Neuroanatomy

EEG rhythms are produced by two-way interactions between the thalamus and cerebral cortex. The thalamus paces the rhythmic potentials generated by cortical pyramidal neurons.

BCIA Blueprint Coverage

This unit covers Neurophysiology (II-A).

Students completing this unit will be able to discuss:

Basic neuroanatomy of ascending sensory pathways to the cortex
Thalamic, cortical, and subcortical generators of the EEG
General cortical and subcortical anatomy
Major functions of cortical lobes and major subcortical structures and Brodmann areas
Overview of connectivity, phase, and coherence concepts related to EEG networks and tracts (e.g., default network, nodes, and modules)

BASIC ANATOMY OF ASCENDING SENSORY PATHWAYS TO THE CORTEX

Sensory input produced by activities like reading a novel and listening to music can desynchronize cortical activity resulting in lower-amplitude, higher-frequency EEG waveforms (Neumann, Strehl, & Birbaumer, 2003). Arousal and specific forms of cognitive activity may reduce alpha amplitude or eliminate it entirely, a phenomenon called alpha blocking, while increasing EEG power in the beta range (Andreassi, 2007).

The classical routes for EEG activation consist of ascending sensory pathways that distribute information to specialized thalamic nuclei and then project the results of thalamic processing to the appropriate cortical regions. The exception to this rule is olfaction (smell), which goes directly to the primary olfactory cortex.

The old school view is that these ascending sensory pathways exercise bottom-up control of perception as feedforward circuits. This overlooks the fact that ten times more cortical efferent neurons target the sensory thalamus as thalamic afferent neurons project to the cortex.

The new school view is that there are extensive interconnections between the thalamus and cortex, which permit a degree of cortical top-down control over perception (Kandel & Schwartz, 2013).

We will examine the visual, auditory, and somatosensory systems to better understand the ascending sensory pathways to the cortex.

Visual system

Retinal ganglion cells, which comprise the optic nerves, ascend to the midline optic chiasm where the two optic nerves meet. Here, temporal axons (toward the side of the head) continue as part of their own side's optic tract and the nasal halves cross over to join the opposite side's optic tract. Most optic tract axons project information to the lateral geniculate nucleus of the thalamus.

While the lateral geniculate nucleus (LGN) relays visual information to the cortex, brainstem and cortical neurons modulate its activity. Brainstem neurons that mediate alertness and attention can adjust the LGN's response to visual input. Moreover, the cortex can exert top-down selection of visual input to increase attention to a salient region of the visual field at the expense of others (Bear, Connors, & Paradiso, 2016).

LGN neurons, which form the optic radiations, project to the primary visual cortex (V1) in the occipital lobe in cortical layer IV. A minority of retinal ganglion cell axons target the dorsal midbrain superior colliculus, which is concerned with visual gaze direction and attention to selected visual objects (Breedlove & Watson, 2013).

The cortex contains many specialist regions to process visual properties like color, shape, location, motion, and orientation. Evolution has organized these visual areas into dorsal and ventral streams that each begin in the primary visual cortex. The dorsal stream, which projects from V1 to the parietal lobe, helps us to localize objects and guide movements toward them. In the adjacent motor association cortex, there are neurons with both visual and motor properties, called mirror neurons. Networks of mirror neurons may play a role in learning how to perform actions by observing others' movements, understanding others' actions and intentions, and empathy

The lower ventral stream, which projects to inferior temporal and frontal areas, allows us to idertify objects and faces.

Auditory System

The inner hair cells of the cochlea within the organ of Corti send 30,000 to 50,000 auditory fibers to several destinations: the midbrain superior olivary nuclei and inferior colliculi, and the medial geniculate nucleus of the thalamus. The superior olivary nuclei processes binaural (two-ear) information to localize sound. All ascending auditory neurons innervate the inferior colliculi, some via intermediate relays.

The inferior colliculi integrate information about spatial localization and multiple sensory modalities, including somatosensory information. They project to the medial geniculate nucleus (MGN) of the thalamus, which projects to several cortical auditory areas using two separate pathways. The MGN mainly relays frequency, amplitude, and binaural information to the auditory cortex in the temporal lobe. Graphic courtesy of www.cochlea.eu.

The auditory cortex processes auditory information within dorsal and ventral streams. The dorsal stream, which extends to the parietal lobe, helps us spatially localize sounds. The lower ventral stream, which projects to the temporal lobe, appears to analyze sound components, perhaps including speech sounds (Breedlove & Watson, 2013).

As with the visual pathways, the auditory system involves extensive feedback. Neurons in the brainstem innervate the outer hair cells that adjust the sensitivity of the basilar membrane within the organ of Corti to specific frequencies. Also, auditory cortex axons innervate both the inferior colliculi and MGN to exercise top-down control (Bear, Connors, & Paradiso, 2016).

Somatosensory System

The somatosensory system employs specialized receptors to perceive itch, pain, temperature, and touch. For touch, the axon of a unipolar neuron enters the dorsal horn of the spinal cord and synapses with a dorsal column neuron in the medulla. Axons from this neuron decussate (cross the midline) and innervate the ventral posterior nucleus (VPN) of the thalamus. The VPN, in turn, distributes this information to the primary somatosensory cortex (S1). While each hemisphere's S1 maps touch information from the opposite side of the body, secondary somatosensory cortex (S2) maps both sides. The maps are overlayed so that the left and right arms are represented in the same region of the body surface map (Breedlove & Watson, 2013). The graphic below is courtesy of www.rci.rutgers.edu.

As with the visual and auditory systems, the ascending pathways do far more than relay information. These networks process and alter sensory information at each successive synapse. The cortex exercises top-down control over neurons in the dorsal column and VPN to dynamically adjust cortical inputs (Bear, Connors, & Paradiso, 2016).

THALAMIC, CORTICAL, AND SUBCORTICAL GENERATORS OF THE EEG

Thalamic Generators

Anderson and Anderson (1968) advanced the facultative pacemaker theory that thalamic neurons activate both cortical neurons and thalamic inhibitory interneurons via recurrent collaterals. While these thalamocortical neurons only excite a limited number of cortical neurons, thalamic interneurons inhibit a large pool of thalamocortical relay neurons. When the inhibition ends after one-tenth of a second, the thalamocortical neurons experience rebound excitation. This synchronized depolarization excites both cortical neurons and thalamic inhibitory interneurons, which will inhibit a more extensive pool of thalamocortical relay neurons and initiate another cycle of excitation and inhibition that produces EEG rhythms (Fisch, 1999). Graphic courtesy of Zachary Barry and featured in Wikipedia's article Recurrent Thalamo-Cortical Resonance.

Caption: Thalamocortical circuit diagram depicting both specific/sensory and non-specific intralaminar thalamocortical systems.

The networking of excitatory and inhibitory thalamic neurons imposes a group rhythm on its members that is transmitted to cortical macrocolumns by thalamocortical neurons (Bear, Connors, & Paradiso, 2016).

The nucleus reticularis of the thalamus may function as a pacemaker by releasing the inhibitory transmitter GABA at synapses with thalamocortical neurons. These neurons depolarize cortical neurons and thalamic inhibitory interneurons via burst discharges when their inhibition ends.

As we discussed in the Neurophysiology unit, oscillatory activity may involve an interaction between thalamocortical relay neurons (TCR), nucleus reticularis neurons (RE), and interneurons. These interactions are mediated by diverse neurotransmitters, including acetylcholine and GABA.

The thalamus is the dominant pacemaker for rhythmic EEG activity, including theta (3-8 Hz), alpha (8-12 Hz), and SMR (13-15 Hz) (Thompson & Thompson, 2016).

Cortical Generators

Vertical cortical macrocolumns contain hundreds of pyramidal neurons and supporting stellate and basket cells (Thompson & Thompson, 2016). Each pyramidal neuron may receive more than 100,000 synapses. These macrocolumns are positioned side by side and perpendicular to the cortical surface.Since neighboring macrocolumns often receive the same afferent messages, this increases the probability that they will fire together and generate a potential that we can detect from the scalp. A reliable scalp EEG requires a minimum of 6 cm² of synchronized cortex (Dyro, 1989).

While thalamic pacemakers generate EEG rhythms, resonant loops between cortical macrocolumns may be another source (Traub et al., 1989). Over 97 percent of the conversations within the brain are cortical-to-cortical (Thompson & Thompson, 2016). This communication is largely confined within the same hemisphere. A resonant loop developes when macrocolumns that share afferent input fire synchronously to generate an electrical potential. The distance between the cortical macrocolumns that participate in a resonant loop is one determinant of EEG frequency. The closer the macrocolumns in a resonant loop, the higher the frequency they can generate (Lubar, 1999)

There are three types of resonant loops that can be driven by afferent input or thalamic pacemakers: local, regional, and global. Local loops couple neighboring macrocolumns and may generate frequencies above 30 Hz in the gamma range. Regional loops couple macrocolumns separated by several cm and may produce alpha and beta rhythms. Finally, global loops couple macrocolumns as distant as 7 cm (for example, between the frontal and parietal lobes) and may create delta and theta rhythms.

While only 3 percent of these linkages are thalamocortical, they greatly influence the EEG by subcortically connecting distant cortical regions and producing most synchronous activity (Steriade, 1990). Lubar (1997) proposed a violin analogy where the thalamic pacemakers that fire at varying frequencies are the strings and the resonant loops that introduce different time delays are the instrument's resonant cavity. The electrical potentials generated by the thalamus can volume conduct near the speed of light through cerebrospinal fluid (CSF), brain tissue, the skull, and the scalp so that nearly identical waveforms can simultaneously appear at distant sites (Fisch, 1999; Thompson & Thompson, 2016).

Additional Subcortical Generators

Ascending projections from the basal forebrain, reticular formation, and locus coeruleus and raphe systems can disrupt brain rhythms. These neurons receive information from most sensory systems and cortical regions, and directly desynchronize the EEG through synapses on cortical neurons and indirectly through innervation of thalamic pacemakers. Desynchronization shifts pyramidal neurons from burst firing to more continuous firing or the generation of single spikes (Fisch, 1999).

The cholinergic basal forebrain, which is located in the ventral frontal lobe and anterior hypothalamus, influences cerebral blood flow and cognitive activity. Graphic courtesy of Newman et al. (2012), Cholinergic modulation of cognitive processing: Insights drawn from computation models.

The reticular formation is a network of 90 nuclei within the central brainstem from the lower medulla through the thalamus that activates the brain to promote wakefulness.

The noradrenergic brainstem locus coeruleus system, which projects to the thalamus, limbic system, and cerebral cortex, also contributes to wakefulness and vigilance for salient stimuli.

Finally, the serotonergic raphe system is a midline network of cell bodies within the brainstem and midbrain that may influence alertness and vigilance through reciprocal connections with the suprachiasmatic nucleus of the hypothalamus (Monti, 2008).

Subcortical Generators of Specific EEG Rhythms

Slow Cortical Potentials

Slow cortical potentials (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 acorticothalamic network that targets these thalamic neurons.

Glial cells generate slow SCPs when they burn sugar, producing negatively-charged bicarbonate ions. Unlike EEG rhythms like delta, SCPs are not the summation of dendritic potentials. The slow oscillations of glial cells may influence the timing of neuronal oscillation through their control of potassium ion outflow (Steriade, 2005).

Delta

There are actually two delta rhythms, a slow oscillation under 1 Hz and traditional 1-4 Hz oscillations. The slow 0.3-0.4 Hz oscillation originates in the neocortex and persists when the thalamus is removed. Thalamocortical neurons generate the 1-4 Hz oscillations observed during human stage 3 and 4 sleep. Slow neocortical oscillations may synchronize the thalamic delta rhythm (Steriade, 2005).

Theta

The mechanisms that generate the theta rhythm are poorly understood. Amzica and Lopes da Silva (2011) consider the classic septal/diagonal band pacemaker model to be incomplete. Hippocampal interneurons innervate the hypothetical medial septum pacemaker, contributing top-down control. The hypothalamic supramammillary nucleus, with extensive connections to the brainstem, diencephalon, and medial septum, may also pace and modulate hippocampal theta. Further, a non-cholinergic theta source has been found within the entorhinal cortex of the hipppcampus

Alpha

The 8-13 Hz alpha rhythm differs from spindle waves in both its source and the activity during which it is observed. Based on experimental studies in dogs, Lopes da Silva et al. (1980) concluded that alpha activity is primarily spread by an intracortical network that lies parallel to the cortical surface and that there is only a moderate contribution from neurons in the lateral geniculate nucleus of the thalamus that project to the cortex. Researchers have correlated the alpha rhythm with relaxed wakefulness. Spindle waves, in contrast, originate in the thalamus and occur during unconsciousness and stage 2 sleep (Steriade, 2005).

Beta-Gamma Rhythms

Fast 20-50 Hz oscillations are generated by activation of the mesencephalic reticular formation. Thalamocortical, rostral thalamic intralaminar, and cortical neurons spontaneously oscillate in this range. Amzica and Lopes da Silva (2011) conclude that gamma oscillations may speed information distribution and processing.

GENERAL CORTICAL AND SUBCORTICAL ANATOMY

Major Divisions

The human nervous consists of the central nervous system and peripheral nervous system. The central nervous system (CNS) consists of the brain and spinal cord. The 3-pound brain consists of approximately 86 billion neurons (Chan et al., 2009; Voytek, 2013). The graphic below © Jasada Sabai/Shutterstock.com.

The cylindrical spinal cord consists of nervous tissue that extends from the medulla (brainstem) to the lumbar (lower back) segment of the vertebral column. The spinal cord distributes sensory from the body to the brain and CNS commands from the brain to the body. The spinal cord also contains networks that control reflexes and central pattern generators. The graphic below © Sabastian Kalulitzki/ Shutterstock.com.

The peripheral nervous system (PNS) consists of neurons and nerves outside of the brain and spinal cord. The persipheral nervous system is comprised of the autonomic nervous system and somatic nervous system. Graphic below is from Connexions web site.

Nerves

Nerves are bundles of axons. Motor nerves distribute instructions from the CNS to the rest of the body. Sensory nerves transmit information from sensory receptors to the CNS.

There are three major systems of nerves: cranial nerves, spinal nerves, and the autonomic nervous system. The 12 pairs of cranial nerves distribute sensory information and motor information. There are three exclusively sensory pathways to the brain: olfactory (I), optic II), and vestibulocochlear (VIII). There are five exclusively motor pathways from the brain: oculomotor (III), trochlear (IV), abducens (VI), spinal accessory (XI), and hypoglossal (XII). Finally, four cranial nerves carry sensory and motor information: trigeminal (V), facial (VII), glossopharyngeal (IX), and vagus (X). Graphic below © Alila Medical Media/Shutterstock.com.

Thirty-one pairs of spinal nerves, each member serving one side of the body, leave the spinal cord through openings in the backbone. Graphic below © yodiyim/Shutterstock.com.

Each spinal nerve carries sensory projections from the body (dorsal root) and motor commands from the spinal cord to skeletal muslces (ventral root). Graphic below © Alila Medical Media/Shutterstock.com.

Autonomic Nervous System

he autonomic nervous system regulates cardiac and smooth muscle, and glands, transmits sensory information to the CNS, and innervates muscle spindles.

The autonomic nervous system is divided into three main systems: sympathetic division, parasympathetic division, and enteric divisions. Check out the YouTube video, The Autonomic Nervous System, when you are connected to the internet.

Sympathetic Division

The sympathetic nervous system (SNS) readies us for action and regulates activities that expend stored energy. Graphic © Kagai19927/Shutterstock.com.

The SNS, in concert with the endocrine system, responds to threats to our safety through mobilization, fight-or-flight, and active avoidance. The SNS responds more slowly (> 5 seconds) and for a longer period of time than the more rapid (<1 second) parasympathetic vagus system (Nunan et al., 2010). Porges (2011) theorized that the SNS inhibits the unmyelinated vagus (dorsal vagal complex) to mobilize us for action.

SNS cell bodies are found in the gray matter of the thoracic (from T1) and lumbar (to L2) segments of the spinal cord. The sympathetic division is thoracolumbar. SNS preganglionic neurons, which originate in the CNS, exit the spinal cord via the ventral root. Most of these axons synapse with the autonomic ganglia (collection of neurons) of the sympathetic chain, which parallels the spinal cord on each side.

Preganglionic neurons branch extensively and can communicate with sympathetic ganglia in complex ways:
1. Divergence – one preganglionic neuron synapses with multiple ganglia.
2. Convergence – many preganglionic neurons from different spinal levels synapse with one
ganglion cell.

Both divergence and convergence produce mass activation, allowing integrated sympathetic action (e.g., increased blood pressure, heart rate, and respiration rate).

SNS preganglionic axons also directly innervate the adrenal medulla (the central portion of the adrenal gland). The adrenal medulla releases epinephrine and norepinephrine when stimulated, which reinforces sympathetic activation of visceral organs. Release of epinephrine and norepinephrine increases muscle blood flow and converts stored nutrients into glucose to power skeletal muscle contraction. Postganglionic neurons exit the sympathetic chain and project axons to target organs, like the heart, lungs, and sweat glands.

SNS preganglionic and postganglionic axons release different neurotransmitters. SNS preganglionic axons secrete acetylcholine, while the postganglionic axons secrete norepinephrine. Sweat glands and skeletal muscle blood vessels are the exceptions to this rule. The postganglionic axons that innervate them release acetylcholine (Fox, 2016). The autonomic nervous system diagram below © 2003 Josephine Wilson.

The SNS is important to heart rate variability (HRV), changes in the time intervals between adjacent heartbeats, since it may contribute to power in the low frequency (LF) band of the ECG (0.04-0.15 Hz).

SNS activity may result in parasympathetic withdrawal, which may increase power in the very low frequency (VLF) band (≤ 0.04 Hz), while lowering power in the high frequency (HF) band (0.15 – 0.40 Hz).

Parasympathetic Division

The parasympathetic division regulates activities that increase the body’s energy reserves, including salivation, gastric (stomach) and intestinal motility, gastric juice secretion, and increased blood flow to the gastrointestinal system (rest and digest). When we discuss Porges' polyvagal theory, we will learn that this system is also involved in self-regulation, social engagement, and passive responses to threats.

PNS cell bodies are found in the nuclei of four of the cranial nerves (especially the vagus) and the sacral region (S2-S4) of the spinal cord. The parasympathetic division is craniosacral.

Unlike the sympathetic division, parasympathetic ganglia are located near their target organs. This arrangement means that preganglionic axons are relatively long, postganglionic axons are relatively short, and PNS changes can be selective.

Preganglionic neurons travel with the oculomotor, facial, glossopharyngeal, and vagus cranial nerves. Preganglionic neurons that exit the vagus (X) nerve at the medulla synapse with terminal ganglia within the heart, lungs, esophagus, stomach, pancreas, liver, and intestines. Both PNS preganglionic and postganglionic axons release acetylcholine (Fox, 2016).

Enteric Division

The enteric division regulates peristalsis and enzyme secretion in the GI tract (Breedlove & Watson, 2013). The enteric division contains approximately 100 million neurons (Boron & Boulpaep, 2005), which release more than 30 neurotransmitters (Gershon, 1999). The gut contains more than 90% of the body’s serotonin (Khazan, 2013) and about 50% of its dopamine. Check out the Khan Academy YouTube video, Control of the GI Tract, when you are connected to the internet.

Enteric neurons are concentrated in the myenteric and submucosal ganglia. While it can operate independently of the CNS, it is innervated by both the sympathetic and parasympathetic divisions. The graphic below depicting the enteric nervous system was created by Goran tek-en and is courtesy of Wikimedia Commons.

Somatic Nervous System

The somatic nervous system is made up of spinal nerves that innervate somatosensory receptors in the skin and joints, and skeletal muscles. While somatic motorneuron cell bodies lie in the CNS, most of their axons are in the PNS. The cell bodies of somatic sensory neurons are in the PNS dorsal root ganglia. Dorsal root graphic © stihii/Shutterstock.com.

Navigating the Brain

Orientations

Three customary planes for viewing the body and brain are the sagittal, coronal, and horizontal. The sagittal plane divides the body into right and left halves. The coronal plane separates the body into front and back parts. Finally, the horizontal plane divides the brain into upper and lower parts (Breedlove & Watson, 2013). Graphic courtesy of Blausen.com staff "Blausen gallery 2014," Wikiversity Journal of Medicine.

Directional Terms

Important directional terms include medial (toward the middle) and lateral (toward the side), ipsilateral (same side) and contralateral (opposite side), superior (above) and inferior (below), anterior/rostral (toward the head) and caudal (toward the tail), proximal (near the center) and distal (toward the periphery). and dorsal (toward or at the back) and ventral (toward the belly) (Breedlove & Watson, 2013). Graphic courtesy of Blausen.com staff "Blausen gallery 2014," Wikiversity Journal of Medicine.

Cortical Features

Anatomists distinguish three topographical features of the convoluted cerebral cortex: gyrus, sulcus, and fissure. A gyrus is a ridged area of the brain. The precentral gyrus, which is anterior to the central sulcus, is the primary motor cortex (controls muscles and movements). The postcentral gyrus, which is posterior to the central sulcus, is the primary somatosensory cortex (receives somatosensory information).

A sulcus is groove in the cortical surface. As we just observed, the central sulcus separates the primary motor cortex from the primary somatosensory cortex. A fissure is a deep groove. The Sylvian fissure (also called the lateral fissure or lateral sulcus) is the upper boundary of the temporal lobe (Breedlove & Watson, 2013). Graphic courtesy of Blausen.com staff "Blausen gallery 2014," Wikiversity Journal of Medicine.

Subdivisions of the Brain

The forebrain consists of the telencephalon (cerebral hemispheres) and the diencephalon. The telencephalon encompasses the cerebral cortex and the deeper structures of the basal ganglia and limbic system. Limbic system graphic © decade3d - anatomy online/Shutterstock.com.

The diencephalon in the posterior forebrain contains the thalamus and hypothalamus. Thalamus graphic © Sebastian Kaulitzki/Shutterstock.com.

The midbrain consists of the mesencephalon, which includes the inferior colliculi, superior colliculi, and substantia nigra. Substantia nigra graphic © Designua/Shutterstock.com.

The hindbrain contains the metencephalon and myelencephalon. The metencephalon is comprised of the cerebellum and pons. Cerebellum graphic © decade3d - anatomy online/Shutterstock.com.

MAJOR FUNCTIONS OF CORTICAL LOBES AND MAJOR SUBCORTICAL STRUCTURES AND BRODMANN AREAS

Cortical Lobes

The four major cortical regions include the frontal, parietal, temporal, and occipital lobes. Cortical lobes graphic © Yoko Design/Shutterstock.com.

The frontal lobe