learning and memory formation (Harris et al., 2012).
But here's where things get even more interesting. Mitochondria also serve as cellular calcium regulators, acting like molecular bouncers that maintain strict control over calcium levels inside neurons. This calcium management is absolutely critical for proper neural signaling - when mitochondria fail at this job, it can trigger a cascade of problems that may lead to neurodegenerative diseases. During intense neural activity, mitochondria buffer incoming calcium waves, preventing toxic buildups while fine-tuning the cellular responses that drive everything from neurotransmitter release to gene expression (Brini et al., 2014).
These organelles also walk a delicate tightrope when it comes to reactive oxygen species (ROS). During energy production, mitochondria generate these highly reactive molecules as a byproduct. In small amounts, ROS actually serve as important signaling molecules. However, excessive ROS production can wreak havoc, damaging cellular components like proteins, lipids, and DNA. This is particularly dangerous in the brain, which is extremely vulnerable to oxidative damage due to its high oxygen consumption and abundance of lipids. Thankfully, mitochondria come equipped with their own antioxidant systems, including superoxide dismutase and glutathione, which help keep ROS levels in check (Lin & Beal, 2006).
Mitochondria are also cellular life-and-death decision makers, playing a crucial role in apoptosis (programmed cell death). This process is essential during brain development, helping to sculpt neural circuits by eliminating unnecessary neurons. Through specific pathways involving cytochrome c release and caspase activation, mitochondria can trigger cellular suicide when needed. However, if this process goes awry, it can contribute to devastating conditions like stroke and traumatic brain injury (Green et al., 2011).
Recent research has unveiled mitochondria's unexpected role in neuroinflammation and immune responses. These organelles are vital for the function of microglia, the brain's immune cells. When mitochondria become damaged, they can release danger signals called DAMPs (damage-associated molecular patterns), including mitochondrial DNA and cytochrome c. These signals can trigger inflammatory responses that contribute to conditions like multiple sclerosis and chronic traumatic encephalopathy (West et al., 2015).
As we age, mitochondrial function gradually declines, leading to decreased ATP production and increased ROS generation. This deterioration affects crucial processes like synaptic function and memory formation. The cellular quality control systems that normally maintain healthy mitochondrial populations also become less effective with age, allowing damaged mitochondria to accumulate and potentially contributing to neurodegenerative diseases (Lopez-Otin et al., 2013).
The dynamic nature of mitochondria is particularly fascinating in the context of brain development and plasticity. These organelles constantly undergo fusion and fission, processes that allow them to adapt to changing energy demands and repair damage. These dynamics are especially important in developing neurons and in maintaining synaptic plasticity, the basis for learning and memory. When these processes malfunction, it can lead to developmental disorders including autism spectrum disorder and intellectual disabilities (López-Doménech et al., 2016).
Understanding mitochondria's diverse roles in the brain opens new avenues for treating neurological disorders. These remarkable organelles are far more than simple power plants - they're sophisticated regulators of brain function, involved in everything from energy production to immune regulation. As research continues to unveil their complexity, it becomes increasingly clear that maintaining mitochondrial health is crucial for preserving brain function and treating neurological diseases.
Dendrites are branched structures designed to receive messages from other neurons via axodendritic synapses (junctions between axons and dendrites shown below) and send messages to other neurons dendrodendritic synapses (junctions between the dendrites of two neurons). Dendrites receive thousands of synaptic contacts and have specialized proteins called receptors for neurotransmitters released into the synaptic cleft (Bear, Connors, & Paradiso, 2016).
A neuron's dendrites are called a dendritic tree, and each branch of the tree is called a dendritic branch. Graphic by BruceBlaus from Wikipedia article Neuron.
Biological psychologists classify neurons based on whether their dendrites feature spines. Dendritic spines are protrusions on the dendrite shaft where axons typically form axodendritic synapses. Graphic © Jose Luis Calvo/Shutterstock.com.
Spiny neurons have dendritic spines, while aspinous neurons do not (Bear, Connors, & Paradiso, 2016).
During learning, spines' number, size, and shape may change to adjust the space for receptors (neuroplasticity).
An axon is a cylindrical structure only found in neurons that is specialized for the distribution of information within the central and peripheral nervous systems. Axons range from 1 to 25 µm in diameter and 0.1 mm to more than a meter in length. Over 90% of neurons are interneurons whose axons and dendrites are very short and do not extend beyond their cell cluster. Axons usually branch repeatedly. Each branch is called an axon collateral.
Axons transmit action potentials toward a neuron's terminal buttons. Using microtubules an axon also bidirectionally transports molecules between the cell body and terminal buttons.
An axon hillock is a swelling of the cell body where the axon begins. The middle of an axon is the axon proper, and the end is the axon terminal (Bear, Connors, & Paradiso, 2016). Graphic by M.alijar3i from the Wikipedia article Axon Hillock.
The axon hillock sums EPSPs and IPSPs over milliseconds to generate an action potential.
Axon terminals are buds located on the ends of axon branches that form synapses and release neurochemicals to other neurons. Axon terminals contain vesicles that store neurotransmitters for release when an action potential arrives. Their presynaptic membrane may have reuptake transporters that return neurotransmitters (NTs) from the synapse or extracellular space for repackaging. The graphic of serotonin reuptake transporters below is courtesy of NIDA.
Old school view: glial cells mainly provide structural support (glia is derived from the Greek for glue).
New school view: glial cells help neurons process information, including modulating neuron excitability.
Check out the YouTube video, Neurology - Glial Cells, White Matter and Gray Matter.
Astrocytes are star-shaped glial cells in the central nervous system (i.e., brain and spinal cord) that perform vital functions. Astrocyte endfeet form junctions with capillaries comprising part of the protective blood-brain barrier. They regulate blood flow to the neuron, delivering stored glucose during peak metabolic demand (Schummers et al., 2008). Astrocyte graphic © Kateryna Kon/Shutterstock.com.
Astrocytes enclose synapses, determine where synapses can form by releasing specialized molecules, regulate synapse maturation, bidirectionally communicate with synapses, prune surplus synapses, help neurons regulate brain microcirculation, and eavesdrop on nearby synapse activity (Breedlove & Watson, 2023; Parri & Crunelli, 2003: Shan et al., 2021).
Astrocytes transport amino acid NTs (e.g., GABA and glutamate) from the synaptic cleft.
Astrocytes are theorized to participate in gliotransmission between neurons and each other (Eroglu & Barres, 2010; Perea et al., 2009). However, gliotransmission remains controversial.
The presynaptic and postsynaptic neurons and astrocytes comprise a tripartite synapse.
Astrocyte glutamate release may be essential for hippocampal long-term depression (LTD), a long-lasting reduction in transmission strength, and long-term memory modulation (Navarrete et al., 2019). Astrocyte calcium and brain-derived neurotrophic factor (BDNF) release appear critical for late-phase hippocampal long-term potentiation (LTP), a long-lasting increase in transmission strength, and long-term memory regulation (Liu et al., 2021).
Astrocytes communicate with each other through gap junctions (Bennett et al., 2003).
Finally, astrocytes may contribute to brainwaves by regulating synapses via gap junctions and calcium signaling.
Description: yellow = neurons, orange = astrocytes, grey = oligodendrocytes, white = microglia.
Oligodendrocytes, which are smaller than astrocytes, form up to 50 segments of myelin that only insulate adjacent axons within the brain and spinal cord of the central nervous system. Graphic © Designua/Shutterstock.com.
Oligodendrocytes block axonal regeneration by releasing growth inhibitory proteins. These molecules are part of the reason for minimal functional recovery in the CNS following spinal cord damage. Multiple sclerosis, a demyelinating disease, destroys oligodendrocytes.
Schwann cells provide myelin for single PNS axons and facilitate axonal regeneration following damage (Breedlove & Watson, 2020). Graphic © Tefi/Shutterstock.com.
An excitatory postsynaptic potential (EPSP) is a subthreshold depolarization that makes the membrane potential more positive and pushes the neuron towards its excitation threshold. EPSPs are produced when neurotransmitters bind to receptors and cause positive sodium ions to enter the cell. At a single synapse, a postsynaptic membrane may have tens to thousands of transmitter-gated ion channels. The amount of transmitter released determines how many of these channels will be activated. The size of an EPSP will be a multiple of the number of vesicles, each containing several thousand transmitter molecules.
An inhibitory postsynaptic potential (IPSP) is a hyperpolarization that makes the membrane potential more negative and pushes the neuron away from its excitation threshold. At most inhibitory synapses, IPSPs are produced when neurotransmitters like GABA or glycine bind to receptors and cause negative chloride ions to enter the cell. When an inhibitory synapse is closer to the soma than an excitatory synapse, it can counteract positive current flow and decrease the size of the EPSP. This mechanism is called shunting inhibition (Bear, Connors, & Paradiso, 2016).
The axon hillock of a postsynaptic neuron uses two methods to sum EPSPs and IPSPs: spatial and temporal summation.
In spatial summation, the axon hillock sums the simultaneous postsynaptic potentials (PSPs) from thousands of synapses on dendrites. In temporal summation, the axon hillock adds the PSPs from presynaptic neurons that repeatedly fire within a 1-15-ms time window.
Each EPSP depolarizes the axon hillock by about 0.5 mV. If there were no competing IPSPs, it would take about 30 EPSPs to trigger an action potential. Each IPSP hyperpolarizes the axon hillock by about 0.5 mV. If the summated EPSPs and IPSPs move the axon hillock from a resting potential of -70 mV to a threshold of excitation of -55 mV, sodium channels in the axon hillock membrane open, and an action potential propagates down the axon. Graphic © 2003 Josephine Wilson.
Check out the YouTube video, Best Action Potential Explanation.
Action potentials travel down axons, which branch multiple times and terminate at synapses. The all-or-none law and rate laws describe action potential transmission. The all-or-none law states that once an action potential is triggered in an axon, it is propagated, without decrement, to the end of the axon. The rate law states that neurons represent the intensity of a stimulus by variation in the rate of axon firing. More intense stimuli shorten the interval before a neuron can fire again, allowing a neuron to fire more rapidly. An intense stimulus can cause a neuron to fire every 2 or 3 ms, while a weak stimulus might lengthen the time lag to every 4 or 5 ms. Action potential graphic © extender_01/Shutterstock.com.
We can compare action potential conduction to the movement of water through a leaky garden hose.
Garden hose: water can take two paths, inside the hose or through holes in its wall, and the majority of the water will flow where movement is easiest. For a small-diameter hose with many large holes, most of the water will travel through the leaks. Conversely, for a large-diameter hose with only a few small holes, the bulk of the water will remain inside.
Axon: positive charge can take two paths, inside the axon or through pores in its membrane. Like water, a positive charge will take the path of least resistance. For a small-diameter axon with many open sodium ion channels, the majority of the current will exit the axonal membrane to the extracellular fluid. Small diameter, unmyelinated axons transmit action potentials without weakening since sodium ion channels constantly regenerate this signal. This method is slow because the signal travels step-by-step, small segment by small segment, and waits for sodium channels to admit enough positive ions to reach the excitation threshold. Graphic © 2003 Josephine Wilson.
This method also consumes considerable energy since sodium-potassium transporters, powered by ATP, are located across the axon membrane to exchange three sodium for two potassium ions.
Conversely, for a large-diameter axon with few open ion channels, the bulk of the current will remain inside the axon's interior. Wider spacing between adjacent ion channels means that the action potential can depolarize a longer axon segment, which increases conduction velocity (Bear, Connors, & Paradiso, 2016).
Medium-to-large diameter myelinated axons transmit action potentials using a method called saltatory conduction. Each segment of insulating myelin is almost 1-mm long. The gaps between segments, called nodes of Ranvier, are 1 to 2 thousandths of a millimeter. An action potential weakens under each myelinated segment (cable properties) and is then regenerated at each Ranvier node. The destruction of this insulation by demyelinating diseases like multiple sclerosis (MS) can be devastating because it disrupts neuron-to-neuron communication.
Saltatory conduction can be 200 times faster because the action potential jumps from node to node, in 1-mm steps,” instead of steps that are a thousand times smaller. This method is also more energy-efficient because sodium-potassium transporters are only needed at the nodes of Ranvier, where ion exchange is possible. These transporters account for about 40% of a neuron’s energy expenditure (Breedlove & Watson, 2023; Garrett, 2003). Graphic © 2003 Josephine Wilson.
Neurons communicate through the release of over 200 neurochemicals and ions. Axon terminal buttons release neurochemicals across a 20-50-nm fluid-filled gap between presynaptic and postsynaptic structures called a synaptic cleft and into the extracellular fluid surrounding the neuron (Bear et al., 2020). Chemical synapses produce short-duration (millisecond) and long-duration (seconds to days) changes in the nervous system. Synapse animation without sound © 3Dme Creative Studio/Shutterstock.com.
They are functionally asymmetrical because the presynaptic neuron sends a chemical message and the postsynaptic neuron receives it. They are structurally asymmetrical because the presynaptic element (axon) contains vesicles containing NTs, and the postsynaptic element (dendrite) doesn’t. NT release from a terminal button is called exocytosis (Breedlove & Watson, 2023). Synapse graphic © SciePro/Shutterstock.com.
In the graphic below, an axon terminal button releases NTs into the synaptic cleft. NTs briefly form covalent bonds with receptors on a dendritic spine and then disengage after they initiate small graded potential changes (e.g., EPSPs or IPSPs) or more diverse, gradual, and long-lived actions (e.g., creating second messengers inside the target neuron). Chemical synapse graphic © nobeastsofierce/Shutterstock.com.
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New-school view: neurons can release a classical NT and a peptide.
Dale's law proposed that a neuron releases only one NT. However, researchers have found increasing evidence of NT co-release (Svensson et al., 2019). A neuron can store different NTs in separate types of vesicles (Hökfelt et al., 2003). Neurons can also store multiple NTs in the same vesicles (e.g., ATP and glutamate), although they may not release them simultaneously (Merighi et al., 2011; Xia et al., 2009).
Neurons release NTs outside of classical synapses. These mechanisms include release from terminal buttons into the extracellular space, axonal varicosities, and retrograde transmission.
Old-school view: axon terminals only release NTs into the synaptic cleft.
New-school view: NT release also occurs outside of the synaptic cleft. Axonal varicosities (swellings in axon walls), dendrites, and the terminal button can release NTs into the extracellular space. Graphic © 3Dme Creative Studio/Shutterstock.com.
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Retrograde NTs can bind to membrane-bound receptors or diffuse into the target cell, initiating second messenger production to adjust synaptic efficiency in learning and memory (Breedlove & Watson, 2023).
Modulation is analogous to a volume control knob instead of an on/off switch on a stereo preamplifier; analog instead of digital.
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We will consider two of countless modulation mechanisms: modulation of NT release and modulation of NT action at its receptor.
Axoaxonic synapses do not affect the generation of an action potential, only the amount of neurotransmitter distributed. In presynaptic facilitation, a neuron increases the
presynaptic neuron's neurotransmitter release by delivering a neurotransmitter that increases calcium ion
entry into its terminal button. In presynaptic inhibition, a neuron decreases
neurotransmitter release by reducing calcium ion entry. These modulatory effects are confined to a single
synapse (Breedlove & Watson, 2023).
The principal NT families include amino acid neurotransmitters (GABA, glutamate), amine neurotransmitters (acetylcholine, dopamine serotonin), peptide neurotransmitters, also called neuropeptides (oxytocin, vasopressin), gas neurotransmitters (nitric oxide, carbon dioxide), and lipid neurotransmitters (anandamide and AG-2). The table below is adapted from Breedlove and Watson (2023).
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Cholinergic cell bodies and their projections originate in the basal forebrain and brainstem. Cholinergic pathways are involved in arousal, attention, memory, motivation, muscle contraction, and sleep.
Two major dopaminergic pathways originate in the midbrain: the mesostriatal and mesolimbocortical pathways. Dopaminergic pathways are involved in addiction, motor control, and salience (reward- and threat-based motivation).
The noradrenergic pathways originate in the midbrain locus coeruleus and lateral tegmental area. Noradrenergic pathways are involved in arousal, attention, memory, vigilance, sleep, and mobilizing the brain and body for action, including the fight-or-flight response.
The serotonergic pathways originate in the brainstem and midbrain raphe nuclei. Serotonergic pathways are involved in appetite, mood, and sleep.
In enzymatic degradation, enzymes located in the synaptic cleft and the cytoplasm of the presynaptic neuron's terminal button split neurotransmitter molecules apart (e.g., acetylcholine). Graphic © Designua/Shutterstock.com.
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Electrical synapses are generally symmetrical. Ions flow across a 3-nm gap junction into the more negatively charged neuron as long as the gap junction remains open. This means that whether neurons are presynaptic or postsynaptic depends on their respective charges. When two neurons are electrically coupled, an action potential in one induces a postsynaptic potential (PSP) in the paired neuron.
Transmission across electrical synapses is nearly instantaneous, compared with the 10-ms or longer delay in chemical synapses. The rapid information transmission that characterizes electrical synapses enables large circuits of neurons to synchronize their activity and simultaneously fire.
Neurons that secrete hormones use electrical synapses to release their chemical messengers simultaneously. Neonatal brains may use gap junctions to activate many neurons at once. Image of long, fibrous astrocyte processes using Golgi's silver chromate technique © Jose Luis Calvo/Shutterstock.com.
Gap junctions may be a preliminary step toward developing chemical synapses between these neurons, eventually replacing their electrical synapses. Prenatally and postnatally, gap junctions enable nearby neurons to coordinate their development by sharing electrical and chemical communications (Bear, Connors, & Paradiso, 2016; Breedlove & Watson, 2023).
Old school view: synapses are either electrical or chemical.
New school view: synapses can be both electrical and chemical
Neuroscientists have learned a great deal more about neuron-to-neuron communication since graduate school. The most important findings are that the adult brain creates new neurons, silent synapses may mediate neuroplasticity in adulthood, the lymphatic system extends to the brain, neuronal networks exhibit mirroring properties, and neurons can release more than one NT, release NTs outside of a synapse, conduct two-way conversations, modulate NT release and action, talk to astrocytes that enclose synapses, and electrically communicate almost instantaneously.
Holly Barker (2022) writing for The Scientist, explained:
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These mirror neurons fired when primates grasped and manipulated objects, and another primate or human performed the same action (Di Pelligrino et al., 1992; Rizzolatti & Craighero, 2004). Mirroring extends across species, including facial expressions.
Molenberghs et al. (2011) unexpectedly found neurons with mirroring properties in the cerebellum, limbic system, and primary visual cortex. Graphic courtesy of Wikimedia Commons.
The authors proposed that a core network is responsible for observing and executing movements. The nervous system recruits additional areas to perform non-motor affective, auditory, and somatosensory functions.
Mirror neurons look like other neurons when examined using a microscope. Their mirror properties emerge from their sensory, motor, and emotional systems connections. Perhaps most mirror neurons may be tuned by experience (Catmur, Walsh, & Heyes, 2007).
The mirror neuron system (MNS) appears to encode the goal of a motor act and its component movements, whether a model manipulates an object or mimes the action. The MNS encodes the actions of others and stores them to predict their future actions (Rajmohan & Mohandas, 2007).
Soon after birth, an immature mirror neuron system may allow babies to imitate their parents' mouth movements, like thrusting out the tongue. Graphic courtesy of Wikimedia Commons.
Note. Image from Gross L. Evolution of neonatal imitation. PLoS Biol.
Ramachandran (2011) has called the mirror neurons activated when they observe others' movements "monkey see—monkey do neurons." He calls mirror neurons activated by others' emotional displays "Gandhi neurons." Check out Ramachandran's TED Talk, The Neurons that Shaped Civilization.
Investigators have speculated that the human MNS may mediate empathy, imitation learning, language, social cognition, and theory of mind (Buccino et al., 2006; Rajmohan & Mohandas, 2007; Schmidt et al., 2021).
Rizzolatti and Sinigaglia (2008) hypothesized that the primary role of the MNS is to help us understand others’ intentions, which allows us to achieve empathy. When we observe others’ facial expressions of emotion, visual information may be directly transmitted to mirror neurons in the insula, producing the visceral changes that color our emotions.
In autism, mirror neurons may not fire when observing other individuals performing actions. This may help explain deficits in empathy, social skills, language, and the development of a theory of mind (Enticott et al., 2011).
Heyes et al. (2021) summarized the state of our knowledge about the MNS.
The cerebral cortex comprises neuronal cell bodies, glial cells, and blood vessels. Beneath the neocortex lies myelinated nerves (white matter), unmyelinated fibers, and glial cells.
The cerebral cortex covers the cerebral hemispheres and consists of gray and white matter. Gray (or grey) matter, which looks grayish brown, comprises cell bodies. White matter gains its opaque white color from myelinated axons. The cerebral cortex of a macaque brain is shown below, courtesy of Wikipedia. Note that staining imparts a darker shade to gray matter.
The convolutions of the cerebral cortex contain two-thirds of its surface area and maximize the volume of cortical tissue housed within the skull. Cerebral cortical convolutions include sulci, which are shallow grooves in the surface of the cerebral hemisphere (central sulcus), fissures, which are deep grooves (lateral fissure), and gyri, which are ridges of cortex demarcated by sulci or fissures (precentral gyrus) (Carlson & Birkett, 2021).
There are two main types of cortex: neocortex and allocortex.
The neocortex or isocortex consists of six layers 3 mm thick with a surface area of about 2360 cm2 with white matter underneath. Layers I-III receive corticocortical afferent fibers that connect the left and right hemispheres. Layer III is the main source of corticocortical efferent fibers. Layer IV is the primary destination of thalamocortical afferents and intra-hemispheric corticocortical afferents. Layer V is the primary origin of efferent fibers that target subcortical structures that have motor functions. Layer VI projects corticothalamic efferent fibers to the thalamus, which together with the thalamocortical afferents, creates a dynamic and reciprocal relationship between these two structures (Creutzfeldt, 1995). Diagram courtesy of Wikimedia Commons.
Allocortex, which means other cortex, usually has between three or four layers, compared with the neocortex's six layers. The allocortex has less volume than the neocortex and comprises the olfactory system and hippocampus.
A transitional region between the neocortex and allocortex is called the paralimbic cortex.
For a basic overview of the cortex, watch the Khan Academy video Cerebral Cortex.
The graphic below depicts dendritic spines.neurons, which have either pyramidal or stellate (star-like)-shaped cell bodies, are usually excitatory. While all pyramidal cells are spiny neurons, stellate cells can be spiny or aspinous (Bear, Connors, & Paradiso, 2020). Spiny and aspinous dendrite graphic redrawn by minaanandag on Fiverr.com.
Dr. John C. Fiala, and Dr. Kristen M. Harris created this reconstruction of a dendritic spine. Creative Commons Attribution-Share Alike 3.0.
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There are many types of aspinous (smooth) neurons which are believed to be inhibitory.
The scalp EEG is the voltage difference between two recording sites recorded over time. The EEG is primarily generated by large pyramidal neurons located in layers 3 and 5 of the 2-4.5-mm-thick cortical gray matter. Image of a pyramidal neuron revealed using Golgi silver chrome © Jose Luis Calvo/Shutterstock.com. Note that the apical dendrite arising from the cell body and basilar dendrites feature an extensive network of spines.
Local activity is a composite of local and network influences. Network communication systems and local cortical functions show different characteristics across the cortex and produce unique and specific EEG patterns in other regions.
The movie below is a BioTrace+/NeXus-32 display of the raw EEG with voltage shown as μV peak to peak © John S. Anderson.
Pyramidal neurons of the cerebral cortex stained with the Golgi silver chromate © Jose Louis Calvo/Shutterstock.com.
Pyramidal neurons are found in all cortical layers, except layer 1, and represent the primary type of output neuron in the cerebral cortex. Pyramidal neuron graphic © Kateryna Kon/Shutterstock.com.
The scalp EEG results from the summation of EPSPs and IPSPs in thousands of cortical columns containing large pyramidal cells perpendicular to the cortical surface. The columns are synchronously polarized (made more negative) and depolarized (made less negative) due to the input of oscillatory or transient evoked activity. Graphic redrawn by minaanandag on Fiverr.com.
Artist: Dani S@unclebelang. This WEBTOON is part of our Real Genius series.
Caption from Wikipedia's article on Neural Oscillation. Simulation of neural oscillations at 10 Hz. The upper panel shows spiking of individual neurons (with each dot representing an individual action potential within the population of neurons). On the lower panel, the local field potential reflects their summed activity. This figure illustrates how synchronized patterns of action potentials may result in macroscopic oscillations that can be measured outside the scalp.
Action potentials reflect neuronal output. They are seen in extracellular recordings as fast (~300 Hz) activity that exceeds 90 mV lasting less than 2 ms. Action potentials play a minor role in scalp surface EEG. They fall below 60 V outside of a 50-μm (0.050-mm) radius. Scalp electrodes are several centimeters from cortical neurons and are generally aligned away from the scalp. Therefore, action potentials are unlikely to contribute significant voltages to the scalp EEG.
The movie is a 19-channel BioTrace+ /NeXus-32 display of SCPs © John S. Anderson. Negative SCPs drift up, and positive SCPs drift down, depending on the software settings. However, the convention in electroencephalography is to show negative up. SCPs represent a global shift in DC voltage across the cortex and represent a generally higher (negative SCPs) or lower (positive SCPs) state of cortical excitability regulating neural networks.
The EEG is a moment-to-moment measure of the excitability of action potential firing, like gates opening and closing on the half cycle. The synchronous activity of large pyramidal neurons networked in cortical columns creates the EEG.
Movie © John S. Anderson. The recording begins with eyes open. The eyes-closed condition starts at 14’01” and clearly shows increased 8-12 Hz voltage (posterior dominant rhythm or PDR) in occipital and parietal locations in the line tracing and topographic maps to the right of the tracing.
The eyes open again at 14’31”, and alpha attenuates (alpha blocking). This shows the posterior dominant rhythm (generally known as "alpha") appearing in the eyes-closed condition when visual sensory input is stopped. The attenuation or blocking of this rhythm as sensory input returns in the eyes-open condition.
The thalamus contributes to slow cortical potentials, 1-4 Hz delta, 8-12 Hz alpha, and 20-38 Hz beta (including 40-Hz activity). The diagram shows the connections between the pulvinar (bottom right) and reticular nuclei (bottom left) of the thalamus and the cortex © Elsevier Inc. - Netterimages.com.
Thalamocortical cells are subject to excitatory drive from their system afferents, from monosynaptic corticothalamic fibers, and from the brainstem reticular formation (ascending reticular activating system, ARAS). They receive inhibitory drive from local interneurons and neurons in the reticular nucleus of the thalamus (RNT). Note that the RNT neurons are excited by activity in thalamocortical cells and corticothalamic cells. The connections are precisely organized. For example, each column in a primary cortical area sends corticothalamic fibers back to the same part of its specific thalamic nucleus that sends its thalamocortical fibers to that cortical column. The corticothalamic fibers also synapse on the RNT cells receiving input from that part of the thalamic nucleus. Each cortical receiving area is said to be "reciprocally connected" with its specific thalamic nucleus. Like the thalamocortical cells, RNT cells and cortical neurons also receive excitatory drive from the ARA (Jackson & Stoney, 2006).
The EEG is generated by thalamocortical (alpha) and cortical-cortical (beta) sources.
Neurons in the ascending reticular activating system produce event-related potentials in response to diverse stimuli like a flashing light or sound. Event-related potentials (ERPs) are the brain's response to externally applied stimuli, events, or cognitive/motor tasks. They are time-locked measures of brain electrical activity. Graphic redrawn by minaanandag on Fiverr.com.
"These oscillations are generated spontaneously in several areas of the cerebral cortex as neuronal networks transiently form assemblies of synchronously firing cells." Klaus Linkenkaer-Hansen.
The postsynaptic potentials (EPSPs and IPSPs) propagated by the apical dendrites in layers 2 and 3 create an extracellular dipole layer parallel to the cortical surface. The dipole layer's electrical polarity is the opposite of the deeper cortical layers 4 and 5 (Fisch, 1999).
A cortical dipole is created when pyramidal neurons depolarize simultaneously. This phenomenon is called local synchrony. Fewer than 5% of pyramidal neurons can generate more than 90% of the power in the EEG signal because most pyramidal neurons usually fire asynchronously so that their potentials counteract each other. A small fraction of these neurons firing in step can produce visible changes in EEG feedback. This creates the potential for operant conditioning to help clients learn to modify EEG activity through neurofeedback.
Cortical dipoles have three properties: site (depends on source), size (oscillation frequency and voltage), and relative position with respect to sulci and gyri (Collura, 2014).
Recall that a gyrus is a ridge of the convoluted cerebral cortex, while a sulcus is a valley. The graphic below is adapted from Wikipedia.com from the article Sulcus (neuroanatomy) by minaanandag.
The EEG is most sensitive to a correlated dipole layer in gyri. The EEG is less sensitive to a correlated dipole layer in sulci, valleys within the cortex. Finally, the EEG is insensitive to an opposing dipole layer in sulci.
The EEG is composed of electrical potentials that vary along the dimensions of amplitude and frequency.
Amplitude measures the amount of energy in the signal and is usually expressed in microvolts.
Greater synchrony in firing among neurons results in higher amplitude, as shown with alpha in the graphic below.
Greater firing synchrony produces larger EEG potentials that can be measured from the scalp surface. Graphic redrawn by minaanandag on Fiverr.com.
The EEG plots voltage changes over time, which can be displayed on a graph. The sampling rate is the number of measurements per second (Hz). Precision is the number of voltage gradations or steps.
The analog-to-digital (A/D) converters that transform voltages into numerical values vary in precision: more bits correspond to greater accuracy. Graphic © Fouad A. Saad/Shutterstock.com.
EEG frequency is measured in cycles per second or Hz. Count the number of peaks or count the number of zero (0.0) crossings divided by 2.
The slower the waves, the lower the EEG frequency. Frequency graphic © Bany's beautiful art/Shutterstock.com.
The longer the wavelength, the slower the frequency.
The movie is a 19-channel BioTrace+ /NeXus-32 display of EEG activity from 1-64 Hz activity broken into its component delta, theta, alpha, and beta frequency bands by digital filters © John S. Anderson.
The movie is a 19-channel BioTrace+ /NeXus-32 display of alpha activity © John S. Anderson. Brighter colors represent higher alpha amplitudes. Frequency histograms are displayed for each channel. Notice the runs of high-amplitude alpha waves.
The movie below is a BioTrace+ /NeXus-32 display of EEG spindling activity © John S. Anderson.
Timing is everything since action potentials arrive from a large number of sources. The nervous system must correctly register arrival times to recognize a face, recall a name, or remember personal history and context.
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The movie below of bursting alpha shows the sequential synchronization/desynchronization of groups of neurons. Higher voltage bursts are followed by voltage decreasing toward zero. These voltage fluctuations reflect rhythmic changes in the local field potential. This BioTrace+ /NeXus-32 video © John S. Anderson.
Sensory evoked potentials are a subset of ERPs elicited by external sensory stimuli (auditory, olfactory, somatosensory, and visual). They have a negative peak at 80-90 ms and a positive peak at about 170 ms following stimulus onset. The orienting response ("What is it?") is a sensory ERP. The N1-P2 complex in the auditory cortex of the temporal cortex reveals whether an uncommunicative person can hear a stimulus.
Motor ERPs are detected over the primary motor cortex (precentral gyrus) during movement, and their amplitude is proportional to the force and rate of skeletal muscle contraction (Thompson & Thompson, 2016).
These potentials include the contingent negative variation (CNV), readiness potential, movement-related potentials (MRPs), and P300 and N400 potentials, and exclude event-related potentials (ERPS) (Andreassi, 2007).
SCPs modulate the firing rate of cortical pyramidal neurons by exciting or inhibiting their apical dendrites. They group the classical EEG rhythms using these synchronizing mechanisms (Steriade, 2005). These potentials are crucial indicators of cortical excitability and are associated with various cognitive and motor processes.
The movie is a 19-channel BioTrace+ /NeXus-32 display of SCPs © John S. Anderson. Brighter colors represent higher SCP amplitudes. Negative SCPs drift down, and positive SCPs drift up. Negative SCPs are produced by the depolarization of apical dendrites and increase the probability of neuron firing. Positive SCPs are produced by the hyperpolarization of these dendrites and decrease the likelihood of neuron firing.
He stated, "The cortex's Direct Current baseline waxes negative whenever it is more active. Gradients of 150-200 μV/mm are noted." He later noted, "when any part of the gray matter is in a state of functional activity, its electric current usually exhibits negative variation." Some later researchers suggested that this signaled the discovery of the "steady potential" or the DC potential of the brain. However, others have noted the possibility of equipment-based artifacts in his recordings (Niedermeyer, 1999).
From the late 1800s through the early 1900s, research into brain electrical activity turned toward observations of electrical stimulation and spontaneous electrical activity in animal studies. As technology improved, the ability of researchers to identify EEG rhythms also improved. Hans Berger is famous for his description of alpha-blocking with cognitive activity, made possible partly because of his use of more sensitive equipment (Niedermeyer, 1999).
SCPs have been identified in cortical neurons, the thalamus, and glial cells. Cortical neurons in layers II to VI generate slow oscillations when the thalamus is removed or when cortical tissue is studied in vitro (in an artificial environment) or in vivo (within a living organism). Thalamic reticular neurons exhibit similar slow spontaneous oscillations when studied in vitro, and synchronized intracortical oscillations may depend on a corticothalamic network that targets these thalamic neurons.
The source and nature of slow cortical potentials are in dispute. The prevailing theory holds that negative SCPs result from synchronous postsynaptic potentials in the apical dendrites of cortical pyramidal cells. Others hold that SCPs are supported and produced by glial cells within the cortex. It appears that pyramidal neurons may be the source of these potentials and that the glial system is the "sink" in electrical terms (Strehl, 2005, personal communication).
Increased neuronal activity is associated with an increased outflow of potassium ions leading to increased extracellular potassium concentrations. Glial cells depolarize when extracellular potassium concentrations increase, resulting in intracellular and extracellular current flows similar to typical neuronal synaptic transmissions (Speckmann & Elger, 1999). Since glial cells are widely interconnected and have extensive processes, it appears likely that the glial system is responsible for the potential changes that produce SCP values recorded from the scalp in response to neuronal activity.
Despite some discussion regarding the source of SCP activity, it is clear that scalp SCPs represent the cortex's excitability potential. SCP negativity is associated with increased cortical excitability. High cortical negativity has been correlated with a greater likelihood of seizures (Speckmann et al., 1984) and migraines (Siniatchkin et al., 2000) in susceptible individuals.
SCP positivity is associated with increased cortical inhibition. Higher-than-expected positive SCPs have been noted in children with elevated blood lead levels (PbB; Otto & Reiter, 1984). Children diagnosed with ADHD show deficient SCP self-regulation skills compared with controls (Heinrich et al., 2004). SCPs have been used to monitor the depth of anesthesia during surgical procedures (Sebel et al., 1997) because they appear to be excellent indicators of the arousal level.
Glial cells generate slow SCPs when they burn sugar, producing negatively charged bicarbonate ions. Unlike EEG rhythms like delta, SCPs do not summate dendritic potentials. SCPs are associated with glial cells and gap junctions. Glial cells chemically communicate among themselves and with neurons. The slow oscillations of glial cells may influence the timing of neuronal firing through their control of potassium ion outflow (Steriade, 2005). Astrocyte graphic © Kateryna Kon/Shutterstock.com.
"The concept of a unified corticothalamic network that generates diverse types of brain rhythms grouped by the cortical slow oscillation is supported by EEG studies in humans" (Mölle et al., 2002).
The negative SCPs detected at the scalp during neuronal depolarization may seem counterintuitive at first.
When neurons are activated, their cell bodies become more positive internally due to the influx of positive ions. This leaves the immediate extracellular space around the neuron more negative. The negative charge in the extracellular space is conducted through brain tissue, cerebrospinal fluid, skull, and scalp. EEG electrodes on the scalp detect this conducted negative potential, resulting in a negative deflection on the EEG trace.
This phenomenon is often referred to as paradoxical negativity in EEG literature (Birbaumer et al., 1990). It's important to note that what we record on the scalp is not a direct measure of neuronal membrane potential, but rather the result of complex electrical field propagation through various tissues (Elbert et al., 1980). Paradoxical positivity occurs when neurons are hyperpolarized.
This relationship is crucial in understanding the neurophysiological mechanisms underlying SCPs (Birbaumer et al., 1990). This paradoxical negativity graphic (Brienza & Mecarelli, 2019) is available under the license CC BY 3.0.
Caton (1875) observed that the cortex's direct current baseline becomes negative whenever it is more active. The voltage gradients range from 150-200 μV. Underlying "tone" or valence factors determine the firing characteristics of neurons within a network. When SCPs are more positive, cortical neurons fire less due to hyperpolarization. When SCPs are more negative, firing increases due to depolarization.
SCPs participate in cognitive processes such as attention, preparation, and intention. Negative SCP shifts are often linked to increased cortical excitability and readiness to respond, while positive shifts are associated with decreased excitability and relaxation (Birbaumer et al., 1990).
Some types of SCPs are event-related. These include the Bereitschaftspotenial (BP or so-called readiness potential), contingent negative variation (CNV), and stimulus-preceding negativity (SPN). These represent slow negative waves related to anticipating a stimulus or preparing for a movement (Brunia et al., 2012). The BP occurs before the execution of a self-paced movement. CNV occurs when a preparatory stimulus foretells the imminent presentation of a stimulus that requires a response. SPN occurs after a movement when waiting for a stimulus that will provide feedback about the accuracy of the movement.
The slow rhythm of SCPs is often combined with delta oscillations, and these rhythms are phase-locked, suggesting a close interaction between different frequency bands in the brain's electrical activity (Steriade, Nuñez, & Amzica, 1993).
SCPs play a crucial role in motor preparation and execution. The readiness potential (Bereitschaftspotential), a type of SCP, precedes voluntary movements and reflects the planning and initiation of motor actions.
SCPs are also associated with emotional and motivational states. Negative SCPs can indicate increased arousal and emotional engagement, whereas positive SCPs can reflect relaxation and disengagement (Hinterberger et al., 2004).
Research has shown that during non-rapid eye movement (NREM) sleep, cortico-basal slow wave delta activity increases, while beta activity decreases. Deep brain stimulation (DBS) further modulates this altered activity, enhancing cortical delta activity and reducing alpha and low beta power. These findings suggest that SCPs and their interaction with other brain rhythms are significantly altered in PD, contributing to sleep dysfunction and spontaneous awakenings (Anjum et al., 2023).
SCPs are used to monitor the effects of therapeutic interventions, such as deep brain stimulation (DBS), on cortical function in PD patients.
Slow cortical potential (SCP) neurofeedback has shown potential efficacy as a complementary treatment for Parkinson's disease (PD). SCP neurofeedback aims to train individuals to self-regulate their brain activity, particularly focusing on slow cortical potentials associated with motor control.
Research suggests that SCP neurofeedback can improve motor function in PD patients (Kober & Wood, 2014). Some studies have reported that participants undergoing SCP neurofeedback training demonstrated better control over motor symptoms, such as tremors and rigidity, and experienced enhanced overall motor performance. Additionally, SCP neurofeedback has been associated with improvements in non-motor symptoms, including mood and cognitive function, which are often affected in PD.
While promising, the current evidence is based on a limited number of studies with small sample sizes. More extensive and rigorous clinical trials are needed to establish SCP neurofeedback's long-term efficacy and generalizability for PD.
Abnormal SCP patterns have been linked to sleep disorders such as insomnia. Neurofeedback training targeting SCPs can improve sleep onset latency and enhance overall sleep quality (Hoedlmoser et al., 2008).
The study of SCPs continued in physiology and animal research. Only recently has there been increased interest in observing SCPl values in the human EEG and correlating them with cognitive activity, sensory processing, and motor activity. SCPs are distinguished from short-latency, event-related potentials (ERP) up to 500 ms. SCPs reflect cortical processes that require more than one second to complete and are associated with more global, task-related activities. Such changes occur in task-specific areas of the cortex and can be displayed using topographic maps. Areas of activation show surface negative potential changes (Altenmuller & Gerloff, 1999).
Operant conditioning of SCP changes is an even more recent study area. One reason for increased interest in SCP training is the excellent work done by Birbaumer and colleagues (1999) at the University of Tubingen in Germany, demonstrating that SCPs can be operantly conditioned with positive outcomes for a variety of disorders. The recent availability of DC-coupled amplifiers for EEG recording has also contributed to this interest (Altenmuller & Gerloff, 1999).
According to Niedermeyer (1999), "DC" can mean several things. DC means direct current, which is a current without oscillations. From an electrophysiological perspective, "DC shifts" are ultra-slow potentials below the typical EEG in the oscillation frequency and are generally around 0.1-0.2 cycles per second. However, they may extend up to 1 cycle per second. So SCPs are not true direct current, though their oscillations are so slow that they are "DC-like" phenomena.
DC also refers to "direct coupling" (Niedermeyer, 1999) and describes a type of amplifier that does not use capacitors between the amplification stages and uses an infinite time constant to provide for optimal DC recording. Until recently, this has been quite difficult to achieve for EEG recording. Most conventional EEG amplifiers use capacitors in the input stage, which reject DC voltages and create a finite time constant that interferes with access to DC phenomena.
An approximation of DC information can be obtained from an alternating current amplifier by using a rectifier or extending the time constant to approximately 10 seconds (Kotchoubey et al., 1999). A thorough discussion of amplifier characteristics is beyond the scope of this article. Several excellent chapters relating to this subject can be found in Niedermeyer and Lopes da Silva (1999).
Recent studies have used SCPs to evaluate various task-oriented responses. Birbaumer and colleagues have trained SCPs to reduce seizures (Daum et al., 1993; Kotchoubey et al., 1997, 1999, 2001, 2002), and other groups have applied SCP feedback training to improve ADHD (Heinrich et al., 2004; Strehl, 2004, personal communication) and schizophrenia (Schneider et al., 1992).
SCP feedback training appears to be an approach that targets general characteristics of arousal using a single measure, compared to other types of EEG training that often reward increases and/or decreases in certain combinations of frequencies to accomplish changes in arousal. SCP feedback may provide a less complex approach to training neuronal activity in the clinical setting, providing greater accessibility via clinician-supervised home training devices.
Most research to date has been conducted using the Cz electrode site. However, at least one investigation involved training left hemisphere language sites. This approach demonstrated improved word processing results following the negativity training condition and diminished performance following the positivity condition (Pulvermuller, 2000). Studying the effects of SCP training at other electrode sites would be interesting.
Some efforts have been to identify SCP values using multiple electrodes in a quantitative EEG assessment paradigm. Basile and colleagues (2004) used four 32-channel DC-coupled amplifiers to identify differences in SCP responses in schizophrenic patients compared with normal controls. They found significant variations in response patterns, with normal controls showing simply-organized positivity and negativity patterns, while schizophrenic patients showed much more complex, fragmented patterns of activation and inhibition.
There are only a few clinically available DC-coupled amplifiers capable of accurately monitoring SCP activity. An Internet search yielded several devices aimed at the research institution market with correspondingly high prices and a couple of other devices with prices within a clinical practice’s reach. A new 32-channel DC-coupled data acquisition device for quantitative EEG assessments has also recently been released.
One potential attraction of using a DC amplifier is the capability of monitoring and/or training both SCPs and typical EEG frequencies. This is because DC amplifiers are optimized for SCP and have the capacity to record faster frequencies. This is particularly true for amplifiers with better analog-to-digital (AD) conversion characteristics (bit size, not sampling rate) because this allows them to record AC potentials without exceeding amplifier capabilities, which can be a problem in an amplifier without capacitors at the input stages.
Higher analog-to-digital (A/D) conversion values (more bits of data per sample) allow newer DC amplifiers to process EEG at a much lower voltage while retaining a high degree of resolution for signals that are often in the millivolt range (compared to microvolt values for most EEG signals).
The training of SCP shifts is a fairly new endeavor. Much remains to be learned about the effects of training both the positivity and negativity conditions at various electrode sites for individuals with various presenting concerns and specific neurophysiological characteristics.
This author's recent, brief clinical experiences suggest that training SCP using new, more accurate amplifiers may result in more pronounced changes occurring more quickly. This occurred on several occasions, even when using previously well-tested protocols alternating 8- to 10-second trials of both the positivity and negativity conditions. Thus, it will be important to develop protocols with more specificity and flexibility to meet the needs of non-homogeneous client populations that also consider changes in equipment and software characteristics that may affect the rate of skill acquisition and subsequent outcomes.
Various approaches to training slow cortical shifts have been applied. Early research (Birbaumer, 1990; Birbaumer, 1999) showed a correlation between cortical negativity and reaction time, signal detection, and short-term memory. This was identified primarily through evoked and event-related potential (EP, ERP) research, which led to a focus on the event-related potential in developing training paradigms for research and clinical interventions. Protocols involved presenting clients/participants with sequences of 8-second trials, training both positive and negative shifts in the cortical gradient by providing visual and/or auditory feedback showing such shifts in real-time. When the goal was greater cortical positivity, more positive shift trials were provided, and the opposite was true when cortical negativity was desired. Additional transfer trials were included that asked the individual to produce a shift but did not provide visual or auditory feedback to test the level of skill acquisition. This approach was the primary paradigm during the early years of SCP research (Strehl, 2009).
Other clinicians and researchers, including Susan and Siegfried Othmer and Mark Smith, addressed these slow gradient shifts with training called variously Infra-Low Frequency Neurofeedback (Othmer, 2020) and Infraslow Neurofeedback (Smith, 2013).
Post-traumatic stress, anxiety, and other characteristics of excessive cortical activation and excitability have been addressed by training to increase overall cortical positivity, using a 4-channel/location approach that rewards a gradual shift in the cortical gradient by providing proportional audio feedback reflecting directional shifts in the gradient. This has resulted in several client self-reports of an altered state experience characterized by a marked decrease in cognitive activity while retaining awareness. The positive shift in cortical gradient appears to correspond with a reduction in conscious thought while allowing a sense of self-awareness to remain (multiple clinical observations shared with John Anderson).
Slow cortical potentials (SCPs) are characterized by low-frequency oscillations in the EEG, typically below 1 Hz, with significant depolarizing-hyperpolarizing components. These potentials, occurring at approximately 0.3 Hz, are crucial indicators of cortical excitability and are associated with various cognitive and motor processes. Generated by cortical neurons, thalamocortical interactions, and glial cells, SCPs reflect shifts in cortical excitability linked to attention, motor preparation, and emotional states. Negative SCP shifts indicate increased excitability and readiness to respond, while positive shifts are associated with relaxation and decreased excitability.
SCPs play roles in psychological and medical disorders like ADHD, epilepsy, and depression, and are vital in sleep regulation and performance enhancement. SCP neurofeedback shows promise in improving symptoms and cognitive functions in various conditions.
The author would like to thank Ute Strehl of the University of Tubingen in Germany, David Seiver of Mind Alive, LTD in Canada, and Erwin Hartsuiker of Mind Media BV in the Netherlands for technical assistance in preparing this article.
Neuroplasticity, the remodeling of neurons and neural networks with experience, is responsible for learning and memory. Memory storage involves the remodeling of neurons in terms of synaptic transmission, interneuron modulation, formation of new synapses, and rewiring of neural pathways (Bear, Connors, & Paradiso, 2020). Animal studies have shown that operant conditioning can induce astrogliogenesis (creation of new astrocytes) and neurogenesis (creation of new neurons) in structures like the medial prefrontal cortex and hippocampus (Rapanelli, Frick, & Zanutto, 2011).
The graphic by Rebeca Cuesta is licensed under the Creative Commons Attribution-Share Alike 4.0 International license.
Neuroplasticity appears to involve a simple rule: when some synapses strengthen, adjacent synapses weaken to prevent overload due to increased input. A protein called Arc is crucial to this process (El-Boustani et al., 2018).
Neurofeedback, which involves the operant conditioning of CNS electrical activity, would be impossible without neuroplasticity. In neurofeedback, clients may learn to change the activity of local, regional, and global cortical resonant loops and the connectivity between brain regions (Collura, 2014; Thompson & Thompson, 2016).
To learn more about neuroplasticity, view the Khan Academy video Neuroplasticity.
In long-term depression (LTD), synaptic transmission that coincides with slight depolarization of the postsynaptic neuron weakens a synapse due to pre- and postsynaptic changes. Relatively low-frequency stimulation of afferent neurons reduces the magnitude of their response to future stimulation
In long-term potentiation (LTP), synaptic transmission that coincides with strong depolarization of the postsynaptic neuron strengthens a synapse due to pre- and postsynaptic changes. Strong stimulation of afferent neurons results in a stable and persistent (weeks or more) increase in synaptic effectiveness. LTP involves diverse changes, including creating new synapses, enhancing previous synapses, and building new dendritic branches and spines (Breedlove & Watson, 2020).
To learn more, watch the Khan Academy video Long Term Potentiation and Synaptic Plasticity.
40-Hz rhythm: gamma rhythm hypothesized to be associated with feature binding (linking an apple's color to its shape) and attributed to the neocortex and thalamocortical neurons.
acetylcholine: an amine neurotransmitter that binds to nicotinic and muscarinic ACh receptors.
acetylcholine esterase (AChE): the enzyme that deactivates ACh.
AChE-R: an abnormal form of acetylcholine esterase (AChE) may render dendrites with acetylcholine receptors more excitable when stressed.
action potential: a propagated electrical signal that usually starts at a neuron’s axon hillock and travels to presynaptic axon terminals.
adenylate cyclase: at a metabotropic receptor, an enzyme that transforms ATP into the second messenger cyclic AMP.
afferent: a neuron that transmits sensory information towards the central nervous system or from one region to another.
allocortex: cortex that contains three or four layers and is comprised of the olfactory system and hippocampus.
all-or-none law: once an action potential is triggered in an axon, it is propagated, without decrement, to the end of the axon. The amplitude of the action potential is unrelated to the intensity of the stimulus that triggers it.
alpha blocking: arousal and specific forms of cognitive activity may reduce alpha amplitude or eliminate it entirely while increasing EEG power in the beta range.
alpha rhythm: 8-12-Hz activity that depends on the interaction between rhythmic burst firing by a subset of thalamocortical (TC) neurons that are linked by gap junctions and rhythmic inhibition by widely distributed reticular nucleus neurons. Researchers have correlated the alpha rhythm with "relaxed wakefulness." Alpha is the dominant rhythm in adults and is located posteriorly. The alpha rhythm may be divided into alpha 1 (8-10 Hz) and alpha 2 (10-12 Hz).
alpha spindles: regular bursts of alpha activity.
alpha-subunit: a subunit of a G protein associated with the neuron membrane that breaks away to activate enzymes within the neuron when a ligand binds to a metabotropic receptor.
amino acid neurotransmitters: the oldest family of transmitters. These molecules bind to ionotropic and metabotropic receptors, so they transmit information and modulate neuronal activity. In the brain, most synaptic communication is accomplished by glutamate (generally excitatory) and GABA (generally inhibitory).
AMPA (glutamate) receptors: ionotropic receptors which open sodium channels, depolarize the neuron's membrane (producing an EPSP), and dislodge a Mg+ ion that blocks an adjacent NMDA (glutamate) receptor's calcium channel. AMPA receptors are responsible for most activity at glutamatergic synapses.
amplitude: the energy or power contained within the EEG signal measured in microvolts or picowatts.
amygdala: the limbic system structure that participates in evaluating whether stimuli are salient (rewarding or threatening), establishing unconscious emotional memories, learning conditioned emotional responses, and producing anxiety and fear responses.
anion: a negative ion, for example, chloride (Cl-).
anterior: near or toward the front of the head, for example, the anterior cingulate.
anterior cingulate: a division of the prefrontal cortex that plays a vital role in attention and is activated during working memory. It mediates emotional and physical pain, and has cognitive (dorsal anterior cingulate) and affective (ventral anterior cingulate) conflict-monitoring components.
anterior commissure: a bundle of nerve fibers that crosses the midline and connects the left and right temporal lobes and the hippocampus and amygdala.
apical dendrite: a dendrite that arises from the top of the pyramid and extends vertically to layer 1 of the neocortex.
arousal: a process that combines alertness and wakefulness, produced by at least five neurotransmitters, including acetylcholine, histamine, hypocretin, norepinephrine, and serotonin.
aspinous (smooth) neurons: neurons without dendritic spines that are believed to be inhibitory.
astrocytes: star-shaped glial cells that communicate with and support neurons and help determine whether synapses will form.
asynchronous waves: neurons depolarize and hyperpolarize independently.
ATP: energy source for a neuron’s sodium-potassium transporters.
autoreceptors: metabotropic receptors that can be located on the membrane of any part of a neuron. They detect neurotransmitters the neuron releases, generate IPSPs that inhibit the neuron from reaching the excitation threshold, and regulate internal processes like transmitter synthesis and release through the second messenger system.
axoaxonic synapses: junctions between two axons that do not affect the generation of an action potential, only the amount of neurotransmitter distributed.
axodendritic synapses: junctions between axons and dendrites that determine whether the axon hillock will initiate an action potential.
axon: long, cylindrical structures that convey information from the soma to the terminal buttons. An axon also transports molecules in both directions along the outer surface of protein bundles called microtubules.
axon hillock: a swelling in the cell body where a neuron integrates the messages it has received from other neurons and decides whether to fire an action potential.
axon terminal: buds located on the ends of axon branches that form synapses and release neurochemicals to other neurons.
axonal varicosity: a swelling in an axon wall that releases neurotransmitters through the wall via volume transmission.
axoplasmic transport: the movement of molecules in both directions along the outer surface of protein bundles called microtubules.
basal dendrite: a dendrite that horizontally branches out from the 30 μm base of the pyramid through the layer where the neuron resides.
basal ganglia: forebrain structures consisting of an egg-shaped nucleus that contains the putamen and globus pallidus and a tail-shaped structure called the caudate, which together are responsible for the production of movement. The basal ganglia have also been implicated in obsessive-compulsive disorder, Parkinson’s disease, and Huntington’s chorea.
beta rhythm: 12-38-Hz activity associated with arousal and attention generated by brainstem mesencephalic reticular stimulation that depolarizes neurons in both the thalamus and cortex. The beta rhythm can be divided into multiple ranges: beta 1 (12-15 Hz), beta 2 (15-18 Hz), beta 3 (18-25 Hz), and beta 4 (25-38 Hz).
bilateral synchronous slow waves: a pathological sign observed in drowsy children. When detected in alert adults, intermittent bursts of high-amplitude slow waves may signify gray matter lesions in deep midline structures.
cation: positive ion, for example, sodium (Na+).
caudal: away from the front of the head.
cell body or soma: part of a neuron that contains machinery for cell life processes and receives and integrates EPSPs and IPSPs from axons generated by axosomatic synapses (junctions between axons and somas). The cell body of a typical neuron is 20 μm in diameter, and its spherical nucleus, which contains chromosomes comprised of DNA, is 5-10 μm across.
central nucleus of the amygdala: nucleus that orchestrates the nervous system's response to important stimuli by activating circuits in the brainstem (autonomic arousal) and the basal ganglia and periaqueductal gray (defensive behavior).
cerebral cortex: the layer of gray matter that covers the cerebral hemispheres. The cerebral cortex consists of gray matter and white matter.
chemical synapses: junctions between neurons that transmit molecules across gaps of less than 300 angstroms. Neurons use chemical synapses to produce short-duration (millisecond) and long-duration (seconds to hours) changes in the nervous system. Chemical synapses are capable of more extensive communication and initiating more diverse and long-lasting changes than electrical synapses.
classical routes for EEG activation: specific sensory pathways like the visual (retina to the visual cortex), auditory (cochlea to the auditory cortex), and somatosensory (chemoreceptors and mechanoreceptors to the somatosensory cortex) systems. Increased transmission of information through these pathways desynchronizes EEG activity in the cortical regions to which these afferent neurons project, as specialized circuits of neurons independently process this information.
commissures: axon tracts. The left and right hemispheres communicate using the corpus callosum, anterior commissure, and posterior commissure.
complex: a sequence of waves.
COMT: a degrading enzyme that only targets the catecholamines dopamine and norepinephrine.
contingent negative variation (CNV): a steady, negative shift in potential (15 microvolts in young adults) detected at the vertex. This slow cortical potential may reflect expectancy, motivation, intention to act, or attention. The CNV appears 200-400 ms after a warning signal (S1), peaks within 400-900 ms, and sharply declines after a second stimulus that requires the performance of a response (S2).
continuous irregular delta: slow waves produced by white matter lesions seen in disorders like multiple sclerosis.
contralateral: structures that are located on opposite sides of the body. For example, neurons in the left primary motor cortex control muscles on the right side of the body.
corpus callosum: the largest commissure that connects the left and right frontal, parietal, and occipital lobes.
cortical negativity: a state where the cortical surface exhibits a negative electrical potential.
cortical positivity: a state where the cortical surface exhibits a positive electrical potential.
cortical neurons: nerve cells in the cortex responsible for generating and transmitting electrical impulses.
corticothalamic network: a unified network that generates diverse types of brain rhythms grouped by slow cortical oscillations.
cyclic AMP: a second messenger that moves about the neuron, activating other enzymes. Protein kinase A, which controls the excitability of ion channels, is a crucial enzyme target of cyclic AMP. Cyclic AMP also travels to the nucleus, where it can regulate gene expression.
Dale's principle: incorrect view that a neuron can only release one neurotransmitter. They often release two to four.
delta rhythm: 0.05-3 Hz oscillations generated by thalamocortical neurons during stage 3 sleep.
dendrite: a branched structure designed to receive messages from other neurons via axodendritic synapses (junctions between axons and dendrites), determining whether the axon hillock will initiate an action potential.
dendritic spines: protrusions on the dendrite shaft where axons typically form axodendritic synapses.
dendrodendritic synapses: junctions between dendrites that communicate chemically across synapses and electrically across gap junctions.
depolarization: to make the membrane potential less negative by making the inside of the neuron less negative with respect to its outside.
diffusion: the distribution of molecules from areas of high concentration to low concentration.
diphasic wave: a wave that contains both a negative and positive deflection from the baseline.
dipole: the electrical field generated between the sink (where current enters the neuron ) and the source (place at the other end of the neuron where current leaves), which may be located anywhere along the dendrite.
dominant frequency: the EEG frequency with the most significant amplitude.
dopamine: a monoamine neurotransmitter exerts its postsynaptic effects on at least six receptors linked to G proteins. This means that dopamine functions as a neuromodulator. The two families include D1 (D1 and D5) and D2 (D2A, D2B, D3, and D4).
dorsal: toward the upper back or head.
dorsolateral prefrontal cortex: the left dorsolateral prefrontal cortex is concerned with approach behavior and positive affect. It helps us select positive goals and organizes and implements behavior to achieve these goals. The right dorsolateral prefrontal cortex organizes withdrawal-related behavior and negative affect and mediates threat-related vigilance. It plays a role in working memory for object location.
D-serine: a neurotransmitter that binds to the glycine site on the NMDA receptor to trigger calcium entry into a dendritic spine when glutamate binds to its site, resulting in a large, prolonged increase in intracellular calcium.
dual-action antidepressants: medications that activate 5-HT1 receptors to produce antidepressant and anxiolytic effects, while they blockade 5-HT2 (agitation, restlessness, and sexual dysfunction) and 5-HT3 (nausea, headache, and vomiting) receptors to minimize their side effects.
EEG activity: single wave or successive waves.
EEG power: the signal energy in the EEG spectrum. Most EEG power falls within the 0-20 Hz frequency range. EEG power is measured in microvolts or picowatts.
efferent: motoneuron that transmits information towards the periphery.
electrical synapse: symmetrical synapse where neurons communicate information bidirectionally across gap junctions between adjacent membranes using ions. Transmission across electrical synapses is instantaneous, compared with the 10-ms or longer delay in chemical synapses. The rapid information transmission that characterizes electrical synapses enables large circuits of distant neurons to synchronize their activity and simultaneously fire.
electroencephalogram (EEG): the voltage difference between at least two electrodes, where at least one electrode is located on the scalp or inside the brain. The EEG is a recording of EPSPs and IPSPs that occur primarily in dendrites in pyramidal cells located in macrocolumns, several millimeters in diameter, in the upper cortical layers.
electrostatic pressure: the attractive or repulsive force between ions that moves them from one region to another.
entorhinal cortex: a structure located in the caudal region of the temporal lobe and receives pre-processed sensory information from all modalities and reports on cognitive operations. The entorhinal cortex provides the main input to the hippocampus, and is involved in memory consolidation, spatial localization, and provides input into the septohippocampal system that may generate the 4-7 Hz theta rhythm.
enzymatic deactivation: the process in which an enzyme breaks a neurotransmitter apart into inactive fragments. For example, acetylcholine transmission is ended by the enzyme acetylcholine esterase (AChE). Deactivating enzymes located in the synaptic cleft degrade a neurotransmitter molecule when it detaches from its binding site.
evoked potential: an event-related potential (ERP) elicited by external sensory stimuli (auditory, olfactory, somatosensory, and visual). An evoked potential has a negative peak at 80-90 ms and a positive peak around 170 ms following stimulus onset. The orienting response ("What is it?") is a sensory ERP. The N1-P2 complex in the auditory cortex of the temporal cortex reveals whether an uncommunicative person can hear a stimulus.
excitability: the ability of neurons to respond to stimuli and generate action potentials.
excitatory postsynaptic potential (EPSP): a brief positive shift in a postsynaptic neuron's potential produced when neurotransmitters bind to receptors and cause positive sodium ions to enter the cell. An EPSP pushes the neuron towards the threshold of excitation when it can initiate an action potential.
exocytosis: the process of neurotransmitter release. When an action potential arrives and depolarizes the terminal button, calcium ions enter the terminal button from the extracellular fluid. Calcium binds with clusters of protein molecules that connect the vesicles to the presynaptic membrane. The clusters move apart, forming a hole through both membranes called a fusion pore, and the neurotransmitter leaves the terminal button for the synaptic cleft or extracellular fluid.
exogenous ERP: an event-related potential (ERP) elicited by external sensory stimuli (auditory, olfactory, somatosensory, and visual).
explicit learning: behavioral changes that occur with our conscious awareness that require processing by the hippocampus.
extracellular dipole layers: macrocolumns of pyramidal cells, which lie parallel to the surface of the cortex, send opposite charges towards the surface and the deepest of the 5-7 layers of cortical neurons.
extracellular fluid: the fluid surrounding a neuron.
fast cortical potentials: EEG rhythms that range from 0.5 Hz-100 Hz. The main frequency ranges include delta, theta, alpha, sensorimotor rhythm, and beta.
feature binding: the process of linking information to perceptual objects (linking an apple's color to its shape) that may involve the 40-Hz rhythm.
fissures: deep grooves, for example, the lateral fissure.
focal waves: EEG waves that are detected within a limited area of the scalp, cerebral cortex, or brain.
frequency: the number of cycles completed each second expressed in hertz (Hz).
frequency synchrony: when identical EEG frequencies are detected at two or more electrode sites. For example, 12 Hz may be simultaneously detected at O1-A1 and O2-A2.
frontal lobes: the most anterior cortical lobes of the brain that are divided into the motor cortex, premotor cortex, and prefrontal cortex.
fusion pore: a hole through a vesicle and presynaptic membrane that allows neurotransmitter to leave the terminal button for the synaptic cleft or extracellular fluid.
G protein: a protein located inside a neuron’s membrane next to a metabotropic receptor that is activated when the receptor binds a ligand. An alpha-subunit of the G protein then breaks away to perform actions within the cell.
GABA: an amino acid that is often inhibitory and that may be the most important inhibitory neurotransmitter in the brain. There are several types of GABA receptors, each of which produces inhibition differently.
gamma rhythm: EEG activity frequencies above 30 or 35 Hz. Frequencies from 25-70 Hz are called low gamma, while those above 70 Hz represent high gamma.
gap junction: narrow space between two cells bridged by connexons (protein channels) that allow ions to travel between them rapidly.
generalized asynchronous slow waves: waves that are seen in sleepy children and those with elevated temperatures. These waves may indicate degenerative disease, dementia, encephalopathy, head injury, high fever, migraine, and Parkinson's disease in adults.
glial cells: nonneural cells that guide, insulate, and repair neurons and provide structural, nutritional, and information-processing support. Glial cells generate slow cortical potentials (SCPs). Glial cells include astrocytes, microglia, oligodendrocytes, radial glial cells, and Schwann cells.
glutamate: an amino acid that is often excitatory and that may be the primary excitatory neurotransmitter in the brain. Its receptors are found on the surface of almost all neurons. There are at least 13 different receptors for glutamate, 5 ionotropic and 8 metabotropic. Most presynaptic neurons in the brain excite postsynaptic neurons via ionotropic glutamate receptors in the postsynaptic membrane. Metabotropic glutamate receptors may play a regulatory function, either augmenting or suppressing the activation of ionotropic glutamate receptors.
glycine: an amino acid that is often inhibitory and has a binding site on the NMDA receptor.
gray matter: brain tissue that looks grayish brown and comprises cell bodies, dendrites, unmyelinated axons, glial cells, and capillaries.
gyrus: ridge of cortex demarcated by sulci or fissures, for example, the precentral gyrus.
hertz (Hz): the unit of frequency, an abbreviation for cycles per second.
hippocampus: a limbic structure located in the medial temporal lobe involved in 4-7 Hz theta activity, control of the endocrine system’s response to stressors, formation of explicit memories, and navigation. Cortisol binding to this structure disrupts these functions, interferes with creating new neurons, and harms and kills hippocampal neurons.
hubs: highly centralized nodes through which other node pairs communicate; hubs allow efficient communication.
hyperpolarization: an increase in membrane potential, making the inside of a cell more negative relative to the outside.
inhibitory postsynaptic potential (IPSP): a brief negative shift in a postsynaptic neuron's potential produced when cations like potassium leave a neuron or anions (negative ions) like chloride enter a neuron, which hyperpolarize the cell. An IPSP pushes the neuron away from its excitation threshold.
integration: the addition of EPSPs and IPSPs at the axon hillock. Neurons sum EPSPs and IPSPs over their surface in spatial integration and over milliseconds in temporal integration to raise the membrane from its resting potential to the excitation threshold. EPSPs and IPSPs last from 15-200 ms, while action potentials occur in 1-2 ms.
interneurons: neurons that receive input from and distribute output to other neurons. They have short processes and are confined to the central nervous system. They provide the integration required for decisions, learning and memory, perception, planning, and movement.
intracellular fluid: the watery cytoplasm contained within a neuron.
ion: a charged atom or molecule with a positive or negative charge. Positive ions are called cations, and negative ions are called anions.
ionotropic receptor: receptor protein that contains a binding site for a ligand and an ion channel that opens when the neurotransmitter attaches to this site.
ipsilateral: structures that are located on the same side of the body. For example, the left olfactory bulb distributes axons to the left hemisphere.
irregular waves: successive waves that constantly alter their shape and duration.
kappa rhythm: bursts of alpha or theta and is detected over the temporal lobes of subjects during cognitive activity.
lambda waves: saw-toothed transient waves from 20-50 μV in amplitude and 100-250 ms in duration detected over the occipital cortex during wakefulness. These positive deflections are time-locked to saccadic movements and observed during visual scanning, as during reading.
lateral: to the side, away from the center, as in the lateral geniculate nucleus.
lateral nucleus of the amygdala: a nucleus that processes sensory information and distributes it throughout the amygdala.
lateralized waves: waves that are primarily detected on one side of the scalp and that may indicate pathology.
Layers I-III: cortical layers that receive corticocortical afferent fibers that connect the left and right hemispheres.
Layer III: the cortical layer that is the primary source of corticocortical efferent fibers.
Layer IV: the cortical layer that is the primary destination of thalamocortical afferents and intra-hemispheric corticocortical afferents.
Layer V: the cortical layer that is the primary origin of efferent fibers that target subcortical structures that have motor functions.
Layer VI: the cortical layer that projects corticothalamic efferent fibers to the thalamus, which, together with the thalamocortical afferents, creates a dynamic and reciprocal relationship between these two structures.
left dorsolateral prefrontal cortex: the division of the prefrontal cortex concerned with approach behavior and positive affect. It helps us select positive goals and organizes and implements behavior to achieve these goals.
local field potential: the aggregate effect of the firing of the interconnected pyramidal neurons within the cortical columns plus additional mechanisms like glial cell modulation of the cortical electrical gradient.
local synchrony: synchrony that occurs when high-amplitude EEG signals are produced by the coordinated firing of cortical neurons.
localized slow waves: waves that may indicate a transient ischemic attack (TIA) or stroke, migraine, mild head injury, or tumors above the tentorium. Deep lesions result in bilateral or unilateral delta.
locus coeruleus: the noradrenergic branch of the ascending reticular activating system, which is responsible for vigilance. Subnormal norepinephrine transmission may contribute to ADHD.
long-latency potentials: potentials that have extended latencies following stimulus onset, for example, P300 and N400 ERPs.
long-term depression (LTD): a persistent decrease in synaptic strength following low-frequency stimulation.
long-term potentiation (LTP): a persistent increase in synaptic strength following high-frequency stimulation.
macrocolumns: circuits of cortical pyramidal neurons several millimeters in diameter that create extracellular dipole layers parallel to the surface of the cortex that send opposite charges towards the surface and the deepest of the 5-7 layers of cortical neurons. Since the pyramidal neurons are all aligned with the cortical surface, the postsynaptic potentials at cells within the same macrocolumn add together. This summation occurs because they share the same charge and the macrocolumns fire synchronously.
medial: toward the center of the body, away from the side. For example, the medial geniculate nucleus.
medial prefrontal cortex: the division of the prefrontal cortex that integrates cognitive-affective information and helps control the hypothalamic–pituitary–adrenal (HPA) axis during emotional stress.
membrane potential: a neuron’s electrical charge created by a difference in ion distribution within and outside the neuron. A typical resting potential is about -70 mV (thousandths of a volt), since the inside of a resting axon is more negatively charged than the outside.
mesocortical neurons: dopaminergic neurons that project from the ventral tegmental area of the midbrain to the prefrontal cortex and excite prefrontal cortical neurons that control working memory, planning, and strategy preparation for problem-solving. Underactivity in this pathway is associated with the negative symptoms of schizophrenia-like attentional deficits.
metabotropic receptors: include all G protein-linked receptors located on neurons, including autoreceptors. Neurotransmitters that bind to G protein-linked receptors are often called neuromodulators. Metabotropic receptors, which indirectly control the cell's operations, expend energy, and produce slower, longer lasting, and more diverse changes than ionotropic receptors. Their effects can last several seconds, instead of milliseconds, because of the long-lived activity of G proteins and cyclic AMP.
microglia: microscopic glial cells that participate in the immune response.
microtubules: hollow cylindrical protein bundles that are involved in axoplasmic transport.
modulating effects: neuromodulators like the monoamines alter the performance of diffuse networks of target neurons by indirectly controlling cellular operations when they bind to metabotropic receptors.
module: a set of interconnected nodes in a neural network.
monoamine neurotransmitters: amine neurotransmitters that include dopamine, norepinephrine, epinephrine (catecholamines), and serotonin (indoleamine). These neurotransmitters are released using volume transmission and generally have modulating effects, altering the performance of diffuse networks of target neurons.
monoamine oxidase (MAO): an enzyme that degrades and inactivates the monoamine neurotransmitters dopamine, norepinephrine, and serotonin.
monoamine oxidase inhibitors (MAOIs): antidepressant drugs that interfere with MAO's breakdown of monoamines and increase monoamine availability to treat clinical depression.
monophasic wave: either a single negative (upward) or positive (downward) deflection from baseline.
motor cortex: the subdivision of the frontal lobe located in the precentral gyrus and guides fine motor coordination (like writing).
motor ERPs: event-related potentials detected over the primary motor cortex (precentral gyrus) during movement. Their amplitude is proportional to the force and rate of skeletal muscle contraction.
motor neurons: efferent neurons that convey commands to glands, muscles, and other neurons.
movement-related potentials (MRPs): slow cortical potentials that occur at 1 second as subjects prepare for unilateral voluntary movements. MRPs are distributed bilaterally with maximum amplitude at Cz. The supplementary motor area and primary motor and somatosensory cortices primarily generate these potentials.
mu rhythm: 7-11-Hz waves resemble wickets and appear as several-second trains over central or centroparietal sites (C3 and C4).
multiple spike-and-slow-wave complex: multiple spikes associated with at least one slow wave.
muscarinic receptors: metabotropic ACh receptors that are stimulated by muscarine and blocked by atropine. Muscarinic receptors control smooth muscle and predominate in the CNS. In the CNS, muscarinic receptors help mediate learning, memory, attention, arousal, EEG, and postural control.
myelinated axons: axons that are insulated by myelin by oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system.
N1-P2: a sensory event-related potential in the auditory cortex of the temporal cortex that reveals whether an uncommunicative person can hear a stimulus.
N400 potential: an event-related potential (ERP) elicited when we encounter semantic violations like ending a sentence with a semantically incongruent word ("The handsome prince married the beautiful fish"), or when the second word of a pair is unrelated to the first (BATTLE/GIRL).
negative SCPs: slow cortical potentials produced by glial cells that increase the probability of neuron firing.
neuroaxis: an imaginary line that runs centrally through the central nervous system (CNS) from the front of the prefrontal cortex to the base of the spinal cord.
neuromodulator: a neurochemical that modifies the effect of neurotransmitters through mechanisms like binding to metabotropic receptors.
neuron: a nerve cell that is the fundamental anatomical unit of the nervous system.
nicotinic ACh receptor: an ionotropic receptor that is stimulated by nicotine and blocked by curare. They are mainly found in the PNS on skeletal muscles. At CNS axoaxonic synapses, they produce presynaptic facilitation (increase neurotransmitter release). In the CNS, nicotinic receptors help regulate cortical blood flow, anxiety reduction, and decision-making.
nigrostriatal pathway: dopaminergic pathway from the substantia nigra to the basal ganglia (caudate nucleus and putamen) that controls movement. The nigrostriatal pathway is progressively destroyed in Parkinson’s disease.
nitric oxide: a gaseous retrograde transmitter that is involved in long-term potentiation (LTP).
NMDA (glutamate) receptors: ligand-gated and voltage-gated glutamate receptors that bind the glutamate agonist NMDA. NMDA receptors play an essential role in long-term potentiation (LTP).
node: vertex within a neural network.
nodes of Ranvier: gaps between myelinated axon segments where the axon membrane is exposed to extracellular fluid and action potentials are regenerated by sodium ion entry.
norepinephrine: a monoamine neurotransmitter that exerts postsynaptic effects at alpha and beta receptors, each with two subtypes. All norepinephrine receptors are G protein-linked. The cell bodies of the core noradrenergic system are located in the locus coeruleus, a nucleus found in the dorsal pons.
nucleus accumbens: a limbic structure that is a target of dopamine released by the mesolimbic pathway. The nucleus accumbens plays a critical role in the reinforcement of diverse activities, including ingestion of drugs like central nervous system stimulants.
occipital lobes: cortical lobes that are posterior to the parietal lobes. They process visual information from the eyes in collaboration with the frontal, parietal, and temporal lobes.
odd-ball stimulus: a meaningful stimulus that is different from others in a series used to elicit the P300 potential. For example, a colored playing card in a series of monochrome cards.
oligodendrocytes: glial cells that insulate adjacent axons within the brain and spinal cord of the central nervous system.
orbitofrontal cortex: the frontal lobe subdivision that is concerned with affective evaluation. It decodes the punishment and reward value of stimuli and helps inhibit inappropriate behavior. Phineas Gage's profound personality changes were produced by damage to this region.
orienting response: Pavlov’s "What is it?" reaction to stimuli like the sound of a vase crashing that includes (1) increased sensory sensitivity, (2) head (and ear) turning toward the stimulus, (3) increased muscle tone (reduced movement), (4) EEG desynchrony, (5) peripheral constriction and cephalic vasodilation, (6) a rise in skin conductance, (7) heart rate slowing, and (8) slower, deeper breathing.
P300 potential: an event-related potential (ERP) with a 300-900-ms latency. The largest amplitude positive peaks are located over the parietal lobe. The P300 potential may reflect an event’s subjective probability, meaning, and transmission of information.
paradoxical negativity: in the context of SCPs, it refers to surface-negative EEG shifts when neurons are depolarized due to volume conduction of negative potentials from the extracellular space to the scalp.
paradoxical positivity: in the context of SCPs, it refers to surface-positive EEG shifts when neurons are hyperpolarized due to volume conduction of positive potentials from the extracellular space to the scalp.
paralimbic cortex: a transitional region between neocortex and allocortex.
parietal lobes: cortical lobes posterior to the frontal lobes that are divided into the primary somatosensory cortex (postcentral gyrus) and secondary somatosensory cortex. Their primary function is to process somatosensory information like pain and touch. The right posterior parietal lobe helps guide movements, locate objects in three-dimensional space, and create body boundaries.
Parkinson's disease (PD): a progressive neurodegenerative disorder characterized primarily by motor symptoms such as tremor, rigidity, bradykinesia (slowness of movement), and postural instability.
phase: the degree to which the peaks and valleys of EEG waveforms coincide.
phase synchrony: synchrony when identical EEG frequencies are detected at two or more electrode sites, and the peaks and valleys of the EEG waveforms coincide. This is also called global synchrony. For example, EEG training may produce phase-synchronous 12-Hz alpha waves at O1-A1 and O2-A2.
polarization: to make the membrane potential more negative by making the inside of the neuron more negative with respect to its outside.
polyphasic (multiphasic) wave: a wave that contains two or more deflections of opposite polarity from baseline.
positive SCPs: slow cortical potentials that are produced by glial cells that decrease the probability of neuron firing.
posterior: near or toward the back of the head.
posterior commissure: axon tracts located below the corpus callosum that connect the right and left diencephalon and mesencephalon.
precision: the number of voltage gradations or steps.
prefrontal cortex: the most anterior frontal lobe division and is subdivided into dorsolateral, medial, orbitofrontal, and anterior cingulate regions responsible for executive functions like attention and planning.
premotor cortex: the frontal lobe subdivision that is anterior to the motor cortex and helps program head, trunk, and limb movements.
presynaptic facilitation: a modulatory process in which a neuron increases the presynaptic neuron's neurotransmitter release by delivering a neurotransmitter that increases calcium ion entry into its terminal button.
presynaptic inhibition: a modulatory process in which a neuron decreases neurotransmitter release by reducing calcium ion entry.
primary somatosensory cortex (S1): the parietal lobe subdivision located at the postcentral gyrus that processes information about touch and pain.
protein kinase A: an intracellular enzyme that controls the excitability of ion channels and is a critical enzyme target of cyclic AMP.
raphe nuclei: serotonergic cell bodies in the midbrain, pons, and medulla give rise to most of the brain’s serotonergic neurons.
rate law: the principle that neurons represent the intensity of a stimulus by variation in the rate of axon firing.
readiness potential: slow-rising, negative potential (10-15 µV) detected at the vertex before voluntary and spontaneous movement. This slow cortical potential precedes voluntary movement by 0.5 to 1 second and peaks when the subject responds.
regular or monomorphic waves: successive waves with identical shapes. Regular waves may resemble sine waves (sinusoidal) or maybe arched (resembling wickets) or saw-toothed (asymmetrical and triangular).
resting potential: the membrane potential of a neuron when it is not influenced by messages from other neurons.
reticular formation: a network of 90 nuclei within the central brainstem from the lower medulla to the upper midbrain. The reticular formation sends axons to the spinal cord, thalamus, and cortex, contributing to diverse functions like neurological reflexes, muscle tone and movement, attention, arousal, and sleep.
reuptake: the primary method that neurons terminate the action of neurotransmitters. Reuptake transporters located in terminal buttons and astrocytes remove neurotransmitters from the synaptic cleft.
reward deficiency syndrome: Blum’s hypothesis that an abnormal form of the A1 allele is present in most severe alcoholics and results in defective D2 receptors. Reduced D2 receptor activity may reduce the activation of the nucleus accumbens and hypothalamus and result in dysphoria, drug craving, and compulsive drug-seeking and abuse.
right dorsolateral prefrontal cortex: the division of the prefrontal cortex that organizes withdrawal-related behavior and negative affect and mediates threat-related vigilance. It plays a role in working memory for object location.
rostral: toward the front of the head.
saltatory conduction: action potential conduction in myelinated axons in which action potentials jump from node to node for 200 times greater speed.
sampling rate: the number of measurements per second (Hz).
Schwann cells: glial cells that provide myelin for single PNS axons and facilitate axonal regeneration following damage.
secondary somatosensory cortex (S2): a region of the parietal lobe that receives somatosensory information from the primary somatosensory cortex (S1).
sensorimotor rhythm (SMR): EEG rhythm that ranges from 12-15 Hz and is located over the sensorimotor cortex (central sulcus). The waves are synchronous. The sensorimotor rhythm is associated with the inhibition of movement and reduced muscle tone. The SMR is generated by "ventrobasal relay cells in the thalamus and thalamocortical feedback loops."
sensorimotor system: in Sterman’s model, ascending pathways that convey information about touch and proprioception to the thalamus, the thalamus and its thalamic projections to the sensorimotor cortex, and the sensorimotor cortex, and its efferent fibers.
sensory event-related potentials (ERPs): event-related potentials evoked by external sensory stimuli (auditory, olfactory, somatosensory, and visual). These evoked potentials or exogenous ERPs have a negative peak at 80-90 ms and a positive peak around 170 ms following stimulus onset. These changes in brain activity in response to specific stimuli. ERPs can be detected throughout the cortex. Investigators monitor ERPs by placing electrodes at locations like the midline (Fz, Cz, and Pz). A computer analyzes a subject's EEG responses to the same stimulus or task over many trials to subtract random EEG activity. ERPs always have the same waveform morphology. Their negative and positive peaks occur at regular intervals following the stimulus.
sensory neurons: neurons specialized for sensory intake. They are called afferent because they transmit sensory information towards the central nervous system (brain and spinal cord).
septal nuclei: in Sieb’s model, when the prefrontal cortex receives information about high-priority environmental events, it signals cell bodies in the septum to induce a beta rhythm in the hippocampus to remove its inhibition of vigilance centers.
septohippocampal system: a subcortical circuit from the septum to hippocampus that contributes to 4-7 Hz theta activity.
septum: a limbic structure that contains several nuclei involved in emotion and addiction and control of aggressive behavior.
sharp transients: a sequence that contains several sharp waves.
sharp waves: waves that resemble spikes with a pointed peak with a longer 70-200-ms duration.
sink: a site where current enters the neuron. Positive sodium ion entry into a neuron creates an active sink, represented by -ve.
slow cortical potentials (SCPs): gradual changes in the membrane potentials of cortical dendrites that last from 300 ms to several seconds. These potentials include the contingent negative variation (CNV), readiness potential, movement-related potentials (MRPs), and P300 and N400 potentials. SCPs modulate the firing rate of cortical pyramidal neurons by exciting or inhibiting their apical dendrites. They group the classical EEG rhythms using these synchronizing mechanisms.
sodium (Na+) ions: positive ions that enter a neuron during EPSPs and action potentials.
sodium-potassium transporters: pumps that are powered by ATP and that exchange three sodium for two potassium ions.
soma or cell body: the region of a neuron that contains machinery for cell life processes and receives and integrates EPSPs and IPSPs from axons generated by axosomatic synapses (junctions between axons and somas). The cell body of a typical neuron is 20 μm in diameter, and its spherical nucleus, which contains chromosomes comprised of DNA, is 5-10 μm across.
source: the place at the end of the neuron opposite of the sink where current leaves, represented by +ve. The extracellular area surrounding the source becomes electrically positive.
spatial summation: the addition of EPSPs and IPSPs over a neuron’s surface.
spike: a negative transient with a pointed peak at conventional paper speeds, 20-70-ms duration, and 40-100 μV amplitude; rare dendritic action potentials.
spike-and-slow-wave complex: a spike followed by a higher amplitude slow wave at 3 Hz. In an absence seizure, the amplitudes are very high (e.g., 160 μV).
spindle waves: waves that originate in the thalamus and occur during unconsciousness and stage II sleep.
spiny neurons: neurons with dendritic spines that are usually excitatory.
stimulus-preceding negativity (spn): a slow negative potential shift observed before a stimulus that signals important or relevant information, such as feedback or a reward. SPN reflects anticipatory attention and affective processes involving regions like the insula and orbitofrontal cortex. spn is associated with emotional and cognitive anticipation.
striatal: basal ganglia (caudate nucleus and putamen).
Stroop test: cognitive monitoring task where color and names conflict.
substantia nigra: midbrain structure that projects to the basal ganglia (caudate nucleus and putamen) to control movement and that is progressively destroyed in Parkinson’s disease.
sulcus: a shallow groove in the surface of the cerebral hemisphere, for example, the central sulcus.
surface-negative: a negative SCP shift typically associated with increased cortical excitability and response readiness.
surface-positive: a positive SCP shift typically associated with decreased cortical excitability and relaxation.
synapse-associated polyribosome complexes (SPRCs): organelles with dendrites that can produce proteins that allow rapid remodeling of synapses. A polyribosome complex consists of several ribosomes bound to messenger RNA (mRNA). SPRCs represent one mechanism underlying synaptic plasticity.
synaptic cleft: 20-40-nm fluid-filled gap between presynaptic and postsynaptic structures.
synchronous: adverb meaning that groups of neurons depolarize and hyperpolarize simultaneously.
synchrony: the coordinated firing of pools of neurons. EEG signals can display local synchrony, frequency synchrony, and phase synchrony.
telencephalon: the frontal subdivision of the forebrain, including the cerebral cortex, basal ganglia, and limbic system.
temporal summation: the addition of EPSPs and IPSPs over time. Summation is more effective when postsynaptic potentials are generated more closely in time.
temporal lobes: lobes separated from the rest of the cortical lobes by the Sylvian fissure. The temporal lobes process hearing, smell, and taste information and help us understand spoken language and recognize visual objects and faces. The amygdala and hippocampus, which lie beneath the temporal cortex, play crucial roles in emotion, declarative, emotional, and working memory, and navigation.
terminal buttons: buds located on the ends of axon branches that form synapses and release neurochemicals to other neurons. They contain vesicles that store neurotransmitters for release when an action potential arrives. A terminal button’s presynaptic membrane may possess reuptake transporters that return neurotransmitters from the synapse or extracellular space for repackaging.
thalamus: forebrain structure above the hypothalamus that receives, filters, and distributes most sensory information. The thalamus contains neurons that can block or relay ascending sensory information. When these thalamic neurons rhythmically fire, this blocks the transmission of information to the cortex. When they depolarize in response to sensory information, this integrates and transmits this information to the cortex. Inputs to the thalamus determine whether these neurons block or relay sensory information.
theta rhythm: 4-8-Hz rhythms generated a cholinergic septohippocampal system that receives input from the ascending reticular formation and a noncholinergic system that originates in the entorhinal cortex, which corresponds to Brodmann areas 28 and 34 at the caudal region of the temporal lobe.
threshold of excitation: the membrane potential at which an axon initiates an action potential, nominally -40 mV.
traveling waves: EEG oscillations that move across the cortex that may mediate large-scale coordination of brain networks and support connectivity.
transient: a single wave or sequence of regular waves, called a complex, distinguishable from background EEG activity.
triphasic wave: a wave that contains three deflections from baseline.
unmyelinated axons: smaller-diameter axons without fatty insulation that conduct more slowly than myelinated axons.
+ve: the source is the place at the other end of the neuron where current leaves, and is represented by +ve.
-ve: a sink is where current enters the neuron. Positive sodium ion entry into a neuron creates an active sink, represented by -ve.
ventral: toward the base of the skull or front of the body.
ventral striatum: the olfactory tubercle and nucleus accumbens.
ventral tegmental area: the midbrain structure that distributes dopaminergic axons to the nucleus accumbens. Serotonin receptors on endorphin-releasing neurons in the hypothalamus may increase the activity of dopaminergic reward pathways by inhibiting the release of GABA at receptors on cell bodies of the ventral tegmental area neurons.
vigilance system: in Sterman’s model, a system that consists of both specific brainstem nuclei (e.g., locus coeruleus and raphe nuclei) and their diffuse connections with the thalamus and other subcortical structures, and the cortex. Several neurotransmitter systems mediate vigilance, including cholinergic/glutamatergic (reticular formation), noradrenergic (locus coeruleus), and serotonergic (raphe) neurons.
volume transmission: extrasynaptic neurotransmitter release from axonal varicosities, dendrites, and terminal buttons into the extracellular space. Monoamines like norepinephrine and serotonin are released outside the synaptic cleft.
waveform: the shape and form of an EEG signal.
white matter: the layer beneath the cortex that mainly consists of myelinated axons.
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Now that you have completed this unit, how would you explain the relationship between local field potentials and the EEG? How does anatomy explain why the EEG is comprised of EPSPs and IPSPs instead of action potentials?
Advokat, C. D., & Comaty, J. E., & Julien, R. M. (2019). Julien's primer of drug action (15th ed.). Worth Publishers.
Aloisi, F. (2001). Immune function of microglia. Glia, 36, 165–179. https://doi.org/10.1002/glia.1106
Altenmuller, E. O., & Gerloff, C. (1999). Psychophysiology and the EEG. In E. Niedermeyer & F. Lopes da Silva (Eds.), Electroencephalography: Basic principles, clinical applications, and related fields (4th ed.). Williams and Wilkins.
Amzica, F., & Steriade, M. (2002). The functional significance of K-complexes. Sleep Medicine Reviews, 6(2), 139–149. https://doi.org/10.1053/smrv.2001.0181 Andreassi, J. L. (2007). Psychophysiology: Human behavior and physiological response (5th ed.). Lawrence Erlbaum and Associates, Inc.
Anjum, M., Smyth, C., Dijk, D., Starr, P., Denison, T., & Little, S. (2023). Multi-night cortico-basal recordings reveal mechanisms of NREM slow wave suppression and spontaneous awakenings at high-temporal resolution in Parkinson’s disease. Research Square. https://doi.org/10.21203/rs.3.rs-3484527/v1
Arnsten, A. F. (2006). Fundamentals of Attention-Deficit/Hyperactivity Disorder: Circuits and pathways. Journal of Clinical Psychiatry, 67 (Suppl. 8), 7-12.
Babiloni, C., Babiloni, F., Carducci, F., Cincotti, F., Del Percio, C., Hallett, M., Moretti, D. V., Romani, G. L., & Rossini, P. M. High resolution EEG of sensorimotor brain functions: Mapping ERPs or mu ERD? In R. C. Reisin, M. R. Nuwer, M. Hallett, & C. Medina (Eds.). Advances in Clinical Neurophysiology (Supplements to Clinical Neurophysiology Vol. 54). Elsevier Science B. V.
Basile, L. F. H., Yacubian, J., Ferreira, B. L. C., Valim, A. C., & Gattaz, W. F. (2004). Topographic abnormality of slow cortical potentials in schizophrenia. Brazilian Journal of Medical and Biological Research, 37(1), 97-109. https://doi.org/10.1590/s0100-879x2004000100014
Bear, M. F., Connors, B. W., & Paradiso, M. A. (2020). Neuroscience: Exploring the brain (4th ed.). Jones & Bartlett Learning.
Birbaumer, N. (1999). Slow cortical potentials: Plasticity, operant control, and behavioral effects. The Neuroscientist, 5, 74–78. https://doi.org/10.1177/1073858499005002
Birbaumer, N., Elbert, T., Canavan, A. G., & Rockstroh, B. (1990). Slow potentials of the cerebral cortex and behavior. Physiological Reviews, 70(1), 1–41. https://doi.org/10.1152/physrev.1990.70.1.1
Breedlove, S. M., & Watson, N. V. (2023). Behavioral neuroscience (10th ed.). Sinauer Associates, Inc.
Brienza, M., & Mecarelli, O. (2019). Neurophysiological basis of EEG. In O. Mecarelli (Ed.), Clinical electroencephalography (pp. 25-45). Springer. https://doi.org/10.1007/978-3-030-04573-9_2
Brini, M., Cali, T., Ottolini, D., & Carafoli, E. (2014). Neuronal calcium signaling: Function and dysfunction. Cellular and Molecular Life Sciences, 71(15), 2787–2814. https://doi.org/10.1007/s00018-013-1550-7
Brunia, C. H. M., van Boxtel, G. J. M., & Böcker, B. E. (2012). Negative slow waves as indices of anticipation: The Bereitschaftspotential, the Contingent Negative Variation, and the Stimulus-Preceding Negativity. In E. S. Kappenman & S. J. Luck (eds.), The Oxford handbook of Event-Related Potential components (pp. 190-208). Oxford Academic. https://doi.org/10.1093/oxfordhb/9780195374148.013.0108
Bullmore, E., & Sporns, O. (2009). Complex brain networks: Graph theoretical analysis of structural and functional systems. Nature, 10, 186-198. https://doi.org/10.1038/nrn2575
Cameron, H. A., & Dayer, A. G. (2008). New interneurons in the adult neocortex: Small, sparse, but significant? Biol Psychiatry, 63(7), 650-655. https://dx.doi.org/10.1016%2Fj.biopsych.2007.09.023
Carlson, N. R., & Birkett, M. A. (2021). Physiology of behavior (13th ed.). Pearson.
Caton, R. (1875). The electric currents of the brain. British Medical Journal, 2, 278.
Chan, C. Y., Ke, D. S., & Chen, J. Y. (2009). Essential fatty acids and human brain. Acta Neurol Taiwan, 18(4), 231-241. PMID: 20329590
Collura, T. F. (2014). Technical foundations of neurofeedback. Taylor & Francis.
Costanzo, R. M. (1991). Regeneration of olfactory receptor cells. CIBA Found Symp, 160, 233-242. https://doi.org/10.1002/9780470514122.ch12
Creuzfeldt, O. D. (1995). Cortex cerebri. Oxford University Press.
Damasio, A. (2010). Self comes to mind. Pantheon Books.
Daum, I., Rockstroh, B., Birbaumer, N., Elbert. T., Canavan, A., & Lutzenberger W. (1993). Behavioural treatment of slow cortical potentials in intractable epilepsy: Neuropsychological predictors of outcome. J Neurol Neurosurg Psychiatry, 56(1) 94-97. https://doi.org/10.1136/jnnp.56.1.94
deCharms, R. C., Fumiko, M., Glover, G. H., Ludlow, D., Pauly, J. M., Soneji, D., Gabrieli, J. D. E., & Mackey, S. C. (2005). Control over brain activation and pain learned by using real-time functional MRI. Proceedings of the National Academy of Sciences, 102(51), 18626-18631. https://doi.org/10.1073/pnas.0505210102
DeLong, M. R. (1990). Primate models of movement disorders of basal ganglia origin. Trends Neurosci, 13(7), 281-285. https://doi.org/10.1016/0166-2236(90)90110-v
Demos, J. N. (2019). Getting started with neurofeedback. (2nd ed.). W. W. Norton & Company.
Eisenberger, N. I., Lieberman, M. D., & Williams, K. D. (2003). Does rejection hurt? An fMRI study of social exclusion. Science, 302, 290-292. https://doi.org/10.1126/science.1089134
Elbert, T., Rockstroh, B., Lutzenberger, W., & Birbaumer, N. (1980). Biofeedback of slow cortical potentials. I. Electroencephalography and Clinical Neurophysiology, 48(3), 293-301. https://doi.org/10.1016/0013-4694(80)90265-5.
El-Boustani, S., Ip, J., Breton-Provencher, V., Knott, G., Okuno, H., Bito, H., & Sur, M. (2018). Locally coordinated synaptic plasticity of visual cortex neurons in vivo. Science, 360(6395), 1349-1354. https://doi.org/10.1126/science.aao0862
Enticott, P. G., Kennedy, H. A., Rinehart, N. J., Tonge, B. J., Bradshaw, J. L., Taffe, J. R., Daskalakis, Z. J., & Fitzgerald, P. B. (2012). Mirror neuron activity associated with social Impairments but not age in Autism Spectrum Disorder. Biol Psychiatry, 71(5), 427-433. https://doi.org/10.1016/j.biopsych.2011.09.001
Evans, J. R., & Abarbanel, A. (1999). Introduction to quantitative EEG and neurofeedback. San Diego: Academic Press.
Farwell, L. A., & Donchin, E. (1991). The truth will out: Interrogative polygraphy (“lie detection”) with event-related brain potentials. Psychophysiology, 28, 531–547. https://doi.org/10.1111/j.1469-8986.1991.tb01990.x
Fischer, F., Hamann, A., & Osiewacz, H. D. (2020). Mitochondrial quality control: An integrated network of pathways. Trends in Biochemical Sciences, 45(3), 179–190. https://doi.org/10.1016/j.tibs.2019.12.008
Fox, S. I., & Rompolski, K. (2022). Human physiology (16th ed.). McGraw-Hill.
Garrett, B. (2003). Brain and behavior. Thompson/Wadsworth.
Green, D. R., Galluzzi, L., & Kroemer, G. (2011). Mitochondria and the autophagy–inflammation–cell death axis in organismal aging. Science, 333(6046), 1109–1112. https://doi.org/10.1126/science.1201940
Hansson, E., & Ronnback, L. (2003.) Glial neuronal signaling in the central nervous system. FASEB J, 17, 341-348. https://doi.org/10.1096/fj.02-0429rev
Harris, J. J., Jolivet, R., & Attwell, D. (2012). Synaptic energy use and supply. Neuron, 75(5), 762–777. https://doi.org/10.1016/j.neuron.2012.08.019
Heinrich, H., Gevensleben, H., Freisleder, F. J., Moll, G. H., & Rothenberger, A. (2004). Training of slow cortical potentials in attention-deficit/hyperactivity disorder: Evidence for positive behavioral and neurophysiologic effects. Biological Psychiatry, 55(7), 772–775. https://doi.org/10.1016/j.biopsych.2003.11.013
Hoedlmoser, K., Pecherstorfer, T., Gruber, G., Anderer, P., Doppelmayr, M., Klimesch, W., & Schabus, M. (2008). Instrumental conditioning of human sensorimotor rhythm (12-15 Hz) and its impact on sleep as well as declarative learning. Sleep, 31(10), 1401–1408.
Hugdahl, K. (1995). Psychophysiology: The mind-body perspective. Harvard University Press.
Kalat, J. W. (2019). Biological psychology (13th ed.). Cengage Learning.
Kalia, L. V., & Lang, A. E. (2015). Parkinson's disease. Lancet (London, England), 386(9996), 896–912. https://doi.org/10.1016/S0140-6736(14)61393-3
Kennerley, S. W., Behrens, T. E., & Wallis, J. D. (2011). Double dissociation of value computations in orbitofrontal and anterior cingulate neurons. Nat Neurosci, 14(12), 1581-1589. doi:10.1038/nn.2961
Kitamura, T., Saitoh, Y., Takashima, N., Murayama, A., Niibori, A., Ageta, H., . . . Inokuchi, K. (2009). Adult neurogenesis modulates the hippocampus-dependent period of associative fear memory. Cell, 139(4), 814-827. https://doi.org/10.1016/j.cell.2009.10.020
Klein, S. B., & Thorne, B. M. (2007). Biological psychology. New York: Worth Publishers.
Kotchoubey, B., Blankenhorn, V., Fröscher, W., Strehl, U. & Birbaumer, N. (1997). Stability of cortical self-regulation in epilepsy patients. Neuroreport, 27(8)1867-1870. https://doi.org/10.1097/00001756-199705260-00015
Kotchoubey, B., Busch, S., Strehl, U. & Birbaumer, N. (1999). Changes in EEG power spectra during biofeedback of slow cortical potentials in epilepsy. Applied Psychophysiology and Biofeedback, 24(4) 213-233. https://doi.org/10.1023/a:1022226412991
Kotchoubey, B., Kubler. A., Strehl. U., Flor, H., & Birbaumer, N. (2002). Can humans perceive their brain states? Consciousness and Cognition, 11(1), 98-113. https://doi.org/10.1006/ccog.2001.0535
Kotchoubey, B., Schneider, D., Schleichert, H., Strehl, U., Uhlmann, C., Blankenhorn, V., Fröscher, W., & Birbaumer, N. (1996). Self-regulation of slow cortical potentials in epilepsy: A retrial with analysis of influencing factors. Epilepsy Research, 25(3), 269-276. https://doi.org/10.1016/s0920-1211(96)00082-4
Kotchoubey, B., Schneider, D., Uhlmann, C., Schleichert, H., & Birbaumer, N. (1997). Beyond habituation: Long-term repetition effects on visual event-related potentials in epileptic patients. Electroencephalographer, 103(4), 450-456. https://doi.org/10.1016/s0013-4694(97)00026-6
Kotchoubey, B., Strehl, U., Holzapfel, S., Blankenhorn, V., Fröscher. W., & Birbaumer, N. (1999). Negative potential shifts and the prediction of the outcome of neurofeedback therapy in epilepsy. Clinical Neurophysiology, 110(4), 683-686. https://doi.org/10.1016/s1388-2457(99)00005-x
Kotchoubey. B., Strehl, U., Holzapfel, S., Schneider. D., Blankenhorn, V., & Birbaumer, N. (1999). Control of cortical excitability in epilepsy. Adv Neurol, 81, 281-290.
Kotchoubey, B., Strehl, U., Uhlmann, C., Holzapfel, S., Konig, M., Fröscher. W., Blankenhorn, V., & Birbaumer, N. (2001). Modification of slow cortical potentials in patients with refractory epilepsy: A controlled outcome study. Epilepsia, 42(3), 406-416.
Kropotov, J. D. (2009). Quantitative EEG, event-related potentials and neurotherapy. Academic Press.
Landisman, C. E., & Connors, B. W. (2005). Long-term modulation of electrical synapses in the mamillimeteralian thalamus. Science, 310(5755), 1809-1813. https://doi.org/10.1126/science.1114655
Lin, M. T., & Beal, M. F. (2006). Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature, 443(7113), 787–795. https://doi.org/10.1038/nature05292
Lopes da Silva, F. (1991). Neural mechanisms underlying brain waves: from neural membranes to networks. Electroencephalography and Clinical Neurophysiology, 79(2), 81–93. https://doi.org/10.1016/0013-4694(91)90044-5
Lopez-Domenech, G., Higgs, N. R., Vaccaro, V., Roš, H., Arancibia-Cárcamo, I. L., & Kittler, J. T. (2016). Loss of dendritic complexity precedes neurodegeneration in a mouse model with disrupted mitochondrial dynamics. Cell Reports, 17(2), 317–327. https://doi.org/10.1016/j.celrep.2016.08.073
Lopez-Otin, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194–1217. https://doi.org/10.1016/j.cell.2013.05.039
Meshorer et al. (2002). Alternative splicing and neuritic mRNA translocation under long-term neuronal hypersensitivity. Science, 295(5554), 508-512. https://doi.org/10.1126/science.1066752
Molenberghs, P., Cunnington, R., & Mattingley, J. B. (2011). Brain regions with mirror properties: A meta-analysis of 125 human fMRI studies. Neurosci Biobehav Rev, 36(1), 341-349. https://doi.org/10.1016/j.neubiorev.2011.07.004
Mölle, M., Marshall, L., Gais, S., & Born, J. (2002). Grouping of spindle activity during slow oscillations in human non-rapid eye movement sleep. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 222(24), 10941–10947. https://doi.org/10.1523/JNEUROSCI.22-24-10941.200
Munro, C. A., McCaul, M. E., Wong, D. F., Oswald, L. M., Zhou, Y., Brasic, J., Kuwabara, H., Kumar, A., Alexander, M., Ye, W., & Wand, G. S. (2006). Sex differences in striatal dopamine release in healthy adults. Biological Psychiatry, 59(10), 966-974. https://doi.org/10.1016/j.biopsych.2006.01.008
Nagano, S., & Araki, T. (2021). Axonal transport and local translation of mRNA in neurodegenerative diseases. Frontiers in Molecular Neuroscience, 14, 697973. https://doi.org/10.3389/fnmol.2021.697973
Nash, J. M. (2011). The gift of mimicry. Your brain: A user's guide. Time.
Niedermeyer, E. (1999). Historical aspects. In E. Niedermeyer & F. Lopes da Silva (Eds.), Electroencephalography: Basic principles, clinical applications, and related fields (4th ed.). Williams and Wilkins.
E. Niedermeyer & F. Lopes da Silva (Eds.) (1999). Electroencephalography: Basic principles, clinical applications, and related fields (4th ed.). Williams and Wilkins.
Othmer, S., & Othmer, S. (2020). Toward a theory of infra-low frequency neurofeedback. In H. W. Kirk (Ed.), Restoring the Brain. Routledge, eBook ISBN 9780429275760
Otto, D., & Reiter, L. (1984) Developmental changes in slow cortical potentials of young children with elevated body lead burden: Neurophysiological considerations. Annals of the New York Academy of Sciences, 425(1), 377-383. https://doi.org/10.1111/j.1749-6632.1984.tb23559.x
Pulvermüller, F., Mohr, B., Schleichert, H., & Veit, R., (2000). Operant conditioning of left-hemispheric slow cortical potentials and its effect on word processing. Biological Psychology, 53(2-3), 177-215. https://doi.org/10.1016/S0301-0511(00)00046-6
Radley, J. J., Arias, C. M., & Sawchenko, P. E. (2006). Regional differentiation of the medial prefrontal cortex in regulating adaptive responses to acute emotional stress. The Journal of Neuroscience, 26(50), 12967-12976. https://doi.org/10.1523/JNEUROSCI.4297-06.2006
Raichle, M. E., & Gusnard, D. A. (2002). Appraising the brain's energy budget. PNAS, 99(16), 10237-10299. https://doi.org/www.pnas.orgcgidoi10.1073pnas.172399499
Rapanelli, M., Frick, L. R., & Zanutto, B. S. (2011). Learning an operant conditioning task differentially induces gliogenesis in the medial prefrontal cortex and neurogenesis in the hippocampus. PLoS ONE, 6(2), e14713. https://doi.org/10.1371/journal.pone.0014713
Rockstroh, B., Elbert, T., Birbaumer, N., Wolf, P., Düchting-Röth, A., Reker, M., Daum, I., Lutzenberger, W., & Dichgans, J. (1993). Cortical self-regulation in patients with epilepsies. Epilepsy Research, 14(1), 63–72. https://doi.org/10.1016/0920-1211(93)90075-i
Sarnthein, J., Petsche, H., Rappelsberger, P., Shaw, G. L., & von Stein, A. (1998). Synchronization between prefrontal and posterior association cortex during human working memory. Proc Natl Acad Sci, 95(12), 7092-7096. https://doi.org/10.1073/pnas.95.12.7092
Schacter, D. L. (1977). EEG theta waves and psychological phenomena: A review and analysis. Biological Psychology, 5, 47-82. https://doi.org/10.1016/0301-0511(77)90028-x
Schneider, F., Rockstroh, B., Heimann, H., Lutzenberger, W., Mattes, R., Elbert, T., Birbaumer, N, & Bartels, M. (1992). Self-regulation of slow cortical potentials in psychiatric patients: Schizophrenia. Biofeedback and Self-Regulation, 17(4), 277-292. https://doi.org/10.1007/bf01000051
M. S. Schwartz, & F. Andrasik (Eds.). (2003). Biofeedback: A practitioner's guide (3rd ed.). The Guilford Press.
Sebel, P. S., Lang, E., Rampil, I. J., White, P. F., Cork, R., Jopling, M., Smith, N. T., Glass, P. S., & Manberg, P. (1997). A multicenter study of bispectral electroencephalogram analysis monitoring anesthetic effect. Anesthesia and Analgesia, 84(4), 891-899. https://doi.org/10.1097/00000539-199704000-00035
Shibasaki, H., & Hallett, M. (2006). What is the Bereitschaftspotential? Clinical Neurophysiology, 117(11), 2341-2356. https://doi.org/10.1016/j.clinph.2006.04.025
Siniatchkin, M., Hierundar, A., Kropp, P., Kuhnert, R., Gerber, W-D., & Stephani, U. (2000). Self-regulation of slow cortical potentials in children with migraine: An exploratory study. Applied Psychophysiology & Biofeedback, 25(1), 13-32. https://doi.org/10.1023/a:1009581321624
Smith, M. L. (2013). Infra-slow fluctuation training; On the down-low in neuromodulation. NeuroConnections.
Speckmann, E.-J., & Elger, C. E. (1984). The neurophysiological basis of epileptic activity: A condensed overview. R. Degen & E. Niedermeyer (Eds.), Epilepsy, sleep, and sleep deprivation (pp.23-34). Elsevier. PMID: 1760082
Speckmann, E.-J., & Elger, C. E. (1999). Introduction to the neurophysiological basis of the EEG and DC potentials. In E. Niedermeyer & F. Lopes da Silva (Eds.), Electroencephalography: Basic principles, clinical applications, and related fields (4th ed.). Williams and Wilkins.
Stahl, S. M. (2008). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (3rd ed.). Cambridge University Press.
Steriade, M. (2005). Cellular substrates of brain rhythms. In E. Niedermeyer, & F. Lopes da Silva (Eds.). Electroencephalography: Basic principles, clinical applications, and related fields (5th ed.). Lippincott Williams & Wilkins.
Steriade, M., Nuñez, A., & Amzica, F. (1993). Intracellular analysis of relations between the slow (< 1 Hz) neocortical oscillation and other sleep rhythms of the electroencephalogram. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 13(8), 3266–3283. https://doi.org/10.1523/JNEUROSCI.13-08-03266.1993
Sterman M. B. (1996). Physiological origins and functional correlates of EEG rhythmic activities: implications for self-regulation. Biofeedback and Self-regulation, 21(1), 3–33. https://doi.org/10.1007/BF02214
Sterman, M. B. (2000). EEG markers for attention deficit disorder: Pharmacological and neurofeedback applications. Child Study Journal, 30(1), 1-24.
Stern, R. M., Ray, W. J., & Quigley, K. S. (2001). Psychophysiological recording (2nd ed.). Oxford University Press.
Strehl, U. (2009). Slow cortical potentials neurofeedback. Journal of Neurotherapy, 13(2), 117–126. https://doi.org/10.1080/10874200902885936
Strehl, U., Aggensteiner, P., Wachtlin, D., Brandeis, D., Albrecht, B., Arana, M., Bach, C., Banaschewski, T., Bogen, T., Flaig-Röhr, A., Freitag, C. M., Fuchsenberger, Y., Gest, S., Gevensleben, H., Herde, L., Hohmann, S., Legenbauer, T., Marx, A. M., Millenet, S., Pniewski, B., … Holtmann, M. (2017). Neurofeedback of slow cortical potentials in children with Attention-Deficit/Hyperactivity Disorder: A multicenter randomized trial controlling for unspecific effects. Frontiers in Human Neuroscience, 11, 135. https://doi.org/10.3389/fnhum.2017.00135
Streit, W. J. (2006). Microglial senescence: Does the brain's immune system have an expiration date? Trends in Neurosciences, 29(9), 506–510. https://doi.org/10.1016/j.tins.2006.07.001
Thompson, M., & Thompson, L. (2015). The neurofeedback book: An introduction to basic concepts in applied psychophysiology (2nd ed.). Association for Applied Psychophysiology and Biofeedback.
Thompson, M., & Thompson, L. (2009). Asperger’s syndrome intervention: Combining neurofeedback, biofeedback, and metacognition. In T. H. Budzynski, H. K. Budzynski, J. R. Evans, & A. Abarbanel (Eds.). Introduction to quantitative EEG and neurofeedback (2nd ed.). Academic Press.
Vernon, D., Egner, T., Cooper, N., Compton, T., Neilands, C., Sheri, A., & Gruzelier, J. (2003). The effect of training distinct neurofeedback protocols on aspects of cognitive performance. International Journal of Psychophysiology: Official Journal of the International Organization of Psychophysiology, 47(1), 75–85. https://doi.org/10.1016/s0167-8760(02)00091-0
Voytek, B. (2013). Brain metrics: How measuring brain biology can explain the phenomena of mind. Scitable by Nature Education.
Warren, A. M., & McIlvane, W. J. (1998). Stimulus equivalence and the N400 effect. Poster presented at the 1998 Annual Meeting of the Cognitive Neuroscience Society in San Francisco, CA.
West, A. P., Shadel, G. S., & Ghosh, S. (2015). Mitochondria in innate immune responses. Nature Reviews Immunology, 15(11), 505–518. https://doi.org/10.1038/nri3850
Wilson, J. (2003). Biological foundations of human behavior. Wadsworth/Thompson Learning.
Wilson, V. E., Thompson, M., Thompson, L., Thompson, J., Fallahpour, K., & Linden, M. K. (2011). Introduction to biofeedback (Neurofeedback). In B. W. Strack, M. K. Linden, & V. S. Wilson (Eds.). Biofeedback & neurofeedback applications in sport psychology. Association for Applied Psychophysiology and Biofeedback.
Winn, P. (2001). (Ed.), Dictionary of biological psychology. Routledge.
Xu, T., Yu, X., Perlik, A., Tobin, W., Zweig, J., Tennant, K., Jones, T., & Zuo, Y. (2009). Rapid formation and selective stabilization of synapses for enduring motor memories. Nature, 462(7275), 915-919. https://doi.org/10.1038/nature08389
Yang, Y., Ge, W., Chen, Y., Zhang, Z., Shen, W., Wu, C., Poo, M., & Duan, S. (2003). Contribution of astrocytes to hippocampal long-term potentiation through release of D-serine. Proceedings of the National Academy of Sciences of the United States of America, 100(25), 15194-15199. https://doi.org10.1073/pnas.2431073100
Zhang, H., Watrous, A., Patel, A., & Jacobs, J. (2018). Theta and alpha oscillations are traveling waves in the human neocortex. Neuron. https://doi.org/10.1016/j.neuron.2018.05.019
The brain uses a sophisticated communication and command-and-control system that monitors and manages interactions between roughly 86 billion neurons, each with 5,000-10,000 synaptic connections, for as many as 500 trillion synapses in adults (Breedlove & Watson, 2023).
An electroencephalograph (EEG) monitors brainwave activity at various frequencies, from DC shifts (slow cortical potentials) to fast potentials exceeding 50 Hz. The EEG records the excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) propagated by the apical dendrites of large pyramidal cells arranged in thousands of cortical columns. Local field potentials, the aggregate effect of interconnected neuron firing and modulation by glial cells, regulate neuron excitability and firing. Action potential animation © NIMEDIA/Shutterstock.com.
Neuroplasticity, the remodeling of neurons and neural networks with experience, is responsible for learning and memory and makes neurofeedback training possible.
BCIA Blueprint Coverage
This unit addresses II. Basic Neurophysiology and Neuroanatomy - A. Neurophysiology.
This unit covers the Bioelectric Origin and Functional Correlates of EEG, Definition of ERPs and SCPs, and Neuroplasticity.
Please click on the podcast icon below to hear a full-length lecture.
Bioelectric Origin and Functional Correlates of EEG
Types of Neurons
Neuron graphic © SciePro/Shutterstock.com.We can divide neurons into sensory, motor, and interneurons. Glial cells like astrocytes and microglia. Glial cells like astrocytes and microglia work in partnership with neurons.
Sensory neurons are specialized for sensory intake. They are called afferent because they transmit sensory information towards the central nervous system (brain and spinal cord). Sensory neuron graphic © TimeLineArtist/Shutterstock.com.
Motor neurons convey commands to glands, muscles, and other neurons. They are called efferent because they convey information towards the periphery. Motor and sensory neuron graphic © iso-form llc/Shutterstock.com.
Interneurons provide the integration required for decisions, learning and memory, perception, planning, and movement. They have short processes, analyze incoming information, and distribute their analysis with other neurons in their network. Interneurons are entirely confined to the central nervous system, account for many of its neurons, and comprise most of the brain (Breedlove & Watson, 2023).
Local interneurons analyze small amounts of information provided by neighboring neurons. Relay interneurons connect networks of local interneurons from separate regions to enable diverse functions like perception, learning, and memory, and executive functions like planning (Carlson & Birkett, 2021). Neuron graphic © Aldona Griskeviciene/Shutterstock.com.
Reflex arc graphic © SANDIP NEOGI/Shutterstock.com.
Neuron Structure
While neurons have over 200 different designs to perform specialized jobs in the nervous system, they generally have five structures: a cell body or soma, dendrites, an axon and axon hillock, and terminal buttons. Graphic © Designua/Shutterstock.com.The cell body or soma contains the machinery for the neuron’s life processes. It receives and integrates EPSPs and IPSPs, small graded positive and negative changes in membrane potential generated by axons. The cell body of a typical neuron is 20 μm in diameter, and its spherical nucleus, which contains chromosomes comprised of DNA, is 5-10 μm across. The cell body is the primarily location where neurons manufacture proteins (like enzymes, receptors, and ion channels) and peptides (neurotransmitters like oxytocin). There is increasing evidence of distributed protein manufacturing via local mRNA translation (Nagano & Araki, 2021). Check out the Khan Academy YouTube video, Anatomy of a Neuron. Cell body graphic © MattL_Images/Shutterstock.com.
Mitochondria power diverse processes throughout neurons like opening ion channels, conducting action potentials, releasing and returning neurotransmitters, and transporting proteins. They are responsible for EEG signal strength since they fuel postsynaptic potentials. Mitochondria are orange in the graphic below © Corona Borealis Studio/Shutterstock.com.
Imagine you're peering into the microscopic world of the brain, where tiny cellular powerhouses called mitochondria are orchestrating an intricate biological symphony. While you might have heard mitochondria described simply as cellular energy factories, their role in the brain is far more fascinating and complex. These remarkable organelles are actually master multitaskers, performing a diverse array of functions that keep our neurons firing and our minds sharp. Their involvement in cellular respiration, calcium homeostasis, and reactive oxygen species (ROS) management makes them integral to the brain's demanding physiological environment (Fischer et al., 2020).
At their most fundamental level, mitochondria are indeed energy producers, generating the ATP that neurons desperately need to function. Think of neurons as particularly demanding cells - they're constantly sending electrical signals, releasing neurotransmitters, and rebuilding connections. This requires an enormous amount of energy, which is why mitochondria cluster at synapses (the communication points between neurons) like miniature power plants, ensuring there's always enough fuel for crucial processes like learning and memory formation (Harris et al., 2012).
But here's where things get even more interesting. Mitochondria also serve as cellular calcium regulators, acting like molecular bouncers that maintain strict control over calcium levels inside neurons. This calcium management is absolutely critical for proper neural signaling - when mitochondria fail at this job, it can trigger a cascade of problems that may lead to neurodegenerative diseases. During intense neural activity, mitochondria buffer incoming calcium waves, preventing toxic buildups while fine-tuning the cellular responses that drive everything from neurotransmitter release to gene expression (Brini et al., 2014).
These organelles also walk a delicate tightrope when it comes to reactive oxygen species (ROS). During energy production, mitochondria generate these highly reactive molecules as a byproduct. In small amounts, ROS actually serve as important signaling molecules. However, excessive ROS production can wreak havoc, damaging cellular components like proteins, lipids, and DNA. This is particularly dangerous in the brain, which is extremely vulnerable to oxidative damage due to its high oxygen consumption and abundance of lipids. Thankfully, mitochondria come equipped with their own antioxidant systems, including superoxide dismutase and glutathione, which help keep ROS levels in check (Lin & Beal, 2006).
Mitochondria are also cellular life-and-death decision makers, playing a crucial role in apoptosis (programmed cell death). This process is essential during brain development, helping to sculpt neural circuits by eliminating unnecessary neurons. Through specific pathways involving cytochrome c release and caspase activation, mitochondria can trigger cellular suicide when needed. However, if this process goes awry, it can contribute to devastating conditions like stroke and traumatic brain injury (Green et al., 2011).
Recent research has unveiled mitochondria's unexpected role in neuroinflammation and immune responses. These organelles are vital for the function of microglia, the brain's immune cells. When mitochondria become damaged, they can release danger signals called DAMPs (damage-associated molecular patterns), including mitochondrial DNA and cytochrome c. These signals can trigger inflammatory responses that contribute to conditions like multiple sclerosis and chronic traumatic encephalopathy (West et al., 2015).
As we age, mitochondrial function gradually declines, leading to decreased ATP production and increased ROS generation. This deterioration affects crucial processes like synaptic function and memory formation. The cellular quality control systems that normally maintain healthy mitochondrial populations also become less effective with age, allowing damaged mitochondria to accumulate and potentially contributing to neurodegenerative diseases (Lopez-Otin et al., 2013).
The dynamic nature of mitochondria is particularly fascinating in the context of brain development and plasticity. These organelles constantly undergo fusion and fission, processes that allow them to adapt to changing energy demands and repair damage. These dynamics are especially important in developing neurons and in maintaining synaptic plasticity, the basis for learning and memory. When these processes malfunction, it can lead to developmental disorders including autism spectrum disorder and intellectual disabilities (López-Doménech et al., 2016).
Understanding mitochondria's diverse roles in the brain opens new avenues for treating neurological disorders. These remarkable organelles are far more than simple power plants - they're sophisticated regulators of brain function, involved in everything from energy production to immune regulation. As research continues to unveil their complexity, it becomes increasingly clear that maintaining mitochondrial health is crucial for preserving brain function and treating neurological diseases.
Dendrites are branched structures designed to receive messages from other neurons via axodendritic synapses (junctions between axons and dendrites shown below) and send messages to other neurons dendrodendritic synapses (junctions between the dendrites of two neurons). Dendrites receive thousands of synaptic contacts and have specialized proteins called receptors for neurotransmitters released into the synaptic cleft (Bear, Connors, & Paradiso, 2016).
A neuron's dendrites are called a dendritic tree, and each branch of the tree is called a dendritic branch. Graphic by BruceBlaus from Wikipedia article Neuron.
Biological psychologists classify neurons based on whether their dendrites feature spines. Dendritic spines are protrusions on the dendrite shaft where axons typically form axodendritic synapses. Graphic © Jose Luis Calvo/Shutterstock.com.
Spiny neurons have dendritic spines, while aspinous neurons do not (Bear, Connors, & Paradiso, 2016).
During learning, spines' number, size, and shape may change to adjust the space for receptors (neuroplasticity).
An axon is a cylindrical structure only found in neurons that is specialized for the distribution of information within the central and peripheral nervous systems. Axons range from 1 to 25 µm in diameter and 0.1 mm to more than a meter in length. Over 90% of neurons are interneurons whose axons and dendrites are very short and do not extend beyond their cell cluster. Axons usually branch repeatedly. Each branch is called an axon collateral.
Axons transmit action potentials toward a neuron's terminal buttons. Using microtubules an axon also bidirectionally transports molecules between the cell body and terminal buttons.
An axon hillock is a swelling of the cell body where the axon begins. The middle of an axon is the axon proper, and the end is the axon terminal (Bear, Connors, & Paradiso, 2016). Graphic by M.alijar3i from the Wikipedia article Axon Hillock.
The axon hillock sums EPSPs and IPSPs over milliseconds to generate an action potential.
Axon terminals are buds located on the ends of axon branches that form synapses and release neurochemicals to other neurons. Axon terminals contain vesicles that store neurotransmitters for release when an action potential arrives. Their presynaptic membrane may have reuptake transporters that return neurotransmitters (NTs) from the synapse or extracellular space for repackaging. The graphic of serotonin reuptake transporters below is courtesy of NIDA.
Types of Glial Cells
While there are hundreds of types of neurons, there are only four main categories of glial cells (astrocytes, microglia, oligodendrocytes, and Schwann cells).Old school view: glial cells mainly provide structural support (glia is derived from the Greek for glue).
New school view: glial cells help neurons process information, including modulating neuron excitability.
Check out the YouTube video, Neurology - Glial Cells, White Matter and Gray Matter.
Astrocytes are star-shaped glial cells in the central nervous system (i.e., brain and spinal cord) that perform vital functions. Astrocyte endfeet form junctions with capillaries comprising part of the protective blood-brain barrier. They regulate blood flow to the neuron, delivering stored glucose during peak metabolic demand (Schummers et al., 2008). Astrocyte graphic © Kateryna Kon/Shutterstock.com.
Astrocytes enclose synapses, determine where synapses can form by releasing specialized molecules, regulate synapse maturation, bidirectionally communicate with synapses, prune surplus synapses, help neurons regulate brain microcirculation, and eavesdrop on nearby synapse activity (Breedlove & Watson, 2023; Parri & Crunelli, 2003: Shan et al., 2021).
Astrocytes transport amino acid NTs (e.g., GABA and glutamate) from the synaptic cleft.
Astrocytes are theorized to participate in gliotransmission between neurons and each other (Eroglu & Barres, 2010; Perea et al., 2009). However, gliotransmission remains controversial.
. . . the physiological role of gliotransmission is highly debatable . . . as gliotransmitter release has been reliably demonstrated only in vitro in cultures and brain slice experiments that are often accompanied by manipulations (e.g., high frequency stimulation) which can affect astrocytic channels or receptors leading to impaired signaling cascades. This experimental design imposes questions about the existence of gliotransmission . . . and whether it plays a physiological role in the brain . . . (Buskila et al., 2019).
The presynaptic and postsynaptic neurons and astrocytes comprise a tripartite synapse.
An essential role of astrocytes is regulating the chemical content of this extracellular space. For example, astrocytes envelop synaptic junctions in the brain, thereby restricting the spread of neurotransmitter molecules that have been released. Astrocytes also have special proteins in their membranes that actively remove many neurotransmitters from the synaptic cleft. A recent and unexpected discovery is that astrocytic membranes also possess neurotransmitter receptors that, like the receptors on neurons, can trigger electrical and biochemical events inside the glial cell (Bear et al., 2020, p. 49).
Astrocyte glutamate release may be essential for hippocampal long-term depression (LTD), a long-lasting reduction in transmission strength, and long-term memory modulation (Navarrete et al., 2019). Astrocyte calcium and brain-derived neurotrophic factor (BDNF) release appear critical for late-phase hippocampal long-term potentiation (LTP), a long-lasting increase in transmission strength, and long-term memory regulation (Liu et al., 2021).
Astrocytes communicate with each other through gap junctions (Bennett et al., 2003).
Finally, astrocytes may contribute to brainwaves by regulating synapses via gap junctions and calcium signaling.
These capabilities allow astrocytes to regulate neuronal excitability via glutamate uptake, gliotransmission and tight control of the extracellular K+ levels via a process termed K+ clearance. Spatio-temporal synchrony of activity across neuronal and astrocytic networks, both locally and distributed across cortical regions, underpins brain states and thereby behavioral states, and it is becoming apparent that astrocytes play an important role in the development and maintenance of neural activity underlying these complex behavioral states (Buskila et al., 2019).
Microglia
Microscopic microglial cells participate in the immune response. Microglial cells scavenge and engulf diverse materials (phagocytosis), release cytotoxins to control infection, present antigens to T-cells, remove branches from neurons near damaged tissue to aid regrowth (synaptic stripping), promote tissue repair, and promote chronic neuroinflammation in the CNS that amplifies neurodegeneration. They assist synaptic remodeling by removing unnecessary synapses. Finally, microglia cross the blood-brain barrier to promote homeostasis (Bear, Connors, & Paradiso, 2016). Graphic © Juan Gaertner/Shutterstock.com.Description: yellow = neurons, orange = astrocytes, grey = oligodendrocytes, white = microglia.
Oligodendrocytes, which are smaller than astrocytes, form up to 50 segments of myelin that only insulate adjacent axons within the brain and spinal cord of the central nervous system. Graphic © Designua/Shutterstock.com.
Oligodendrocytes block axonal regeneration by releasing growth inhibitory proteins. These molecules are part of the reason for minimal functional recovery in the CNS following spinal cord damage. Multiple sclerosis, a demyelinating disease, destroys oligodendrocytes.
Schwann cells provide myelin for single PNS axons and facilitate axonal regeneration following damage (Breedlove & Watson, 2020). Graphic © Tefi/Shutterstock.com.
Excitatory and Inhibitory Postsynaptic Potentials
Graded positive and negative changes in membrane potential, called excitatory postsynaptic potentials and inhibitory postsynaptic potentials, are essential to the EEG and communication among neurons.An excitatory postsynaptic potential (EPSP) is a subthreshold depolarization that makes the membrane potential more positive and pushes the neuron towards its excitation threshold. EPSPs are produced when neurotransmitters bind to receptors and cause positive sodium ions to enter the cell. At a single synapse, a postsynaptic membrane may have tens to thousands of transmitter-gated ion channels. The amount of transmitter released determines how many of these channels will be activated. The size of an EPSP will be a multiple of the number of vesicles, each containing several thousand transmitter molecules.
An inhibitory postsynaptic potential (IPSP) is a hyperpolarization that makes the membrane potential more negative and pushes the neuron away from its excitation threshold. At most inhibitory synapses, IPSPs are produced when neurotransmitters like GABA or glycine bind to receptors and cause negative chloride ions to enter the cell. When an inhibitory synapse is closer to the soma than an excitatory synapse, it can counteract positive current flow and decrease the size of the EPSP. This mechanism is called shunting inhibition (Bear, Connors, & Paradiso, 2016).
Integrating Postsynaptic Potentials
Integration is the summation of EPSPs and IPSPs at the unmyelinated axon hillock. Interneuron graphic © Dee-sign/Shutterstock.com. The axon hillock of a postsynaptic neuron uses two methods to sum EPSPs and IPSPs: spatial and temporal summation.
In spatial summation, the axon hillock sums the simultaneous postsynaptic potentials (PSPs) from thousands of synapses on dendrites. In temporal summation, the axon hillock adds the PSPs from presynaptic neurons that repeatedly fire within a 1-15-ms time window.
Each EPSP depolarizes the axon hillock by about 0.5 mV. If there were no competing IPSPs, it would take about 30 EPSPs to trigger an action potential. Each IPSP hyperpolarizes the axon hillock by about 0.5 mV. If the summated EPSPs and IPSPs move the axon hillock from a resting potential of -70 mV to a threshold of excitation of -55 mV, sodium channels in the axon hillock membrane open, and an action potential propagates down the axon. Graphic © 2003 Josephine Wilson.
Check out the YouTube video, Best Action Potential Explanation.
Action Potentials
An action potential is a brief electrical impulse that transmits information from the axon hillock to the terminal button. This wave of positive charge only travels in one direction because the preceding segment is refractory due to the closing of its sodium channels. An action potential takes 1-2 ms from the point the axon hillock reaches its threshold to its repolarization to a negative resting potential.Action potentials travel down axons, which branch multiple times and terminate at synapses. The all-or-none law and rate laws describe action potential transmission. The all-or-none law states that once an action potential is triggered in an axon, it is propagated, without decrement, to the end of the axon. The rate law states that neurons represent the intensity of a stimulus by variation in the rate of axon firing. More intense stimuli shorten the interval before a neuron can fire again, allowing a neuron to fire more rapidly. An intense stimulus can cause a neuron to fire every 2 or 3 ms, while a weak stimulus might lengthen the time lag to every 4 or 5 ms. Action potential graphic © extender_01/Shutterstock.com.
We can compare action potential conduction to the movement of water through a leaky garden hose.
Garden hose: water can take two paths, inside the hose or through holes in its wall, and the majority of the water will flow where movement is easiest. For a small-diameter hose with many large holes, most of the water will travel through the leaks. Conversely, for a large-diameter hose with only a few small holes, the bulk of the water will remain inside.
Axon: positive charge can take two paths, inside the axon or through pores in its membrane. Like water, a positive charge will take the path of least resistance. For a small-diameter axon with many open sodium ion channels, the majority of the current will exit the axonal membrane to the extracellular fluid. Small diameter, unmyelinated axons transmit action potentials without weakening since sodium ion channels constantly regenerate this signal. This method is slow because the signal travels step-by-step, small segment by small segment, and waits for sodium channels to admit enough positive ions to reach the excitation threshold. Graphic © 2003 Josephine Wilson.
This method also consumes considerable energy since sodium-potassium transporters, powered by ATP, are located across the axon membrane to exchange three sodium for two potassium ions.
Conversely, for a large-diameter axon with few open ion channels, the bulk of the current will remain inside the axon's interior. Wider spacing between adjacent ion channels means that the action potential can depolarize a longer axon segment, which increases conduction velocity (Bear, Connors, & Paradiso, 2016).
Medium-to-large diameter myelinated axons transmit action potentials using a method called saltatory conduction. Each segment of insulating myelin is almost 1-mm long. The gaps between segments, called nodes of Ranvier, are 1 to 2 thousandths of a millimeter. An action potential weakens under each myelinated segment (cable properties) and is then regenerated at each Ranvier node. The destruction of this insulation by demyelinating diseases like multiple sclerosis (MS) can be devastating because it disrupts neuron-to-neuron communication.
Saltatory conduction can be 200 times faster because the action potential jumps from node to node, in 1-mm steps,” instead of steps that are a thousand times smaller. This method is also more energy-efficient because sodium-potassium transporters are only needed at the nodes of Ranvier, where ion exchange is possible. These transporters account for about 40% of a neuron’s energy expenditure (Breedlove & Watson, 2023; Garrett, 2003). Graphic © 2003 Josephine Wilson.
Synaptic Transmission
Neurons communicate through the release of over 200 neurochemicals and ions. Axon terminal buttons release neurochemicals across a 20-50-nm fluid-filled gap between presynaptic and postsynaptic structures called a synaptic cleft and into the extracellular fluid surrounding the neuron (Bear et al., 2020). Chemical synapses produce short-duration (millisecond) and long-duration (seconds to days) changes in the nervous system. Synapse animation without sound © 3Dme Creative Studio/Shutterstock.com.
They are functionally asymmetrical because the presynaptic neuron sends a chemical message and the postsynaptic neuron receives it. They are structurally asymmetrical because the presynaptic element (axon) contains vesicles containing NTs, and the postsynaptic element (dendrite) doesn’t. NT release from a terminal button is called exocytosis (Breedlove & Watson, 2023). Synapse graphic © SciePro/Shutterstock.com.
In the graphic below, an axon terminal button releases NTs into the synaptic cleft. NTs briefly form covalent bonds with receptors on a dendritic spine and then disengage after they initiate small graded potential changes (e.g., EPSPs or IPSPs) or more diverse, gradual, and long-lived actions (e.g., creating second messengers inside the target neuron). Chemical synapse graphic © nobeastsofierce/Shutterstock.com.
Neurotransmitter Co-Release
Old-school view: according to Dale’s law, a neuron can only release one NT at a synapse.New-school view: neurons can release a classical NT and a peptide.
Dale's law proposed that a neuron releases only one NT. However, researchers have found increasing evidence of NT co-release (Svensson et al., 2019). A neuron can store different NTs in separate types of vesicles (Hökfelt et al., 2003). Neurons can also store multiple NTs in the same vesicles (e.g., ATP and glutamate), although they may not release them simultaneously (Merighi et al., 2011; Xia et al., 2009).
Extra-Synaptic Transmission: Think Outside the Cleft
Neurons release NTs outside of classical synapses. These mechanisms include release from terminal buttons into the extracellular space, axonal varicosities, and retrograde transmission.
Old-school view: axon terminals only release NTs into the synaptic cleft.
New-school view: NT release also occurs outside of the synaptic cleft. Axonal varicosities (swellings in axon walls), dendrites, and the terminal button can release NTs into the extracellular space. Graphic © 3Dme Creative Studio/Shutterstock.com.
Volume Transmission
Volume transmission involves NT release and eventual binding to a receptor outside the synaptic cleft (Coggan et al., 2005). Don't confuse this process with volume conduction, which is the spread of an electrical signal when measured at some distance from its source. Graphic adapted from the American Scientist. Axonal Varicosities
Axons can release NTs into the extracellular space through varicosities (swellings) along their length, analogous to drip irrigation (Breedlove & Watson, 2023).Most neurons that release norepinephrine do not do so through terminal buttons on the ends of axonal branches. Instead, they usually release them through axonal varicosities, beadlike swellings of the axonal branches (Carlson & Birkett, 2019, pp. 82-83).
Retrograde Transmission
In retrograde transmission, a presynaptic neuron sends a chemical message to the postsynaptic neuron. In response, the postsynaptic neuron synthesizes and distributes an endocannabinoid (e.g., anandamide) or gas (e.g., nitrous oxide) to the presynaptic neuron and its immediate active neighbors. Neurons synthesize these NTs on demand since they cannot be contained by vesicles.. . . this gaseous signal has a range of influence that extends well beyond the cell of origin, diffusing a few tens of micrometers from its site of production before it is degraded. This property makes NO a potentially useful agent for coordinating the activities of multiple cells in a localized region and may mediate certain forms of synaptic plasticity that spread within small networks of neurons (Purves, 2017, pp. 142-143).
Retrograde NTs can bind to membrane-bound receptors or diffuse into the target cell, initiating second messenger production to adjust synaptic efficiency in learning and memory (Breedlove & Watson, 2023).
Modulation
Modulation is analogous to a volume control knob instead of an on/off switch on a stereo preamplifier; analog instead of digital.
We will consider two of countless modulation mechanisms: modulation of NT release and modulation of NT action at its receptor.
Neurotransmitter Release Modulation
Axons can influence the amount of NTs released when an action potential arrives at an axon terminal through axoaxonic synapses (junctions between two axons). Axoaxonic synapse graphic (see examples 2 and 6) by Blausen.com staff (2014) under Creative Commons Attribution 3.0. Axoaxonic synapses do not affect the generation of an action potential, only the amount of neurotransmitter distributed. In presynaptic facilitation, a neuron increases the
presynaptic neuron's neurotransmitter release by delivering a neurotransmitter that increases calcium ion
entry into its terminal button. In presynaptic inhibition, a neuron decreases
neurotransmitter release by reducing calcium ion entry. These modulatory effects are confined to a single
synapse (Breedlove & Watson, 2023).
Autoreceptors Modulate Neurotransmitter Release
Autoreceptors are metabotropic receptors on the presynaptic membrane. When NTs released into the synaptic cleft bind to autoreceptors, this hyperpolarizes the axon terminal button so it will release less NT when the next action potential arrives. Autoreceptor graphic © gritsalak karalak/Shutterstock.com. Neuromodulators Adjust Neurotransmitter Action
Receptors contain binding sites for a NT like GABA and drugs like alcohol. When alcohol binds to its allosteric site, it strengthens GABA's covalent bond with its orthosteric site, causing greater chloride entry into the neuron, increasing its hyperpolarization. Ingesting multiple CNS depressants (e.g., alcohol and barbiturates) can yield dangerous additive effects, amplifying GABA's action to a level that can depress or stop breathing.Types of Neurotransmitters
While the actual number of NTs is not known, more than 200 molecules have been identified. Each neurotransmitter may have multiple receptors. A NT's effect, excitatory or inhibitory, depends on its interaction with specific receptors. The same NT can produce opposite results at different receptor subtypes (Breedlove & Watson, 2023).The principal NT families include amino acid neurotransmitters (GABA, glutamate), amine neurotransmitters (acetylcholine, dopamine serotonin), peptide neurotransmitters, also called neuropeptides (oxytocin, vasopressin), gas neurotransmitters (nitric oxide, carbon dioxide), and lipid neurotransmitters (anandamide and AG-2). The table below is adapted from Breedlove and Watson (2023).
Neurotransmitter Pathways
Researchers have identified pathways for acetylcholine, dopamine, norepinephrine, and serotonin. The reproduced diagrams are © Vasilisa Tsoy/Shutterstock.com.Cholinergic pathways
Cholinergic cell bodies and their projections originate in the basal forebrain and brainstem. Cholinergic pathways are involved in arousal, attention, memory, motivation, muscle contraction, and sleep.
Dopaminergic pathways
Two major dopaminergic pathways originate in the midbrain: the mesostriatal and mesolimbocortical pathways. Dopaminergic pathways are involved in addiction, motor control, and salience (reward- and threat-based motivation).
Noradrenergic pathways
The noradrenergic pathways originate in the midbrain locus coeruleus and lateral tegmental area. Noradrenergic pathways are involved in arousal, attention, memory, vigilance, sleep, and mobilizing the brain and body for action, including the fight-or-flight response.
Serotonergic pathways
The serotonergic pathways originate in the brainstem and midbrain raphe nuclei. Serotonergic pathways are involved in appetite, mood, and sleep.
Termination of Neurotransmitter Action
Following exocytosis, NT action is terminated by reuptake and enzymatic degradation. In reuptake, reuptake transporters located in the presynaptic terminal and astrocytes that enclose the synapse return NT molecules to the presynaptic neuron. Astrocytes remove glutamate from the synapse. Graphic © Blamb/Shutterstock.com.In enzymatic degradation, enzymes located in the synaptic cleft and the cytoplasm of the presynaptic neuron's terminal button split neurotransmitter molecules apart (e.g., acetylcholine). Graphic © Designua/Shutterstock.com.
Electrical Synapses
Electrical synapses communicate information across gap junctions between adjacent membranes using ions. Gap junctions are narrow spaces between two cells bridged by connexons (protein channels) that allow ions near-instantaneous travel. Gap junction illustration © VectorMine/Shutterstock.com.Electrical synapses are generally symmetrical. Ions flow across a 3-nm gap junction into the more negatively charged neuron as long as the gap junction remains open. This means that whether neurons are presynaptic or postsynaptic depends on their respective charges. When two neurons are electrically coupled, an action potential in one induces a postsynaptic potential (PSP) in the paired neuron.
Transmission across electrical synapses is nearly instantaneous, compared with the 10-ms or longer delay in chemical synapses. The rapid information transmission that characterizes electrical synapses enables large circuits of neurons to synchronize their activity and simultaneously fire.
Studies in recent years have revealed that electrical synapses are common in every part of the mammalian CNS. When two neurons are electrically coupled, an action potential in the presynaptic neuron causes a small amount of ionic current to flow across the gap junction channels into the other neuron. This current causes an electrically mediated postsynaptic potential (PSP) in the second neuron. Note that, because most electrical synapses are bidirectional, when that second neuron generates an action potential, it will in turn induce a PSP in the first neuron (Bear et al., 2020, p. 113).
Neurons that secrete hormones use electrical synapses to release their chemical messengers simultaneously. Neonatal brains may use gap junctions to activate many neurons at once. Image of long, fibrous astrocyte processes using Golgi's silver chromate technique © Jose Luis Calvo/Shutterstock.com.
Gap junctions may be a preliminary step toward developing chemical synapses between these neurons, eventually replacing their electrical synapses. Prenatally and postnatally, gap junctions enable nearby neurons to coordinate their development by sharing electrical and chemical communications (Bear, Connors, & Paradiso, 2016; Breedlove & Watson, 2023).
Old school view: synapses are either electrical or chemical.
New school view: synapses can be both electrical and chemical
Discoveries Since Graduate School
Neuroscientists have learned a great deal more about neuron-to-neuron communication since graduate school. The most important findings are that the adult brain creates new neurons, silent synapses may mediate neuroplasticity in adulthood, the lymphatic system extends to the brain, neuronal networks exhibit mirroring properties, and neurons can release more than one NT, release NTs outside of a synapse, conduct two-way conversations, modulate NT release and action, talk to astrocytes that enclose synapses, and electrically communicate almost instantaneously.
Neurogenesis
Neuroscience has challenged the doctrine that the adult human brain does not create new neurons. There is a consensus that neurogenesis, the creation of new neurons in adults, occurs in the hippocampus (Eriksson et al., 1998) and olfactory bulb (Lim & Alvarez-Buylla, 2016). However, neurogenesis outside the hippocampus remains controversial. Animal research has yielded evidence of functionally significant neurogenesis in the amygdala, caudate nucleus and putamen (striatum), cortex, hypothalamus, and substantial nigra (Jurkowski et al., 2020). The neurogenesis graphic by Rebeca Cuesta is licensed under the Creative Commons Attribution-Share Alike 4.0 International license.Silent Synapses
Silent synapses are inactive due to the absence of glutamate AMPA receptors. Researchers studying adult mice discovered these synapses on the ends of threadlike filopodia. The simultaneous firing of two neurons connected by a silent synapse causes missing AMPA receptors to appear on the filopodia cell membrane and remodel it to resemble a dendritic spine (Vardalaki et al., 2022). The next step is to determine whether the adult human brain also contains silent synapses. If it does, they are a potential target for increasing cognitive flexibility in the elderly. Filopodia photomicrograph by Aurea D. Sousa and Richard E. Cheney under the Creative Commons Attribution-Share Alike 4.0 International license.Caption: A CAD cell (a neuronal cell line) expressing GFP-Myo10 (green) was stained for actin filaments (red) to visualize the slender cellular protrusions known as filopodia. Overexpressing Myo10 induces large numbers of filopodia and is responsible for the unusually large number of filopodia on this cell.
Holly Barker (2022) writing for The Scientist, explained:
The study may explain how the brain is able to learn new things without having to sacrifice existing connections, the researchers say. The ability of the brain to use different synapses 'solves the plasticity versus flexibility dilemma,' says Harnett. If all the brain’s synapses are flexible, then you can’t preserve old information. But if they’re all stable, then it is difficult to learn new things, he says. Instead, the brain employs both: spiny synapses for stability and filopodia for flexibility.
But instead of distinct categories, Harnett’s group are beginning to think about dendritic projections as existing on a continuum, from filopodia on one end to mature spines at the other. 'It is a spectrum of maturity, strength, and plasticity,' says study author Dimitra Vardalaki, a PhD candidate in Harnett’s lab.
Mirror Neuron System
Researchers discovered primate neurons with motor and visual properties in the premotor cortex. The mirror properties are due to a neuron's connections and not its construction. The cortex graphic © Vasilisa Tsoy/Shutterstock.com.These mirror neurons fired when primates grasped and manipulated objects, and another primate or human performed the same action (Di Pelligrino et al., 1992; Rizzolatti & Craighero, 2004). Mirroring extends across species, including facial expressions.
Molenberghs et al. (2011) unexpectedly found neurons with mirroring properties in the cerebellum, limbic system, and primary visual cortex. Graphic courtesy of Wikimedia Commons.
The authors proposed that a core network is responsible for observing and executing movements. The nervous system recruits additional areas to perform non-motor affective, auditory, and somatosensory functions.
Mirror neurons look like other neurons when examined using a microscope. Their mirror properties emerge from their sensory, motor, and emotional systems connections. Perhaps most mirror neurons may be tuned by experience (Catmur, Walsh, & Heyes, 2007).
The mirror neuron system (MNS) appears to encode the goal of a motor act and its component movements, whether a model manipulates an object or mimes the action. The MNS encodes the actions of others and stores them to predict their future actions (Rajmohan & Mohandas, 2007).
Soon after birth, an immature mirror neuron system may allow babies to imitate their parents' mouth movements, like thrusting out the tongue. Graphic courtesy of Wikimedia Commons.
Note. Image from Gross L. Evolution of neonatal imitation. PLoS Biol.
Ramachandran (2011) has called the mirror neurons activated when they observe others' movements "monkey see—monkey do neurons." He calls mirror neurons activated by others' emotional displays "Gandhi neurons." Check out Ramachandran's TED Talk, The Neurons that Shaped Civilization.
Investigators have speculated that the human MNS may mediate empathy, imitation learning, language, social cognition, and theory of mind (Buccino et al., 2006; Rajmohan & Mohandas, 2007; Schmidt et al., 2021).
Rizzolatti and Sinigaglia (2008) hypothesized that the primary role of the MNS is to help us understand others’ intentions, which allows us to achieve empathy. When we observe others’ facial expressions of emotion, visual information may be directly transmitted to mirror neurons in the insula, producing the visceral changes that color our emotions.
In autism, mirror neurons may not fire when observing other individuals performing actions. This may help explain deficits in empathy, social skills, language, and the development of a theory of mind (Enticott et al., 2011).
Heyes et al. (2021) summarized the state of our knowledge about the MNS.
For action understanding, multivoxel pattern analysis, patient studies, and brain stimulation suggest that mirror-neuron brain areas contribute to low-level processing of observed actions (e.g., distinguishing types of grip) but not to high-level action interpretation (e.g., inferring actors’ intentions). In the area of speech perception, although it remains unclear whether mirror neurons play a specific, causal role in speech perception, there is compelling evidence for the involvement of the motor system in the discrimination of speech in perceptually noisy conditions. For imitation, there is strong evidence from patient, brain-stimulation, and brain-imaging studies that mirror-neuron brain areas play a causal role in copying of body movement topography. In the area of autism, studies using behavioral and neurological measures have tried and failed to find evidence supporting the 'broken-mirror theory' of autism.
Cortical Architecture
While no one has counted the neurons in the human nervous system, a recent estimate is that an adult brain contains about 86 billion neurons (Voytek, 2013). Each neuron connects with an average of 40,000 synapses. There are 10 times more glial cells than neurons, and they comprise 50% of the brain’s volume (Breedlove & Watson, 2023). The 2 trillion glial cells are considerably smaller than neurons, with somas between 6 to 10 μm in diameter (Hammond, 1996). Animation © nmlfd/iStockphoto.com.The cerebral cortex comprises neuronal cell bodies, glial cells, and blood vessels. Beneath the neocortex lies myelinated nerves (white matter), unmyelinated fibers, and glial cells.
The cerebral cortex covers the cerebral hemispheres and consists of gray and white matter. Gray (or grey) matter, which looks grayish brown, comprises cell bodies. White matter gains its opaque white color from myelinated axons. The cerebral cortex of a macaque brain is shown below, courtesy of Wikipedia. Note that staining imparts a darker shade to gray matter.
The convolutions of the cerebral cortex contain two-thirds of its surface area and maximize the volume of cortical tissue housed within the skull. Cerebral cortical convolutions include sulci, which are shallow grooves in the surface of the cerebral hemisphere (central sulcus), fissures, which are deep grooves (lateral fissure), and gyri, which are ridges of cortex demarcated by sulci or fissures (precentral gyrus) (Carlson & Birkett, 2021).
There are two main types of cortex: neocortex and allocortex.
The neocortex or isocortex consists of six layers 3 mm thick with a surface area of about 2360 cm2 with white matter underneath. Layers I-III receive corticocortical afferent fibers that connect the left and right hemispheres. Layer III is the main source of corticocortical efferent fibers. Layer IV is the primary destination of thalamocortical afferents and intra-hemispheric corticocortical afferents. Layer V is the primary origin of efferent fibers that target subcortical structures that have motor functions. Layer VI projects corticothalamic efferent fibers to the thalamus, which together with the thalamocortical afferents, creates a dynamic and reciprocal relationship between these two structures (Creutzfeldt, 1995). Diagram courtesy of Wikimedia Commons.
Allocortex, which means other cortex, usually has between three or four layers, compared with the neocortex's six layers. The allocortex has less volume than the neocortex and comprises the olfactory system and hippocampus.
A transitional region between the neocortex and allocortex is called the paralimbic cortex.
For a basic overview of the cortex, watch the Khan Academy video Cerebral Cortex.
Neurons in the Cortex
We can classify cerebral cortical neurons as whether their dendrites display spines. Spiny neurons, which have either pyramidal or stellate (star-like)-shaped cell bodies, are usually excitatory. While all pyramidal cells are spiny neurons, stellate cells can be spiny or aspinous (Bear, Connors, & Paradiso, 2016).The graphic below depicts dendritic spines.neurons, which have either pyramidal or stellate (star-like)-shaped cell bodies, are usually excitatory. While all pyramidal cells are spiny neurons, stellate cells can be spiny or aspinous (Bear, Connors, & Paradiso, 2020). Spiny and aspinous dendrite graphic redrawn by minaanandag on Fiverr.com.
Dr. John C. Fiala, and Dr. Kristen M. Harris created this reconstruction of a dendritic spine. Creative Commons Attribution-Share Alike 3.0.
There are many types of aspinous (smooth) neurons which are believed to be inhibitory.
What is the EEG?
The scalp EEG is the voltage difference between two recording sites recorded over time. The EEG is primarily generated by large pyramidal neurons located in layers 3 and 5 of the 2-4.5-mm-thick cortical gray matter. Image of a pyramidal neuron revealed using Golgi silver chrome © Jose Luis Calvo/Shutterstock.com. Note that the apical dendrite arising from the cell body and basilar dendrites feature an extensive network of spines.
Local activity is a composite of local and network influences. Network communication systems and local cortical functions show different characteristics across the cortex and produce unique and specific EEG patterns in other regions.
The movie below is a BioTrace+/NeXus-32 display of the raw EEG with voltage shown as μV peak to peak © John S. Anderson.
What Can the EEG Tell Us?
With the EEG, we can follow the progression from stimulus to behavior response. This allows us to determine the correct function at each step and identify causal factors in dysfunctional outcomes or responses.Source of the Scalp EEG
The scalp EEG results from the summation of large areas of gray matter activity. Areas are polarized synchronously due to the input of oscillatory or transient evoked activity. These areas comprise thousands of cortical columns containing large pyramidal cells aligned perpendicularly to the cortical surface. Cortical layer graphic © Anna Him/Shutterstock.com.Pyramidal neurons of the cerebral cortex stained with the Golgi silver chromate © Jose Louis Calvo/Shutterstock.com.
Pyramidal neurons are found in all cortical layers, except layer 1, and represent the primary type of output neuron in the cerebral cortex. Pyramidal neuron graphic © Kateryna Kon/Shutterstock.com.
The scalp EEG results from the summation of EPSPs and IPSPs in thousands of cortical columns containing large pyramidal cells perpendicular to the cortical surface. The columns are synchronously polarized (made more negative) and depolarized (made less negative) due to the input of oscillatory or transient evoked activity. Graphic redrawn by minaanandag on Fiverr.com.
Artist: Dani S@unclebelang. This WEBTOON is part of our Real Genius series.
Local Field Potentials
The local field potential (LFP) is the aggregate effect of the firing of the interconnected pyramidal neurons within the cortical columns, plus additional mechanisms like glial cell modulation of the cortical electrical gradient. Caption from Wikipedia's article on Neural Oscillation. Simulation of neural oscillations at 10 Hz. The upper panel shows spiking of individual neurons (with each dot representing an individual action potential within the population of neurons). On the lower panel, the local field potential reflects their summed activity. This figure illustrates how synchronized patterns of action potentials may result in macroscopic oscillations that can be measured outside the scalp.
Do not confuse the "spiking" of individual neurons with epileptogenic spikes in the scalp EEG.
Scalp Electrical Potentials
Scalp electrical potentials represent the sum of all available electrical fields. Fields of opposite polarity (+/-) cancel each other out so that scalp potentials are greater when large aggregates of neurons polarize and depolarize synchronously. The scalp EEG represents a weighted sum of all active currents with the brain that generate open fields, including non-cortical sources.Action potentials reflect neuronal output. They are seen in extracellular recordings as fast (~300 Hz) activity that exceeds 90 mV lasting less than 2 ms. Action potentials play a minor role in scalp surface EEG. They fall below 60 V outside of a 50-μm (0.050-mm) radius. Scalp electrodes are several centimeters from cortical neurons and are generally aligned away from the scalp. Therefore, action potentials are unlikely to contribute significant voltages to the scalp EEG.
Local Field Potentials Regulate Neuron Excitability and Firing
Neurons are most likely to fire during the depolarizing phase of the local field potential. Neurons are more excitable when they are "in phase" with respect to the local field potential (LFP) and are inhibited when they are out of phase with the LFP. Thus, at any instant of time, the amplitude and frequency of the EEG are regulated by the LFP, which in turn, is influenced by oscillatory mechanisms such as slow cortical potentials.The movie is a 19-channel BioTrace+ /NeXus-32 display of SCPs © John S. Anderson. Negative SCPs drift up, and positive SCPs drift down, depending on the software settings. However, the convention in electroencephalography is to show negative up. SCPs represent a global shift in DC voltage across the cortex and represent a generally higher (negative SCPs) or lower (positive SCPs) state of cortical excitability regulating neural networks.
The EEG is a moment-to-moment measure of the excitability of action potential firing, like gates opening and closing on the half cycle. The synchronous activity of large pyramidal neurons networked in cortical columns creates the EEG.
The Composition of the EEG
The EEG is composed of electrical potentials, varying in two dimensions, frequency and amplitude.Sources of IPSP and EPSP Inputs
Many sources contribute input that results in IPSP and EPSP activity within cortical neurons. These sources primarily contribute influences such as oscillatory generator input or ascending event-related evoked input.EEG Sources
Generators like the thalamus produce oscillatory activity among many interconnected neurons, including EEG patterns like the alpha rhythm.
Movie © John S. Anderson. The recording begins with eyes open. The eyes-closed condition starts at 14’01” and clearly shows increased 8-12 Hz voltage (posterior dominant rhythm or PDR) in occipital and parietal locations in the line tracing and topographic maps to the right of the tracing.
The eyes open again at 14’31”, and alpha attenuates (alpha blocking). This shows the posterior dominant rhythm (generally known as "alpha") appearing in the eyes-closed condition when visual sensory input is stopped. The attenuation or blocking of this rhythm as sensory input returns in the eyes-open condition.
The thalamus contributes to slow cortical potentials, 1-4 Hz delta, 8-12 Hz alpha, and 20-38 Hz beta (including 40-Hz activity). The diagram shows the connections between the pulvinar (bottom right) and reticular nuclei (bottom left) of the thalamus and the cortex © Elsevier Inc. - Netterimages.com.
Thalamocortical cells are subject to excitatory drive from their system afferents, from monosynaptic corticothalamic fibers, and from the brainstem reticular formation (ascending reticular activating system, ARAS). They receive inhibitory drive from local interneurons and neurons in the reticular nucleus of the thalamus (RNT). Note that the RNT neurons are excited by activity in thalamocortical cells and corticothalamic cells. The connections are precisely organized. For example, each column in a primary cortical area sends corticothalamic fibers back to the same part of its specific thalamic nucleus that sends its thalamocortical fibers to that cortical column. The corticothalamic fibers also synapse on the RNT cells receiving input from that part of the thalamic nucleus. Each cortical receiving area is said to be "reciprocally connected" with its specific thalamic nucleus. Like the thalamocortical cells, RNT cells and cortical neurons also receive excitatory drive from the ARA (Jackson & Stoney, 2006).
The EEG is generated by thalamocortical (alpha) and cortical-cortical (beta) sources.
Neurons in the ascending reticular activating system produce event-related potentials in response to diverse stimuli like a flashing light or sound. Event-related potentials (ERPs) are the brain's response to externally applied stimuli, events, or cognitive/motor tasks. They are time-locked measures of brain electrical activity. Graphic redrawn by minaanandag on Fiverr.com.
Dipole Generators
Large cortical pyramidal neurons organized in macrocolumns are oriented with an apical dendrite projecting toward the scalp and an axon descending in the opposite direction. An "Equivalent Dipole Generator" usually represents the sum of all multipolar current sources. Summed generators are modeled as dipoles to aid the conceptual understanding of the electrical fields involved. Graphic adapted from Lipping (2017).EEG Signals (Brainwaves)
The EEG represents changes in a brain area's electrical activity (potential) compared to a "neutral" site or another brain area. The EEG is displayed as oscillations or voltage fluctuations, which show a "wave" pattern when plotted on a graph. "These oscillations are generated spontaneously in several areas of the cerebral cortex as neuronal networks transiently form assemblies of synchronously firing cells." Klaus Linkenkaer-Hansen.
Sink, Source, and Dipole
We can describe pyramidal cells in terms of their sink, source, and dipole. A sink (-ve), which may be located at the bottom, middle, or top of the apical dendrite, is where positive ions enter the dendrite. Cation (positive ion) entry gives the extracellular space a negative charge. The source (+ve) is where the current exits the cell. Finally, the dipole is the field created between the sink and source (Thompson & Thompson, 2016).The postsynaptic potentials (EPSPs and IPSPs) propagated by the apical dendrites in layers 2 and 3 create an extracellular dipole layer parallel to the cortical surface. The dipole layer's electrical polarity is the opposite of the deeper cortical layers 4 and 5 (Fisch, 1999).
A cortical dipole is created when pyramidal neurons depolarize simultaneously. This phenomenon is called local synchrony. Fewer than 5% of pyramidal neurons can generate more than 90% of the power in the EEG signal because most pyramidal neurons usually fire asynchronously so that their potentials counteract each other. A small fraction of these neurons firing in step can produce visible changes in EEG feedback. This creates the potential for operant conditioning to help clients learn to modify EEG activity through neurofeedback.
Cortical dipoles have three properties: site (depends on source), size (oscillation frequency and voltage), and relative position with respect to sulci and gyri (Collura, 2014).
The EEG is Mainly Sensitive to Radially Oriented Dipoles
Evolution has convoluted the human brain to increase its computing power without enlarging the skull. This enfolding has created two easily visible anatomical features: gyri and sulci. Cortex photograph © IdeaGeneration/Shutterstock.com.Recall that a gyrus is a ridge of the convoluted cerebral cortex, while a sulcus is a valley. The graphic below is adapted from Wikipedia.com from the article Sulcus (neuroanatomy) by minaanandag.
The EEG is most sensitive to a correlated dipole layer in gyri. The EEG is less sensitive to a correlated dipole layer in sulci, valleys within the cortex. Finally, the EEG is insensitive to an opposing dipole layer in sulci.
The EEG is composed of electrical potentials that vary along the dimensions of amplitude and frequency.
EEG Amplitude
The "amount" or amplitude and the "pattern" or morphology of any EEG frequency band reflect the number of neurons discharging simultaneously at that frequency. Lower neuron firing rates correspond to lower signal amplitude. Amplitude graphic © petrroudny43/Shutterstock.com. Amplitude measures the amount of energy in the signal and is usually expressed in microvolts.
Greater synchrony in firing among neurons results in higher amplitude, as shown with alpha in the graphic below.
Greater firing synchrony produces larger EEG potentials that can be measured from the scalp surface. Graphic redrawn by minaanandag on Fiverr.com.
The EEG plots voltage changes over time, which can be displayed on a graph. The sampling rate is the number of measurements per second (Hz). Precision is the number of voltage gradations or steps.
The analog-to-digital (A/D) converters that transform voltages into numerical values vary in precision: more bits correspond to greater accuracy. Graphic © Fouad A. Saad/Shutterstock.com.
EEG Frequencies
The raw EEG contains all EEG frequencies, just as white light contains all light frequencies. Digital filters separate the EEG frequencies just as a prism separates individual colors. Graphic © kmls/ Shutterstock.com.EEG frequency is measured in cycles per second or Hz. Count the number of peaks or count the number of zero (0.0) crossings divided by 2.
The slower the waves, the lower the EEG frequency. Frequency graphic © Bany's beautiful art/Shutterstock.com.
The longer the wavelength, the slower the frequency.
The movie is a 19-channel BioTrace+ /NeXus-32 display of EEG activity from 1-64 Hz activity broken into its component delta, theta, alpha, and beta frequency bands by digital filters © John S. Anderson.
The movie is a 19-channel BioTrace+ /NeXus-32 display of alpha activity © John S. Anderson. Brighter colors represent higher alpha amplitudes. Frequency histograms are displayed for each channel. Notice the runs of high-amplitude alpha waves.
EEG Oscillations
The generation of oscillatory activity, sometimes called spindle behavior, is likely due to the interaction between thalamocortical relay neurons (TCR), reticular nucleus neurons (RE), and interneurons. These interactions are mediated by diverse neurotransmitters, including acetylcholine and GABA.Circuits Contributing to the EEG
Feedforward, thalamocortical, and intra-cortical networks help generate the EEG.Spindling or Bursting Activity
Spindling is a synaptically-generated oscillation in a circuit that necessarily includes reticular nucleus neurons (RE).The movie below is a BioTrace+ /NeXus-32 display of EEG spindling activity © John S. Anderson.
The various spindle frequencies, which have often been interpreted as reflecting different types of oscillations, merely depend on various durations of the hyperpolarizations (negative shifts) in thalamic-cortical relay neurons. Long duration hyperpolarizations, as during ... deeply EEG-synchronized states, are associated with 7 Hz or even lower-frequency spindles, while relatively short hyperpolarizations result in ... higher frequencies (14 Hz) (Steriade, 2005).
The Purpose of Oscillatory Activity
A single neuron can influence multiple postsynaptic targets located between 0.5 and 5 mm away with conduction periods of between 1 and 10 ms. This time difference becomes progressively more pronounced when more complex events involve progressively larger assemblies of neurons. It may take hundreds of thousands of neurons, stimulating multiple postsynaptic neurons, for the desired outcome to occur. When these many neurons are involved, it becomes increasingly clear that there is a need for organization and structure to manage this diverse activity.Timing is everything since action potentials arrive from a large number of sources. The nervous system must correctly register arrival times to recognize a face, recall a name, or remember personal history and context.
Hierarchical Processing
Complex events require that the systems involved operate within a spatial and temporal hierarchy. Each oscillatory cycle is a window of time within which processing can occur. Each cycle has a beginning, and an end within which encoded or transferred messages must complete their tasks. Groups of neurons, close or distant, interact most effectively when firing windows are synchronous. The brain does not operate continuously but in discontinuous packets.Multiple Oscillators
"Oscillatory classes in the cerebral cortex show a linear progression of the frequency classes on the log scale. In each class, the frequency ranges ('bandwidth') overlap with those of the neighboring classes, so that frequency coverage is more than four orders of magnitude" (Buzaki, 2006). Graphic adapted from Buzaki by minaanandag at Fiverr.com.Frequency Determines Complexity
The wavelength or frequency of the EEG band determines how long the processing window will remain open and, therefore, the size of the neuronal pool involved. Because of the distances involved, longer wavelengths (slower frequencies) allow larger groups of more distant neurons to be assembled and coordinated. Different frequencies organize different types of connections and different levels of computational complexity.Local Versus Global Decision-Making
Short time windows of fast oscillators facilitate local integration, primarily because of the limitations of axon conduction delays. Fast oscillations favor local decisions. Slow oscillators can involve many neurons in large and/or distant brain areas. Slow oscillations favor complex, global decisions.Complexity Versus Frequency
Complex tasks involving sensory integration and decision-making were associated with 4-7 Hz synchronization. Intermediate tasks such as identifying spoken and written words and pictures increased 13-18 Hz beta activity. Simpler, more localized tasks, such as the visual processing of grid displays, were associated with faster-frequency activity (24-32 Hz) (Sarnthein et al., 1998; Von Stein et al., 1999).Traveling Waves Help Coordinate Widespread Brain Networks
Zhang et al. (2018) proposed that traveling waves between 2 to 15 Hz, moving at 0.25-0.75 meters per second across the cortex, mediate large-scale coordination of brain networks and support connectivity.Summary of EEG Oscillations
When the CNS processes incoming content, separate areas detect features of salient content, including visual, auditory, tactile, kinesthetic, and olfactory information. The CNS shares, integrates, compares current with previous content, analyzes, and makes decisions regarding memory and responses. Interacting networks linked by electrical and chemical signals perform this work. We record the electrical potentials generated by this complex and dynamic network activity as the EEG.The movie below of bursting alpha shows the sequential synchronization/desynchronization of groups of neurons. Higher voltage bursts are followed by voltage decreasing toward zero. These voltage fluctuations reflect rhythmic changes in the local field potential. This BioTrace+ /NeXus-32 video © John S. Anderson.
DEFINITION OF ERPs AND SCPs
Sensory evoked potentials are a subset of event-related potentials (ERPs)
Event-related potentials (ERPs) represent the brain's responses to external stimuli, events, or cognitive/motor tasks. ERPs can be detected throughout the cortex. Investigators monitor ERPs by placing electrodes at areas like the midline (Fz, Cz, and Pz). A computer analyzes a subject's EEG responses to the same stimulus or task over many trials to subtract random EEG activity. ERPs always have the same waveform morphology. Their negative and positive peaks occur at regular intervals following the stimulus.Sensory evoked potentials are a subset of ERPs elicited by external sensory stimuli (auditory, olfactory, somatosensory, and visual). They have a negative peak at 80-90 ms and a positive peak at about 170 ms following stimulus onset. The orienting response ("What is it?") is a sensory ERP. The N1-P2 complex in the auditory cortex of the temporal cortex reveals whether an uncommunicative person can hear a stimulus.
Motor ERPs are detected over the primary motor cortex (precentral gyrus) during movement, and their amplitude is proportional to the force and rate of skeletal muscle contraction (Thompson & Thompson, 2016).
Slow cortical potentials modulate the excitability of associated neurons
Slow cortical potentials (SCPs) are gradual changes in the membrane potentials of cortical dendrites that last from 300 ms to several seconds. SCPs are characterized by low-frequency oscillations, typically below 1 Hz. These oscillations are distinct from other brain rhythms, such as delta (1-4 Hz) and spindle (7-14 Hz). SCPs have been observed to occur at approximatel y 0.3 Hz, and their depolarizing-hyperpolarizing components have been extensively analyzed. These potentials include the contingent negative variation (CNV), readiness potential, movement-related potentials (MRPs), and P300 and N400 potentials, and exclude event-related potentials (ERPS) (Andreassi, 2007).
SCPs modulate the firing rate of cortical pyramidal neurons by exciting or inhibiting their apical dendrites. They group the classical EEG rhythms using these synchronizing mechanisms (Steriade, 2005). These potentials are crucial indicators of cortical excitability and are associated with various cognitive and motor processes.
The movie is a 19-channel BioTrace+ /NeXus-32 display of SCPs © John S. Anderson. Brighter colors represent higher SCP amplitudes. Negative SCPs drift down, and positive SCPs drift up. Negative SCPs are produced by the depolarization of apical dendrites and increase the probability of neuron firing. Positive SCPs are produced by the hyperpolarization of these dendrites and decrease the likelihood of neuron firing.
The contingent negative variation (CNV) is a steady, negative shift in
potential (15 µV in young adults) detected at the vertex. This
slow cortical potential may reflect expectancy, motivation, intention to
act, or attention. The CNV appears 200-400 ms after a warning signal
(S1), peaks within 400-900 ms, and sharply declines after a second
stimulus that requires the performance of a response (S2). John Balven adapted the graphic below from Stern, Ray,
and Quigley (2001).
The readiness potential is a slow-rising, negative potential (10-15
µV) detected at the vertex before voluntary and spontaneous
movement. This slow cortical potential precedes voluntary movement by 0.5
to 1 second and peaks when the subject responds. This potential is
separate from the CNV. John Balven adapted the graphic below from Stern, Ray, and Quigley (2001).
Movement-related potentials (MRPs) occur at 1 second as subjects prepare for
unilateral voluntary movements.
MRPs are distributed bilaterally with maximum amplitude at Cz. The
supplementary motor area and primary motor and somatosensory cortices
generate these potentials (Babiloni et al., 2002).
P300 and N400 ERPs are classified as long-latency potentials due to their
extended latencies
following stimulus onset.
The P300 potential is an event-related potential (ERP) with a 300-900-ms
latency.
The largest amplitude positive peaks are located over the parietal lobe. Researchers
elicit the P300 potential by exposing subjects to an odd-ball stimulus, a
meaningful
stimulus that is different from others in a series (a colored playing card
presented in a series of monochrome cards). The P300
potential may reflect an event’s subjective probability, meaning, and
transmission of information. Research shows this is separate from
the contingent negative variation (CNV) (Stern, Ray, & Quigley, 2001).
Shorter P300 latencies may reflect better allocation of attention, and
researchers have measured longer P300 latencies in ADD than non-ADD
samples. Experimental subjects show longer latencies when lying than when
telling the truth (Farwell & Donchin, 1991; Thompson & Thompson, 2016).
The N400 potential is an
event-related potential (ERP) elicited when we encounter semantic
violations like ending a sentence with a semantically incongruent word
("The handsome prince married the beautiful fish"),
or when the second word of a pair is unrelated to the first (BATTLE/GIRL). Warren and
McIlvane (1998) speculate that the N400 potential is evoked
whenever a general conceptual system that produces category judgments
encounters a mismatch that violates equivalence relations. Halgren and
colleagues (2002) consider it an index of the difficulty of semantic
processing.
A Deep Dive Into SCPs
In 1875, Richard Caton identified what may have been the first evidence of SCPs in an article in the British Medical Journal titled "The Electric Currents of the Brain."He stated, "The cortex's Direct Current baseline waxes negative whenever it is more active. Gradients of 150-200 μV/mm are noted." He later noted, "when any part of the gray matter is in a state of functional activity, its electric current usually exhibits negative variation." Some later researchers suggested that this signaled the discovery of the "steady potential" or the DC potential of the brain. However, others have noted the possibility of equipment-based artifacts in his recordings (Niedermeyer, 1999).
From the late 1800s through the early 1900s, research into brain electrical activity turned toward observations of electrical stimulation and spontaneous electrical activity in animal studies. As technology improved, the ability of researchers to identify EEG rhythms also improved. Hans Berger is famous for his description of alpha-blocking with cognitive activity, made possible partly because of his use of more sensitive equipment (Niedermeyer, 1999).
Slow Cortical Potential Generators
Several neural mechanisms and structures within the brain generate SCPs. The generation of SCPs is primarily cortical, as evidenced by their persistence even after extensive thalamic destruction and corpus callosum transection, indicating that the thalamus is not essential for their genesis (Steriade, Nuñez, & Amzica, 1993).SCPs have been identified in cortical neurons, the thalamus, and glial cells. Cortical neurons in layers II to VI generate slow oscillations when the thalamus is removed or when cortical tissue is studied in vitro (in an artificial environment) or in vivo (within a living organism). Thalamic reticular neurons exhibit similar slow spontaneous oscillations when studied in vitro, and synchronized intracortical oscillations may depend on a corticothalamic network that targets these thalamic neurons.
The source and nature of slow cortical potentials are in dispute. The prevailing theory holds that negative SCPs result from synchronous postsynaptic potentials in the apical dendrites of cortical pyramidal cells. Others hold that SCPs are supported and produced by glial cells within the cortex. It appears that pyramidal neurons may be the source of these potentials and that the glial system is the "sink" in electrical terms (Strehl, 2005, personal communication).
Increased neuronal activity is associated with an increased outflow of potassium ions leading to increased extracellular potassium concentrations. Glial cells depolarize when extracellular potassium concentrations increase, resulting in intracellular and extracellular current flows similar to typical neuronal synaptic transmissions (Speckmann & Elger, 1999). Since glial cells are widely interconnected and have extensive processes, it appears likely that the glial system is responsible for the potential changes that produce SCP values recorded from the scalp in response to neuronal activity.
Despite some discussion regarding the source of SCP activity, it is clear that scalp SCPs represent the cortex's excitability potential. SCP negativity is associated with increased cortical excitability. High cortical negativity has been correlated with a greater likelihood of seizures (Speckmann et al., 1984) and migraines (Siniatchkin et al., 2000) in susceptible individuals.
SCP positivity is associated with increased cortical inhibition. Higher-than-expected positive SCPs have been noted in children with elevated blood lead levels (PbB; Otto & Reiter, 1984). Children diagnosed with ADHD show deficient SCP self-regulation skills compared with controls (Heinrich et al., 2004). SCPs have been used to monitor the depth of anesthesia during surgical procedures (Sebel et al., 1997) because they appear to be excellent indicators of the arousal level.
Cortical Neurons
SCPs are primarily generated by the synchronized activity of large populations of cortical neurons. The slow shifts in membrane potential are thought to reflect changes in the overall excitability of cortical networks (Birbaumer et al., 1990). Neuron graphic © SciePro/Shutterstock.com.Thalamocortical Interactions
Interactions between the thalamus and cortex also play a significant role in generating SCPs. Through its relay and integrative functions, the thalamus modulates cortical excitability and contributes to the slow potential changes observed in SCPs (Lopes da Silva, 1991). Thalamocortical graphic © Netter.
Glial Cells
Emerging evidence suggests that glial cells, particularly astrocytes, may influence SCPs by modulating the extracellular environment and supporting neuronal function (Amzica & Steriade, 2002).Glial cells generate slow SCPs when they burn sugar, producing negatively charged bicarbonate ions. Unlike EEG rhythms like delta, SCPs do not summate dendritic potentials. SCPs are associated with glial cells and gap junctions. Glial cells chemically communicate among themselves and with neurons. The slow oscillations of glial cells may influence the timing of neuronal firing through their control of potassium ion outflow (Steriade, 2005). Astrocyte graphic © Kateryna Kon/Shutterstock.com.
"The concept of a unified corticothalamic network that generates diverse types of brain rhythms grouped by the cortical slow oscillation is supported by EEG studies in humans" (Mölle et al., 2002).
The Meaning of SCP EEG Activity
SCPs indicate shifts in cortical excitability and are associated with various functional states of the brain. Surface-negative SCPs reflect synchronized depolarization of neuronal assemblies, indicating increased cortical activity. Surface-positive SCPs correspond to decreased cortical excitation, often involving inhibitory processes (Hinterberger et al., 2003).The negative SCPs detected at the scalp during neuronal depolarization may seem counterintuitive at first.
When neurons are activated, their cell bodies become more positive internally due to the influx of positive ions. This leaves the immediate extracellular space around the neuron more negative. The negative charge in the extracellular space is conducted through brain tissue, cerebrospinal fluid, skull, and scalp. EEG electrodes on the scalp detect this conducted negative potential, resulting in a negative deflection on the EEG trace.
This phenomenon is often referred to as paradoxical negativity in EEG literature (Birbaumer et al., 1990). It's important to note that what we record on the scalp is not a direct measure of neuronal membrane potential, but rather the result of complex electrical field propagation through various tissues (Elbert et al., 1980). Paradoxical positivity occurs when neurons are hyperpolarized.
This relationship is crucial in understanding the neurophysiological mechanisms underlying SCPs (Birbaumer et al., 1990). This paradoxical negativity graphic (Brienza & Mecarelli, 2019) is available under the license CC BY 3.0.
Caption: Schematic drawing of the scalp EEG registering negative (A) and positive (B) deflections elicited from summated EPSPs and IPSPs derived from pooled pyramidal cells. Cells releasing glutamate and GABA provide excitatory and inhibitory superficial and deep synaptic connections, resulting in an electrophysiological sink or source. EEG = electroencephalography; EPSPs = excitatory postsynaptic potentials; GABA = gamma-aminobutyric acid; IPSPs = inhibitory postsynaptic potentials. Figure courtesy of Anteneh Feyissa M.D. and Mayo Clinic.
Caton (1875) observed that the cortex's direct current baseline becomes negative whenever it is more active. The voltage gradients range from 150-200 μV. Underlying "tone" or valence factors determine the firing characteristics of neurons within a network. When SCPs are more positive, cortical neurons fire less due to hyperpolarization. When SCPs are more negative, firing increases due to depolarization.
SCPs participate in cognitive processes such as attention, preparation, and intention. Negative SCP shifts are often linked to increased cortical excitability and readiness to respond, while positive shifts are associated with decreased excitability and relaxation (Birbaumer et al., 1990).
Some types of SCPs are event-related. These include the Bereitschaftspotenial (BP or so-called readiness potential), contingent negative variation (CNV), and stimulus-preceding negativity (SPN). These represent slow negative waves related to anticipating a stimulus or preparing for a movement (Brunia et al., 2012). The BP occurs before the execution of a self-paced movement. CNV occurs when a preparatory stimulus foretells the imminent presentation of a stimulus that requires a response. SPN occurs after a movement when waiting for a stimulus that will provide feedback about the accuracy of the movement.
The slow rhythm of SCPs is often combined with delta oscillations, and these rhythms are phase-locked, suggesting a close interaction between different frequency bands in the brain's electrical activity (Steriade, Nuñez, & Amzica, 1993).
SCPs play a crucial role in motor preparation and execution. The readiness potential (Bereitschaftspotential), a type of SCP, precedes voluntary movements and reflects the planning and initiation of motor actions.
SCPs are also associated with emotional and motivational states. Negative SCPs can indicate increased arousal and emotional engagement, whereas positive SCPs can reflect relaxation and disengagement (Hinterberger et al., 2004).
Psychological and Medical Disorders
SCPs have been extensively studied in various psychological and medical conditions.Attention-Deficit/Hyperactivity Disorder (ADHD)
Individuals with ADHD often exhibit abnormal SCP patterns, with a reduced ability to generate negative SCP shifts. Neurofeedback training targeting SCPs has shown promise in improving attention and reducing hyperactivity in these individuals (Heinrich et al., 2004). Epilepsy SCP neurofeedback has been explored as a treatment for epilepsy. Training individuals to increase positive SCP shifts can reduce cortical excitability and decrease the frequency of seizures (Rockstroh et al., 1993). Parkinson's Disease Studies have shown that patients with Parkinson's disease (PD) exhibit abnormal SCP patterns, particularly during motor tasks (Brittain & Brown, 2014). These abnormalities include altered amplitude and timing of SCPs, associated with the impaired initiation and execution of voluntary movements seen in PD.Research has shown that during non-rapid eye movement (NREM) sleep, cortico-basal slow wave delta activity increases, while beta activity decreases. Deep brain stimulation (DBS) further modulates this altered activity, enhancing cortical delta activity and reducing alpha and low beta power. These findings suggest that SCPs and their interaction with other brain rhythms are significantly altered in PD, contributing to sleep dysfunction and spontaneous awakenings (Anjum et al., 2023).
SCPs are used to monitor the effects of therapeutic interventions, such as deep brain stimulation (DBS), on cortical function in PD patients.
Slow cortical potential (SCP) neurofeedback has shown potential efficacy as a complementary treatment for Parkinson's disease (PD). SCP neurofeedback aims to train individuals to self-regulate their brain activity, particularly focusing on slow cortical potentials associated with motor control.
Research suggests that SCP neurofeedback can improve motor function in PD patients (Kober & Wood, 2014). Some studies have reported that participants undergoing SCP neurofeedback training demonstrated better control over motor symptoms, such as tremors and rigidity, and experienced enhanced overall motor performance. Additionally, SCP neurofeedback has been associated with improvements in non-motor symptoms, including mood and cognitive function, which are often affected in PD.
While promising, the current evidence is based on a limited number of studies with small sample sizes. More extensive and rigorous clinical trials are needed to establish SCP neurofeedback's long-term efficacy and generalizability for PD.
Depression
SCP abnormalities are observed in depression, with patients often showing reduced amplitude of SCP shifts. Neurofeedback interventions aiming to normalize SCP patterns have shown potential in alleviating depressive symptoms (Strehl et al., 2017).Sleep
SCPs play a role in sleep regulation and quality.Sleep Onset and Maintenance
SCPs are involved in the transition from wakefulness to sleep. Positive SCP shifts are associated with sleep initiation and maintaining sleep stability (Sterman, 1996).Sleep Disorders
SCPs are closely linked to sleep rhythms, particularly during NREM sleep (Anjum et al., 2023). The slow oscillations of SCPs facilitate the synchronization of neuronal activity, which is essential for the restorative functions of sleep. In PD, the suppression of slow waves and the increase in subcortical beta activity before spontaneous awakenings highlight the critical role of SCPs in maintaining sleep stability and quality.Abnormal SCP patterns have been linked to sleep disorders such as insomnia. Neurofeedback training targeting SCPs can improve sleep onset latency and enhance overall sleep quality (Hoedlmoser et al., 2008).
Performance
Enhancing SCP activity through neurofeedback training has improved performance in various cognitive and motor tasks.Cognitive Performance
SCP training can enhance cognitive performance, including attention, memory, and executive function. This is likely due to the improved cortical excitability and better regulation of cognitive states (Vernon et al., 2003).Motor Performance
SCP neurofeedback has been shown to improve motor performance, particularly in tasks requiring precise timing and coordination. This enhancement is attributed to the role of SCPs in motor preparation and execution (Gruzelier et al., 2014).SCP Research
Research into the electrical characteristics of the human brain became primarily focused on phasic phenomena from AC-coupled recordings. This trend continues today with the current practice of EEG biofeedback or neurofeedback, focusing primarily on training AC frequencies, generally in the range of 1 to 60 Hz.The study of SCPs continued in physiology and animal research. Only recently has there been increased interest in observing SCPl values in the human EEG and correlating them with cognitive activity, sensory processing, and motor activity. SCPs are distinguished from short-latency, event-related potentials (ERP) up to 500 ms. SCPs reflect cortical processes that require more than one second to complete and are associated with more global, task-related activities. Such changes occur in task-specific areas of the cortex and can be displayed using topographic maps. Areas of activation show surface negative potential changes (Altenmuller & Gerloff, 1999).
Operant conditioning of SCP changes is an even more recent study area. One reason for increased interest in SCP training is the excellent work done by Birbaumer and colleagues (1999) at the University of Tubingen in Germany, demonstrating that SCPs can be operantly conditioned with positive outcomes for a variety of disorders. The recent availability of DC-coupled amplifiers for EEG recording has also contributed to this interest (Altenmuller & Gerloff, 1999).
According to Niedermeyer (1999), "DC" can mean several things. DC means direct current, which is a current without oscillations. From an electrophysiological perspective, "DC shifts" are ultra-slow potentials below the typical EEG in the oscillation frequency and are generally around 0.1-0.2 cycles per second. However, they may extend up to 1 cycle per second. So SCPs are not true direct current, though their oscillations are so slow that they are "DC-like" phenomena.
DC also refers to "direct coupling" (Niedermeyer, 1999) and describes a type of amplifier that does not use capacitors between the amplification stages and uses an infinite time constant to provide for optimal DC recording. Until recently, this has been quite difficult to achieve for EEG recording. Most conventional EEG amplifiers use capacitors in the input stage, which reject DC voltages and create a finite time constant that interferes with access to DC phenomena.
An approximation of DC information can be obtained from an alternating current amplifier by using a rectifier or extending the time constant to approximately 10 seconds (Kotchoubey et al., 1999). A thorough discussion of amplifier characteristics is beyond the scope of this article. Several excellent chapters relating to this subject can be found in Niedermeyer and Lopes da Silva (1999).
Recent studies have used SCPs to evaluate various task-oriented responses. Birbaumer and colleagues have trained SCPs to reduce seizures (Daum et al., 1993; Kotchoubey et al., 1997, 1999, 2001, 2002), and other groups have applied SCP feedback training to improve ADHD (Heinrich et al., 2004; Strehl, 2004, personal communication) and schizophrenia (Schneider et al., 1992).
SCP feedback training appears to be an approach that targets general characteristics of arousal using a single measure, compared to other types of EEG training that often reward increases and/or decreases in certain combinations of frequencies to accomplish changes in arousal. SCP feedback may provide a less complex approach to training neuronal activity in the clinical setting, providing greater accessibility via clinician-supervised home training devices.
Most research to date has been conducted using the Cz electrode site. However, at least one investigation involved training left hemisphere language sites. This approach demonstrated improved word processing results following the negativity training condition and diminished performance following the positivity condition (Pulvermuller, 2000). Studying the effects of SCP training at other electrode sites would be interesting.
Some efforts have been to identify SCP values using multiple electrodes in a quantitative EEG assessment paradigm. Basile and colleagues (2004) used four 32-channel DC-coupled amplifiers to identify differences in SCP responses in schizophrenic patients compared with normal controls. They found significant variations in response patterns, with normal controls showing simply-organized positivity and negativity patterns, while schizophrenic patients showed much more complex, fragmented patterns of activation and inhibition.
There are only a few clinically available DC-coupled amplifiers capable of accurately monitoring SCP activity. An Internet search yielded several devices aimed at the research institution market with correspondingly high prices and a couple of other devices with prices within a clinical practice’s reach. A new 32-channel DC-coupled data acquisition device for quantitative EEG assessments has also recently been released.
One potential attraction of using a DC amplifier is the capability of monitoring and/or training both SCPs and typical EEG frequencies. This is because DC amplifiers are optimized for SCP and have the capacity to record faster frequencies. This is particularly true for amplifiers with better analog-to-digital (AD) conversion characteristics (bit size, not sampling rate) because this allows them to record AC potentials without exceeding amplifier capabilities, which can be a problem in an amplifier without capacitors at the input stages.
Higher analog-to-digital (A/D) conversion values (more bits of data per sample) allow newer DC amplifiers to process EEG at a much lower voltage while retaining a high degree of resolution for signals that are often in the millivolt range (compared to microvolt values for most EEG signals).
The training of SCP shifts is a fairly new endeavor. Much remains to be learned about the effects of training both the positivity and negativity conditions at various electrode sites for individuals with various presenting concerns and specific neurophysiological characteristics.
This author's recent, brief clinical experiences suggest that training SCP using new, more accurate amplifiers may result in more pronounced changes occurring more quickly. This occurred on several occasions, even when using previously well-tested protocols alternating 8- to 10-second trials of both the positivity and negativity conditions. Thus, it will be important to develop protocols with more specificity and flexibility to meet the needs of non-homogeneous client populations that also consider changes in equipment and software characteristics that may affect the rate of skill acquisition and subsequent outcomes.
Training SCP
Various approaches to training slow cortical shifts have been applied. Early research (Birbaumer, 1990; Birbaumer, 1999) showed a correlation between cortical negativity and reaction time, signal detection, and short-term memory. This was identified primarily through evoked and event-related potential (EP, ERP) research, which led to a focus on the event-related potential in developing training paradigms for research and clinical interventions. Protocols involved presenting clients/participants with sequences of 8-second trials, training both positive and negative shifts in the cortical gradient by providing visual and/or auditory feedback showing such shifts in real-time. When the goal was greater cortical positivity, more positive shift trials were provided, and the opposite was true when cortical negativity was desired. Additional transfer trials were included that asked the individual to produce a shift but did not provide visual or auditory feedback to test the level of skill acquisition. This approach was the primary paradigm during the early years of SCP research (Strehl, 2009).
Other clinicians and researchers, including Susan and Siegfried Othmer and Mark Smith, addressed these slow gradient shifts with training called variously Infra-Low Frequency Neurofeedback (Othmer, 2020) and Infraslow Neurofeedback (Smith, 2013).
Post-traumatic stress, anxiety, and other characteristics of excessive cortical activation and excitability have been addressed by training to increase overall cortical positivity, using a 4-channel/location approach that rewards a gradual shift in the cortical gradient by providing proportional audio feedback reflecting directional shifts in the gradient. This has resulted in several client self-reports of an altered state experience characterized by a marked decrease in cognitive activity while retaining awareness. The positive shift in cortical gradient appears to correspond with a reduction in conscious thought while allowing a sense of self-awareness to remain (multiple clinical observations shared with John Anderson).
Conclusion
Slow cortical potentials (SCPs) are characterized by low-frequency oscillations in the EEG, typically below 1 Hz, with significant depolarizing-hyperpolarizing components. These potentials, occurring at approximately 0.3 Hz, are crucial indicators of cortical excitability and are associated with various cognitive and motor processes. Generated by cortical neurons, thalamocortical interactions, and glial cells, SCPs reflect shifts in cortical excitability linked to attention, motor preparation, and emotional states. Negative SCP shifts indicate increased excitability and readiness to respond, while positive shifts are associated with relaxation and decreased excitability.
SCPs play roles in psychological and medical disorders like ADHD, epilepsy, and depression, and are vital in sleep regulation and performance enhancement. SCP neurofeedback shows promise in improving symptoms and cognitive functions in various conditions.
The author would like to thank Ute Strehl of the University of Tubingen in Germany, David Seiver of Mind Alive, LTD in Canada, and Erwin Hartsuiker of Mind Media BV in the Netherlands for technical assistance in preparing this article.
NEUROPLASTICITY (LTD AND LTP)
Neuroplasticity, the remodeling of neurons and neural networks with experience, is responsible for learning and memory. Memory storage involves the remodeling of neurons in terms of synaptic transmission, interneuron modulation, formation of new synapses, and rewiring of neural pathways (Bear, Connors, & Paradiso, 2020). Animal studies have shown that operant conditioning can induce astrogliogenesis (creation of new astrocytes) and neurogenesis (creation of new neurons) in structures like the medial prefrontal cortex and hippocampus (Rapanelli, Frick, & Zanutto, 2011).
The graphic by Rebeca Cuesta is licensed under the Creative Commons Attribution-Share Alike 4.0 International license.
Neuroplasticity appears to involve a simple rule: when some synapses strengthen, adjacent synapses weaken to prevent overload due to increased input. A protein called Arc is crucial to this process (El-Boustani et al., 2018).
Neurofeedback, which involves the operant conditioning of CNS electrical activity, would be impossible without neuroplasticity. In neurofeedback, clients may learn to change the activity of local, regional, and global cortical resonant loops and the connectivity between brain regions (Collura, 2014; Thompson & Thompson, 2016).
To learn more about neuroplasticity, view the Khan Academy video Neuroplasticity.
Long-Term Depression and Long-term Potentiation
Two of the diverse processes involved in neuroplasticity are long-term depression and long-term potentiation.In long-term depression (LTD), synaptic transmission that coincides with slight depolarization of the postsynaptic neuron weakens a synapse due to pre- and postsynaptic changes. Relatively low-frequency stimulation of afferent neurons reduces the magnitude of their response to future stimulation
In long-term potentiation (LTP), synaptic transmission that coincides with strong depolarization of the postsynaptic neuron strengthens a synapse due to pre- and postsynaptic changes. Strong stimulation of afferent neurons results in a stable and persistent (weeks or more) increase in synaptic effectiveness. LTP involves diverse changes, including creating new synapses, enhancing previous synapses, and building new dendritic branches and spines (Breedlove & Watson, 2020).
To learn more, watch the Khan Academy video Long Term Potentiation and Synaptic Plasticity.
Glossary
40-Hz rhythm: gamma rhythm hypothesized to be associated with feature binding (linking an apple's color to its shape) and attributed to the neocortex and thalamocortical neurons.
acetylcholine: an amine neurotransmitter that binds to nicotinic and muscarinic ACh receptors.
acetylcholine esterase (AChE): the enzyme that deactivates ACh.
AChE-R: an abnormal form of acetylcholine esterase (AChE) may render dendrites with acetylcholine receptors more excitable when stressed.
action potential: a propagated electrical signal that usually starts at a neuron’s axon hillock and travels to presynaptic axon terminals.
adenylate cyclase: at a metabotropic receptor, an enzyme that transforms ATP into the second messenger cyclic AMP.
afferent: a neuron that transmits sensory information towards the central nervous system or from one region to another.
allocortex: cortex that contains three or four layers and is comprised of the olfactory system and hippocampus.
all-or-none law: once an action potential is triggered in an axon, it is propagated, without decrement, to the end of the axon. The amplitude of the action potential is unrelated to the intensity of the stimulus that triggers it.
alpha blocking: arousal and specific forms of cognitive activity may reduce alpha amplitude or eliminate it entirely while increasing EEG power in the beta range.
alpha rhythm: 8-12-Hz activity that depends on the interaction between rhythmic burst firing by a subset of thalamocortical (TC) neurons that are linked by gap junctions and rhythmic inhibition by widely distributed reticular nucleus neurons. Researchers have correlated the alpha rhythm with "relaxed wakefulness." Alpha is the dominant rhythm in adults and is located posteriorly. The alpha rhythm may be divided into alpha 1 (8-10 Hz) and alpha 2 (10-12 Hz).
alpha spindles: regular bursts of alpha activity.
alpha-subunit: a subunit of a G protein associated with the neuron membrane that breaks away to activate enzymes within the neuron when a ligand binds to a metabotropic receptor.
amino acid neurotransmitters: the oldest family of transmitters. These molecules bind to ionotropic and metabotropic receptors, so they transmit information and modulate neuronal activity. In the brain, most synaptic communication is accomplished by glutamate (generally excitatory) and GABA (generally inhibitory).
AMPA (glutamate) receptors: ionotropic receptors which open sodium channels, depolarize the neuron's membrane (producing an EPSP), and dislodge a Mg+ ion that blocks an adjacent NMDA (glutamate) receptor's calcium channel. AMPA receptors are responsible for most activity at glutamatergic synapses.
amplitude: the energy or power contained within the EEG signal measured in microvolts or picowatts.
amygdala: the limbic system structure that participates in evaluating whether stimuli are salient (rewarding or threatening), establishing unconscious emotional memories, learning conditioned emotional responses, and producing anxiety and fear responses.
anion: a negative ion, for example, chloride (Cl-).
anterior: near or toward the front of the head, for example, the anterior cingulate.
anterior cingulate: a division of the prefrontal cortex that plays a vital role in attention and is activated during working memory. It mediates emotional and physical pain, and has cognitive (dorsal anterior cingulate) and affective (ventral anterior cingulate) conflict-monitoring components.
anterior commissure: a bundle of nerve fibers that crosses the midline and connects the left and right temporal lobes and the hippocampus and amygdala.
apical dendrite: a dendrite that arises from the top of the pyramid and extends vertically to layer 1 of the neocortex.
arousal: a process that combines alertness and wakefulness, produced by at least five neurotransmitters, including acetylcholine, histamine, hypocretin, norepinephrine, and serotonin.
aspinous (smooth) neurons: neurons without dendritic spines that are believed to be inhibitory.
astrocytes: star-shaped glial cells that communicate with and support neurons and help determine whether synapses will form.
asynchronous waves: neurons depolarize and hyperpolarize independently.
ATP: energy source for a neuron’s sodium-potassium transporters.
autoreceptors: metabotropic receptors that can be located on the membrane of any part of a neuron. They detect neurotransmitters the neuron releases, generate IPSPs that inhibit the neuron from reaching the excitation threshold, and regulate internal processes like transmitter synthesis and release through the second messenger system.
axoaxonic synapses: junctions between two axons that do not affect the generation of an action potential, only the amount of neurotransmitter distributed.
axodendritic synapses: junctions between axons and dendrites that determine whether the axon hillock will initiate an action potential.
axon: long, cylindrical structures that convey information from the soma to the terminal buttons. An axon also transports molecules in both directions along the outer surface of protein bundles called microtubules.
axon hillock: a swelling in the cell body where a neuron integrates the messages it has received from other neurons and decides whether to fire an action potential.
axon terminal: buds located on the ends of axon branches that form synapses and release neurochemicals to other neurons.
axonal varicosity: a swelling in an axon wall that releases neurotransmitters through the wall via volume transmission.
axoplasmic transport: the movement of molecules in both directions along the outer surface of protein bundles called microtubules.
basal dendrite: a dendrite that horizontally branches out from the 30 μm base of the pyramid through the layer where the neuron resides.
basal ganglia: forebrain structures consisting of an egg-shaped nucleus that contains the putamen and globus pallidus and a tail-shaped structure called the caudate, which together are responsible for the production of movement. The basal ganglia have also been implicated in obsessive-compulsive disorder, Parkinson’s disease, and Huntington’s chorea.
beta rhythm: 12-38-Hz activity associated with arousal and attention generated by brainstem mesencephalic reticular stimulation that depolarizes neurons in both the thalamus and cortex. The beta rhythm can be divided into multiple ranges: beta 1 (12-15 Hz), beta 2 (15-18 Hz), beta 3 (18-25 Hz), and beta 4 (25-38 Hz).
bilateral synchronous slow waves: a pathological sign observed in drowsy children. When detected in alert adults, intermittent bursts of high-amplitude slow waves may signify gray matter lesions in deep midline structures.
cation: positive ion, for example, sodium (Na+).
caudal: away from the front of the head.
cell body or soma: part of a neuron that contains machinery for cell life processes and receives and integrates EPSPs and IPSPs from axons generated by axosomatic synapses (junctions between axons and somas). The cell body of a typical neuron is 20 μm in diameter, and its spherical nucleus, which contains chromosomes comprised of DNA, is 5-10 μm across.
central nucleus of the amygdala: nucleus that orchestrates the nervous system's response to important stimuli by activating circuits in the brainstem (autonomic arousal) and the basal ganglia and periaqueductal gray (defensive behavior).
cerebral cortex: the layer of gray matter that covers the cerebral hemispheres. The cerebral cortex consists of gray matter and white matter.
chemical synapses: junctions between neurons that transmit molecules across gaps of less than 300 angstroms. Neurons use chemical synapses to produce short-duration (millisecond) and long-duration (seconds to hours) changes in the nervous system. Chemical synapses are capable of more extensive communication and initiating more diverse and long-lasting changes than electrical synapses.
classical routes for EEG activation: specific sensory pathways like the visual (retina to the visual cortex), auditory (cochlea to the auditory cortex), and somatosensory (chemoreceptors and mechanoreceptors to the somatosensory cortex) systems. Increased transmission of information through these pathways desynchronizes EEG activity in the cortical regions to which these afferent neurons project, as specialized circuits of neurons independently process this information.
commissures: axon tracts. The left and right hemispheres communicate using the corpus callosum, anterior commissure, and posterior commissure.
complex: a sequence of waves.
COMT: a degrading enzyme that only targets the catecholamines dopamine and norepinephrine.
contingent negative variation (CNV): a steady, negative shift in potential (15 microvolts in young adults) detected at the vertex. This slow cortical potential may reflect expectancy, motivation, intention to act, or attention. The CNV appears 200-400 ms after a warning signal (S1), peaks within 400-900 ms, and sharply declines after a second stimulus that requires the performance of a response (S2).
continuous irregular delta: slow waves produced by white matter lesions seen in disorders like multiple sclerosis.
contralateral: structures that are located on opposite sides of the body. For example, neurons in the left primary motor cortex control muscles on the right side of the body.
corpus callosum: the largest commissure that connects the left and right frontal, parietal, and occipital lobes.
cortical negativity: a state where the cortical surface exhibits a negative electrical potential.
cortical positivity: a state where the cortical surface exhibits a positive electrical potential.
cortical neurons: nerve cells in the cortex responsible for generating and transmitting electrical impulses.
corticothalamic network: a unified network that generates diverse types of brain rhythms grouped by slow cortical oscillations.
cyclic AMP: a second messenger that moves about the neuron, activating other enzymes. Protein kinase A, which controls the excitability of ion channels, is a crucial enzyme target of cyclic AMP. Cyclic AMP also travels to the nucleus, where it can regulate gene expression.
Dale's principle: incorrect view that a neuron can only release one neurotransmitter. They often release two to four.
delta rhythm: 0.05-3 Hz oscillations generated by thalamocortical neurons during stage 3 sleep.
dendrite: a branched structure designed to receive messages from other neurons via axodendritic synapses (junctions between axons and dendrites), determining whether the axon hillock will initiate an action potential.
dendritic spines: protrusions on the dendrite shaft where axons typically form axodendritic synapses.
dendrodendritic synapses: junctions between dendrites that communicate chemically across synapses and electrically across gap junctions.
depolarization: to make the membrane potential less negative by making the inside of the neuron less negative with respect to its outside.
diffusion: the distribution of molecules from areas of high concentration to low concentration.
diphasic wave: a wave that contains both a negative and positive deflection from the baseline.
dipole: the electrical field generated between the sink (where current enters the neuron ) and the source (place at the other end of the neuron where current leaves), which may be located anywhere along the dendrite.
dominant frequency: the EEG frequency with the most significant amplitude.
dopamine: a monoamine neurotransmitter exerts its postsynaptic effects on at least six receptors linked to G proteins. This means that dopamine functions as a neuromodulator. The two families include D1 (D1 and D5) and D2 (D2A, D2B, D3, and D4).
dorsal: toward the upper back or head.
dorsolateral prefrontal cortex: the left dorsolateral prefrontal cortex is concerned with approach behavior and positive affect. It helps us select positive goals and organizes and implements behavior to achieve these goals. The right dorsolateral prefrontal cortex organizes withdrawal-related behavior and negative affect and mediates threat-related vigilance. It plays a role in working memory for object location.
D-serine: a neurotransmitter that binds to the glycine site on the NMDA receptor to trigger calcium entry into a dendritic spine when glutamate binds to its site, resulting in a large, prolonged increase in intracellular calcium.
dual-action antidepressants: medications that activate 5-HT1 receptors to produce antidepressant and anxiolytic effects, while they blockade 5-HT2 (agitation, restlessness, and sexual dysfunction) and 5-HT3 (nausea, headache, and vomiting) receptors to minimize their side effects.
EEG activity: single wave or successive waves.
EEG power: the signal energy in the EEG spectrum. Most EEG power falls within the 0-20 Hz frequency range. EEG power is measured in microvolts or picowatts.
efferent: motoneuron that transmits information towards the periphery.
electrical synapse: symmetrical synapse where neurons communicate information bidirectionally across gap junctions between adjacent membranes using ions. Transmission across electrical synapses is instantaneous, compared with the 10-ms or longer delay in chemical synapses. The rapid information transmission that characterizes electrical synapses enables large circuits of distant neurons to synchronize their activity and simultaneously fire.
electroencephalogram (EEG): the voltage difference between at least two electrodes, where at least one electrode is located on the scalp or inside the brain. The EEG is a recording of EPSPs and IPSPs that occur primarily in dendrites in pyramidal cells located in macrocolumns, several millimeters in diameter, in the upper cortical layers.
electrostatic pressure: the attractive or repulsive force between ions that moves them from one region to another.
entorhinal cortex: a structure located in the caudal region of the temporal lobe and receives pre-processed sensory information from all modalities and reports on cognitive operations. The entorhinal cortex provides the main input to the hippocampus, and is involved in memory consolidation, spatial localization, and provides input into the septohippocampal system that may generate the 4-7 Hz theta rhythm.
enzymatic deactivation: the process in which an enzyme breaks a neurotransmitter apart into inactive fragments. For example, acetylcholine transmission is ended by the enzyme acetylcholine esterase (AChE). Deactivating enzymes located in the synaptic cleft degrade a neurotransmitter molecule when it detaches from its binding site.
evoked potential: an event-related potential (ERP) elicited by external sensory stimuli (auditory, olfactory, somatosensory, and visual). An evoked potential has a negative peak at 80-90 ms and a positive peak around 170 ms following stimulus onset. The orienting response ("What is it?") is a sensory ERP. The N1-P2 complex in the auditory cortex of the temporal cortex reveals whether an uncommunicative person can hear a stimulus.
excitability: the ability of neurons to respond to stimuli and generate action potentials.
excitatory postsynaptic potential (EPSP): a brief positive shift in a postsynaptic neuron's potential produced when neurotransmitters bind to receptors and cause positive sodium ions to enter the cell. An EPSP pushes the neuron towards the threshold of excitation when it can initiate an action potential.
exocytosis: the process of neurotransmitter release. When an action potential arrives and depolarizes the terminal button, calcium ions enter the terminal button from the extracellular fluid. Calcium binds with clusters of protein molecules that connect the vesicles to the presynaptic membrane. The clusters move apart, forming a hole through both membranes called a fusion pore, and the neurotransmitter leaves the terminal button for the synaptic cleft or extracellular fluid.
exogenous ERP: an event-related potential (ERP) elicited by external sensory stimuli (auditory, olfactory, somatosensory, and visual).
explicit learning: behavioral changes that occur with our conscious awareness that require processing by the hippocampus.
extracellular dipole layers: macrocolumns of pyramidal cells, which lie parallel to the surface of the cortex, send opposite charges towards the surface and the deepest of the 5-7 layers of cortical neurons.
extracellular fluid: the fluid surrounding a neuron.
fast cortical potentials: EEG rhythms that range from 0.5 Hz-100 Hz. The main frequency ranges include delta, theta, alpha, sensorimotor rhythm, and beta.
feature binding: the process of linking information to perceptual objects (linking an apple's color to its shape) that may involve the 40-Hz rhythm.
fissures: deep grooves, for example, the lateral fissure.
focal waves: EEG waves that are detected within a limited area of the scalp, cerebral cortex, or brain.
frequency: the number of cycles completed each second expressed in hertz (Hz).
frequency synchrony: when identical EEG frequencies are detected at two or more electrode sites. For example, 12 Hz may be simultaneously detected at O1-A1 and O2-A2.
frontal lobes: the most anterior cortical lobes of the brain that are divided into the motor cortex, premotor cortex, and prefrontal cortex.
fusion pore: a hole through a vesicle and presynaptic membrane that allows neurotransmitter to leave the terminal button for the synaptic cleft or extracellular fluid.
G protein: a protein located inside a neuron’s membrane next to a metabotropic receptor that is activated when the receptor binds a ligand. An alpha-subunit of the G protein then breaks away to perform actions within the cell.
GABA: an amino acid that is often inhibitory and that may be the most important inhibitory neurotransmitter in the brain. There are several types of GABA receptors, each of which produces inhibition differently.
gamma rhythm: EEG activity frequencies above 30 or 35 Hz. Frequencies from 25-70 Hz are called low gamma, while those above 70 Hz represent high gamma.
gap junction: narrow space between two cells bridged by connexons (protein channels) that allow ions to travel between them rapidly.
generalized asynchronous slow waves: waves that are seen in sleepy children and those with elevated temperatures. These waves may indicate degenerative disease, dementia, encephalopathy, head injury, high fever, migraine, and Parkinson's disease in adults.
glial cells: nonneural cells that guide, insulate, and repair neurons and provide structural, nutritional, and information-processing support. Glial cells generate slow cortical potentials (SCPs). Glial cells include astrocytes, microglia, oligodendrocytes, radial glial cells, and Schwann cells.
glutamate: an amino acid that is often excitatory and that may be the primary excitatory neurotransmitter in the brain. Its receptors are found on the surface of almost all neurons. There are at least 13 different receptors for glutamate, 5 ionotropic and 8 metabotropic. Most presynaptic neurons in the brain excite postsynaptic neurons via ionotropic glutamate receptors in the postsynaptic membrane. Metabotropic glutamate receptors may play a regulatory function, either augmenting or suppressing the activation of ionotropic glutamate receptors.
glycine: an amino acid that is often inhibitory and has a binding site on the NMDA receptor.
gray matter: brain tissue that looks grayish brown and comprises cell bodies, dendrites, unmyelinated axons, glial cells, and capillaries.
gyrus: ridge of cortex demarcated by sulci or fissures, for example, the precentral gyrus.
hertz (Hz): the unit of frequency, an abbreviation for cycles per second.
hippocampus: a limbic structure located in the medial temporal lobe involved in 4-7 Hz theta activity, control of the endocrine system’s response to stressors, formation of explicit memories, and navigation. Cortisol binding to this structure disrupts these functions, interferes with creating new neurons, and harms and kills hippocampal neurons.
hubs: highly centralized nodes through which other node pairs communicate; hubs allow efficient communication.
hyperpolarization: an increase in membrane potential, making the inside of a cell more negative relative to the outside.
inhibitory postsynaptic potential (IPSP): a brief negative shift in a postsynaptic neuron's potential produced when cations like potassium leave a neuron or anions (negative ions) like chloride enter a neuron, which hyperpolarize the cell. An IPSP pushes the neuron away from its excitation threshold.
integration: the addition of EPSPs and IPSPs at the axon hillock. Neurons sum EPSPs and IPSPs over their surface in spatial integration and over milliseconds in temporal integration to raise the membrane from its resting potential to the excitation threshold. EPSPs and IPSPs last from 15-200 ms, while action potentials occur in 1-2 ms.
interneurons: neurons that receive input from and distribute output to other neurons. They have short processes and are confined to the central nervous system. They provide the integration required for decisions, learning and memory, perception, planning, and movement.
intracellular fluid: the watery cytoplasm contained within a neuron.
ion: a charged atom or molecule with a positive or negative charge. Positive ions are called cations, and negative ions are called anions.
ionotropic receptor: receptor protein that contains a binding site for a ligand and an ion channel that opens when the neurotransmitter attaches to this site.
ipsilateral: structures that are located on the same side of the body. For example, the left olfactory bulb distributes axons to the left hemisphere.
irregular waves: successive waves that constantly alter their shape and duration.
kappa rhythm: bursts of alpha or theta and is detected over the temporal lobes of subjects during cognitive activity.
lambda waves: saw-toothed transient waves from 20-50 μV in amplitude and 100-250 ms in duration detected over the occipital cortex during wakefulness. These positive deflections are time-locked to saccadic movements and observed during visual scanning, as during reading.
lateral: to the side, away from the center, as in the lateral geniculate nucleus.
lateral nucleus of the amygdala: a nucleus that processes sensory information and distributes it throughout the amygdala.
lateralized waves: waves that are primarily detected on one side of the scalp and that may indicate pathology.
Layers I-III: cortical layers that receive corticocortical afferent fibers that connect the left and right hemispheres.
Layer III: the cortical layer that is the primary source of corticocortical efferent fibers.
Layer IV: the cortical layer that is the primary destination of thalamocortical afferents and intra-hemispheric corticocortical afferents.
Layer V: the cortical layer that is the primary origin of efferent fibers that target subcortical structures that have motor functions.
Layer VI: the cortical layer that projects corticothalamic efferent fibers to the thalamus, which, together with the thalamocortical afferents, creates a dynamic and reciprocal relationship between these two structures.
left dorsolateral prefrontal cortex: the division of the prefrontal cortex concerned with approach behavior and positive affect. It helps us select positive goals and organizes and implements behavior to achieve these goals.
local field potential: the aggregate effect of the firing of the interconnected pyramidal neurons within the cortical columns plus additional mechanisms like glial cell modulation of the cortical electrical gradient.
local synchrony: synchrony that occurs when high-amplitude EEG signals are produced by the coordinated firing of cortical neurons.
localized slow waves: waves that may indicate a transient ischemic attack (TIA) or stroke, migraine, mild head injury, or tumors above the tentorium. Deep lesions result in bilateral or unilateral delta.
locus coeruleus: the noradrenergic branch of the ascending reticular activating system, which is responsible for vigilance. Subnormal norepinephrine transmission may contribute to ADHD.
long-latency potentials: potentials that have extended latencies following stimulus onset, for example, P300 and N400 ERPs.
long-term depression (LTD): a persistent decrease in synaptic strength following low-frequency stimulation.
long-term potentiation (LTP): a persistent increase in synaptic strength following high-frequency stimulation.
macrocolumns: circuits of cortical pyramidal neurons several millimeters in diameter that create extracellular dipole layers parallel to the surface of the cortex that send opposite charges towards the surface and the deepest of the 5-7 layers of cortical neurons. Since the pyramidal neurons are all aligned with the cortical surface, the postsynaptic potentials at cells within the same macrocolumn add together. This summation occurs because they share the same charge and the macrocolumns fire synchronously.
medial: toward the center of the body, away from the side. For example, the medial geniculate nucleus.
medial prefrontal cortex: the division of the prefrontal cortex that integrates cognitive-affective information and helps control the hypothalamic–pituitary–adrenal (HPA) axis during emotional stress.
membrane potential: a neuron’s electrical charge created by a difference in ion distribution within and outside the neuron. A typical resting potential is about -70 mV (thousandths of a volt), since the inside of a resting axon is more negatively charged than the outside.
mesocortical neurons: dopaminergic neurons that project from the ventral tegmental area of the midbrain to the prefrontal cortex and excite prefrontal cortical neurons that control working memory, planning, and strategy preparation for problem-solving. Underactivity in this pathway is associated with the negative symptoms of schizophrenia-like attentional deficits.
metabotropic receptors: include all G protein-linked receptors located on neurons, including autoreceptors. Neurotransmitters that bind to G protein-linked receptors are often called neuromodulators. Metabotropic receptors, which indirectly control the cell's operations, expend energy, and produce slower, longer lasting, and more diverse changes than ionotropic receptors. Their effects can last several seconds, instead of milliseconds, because of the long-lived activity of G proteins and cyclic AMP.
microglia: microscopic glial cells that participate in the immune response.
microtubules: hollow cylindrical protein bundles that are involved in axoplasmic transport.
modulating effects: neuromodulators like the monoamines alter the performance of diffuse networks of target neurons by indirectly controlling cellular operations when they bind to metabotropic receptors.
module: a set of interconnected nodes in a neural network.
monoamine neurotransmitters: amine neurotransmitters that include dopamine, norepinephrine, epinephrine (catecholamines), and serotonin (indoleamine). These neurotransmitters are released using volume transmission and generally have modulating effects, altering the performance of diffuse networks of target neurons.
monoamine oxidase (MAO): an enzyme that degrades and inactivates the monoamine neurotransmitters dopamine, norepinephrine, and serotonin.
monoamine oxidase inhibitors (MAOIs): antidepressant drugs that interfere with MAO's breakdown of monoamines and increase monoamine availability to treat clinical depression.
monophasic wave: either a single negative (upward) or positive (downward) deflection from baseline.
motor cortex: the subdivision of the frontal lobe located in the precentral gyrus and guides fine motor coordination (like writing).
motor ERPs: event-related potentials detected over the primary motor cortex (precentral gyrus) during movement. Their amplitude is proportional to the force and rate of skeletal muscle contraction.
motor neurons: efferent neurons that convey commands to glands, muscles, and other neurons.
movement-related potentials (MRPs): slow cortical potentials that occur at 1 second as subjects prepare for unilateral voluntary movements. MRPs are distributed bilaterally with maximum amplitude at Cz. The supplementary motor area and primary motor and somatosensory cortices primarily generate these potentials.
mu rhythm: 7-11-Hz waves resemble wickets and appear as several-second trains over central or centroparietal sites (C3 and C4).
multiple spike-and-slow-wave complex: multiple spikes associated with at least one slow wave.
muscarinic receptors: metabotropic ACh receptors that are stimulated by muscarine and blocked by atropine. Muscarinic receptors control smooth muscle and predominate in the CNS. In the CNS, muscarinic receptors help mediate learning, memory, attention, arousal, EEG, and postural control.
myelinated axons: axons that are insulated by myelin by oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system.
N1-P2: a sensory event-related potential in the auditory cortex of the temporal cortex that reveals whether an uncommunicative person can hear a stimulus.
N400 potential: an event-related potential (ERP) elicited when we encounter semantic violations like ending a sentence with a semantically incongruent word ("The handsome prince married the beautiful fish"), or when the second word of a pair is unrelated to the first (BATTLE/GIRL).
negative SCPs: slow cortical potentials produced by glial cells that increase the probability of neuron firing.
neuroaxis: an imaginary line that runs centrally through the central nervous system (CNS) from the front of the prefrontal cortex to the base of the spinal cord.
neuromodulator: a neurochemical that modifies the effect of neurotransmitters through mechanisms like binding to metabotropic receptors.
neuron: a nerve cell that is the fundamental anatomical unit of the nervous system.
nicotinic ACh receptor: an ionotropic receptor that is stimulated by nicotine and blocked by curare. They are mainly found in the PNS on skeletal muscles. At CNS axoaxonic synapses, they produce presynaptic facilitation (increase neurotransmitter release). In the CNS, nicotinic receptors help regulate cortical blood flow, anxiety reduction, and decision-making.
nigrostriatal pathway: dopaminergic pathway from the substantia nigra to the basal ganglia (caudate nucleus and putamen) that controls movement. The nigrostriatal pathway is progressively destroyed in Parkinson’s disease.
nitric oxide: a gaseous retrograde transmitter that is involved in long-term potentiation (LTP).
NMDA (glutamate) receptors: ligand-gated and voltage-gated glutamate receptors that bind the glutamate agonist NMDA. NMDA receptors play an essential role in long-term potentiation (LTP).
node: vertex within a neural network.
nodes of Ranvier: gaps between myelinated axon segments where the axon membrane is exposed to extracellular fluid and action potentials are regenerated by sodium ion entry.
norepinephrine: a monoamine neurotransmitter that exerts postsynaptic effects at alpha and beta receptors, each with two subtypes. All norepinephrine receptors are G protein-linked. The cell bodies of the core noradrenergic system are located in the locus coeruleus, a nucleus found in the dorsal pons.
nucleus accumbens: a limbic structure that is a target of dopamine released by the mesolimbic pathway. The nucleus accumbens plays a critical role in the reinforcement of diverse activities, including ingestion of drugs like central nervous system stimulants.
occipital lobes: cortical lobes that are posterior to the parietal lobes. They process visual information from the eyes in collaboration with the frontal, parietal, and temporal lobes.
odd-ball stimulus: a meaningful stimulus that is different from others in a series used to elicit the P300 potential. For example, a colored playing card in a series of monochrome cards.
oligodendrocytes: glial cells that insulate adjacent axons within the brain and spinal cord of the central nervous system.
orbitofrontal cortex: the frontal lobe subdivision that is concerned with affective evaluation. It decodes the punishment and reward value of stimuli and helps inhibit inappropriate behavior. Phineas Gage's profound personality changes were produced by damage to this region.
orienting response: Pavlov’s "What is it?" reaction to stimuli like the sound of a vase crashing that includes (1) increased sensory sensitivity, (2) head (and ear) turning toward the stimulus, (3) increased muscle tone (reduced movement), (4) EEG desynchrony, (5) peripheral constriction and cephalic vasodilation, (6) a rise in skin conductance, (7) heart rate slowing, and (8) slower, deeper breathing.
P300 potential: an event-related potential (ERP) with a 300-900-ms latency. The largest amplitude positive peaks are located over the parietal lobe. The P300 potential may reflect an event’s subjective probability, meaning, and transmission of information.
paradoxical negativity: in the context of SCPs, it refers to surface-negative EEG shifts when neurons are depolarized due to volume conduction of negative potentials from the extracellular space to the scalp.
paradoxical positivity: in the context of SCPs, it refers to surface-positive EEG shifts when neurons are hyperpolarized due to volume conduction of positive potentials from the extracellular space to the scalp.
paralimbic cortex: a transitional region between neocortex and allocortex.
parietal lobes: cortical lobes posterior to the frontal lobes that are divided into the primary somatosensory cortex (postcentral gyrus) and secondary somatosensory cortex. Their primary function is to process somatosensory information like pain and touch. The right posterior parietal lobe helps guide movements, locate objects in three-dimensional space, and create body boundaries.
Parkinson's disease (PD): a progressive neurodegenerative disorder characterized primarily by motor symptoms such as tremor, rigidity, bradykinesia (slowness of movement), and postural instability.
phase: the degree to which the peaks and valleys of EEG waveforms coincide.
phase synchrony: synchrony when identical EEG frequencies are detected at two or more electrode sites, and the peaks and valleys of the EEG waveforms coincide. This is also called global synchrony. For example, EEG training may produce phase-synchronous 12-Hz alpha waves at O1-A1 and O2-A2.
polarization: to make the membrane potential more negative by making the inside of the neuron more negative with respect to its outside.
polyphasic (multiphasic) wave: a wave that contains two or more deflections of opposite polarity from baseline.
positive SCPs: slow cortical potentials that are produced by glial cells that decrease the probability of neuron firing.
posterior: near or toward the back of the head.
posterior commissure: axon tracts located below the corpus callosum that connect the right and left diencephalon and mesencephalon.
precision: the number of voltage gradations or steps.
prefrontal cortex: the most anterior frontal lobe division and is subdivided into dorsolateral, medial, orbitofrontal, and anterior cingulate regions responsible for executive functions like attention and planning.
premotor cortex: the frontal lobe subdivision that is anterior to the motor cortex and helps program head, trunk, and limb movements.
presynaptic facilitation: a modulatory process in which a neuron increases the presynaptic neuron's neurotransmitter release by delivering a neurotransmitter that increases calcium ion entry into its terminal button.
presynaptic inhibition: a modulatory process in which a neuron decreases neurotransmitter release by reducing calcium ion entry.
primary somatosensory cortex (S1): the parietal lobe subdivision located at the postcentral gyrus that processes information about touch and pain.
protein kinase A: an intracellular enzyme that controls the excitability of ion channels and is a critical enzyme target of cyclic AMP.
raphe nuclei: serotonergic cell bodies in the midbrain, pons, and medulla give rise to most of the brain’s serotonergic neurons.
rate law: the principle that neurons represent the intensity of a stimulus by variation in the rate of axon firing.
readiness potential: slow-rising, negative potential (10-15 µV) detected at the vertex before voluntary and spontaneous movement. This slow cortical potential precedes voluntary movement by 0.5 to 1 second and peaks when the subject responds.
regular or monomorphic waves: successive waves with identical shapes. Regular waves may resemble sine waves (sinusoidal) or maybe arched (resembling wickets) or saw-toothed (asymmetrical and triangular).
resting potential: the membrane potential of a neuron when it is not influenced by messages from other neurons.
reticular formation: a network of 90 nuclei within the central brainstem from the lower medulla to the upper midbrain. The reticular formation sends axons to the spinal cord, thalamus, and cortex, contributing to diverse functions like neurological reflexes, muscle tone and movement, attention, arousal, and sleep.
reuptake: the primary method that neurons terminate the action of neurotransmitters. Reuptake transporters located in terminal buttons and astrocytes remove neurotransmitters from the synaptic cleft.
reward deficiency syndrome: Blum’s hypothesis that an abnormal form of the A1 allele is present in most severe alcoholics and results in defective D2 receptors. Reduced D2 receptor activity may reduce the activation of the nucleus accumbens and hypothalamus and result in dysphoria, drug craving, and compulsive drug-seeking and abuse.
right dorsolateral prefrontal cortex: the division of the prefrontal cortex that organizes withdrawal-related behavior and negative affect and mediates threat-related vigilance. It plays a role in working memory for object location.
rostral: toward the front of the head.
saltatory conduction: action potential conduction in myelinated axons in which action potentials jump from node to node for 200 times greater speed.
sampling rate: the number of measurements per second (Hz).
Schwann cells: glial cells that provide myelin for single PNS axons and facilitate axonal regeneration following damage.
secondary somatosensory cortex (S2): a region of the parietal lobe that receives somatosensory information from the primary somatosensory cortex (S1).
sensorimotor rhythm (SMR): EEG rhythm that ranges from 12-15 Hz and is located over the sensorimotor cortex (central sulcus). The waves are synchronous. The sensorimotor rhythm is associated with the inhibition of movement and reduced muscle tone. The SMR is generated by "ventrobasal relay cells in the thalamus and thalamocortical feedback loops."
sensorimotor system: in Sterman’s model, ascending pathways that convey information about touch and proprioception to the thalamus, the thalamus and its thalamic projections to the sensorimotor cortex, and the sensorimotor cortex, and its efferent fibers.
sensory event-related potentials (ERPs): event-related potentials evoked by external sensory stimuli (auditory, olfactory, somatosensory, and visual). These evoked potentials or exogenous ERPs have a negative peak at 80-90 ms and a positive peak around 170 ms following stimulus onset. These changes in brain activity in response to specific stimuli. ERPs can be detected throughout the cortex. Investigators monitor ERPs by placing electrodes at locations like the midline (Fz, Cz, and Pz). A computer analyzes a subject's EEG responses to the same stimulus or task over many trials to subtract random EEG activity. ERPs always have the same waveform morphology. Their negative and positive peaks occur at regular intervals following the stimulus.
sensory neurons: neurons specialized for sensory intake. They are called afferent because they transmit sensory information towards the central nervous system (brain and spinal cord).
septal nuclei: in Sieb’s model, when the prefrontal cortex receives information about high-priority environmental events, it signals cell bodies in the septum to induce a beta rhythm in the hippocampus to remove its inhibition of vigilance centers.
septohippocampal system: a subcortical circuit from the septum to hippocampus that contributes to 4-7 Hz theta activity.
septum: a limbic structure that contains several nuclei involved in emotion and addiction and control of aggressive behavior.
sharp transients: a sequence that contains several sharp waves.
sharp waves: waves that resemble spikes with a pointed peak with a longer 70-200-ms duration.
sink: a site where current enters the neuron. Positive sodium ion entry into a neuron creates an active sink, represented by -ve.
slow cortical potentials (SCPs): gradual changes in the membrane potentials of cortical dendrites that last from 300 ms to several seconds. These potentials include the contingent negative variation (CNV), readiness potential, movement-related potentials (MRPs), and P300 and N400 potentials. SCPs modulate the firing rate of cortical pyramidal neurons by exciting or inhibiting their apical dendrites. They group the classical EEG rhythms using these synchronizing mechanisms.
sodium (Na+) ions: positive ions that enter a neuron during EPSPs and action potentials.
sodium-potassium transporters: pumps that are powered by ATP and that exchange three sodium for two potassium ions.
soma or cell body: the region of a neuron that contains machinery for cell life processes and receives and integrates EPSPs and IPSPs from axons generated by axosomatic synapses (junctions between axons and somas). The cell body of a typical neuron is 20 μm in diameter, and its spherical nucleus, which contains chromosomes comprised of DNA, is 5-10 μm across.
source: the place at the end of the neuron opposite of the sink where current leaves, represented by +ve. The extracellular area surrounding the source becomes electrically positive.
spatial summation: the addition of EPSPs and IPSPs over a neuron’s surface.
spike: a negative transient with a pointed peak at conventional paper speeds, 20-70-ms duration, and 40-100 μV amplitude; rare dendritic action potentials.
spike-and-slow-wave complex: a spike followed by a higher amplitude slow wave at 3 Hz. In an absence seizure, the amplitudes are very high (e.g., 160 μV).
spindle waves: waves that originate in the thalamus and occur during unconsciousness and stage II sleep.
spiny neurons: neurons with dendritic spines that are usually excitatory.
stimulus-preceding negativity (spn): a slow negative potential shift observed before a stimulus that signals important or relevant information, such as feedback or a reward. SPN reflects anticipatory attention and affective processes involving regions like the insula and orbitofrontal cortex. spn is associated with emotional and cognitive anticipation.
striatal: basal ganglia (caudate nucleus and putamen).
Stroop test: cognitive monitoring task where color and names conflict.
substantia nigra: midbrain structure that projects to the basal ganglia (caudate nucleus and putamen) to control movement and that is progressively destroyed in Parkinson’s disease.
sulcus: a shallow groove in the surface of the cerebral hemisphere, for example, the central sulcus.
surface-negative: a negative SCP shift typically associated with increased cortical excitability and response readiness.
surface-positive: a positive SCP shift typically associated with decreased cortical excitability and relaxation.
synapse-associated polyribosome complexes (SPRCs): organelles with dendrites that can produce proteins that allow rapid remodeling of synapses. A polyribosome complex consists of several ribosomes bound to messenger RNA (mRNA). SPRCs represent one mechanism underlying synaptic plasticity.
synaptic cleft: 20-40-nm fluid-filled gap between presynaptic and postsynaptic structures.
synchronous: adverb meaning that groups of neurons depolarize and hyperpolarize simultaneously.
synchrony: the coordinated firing of pools of neurons. EEG signals can display local synchrony, frequency synchrony, and phase synchrony.
telencephalon: the frontal subdivision of the forebrain, including the cerebral cortex, basal ganglia, and limbic system.
temporal summation: the addition of EPSPs and IPSPs over time. Summation is more effective when postsynaptic potentials are generated more closely in time.
temporal lobes: lobes separated from the rest of the cortical lobes by the Sylvian fissure. The temporal lobes process hearing, smell, and taste information and help us understand spoken language and recognize visual objects and faces. The amygdala and hippocampus, which lie beneath the temporal cortex, play crucial roles in emotion, declarative, emotional, and working memory, and navigation.
terminal buttons: buds located on the ends of axon branches that form synapses and release neurochemicals to other neurons. They contain vesicles that store neurotransmitters for release when an action potential arrives. A terminal button’s presynaptic membrane may possess reuptake transporters that return neurotransmitters from the synapse or extracellular space for repackaging.
thalamus: forebrain structure above the hypothalamus that receives, filters, and distributes most sensory information. The thalamus contains neurons that can block or relay ascending sensory information. When these thalamic neurons rhythmically fire, this blocks the transmission of information to the cortex. When they depolarize in response to sensory information, this integrates and transmits this information to the cortex. Inputs to the thalamus determine whether these neurons block or relay sensory information.
theta rhythm: 4-8-Hz rhythms generated a cholinergic septohippocampal system that receives input from the ascending reticular formation and a noncholinergic system that originates in the entorhinal cortex, which corresponds to Brodmann areas 28 and 34 at the caudal region of the temporal lobe.
threshold of excitation: the membrane potential at which an axon initiates an action potential, nominally -40 mV.
traveling waves: EEG oscillations that move across the cortex that may mediate large-scale coordination of brain networks and support connectivity.
transient: a single wave or sequence of regular waves, called a complex, distinguishable from background EEG activity.
triphasic wave: a wave that contains three deflections from baseline.
unmyelinated axons: smaller-diameter axons without fatty insulation that conduct more slowly than myelinated axons.
+ve: the source is the place at the other end of the neuron where current leaves, and is represented by +ve.
-ve: a sink is where current enters the neuron. Positive sodium ion entry into a neuron creates an active sink, represented by -ve.
ventral: toward the base of the skull or front of the body.
ventral striatum: the olfactory tubercle and nucleus accumbens.
ventral tegmental area: the midbrain structure that distributes dopaminergic axons to the nucleus accumbens. Serotonin receptors on endorphin-releasing neurons in the hypothalamus may increase the activity of dopaminergic reward pathways by inhibiting the release of GABA at receptors on cell bodies of the ventral tegmental area neurons.
vigilance system: in Sterman’s model, a system that consists of both specific brainstem nuclei (e.g., locus coeruleus and raphe nuclei) and their diffuse connections with the thalamus and other subcortical structures, and the cortex. Several neurotransmitter systems mediate vigilance, including cholinergic/glutamatergic (reticular formation), noradrenergic (locus coeruleus), and serotonergic (raphe) neurons.
volume transmission: extrasynaptic neurotransmitter release from axonal varicosities, dendrites, and terminal buttons into the extracellular space. Monoamines like norepinephrine and serotonin are released outside the synaptic cleft.
waveform: the shape and form of an EEG signal.
white matter: the layer beneath the cortex that mainly consists of myelinated axons.
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Assignment
Now that you have completed this unit, how would you explain the relationship between local field potentials and the EEG? How does anatomy explain why the EEG is comprised of EPSPs and IPSPs instead of action potentials?
References
Advokat, C. D., & Comaty, J. E., & Julien, R. M. (2019). Julien's primer of drug action (15th ed.). Worth Publishers.
Aloisi, F. (2001). Immune function of microglia. Glia, 36, 165–179. https://doi.org/10.1002/glia.1106
Altenmuller, E. O., & Gerloff, C. (1999). Psychophysiology and the EEG. In E. Niedermeyer & F. Lopes da Silva (Eds.), Electroencephalography: Basic principles, clinical applications, and related fields (4th ed.). Williams and Wilkins.
Amzica, F., & Steriade, M. (2002). The functional significance of K-complexes. Sleep Medicine Reviews, 6(2), 139–149. https://doi.org/10.1053/smrv.2001.0181 Andreassi, J. L. (2007). Psychophysiology: Human behavior and physiological response (5th ed.). Lawrence Erlbaum and Associates, Inc.
Anjum, M., Smyth, C., Dijk, D., Starr, P., Denison, T., & Little, S. (2023). Multi-night cortico-basal recordings reveal mechanisms of NREM slow wave suppression and spontaneous awakenings at high-temporal resolution in Parkinson’s disease. Research Square. https://doi.org/10.21203/rs.3.rs-3484527/v1
Arnsten, A. F. (2006). Fundamentals of Attention-Deficit/Hyperactivity Disorder: Circuits and pathways. Journal of Clinical Psychiatry, 67 (Suppl. 8), 7-12.
Babiloni, C., Babiloni, F., Carducci, F., Cincotti, F., Del Percio, C., Hallett, M., Moretti, D. V., Romani, G. L., & Rossini, P. M. High resolution EEG of sensorimotor brain functions: Mapping ERPs or mu ERD? In R. C. Reisin, M. R. Nuwer, M. Hallett, & C. Medina (Eds.). Advances in Clinical Neurophysiology (Supplements to Clinical Neurophysiology Vol. 54). Elsevier Science B. V.
Basile, L. F. H., Yacubian, J., Ferreira, B. L. C., Valim, A. C., & Gattaz, W. F. (2004). Topographic abnormality of slow cortical potentials in schizophrenia. Brazilian Journal of Medical and Biological Research, 37(1), 97-109. https://doi.org/10.1590/s0100-879x2004000100014
Bear, M. F., Connors, B. W., & Paradiso, M. A. (2020). Neuroscience: Exploring the brain (4th ed.). Jones & Bartlett Learning.
Birbaumer, N. (1999). Slow cortical potentials: Plasticity, operant control, and behavioral effects. The Neuroscientist, 5, 74–78. https://doi.org/10.1177/1073858499005002
Birbaumer, N., Elbert, T., Canavan, A. G., & Rockstroh, B. (1990). Slow potentials of the cerebral cortex and behavior. Physiological Reviews, 70(1), 1–41. https://doi.org/10.1152/physrev.1990.70.1.1
Breedlove, S. M., & Watson, N. V. (2023). Behavioral neuroscience (10th ed.). Sinauer Associates, Inc.
Brienza, M., & Mecarelli, O. (2019). Neurophysiological basis of EEG. In O. Mecarelli (Ed.), Clinical electroencephalography (pp. 25-45). Springer. https://doi.org/10.1007/978-3-030-04573-9_2
Brini, M., Cali, T., Ottolini, D., & Carafoli, E. (2014). Neuronal calcium signaling: Function and dysfunction. Cellular and Molecular Life Sciences, 71(15), 2787–2814. https://doi.org/10.1007/s00018-013-1550-7
Brunia, C. H. M., van Boxtel, G. J. M., & Böcker, B. E. (2012). Negative slow waves as indices of anticipation: The Bereitschaftspotential, the Contingent Negative Variation, and the Stimulus-Preceding Negativity. In E. S. Kappenman & S. J. Luck (eds.), The Oxford handbook of Event-Related Potential components (pp. 190-208). Oxford Academic. https://doi.org/10.1093/oxfordhb/9780195374148.013.0108
Bullmore, E., & Sporns, O. (2009). Complex brain networks: Graph theoretical analysis of structural and functional systems. Nature, 10, 186-198. https://doi.org/10.1038/nrn2575
Cameron, H. A., & Dayer, A. G. (2008). New interneurons in the adult neocortex: Small, sparse, but significant? Biol Psychiatry, 63(7), 650-655. https://dx.doi.org/10.1016%2Fj.biopsych.2007.09.023
Carlson, N. R., & Birkett, M. A. (2021). Physiology of behavior (13th ed.). Pearson.
Caton, R. (1875). The electric currents of the brain. British Medical Journal, 2, 278.
Chan, C. Y., Ke, D. S., & Chen, J. Y. (2009). Essential fatty acids and human brain. Acta Neurol Taiwan, 18(4), 231-241. PMID: 20329590
Collura, T. F. (2014). Technical foundations of neurofeedback. Taylor & Francis.
Costanzo, R. M. (1991). Regeneration of olfactory receptor cells. CIBA Found Symp, 160, 233-242. https://doi.org/10.1002/9780470514122.ch12
Creuzfeldt, O. D. (1995). Cortex cerebri. Oxford University Press.
Damasio, A. (2010). Self comes to mind. Pantheon Books.
Daum, I., Rockstroh, B., Birbaumer, N., Elbert. T., Canavan, A., & Lutzenberger W. (1993). Behavioural treatment of slow cortical potentials in intractable epilepsy: Neuropsychological predictors of outcome. J Neurol Neurosurg Psychiatry, 56(1) 94-97. https://doi.org/10.1136/jnnp.56.1.94
deCharms, R. C., Fumiko, M., Glover, G. H., Ludlow, D., Pauly, J. M., Soneji, D., Gabrieli, J. D. E., & Mackey, S. C. (2005). Control over brain activation and pain learned by using real-time functional MRI. Proceedings of the National Academy of Sciences, 102(51), 18626-18631. https://doi.org/10.1073/pnas.0505210102
DeLong, M. R. (1990). Primate models of movement disorders of basal ganglia origin. Trends Neurosci, 13(7), 281-285. https://doi.org/10.1016/0166-2236(90)90110-v
Demos, J. N. (2019). Getting started with neurofeedback. (2nd ed.). W. W. Norton & Company.
Eisenberger, N. I., Lieberman, M. D., & Williams, K. D. (2003). Does rejection hurt? An fMRI study of social exclusion. Science, 302, 290-292. https://doi.org/10.1126/science.1089134
Elbert, T., Rockstroh, B., Lutzenberger, W., & Birbaumer, N. (1980). Biofeedback of slow cortical potentials. I. Electroencephalography and Clinical Neurophysiology, 48(3), 293-301. https://doi.org/10.1016/0013-4694(80)90265-5.
El-Boustani, S., Ip, J., Breton-Provencher, V., Knott, G., Okuno, H., Bito, H., & Sur, M. (2018). Locally coordinated synaptic plasticity of visual cortex neurons in vivo. Science, 360(6395), 1349-1354. https://doi.org/10.1126/science.aao0862
Enticott, P. G., Kennedy, H. A., Rinehart, N. J., Tonge, B. J., Bradshaw, J. L., Taffe, J. R., Daskalakis, Z. J., & Fitzgerald, P. B. (2012). Mirror neuron activity associated with social Impairments but not age in Autism Spectrum Disorder. Biol Psychiatry, 71(5), 427-433. https://doi.org/10.1016/j.biopsych.2011.09.001
Evans, J. R., & Abarbanel, A. (1999). Introduction to quantitative EEG and neurofeedback. San Diego: Academic Press.
Farwell, L. A., & Donchin, E. (1991). The truth will out: Interrogative polygraphy (“lie detection”) with event-related brain potentials. Psychophysiology, 28, 531–547. https://doi.org/10.1111/j.1469-8986.1991.tb01990.x
Fischer, F., Hamann, A., & Osiewacz, H. D. (2020). Mitochondrial quality control: An integrated network of pathways. Trends in Biochemical Sciences, 45(3), 179–190. https://doi.org/10.1016/j.tibs.2019.12.008
Fox, S. I., & Rompolski, K. (2022). Human physiology (16th ed.). McGraw-Hill.
Garrett, B. (2003). Brain and behavior. Thompson/Wadsworth.
Green, D. R., Galluzzi, L., & Kroemer, G. (2011). Mitochondria and the autophagy–inflammation–cell death axis in organismal aging. Science, 333(6046), 1109–1112. https://doi.org/10.1126/science.1201940
Hansson, E., & Ronnback, L. (2003.) Glial neuronal signaling in the central nervous system. FASEB J, 17, 341-348. https://doi.org/10.1096/fj.02-0429rev
Harris, J. J., Jolivet, R., & Attwell, D. (2012). Synaptic energy use and supply. Neuron, 75(5), 762–777. https://doi.org/10.1016/j.neuron.2012.08.019
Heinrich, H., Gevensleben, H., Freisleder, F. J., Moll, G. H., & Rothenberger, A. (2004). Training of slow cortical potentials in attention-deficit/hyperactivity disorder: Evidence for positive behavioral and neurophysiologic effects. Biological Psychiatry, 55(7), 772–775. https://doi.org/10.1016/j.biopsych.2003.11.013
Hoedlmoser, K., Pecherstorfer, T., Gruber, G., Anderer, P., Doppelmayr, M., Klimesch, W., & Schabus, M. (2008). Instrumental conditioning of human sensorimotor rhythm (12-15 Hz) and its impact on sleep as well as declarative learning. Sleep, 31(10), 1401–1408.
Hugdahl, K. (1995). Psychophysiology: The mind-body perspective. Harvard University Press.
Kalat, J. W. (2019). Biological psychology (13th ed.). Cengage Learning.
Kalia, L. V., & Lang, A. E. (2015). Parkinson's disease. Lancet (London, England), 386(9996), 896–912. https://doi.org/10.1016/S0140-6736(14)61393-3
Kennerley, S. W., Behrens, T. E., & Wallis, J. D. (2011). Double dissociation of value computations in orbitofrontal and anterior cingulate neurons. Nat Neurosci, 14(12), 1581-1589. doi:10.1038/nn.2961
Kitamura, T., Saitoh, Y., Takashima, N., Murayama, A., Niibori, A., Ageta, H., . . . Inokuchi, K. (2009). Adult neurogenesis modulates the hippocampus-dependent period of associative fear memory. Cell, 139(4), 814-827. https://doi.org/10.1016/j.cell.2009.10.020
Klein, S. B., & Thorne, B. M. (2007). Biological psychology. New York: Worth Publishers.
Kotchoubey, B., Blankenhorn, V., Fröscher, W., Strehl, U. & Birbaumer, N. (1997). Stability of cortical self-regulation in epilepsy patients. Neuroreport, 27(8)1867-1870. https://doi.org/10.1097/00001756-199705260-00015
Kotchoubey, B., Busch, S., Strehl, U. & Birbaumer, N. (1999). Changes in EEG power spectra during biofeedback of slow cortical potentials in epilepsy. Applied Psychophysiology and Biofeedback, 24(4) 213-233. https://doi.org/10.1023/a:1022226412991
Kotchoubey, B., Kubler. A., Strehl. U., Flor, H., & Birbaumer, N. (2002). Can humans perceive their brain states? Consciousness and Cognition, 11(1), 98-113. https://doi.org/10.1006/ccog.2001.0535
Kotchoubey, B., Schneider, D., Schleichert, H., Strehl, U., Uhlmann, C., Blankenhorn, V., Fröscher, W., & Birbaumer, N. (1996). Self-regulation of slow cortical potentials in epilepsy: A retrial with analysis of influencing factors. Epilepsy Research, 25(3), 269-276. https://doi.org/10.1016/s0920-1211(96)00082-4
Kotchoubey, B., Schneider, D., Uhlmann, C., Schleichert, H., & Birbaumer, N. (1997). Beyond habituation: Long-term repetition effects on visual event-related potentials in epileptic patients. Electroencephalographer, 103(4), 450-456. https://doi.org/10.1016/s0013-4694(97)00026-6
Kotchoubey, B., Strehl, U., Holzapfel, S., Blankenhorn, V., Fröscher. W., & Birbaumer, N. (1999). Negative potential shifts and the prediction of the outcome of neurofeedback therapy in epilepsy. Clinical Neurophysiology, 110(4), 683-686. https://doi.org/10.1016/s1388-2457(99)00005-x
Kotchoubey. B., Strehl, U., Holzapfel, S., Schneider. D., Blankenhorn, V., & Birbaumer, N. (1999). Control of cortical excitability in epilepsy. Adv Neurol, 81, 281-290.
Kotchoubey, B., Strehl, U., Uhlmann, C., Holzapfel, S., Konig, M., Fröscher. W., Blankenhorn, V., & Birbaumer, N. (2001). Modification of slow cortical potentials in patients with refractory epilepsy: A controlled outcome study. Epilepsia, 42(3), 406-416.
Kropotov, J. D. (2009). Quantitative EEG, event-related potentials and neurotherapy. Academic Press.
Landisman, C. E., & Connors, B. W. (2005). Long-term modulation of electrical synapses in the mamillimeteralian thalamus. Science, 310(5755), 1809-1813. https://doi.org/10.1126/science.1114655
Lin, M. T., & Beal, M. F. (2006). Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature, 443(7113), 787–795. https://doi.org/10.1038/nature05292
Lopes da Silva, F. (1991). Neural mechanisms underlying brain waves: from neural membranes to networks. Electroencephalography and Clinical Neurophysiology, 79(2), 81–93. https://doi.org/10.1016/0013-4694(91)90044-5
Lopez-Domenech, G., Higgs, N. R., Vaccaro, V., Roš, H., Arancibia-Cárcamo, I. L., & Kittler, J. T. (2016). Loss of dendritic complexity precedes neurodegeneration in a mouse model with disrupted mitochondrial dynamics. Cell Reports, 17(2), 317–327. https://doi.org/10.1016/j.celrep.2016.08.073
Lopez-Otin, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194–1217. https://doi.org/10.1016/j.cell.2013.05.039
Meshorer et al. (2002). Alternative splicing and neuritic mRNA translocation under long-term neuronal hypersensitivity. Science, 295(5554), 508-512. https://doi.org/10.1126/science.1066752
Molenberghs, P., Cunnington, R., & Mattingley, J. B. (2011). Brain regions with mirror properties: A meta-analysis of 125 human fMRI studies. Neurosci Biobehav Rev, 36(1), 341-349. https://doi.org/10.1016/j.neubiorev.2011.07.004
Mölle, M., Marshall, L., Gais, S., & Born, J. (2002). Grouping of spindle activity during slow oscillations in human non-rapid eye movement sleep. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 222(24), 10941–10947. https://doi.org/10.1523/JNEUROSCI.22-24-10941.200
Munro, C. A., McCaul, M. E., Wong, D. F., Oswald, L. M., Zhou, Y., Brasic, J., Kuwabara, H., Kumar, A., Alexander, M., Ye, W., & Wand, G. S. (2006). Sex differences in striatal dopamine release in healthy adults. Biological Psychiatry, 59(10), 966-974. https://doi.org/10.1016/j.biopsych.2006.01.008
Nagano, S., & Araki, T. (2021). Axonal transport and local translation of mRNA in neurodegenerative diseases. Frontiers in Molecular Neuroscience, 14, 697973. https://doi.org/10.3389/fnmol.2021.697973
Nash, J. M. (2011). The gift of mimicry. Your brain: A user's guide. Time.
Niedermeyer, E. (1999). Historical aspects. In E. Niedermeyer & F. Lopes da Silva (Eds.), Electroencephalography: Basic principles, clinical applications, and related fields (4th ed.). Williams and Wilkins.
E. Niedermeyer & F. Lopes da Silva (Eds.) (1999). Electroencephalography: Basic principles, clinical applications, and related fields (4th ed.). Williams and Wilkins.
Othmer, S., & Othmer, S. (2020). Toward a theory of infra-low frequency neurofeedback. In H. W. Kirk (Ed.), Restoring the Brain. Routledge, eBook ISBN 9780429275760
Otto, D., & Reiter, L. (1984) Developmental changes in slow cortical potentials of young children with elevated body lead burden: Neurophysiological considerations. Annals of the New York Academy of Sciences, 425(1), 377-383. https://doi.org/10.1111/j.1749-6632.1984.tb23559.x
Pulvermüller, F., Mohr, B., Schleichert, H., & Veit, R., (2000). Operant conditioning of left-hemispheric slow cortical potentials and its effect on word processing. Biological Psychology, 53(2-3), 177-215. https://doi.org/10.1016/S0301-0511(00)00046-6
Radley, J. J., Arias, C. M., & Sawchenko, P. E. (2006). Regional differentiation of the medial prefrontal cortex in regulating adaptive responses to acute emotional stress. The Journal of Neuroscience, 26(50), 12967-12976. https://doi.org/10.1523/JNEUROSCI.4297-06.2006
Raichle, M. E., & Gusnard, D. A. (2002). Appraising the brain's energy budget. PNAS, 99(16), 10237-10299. https://doi.org/www.pnas.orgcgidoi10.1073pnas.172399499
Rapanelli, M., Frick, L. R., & Zanutto, B. S. (2011). Learning an operant conditioning task differentially induces gliogenesis in the medial prefrontal cortex and neurogenesis in the hippocampus. PLoS ONE, 6(2), e14713. https://doi.org/10.1371/journal.pone.0014713
Rockstroh, B., Elbert, T., Birbaumer, N., Wolf, P., Düchting-Röth, A., Reker, M., Daum, I., Lutzenberger, W., & Dichgans, J. (1993). Cortical self-regulation in patients with epilepsies. Epilepsy Research, 14(1), 63–72. https://doi.org/10.1016/0920-1211(93)90075-i
Sarnthein, J., Petsche, H., Rappelsberger, P., Shaw, G. L., & von Stein, A. (1998). Synchronization between prefrontal and posterior association cortex during human working memory. Proc Natl Acad Sci, 95(12), 7092-7096. https://doi.org/10.1073/pnas.95.12.7092
Schacter, D. L. (1977). EEG theta waves and psychological phenomena: A review and analysis. Biological Psychology, 5, 47-82. https://doi.org/10.1016/0301-0511(77)90028-x
Schneider, F., Rockstroh, B., Heimann, H., Lutzenberger, W., Mattes, R., Elbert, T., Birbaumer, N, & Bartels, M. (1992). Self-regulation of slow cortical potentials in psychiatric patients: Schizophrenia. Biofeedback and Self-Regulation, 17(4), 277-292. https://doi.org/10.1007/bf01000051
M. S. Schwartz, & F. Andrasik (Eds.). (2003). Biofeedback: A practitioner's guide (3rd ed.). The Guilford Press.
Sebel, P. S., Lang, E., Rampil, I. J., White, P. F., Cork, R., Jopling, M., Smith, N. T., Glass, P. S., & Manberg, P. (1997). A multicenter study of bispectral electroencephalogram analysis monitoring anesthetic effect. Anesthesia and Analgesia, 84(4), 891-899. https://doi.org/10.1097/00000539-199704000-00035
Shibasaki, H., & Hallett, M. (2006). What is the Bereitschaftspotential? Clinical Neurophysiology, 117(11), 2341-2356. https://doi.org/10.1016/j.clinph.2006.04.025
Siniatchkin, M., Hierundar, A., Kropp, P., Kuhnert, R., Gerber, W-D., & Stephani, U. (2000). Self-regulation of slow cortical potentials in children with migraine: An exploratory study. Applied Psychophysiology & Biofeedback, 25(1), 13-32. https://doi.org/10.1023/a:1009581321624
Smith, M. L. (2013). Infra-slow fluctuation training; On the down-low in neuromodulation. NeuroConnections.
Speckmann, E.-J., & Elger, C. E. (1984). The neurophysiological basis of epileptic activity: A condensed overview. R. Degen & E. Niedermeyer (Eds.), Epilepsy, sleep, and sleep deprivation (pp.23-34). Elsevier. PMID: 1760082
Speckmann, E.-J., & Elger, C. E. (1999). Introduction to the neurophysiological basis of the EEG and DC potentials. In E. Niedermeyer & F. Lopes da Silva (Eds.), Electroencephalography: Basic principles, clinical applications, and related fields (4th ed.). Williams and Wilkins.
Stahl, S. M. (2008). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (3rd ed.). Cambridge University Press.
Steriade, M. (2005). Cellular substrates of brain rhythms. In E. Niedermeyer, & F. Lopes da Silva (Eds.). Electroencephalography: Basic principles, clinical applications, and related fields (5th ed.). Lippincott Williams & Wilkins.
Steriade, M., Nuñez, A., & Amzica, F. (1993). Intracellular analysis of relations between the slow (< 1 Hz) neocortical oscillation and other sleep rhythms of the electroencephalogram. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 13(8), 3266–3283. https://doi.org/10.1523/JNEUROSCI.13-08-03266.1993
Sterman M. B. (1996). Physiological origins and functional correlates of EEG rhythmic activities: implications for self-regulation. Biofeedback and Self-regulation, 21(1), 3–33. https://doi.org/10.1007/BF02214
Sterman, M. B. (2000). EEG markers for attention deficit disorder: Pharmacological and neurofeedback applications. Child Study Journal, 30(1), 1-24.
Stern, R. M., Ray, W. J., & Quigley, K. S. (2001). Psychophysiological recording (2nd ed.). Oxford University Press.
Strehl, U. (2009). Slow cortical potentials neurofeedback. Journal of Neurotherapy, 13(2), 117–126. https://doi.org/10.1080/10874200902885936
Strehl, U., Aggensteiner, P., Wachtlin, D., Brandeis, D., Albrecht, B., Arana, M., Bach, C., Banaschewski, T., Bogen, T., Flaig-Röhr, A., Freitag, C. M., Fuchsenberger, Y., Gest, S., Gevensleben, H., Herde, L., Hohmann, S., Legenbauer, T., Marx, A. M., Millenet, S., Pniewski, B., … Holtmann, M. (2017). Neurofeedback of slow cortical potentials in children with Attention-Deficit/Hyperactivity Disorder: A multicenter randomized trial controlling for unspecific effects. Frontiers in Human Neuroscience, 11, 135. https://doi.org/10.3389/fnhum.2017.00135
Streit, W. J. (2006). Microglial senescence: Does the brain's immune system have an expiration date? Trends in Neurosciences, 29(9), 506–510. https://doi.org/10.1016/j.tins.2006.07.001
Thompson, M., & Thompson, L. (2015). The neurofeedback book: An introduction to basic concepts in applied psychophysiology (2nd ed.). Association for Applied Psychophysiology and Biofeedback.
Thompson, M., & Thompson, L. (2009). Asperger’s syndrome intervention: Combining neurofeedback, biofeedback, and metacognition. In T. H. Budzynski, H. K. Budzynski, J. R. Evans, & A. Abarbanel (Eds.). Introduction to quantitative EEG and neurofeedback (2nd ed.). Academic Press.
Vernon, D., Egner, T., Cooper, N., Compton, T., Neilands, C., Sheri, A., & Gruzelier, J. (2003). The effect of training distinct neurofeedback protocols on aspects of cognitive performance. International Journal of Psychophysiology: Official Journal of the International Organization of Psychophysiology, 47(1), 75–85. https://doi.org/10.1016/s0167-8760(02)00091-0
Voytek, B. (2013). Brain metrics: How measuring brain biology can explain the phenomena of mind. Scitable by Nature Education.
Warren, A. M., & McIlvane, W. J. (1998). Stimulus equivalence and the N400 effect. Poster presented at the 1998 Annual Meeting of the Cognitive Neuroscience Society in San Francisco, CA.
West, A. P., Shadel, G. S., & Ghosh, S. (2015). Mitochondria in innate immune responses. Nature Reviews Immunology, 15(11), 505–518. https://doi.org/10.1038/nri3850
Wilson, J. (2003). Biological foundations of human behavior. Wadsworth/Thompson Learning.
Wilson, V. E., Thompson, M., Thompson, L., Thompson, J., Fallahpour, K., & Linden, M. K. (2011). Introduction to biofeedback (Neurofeedback). In B. W. Strack, M. K. Linden, & V. S. Wilson (Eds.). Biofeedback & neurofeedback applications in sport psychology. Association for Applied Psychophysiology and Biofeedback.
Winn, P. (2001). (Ed.), Dictionary of biological psychology. Routledge.
Xu, T., Yu, X., Perlik, A., Tobin, W., Zweig, J., Tennant, K., Jones, T., & Zuo, Y. (2009). Rapid formation and selective stabilization of synapses for enduring motor memories. Nature, 462(7275), 915-919. https://doi.org/10.1038/nature08389
Yang, Y., Ge, W., Chen, Y., Zhang, Z., Shen, W., Wu, C., Poo, M., & Duan, S. (2003). Contribution of astrocytes to hippocampal long-term potentiation through release of D-serine. Proceedings of the National Academy of Sciences of the United States of America, 100(25), 15194-15199. https://doi.org10.1073/pnas.2431073100
Zhang, H., Watrous, A., Patel, A., & Jacobs, J. (2018). Theta and alpha oscillations are traveling waves in the human neocortex. Neuron. https://doi.org/10.1016/j.neuron.2018.05.019