History of Quantitative Electrophysiology

Learning Objectives

After completing this section, you will be able to:

Quantitative electrophysiology refers to the use of mathematical and statistical methods to analyze electrical activity measured from the brain, typically obtained through an electroencephalogram (EEG). This form of analysis is generally conducted to obtain objective, numerical descriptions of the complex patterns of neural activity.

When we discuss quantitative electrophysiology in the context of the quantitative EEG (qEEG), we're referring to the techniques used to process and analyze the raw EEG data. The EEG captures the brain's electrical activity, with millions of neurons firing and creating oscillating patterns of electrical potentials. However, interpreting these complex patterns is not straightforward.

The qEEG provides a solution by converting these raw data into a form that can be more readily understood. It applies various computational algorithms to extract meaningful metrics or features from the raw EEG signals. These could include measures like power spectral density (how power is distributed across different frequency bands), coherence (how two signals correlate), or connectivity metrics (how different brain regions interact).

Quantitative electrophysiology, therefore, provides a deeper, more detailed view of the brain's electrical activity, which can be used for diagnostic purposes, monitoring treatment efficacy, and conducting research into various aspects of brain function and dysfunction.

The history of quantitative electrophysiology, specifically quantitative electroencephalography (qEEG), is a story of gradual scientific and technological advances marked by the integration of mathematical models, statistical analyses, and advanced computational tools.

Below is a chronological breakdown of the major developments we will explore in greater detail.

Late 19th Century to Early 20th Century: The Foundations

The underpinnings of electrophysiology are rooted in the late 19th century, with the discovery of electrical activity in the brain. Richard Caton, a British physician, first observed electrical phenomena in the exposed cerebral hemispheres of rabbits and monkeys in 1875, setting the groundwork for future developments (Caton, 1875).

1920s-1930s: Birth of the EEG

The formal discovery of the EEG was by Hans Berger, a German psychiatrist, in the late 1920s. Berger's work led to the publication of the first human EEG in 1929, marking a significant step in the evolution of quantitative electrophysiology (Berger, 1929).

1940s-1960s: Quantitative Analysis and EEG

Quantitative approaches to EEG analysis began to emerge during the mid-20th century. In the early 1950s, Grey Walter developed the toposcope to record and display EEG from a large number of electrodes, pioneering topographic mapping (Walter, 1953).

In the early 1960s, the implementation of Fast Fourier Transform (FFT) enabled the transformation of time-domain EEG signals into frequency-domain signals. This development revolutionized EEG analysis, providing deeper insights into brain dynamics (Cooley & Tukey, 1965).

1970s-1980s: Computer-Aided Analysis and The Birth of the qEEG

The advent of computer technology and digital signal processing in the 1970s allowed for a shift from visual inspection to quantitative analysis of EEG data, thereby leading to the birth of the quantitative EEG (qEEG). Duffy and his colleagues (1994) were among the pioneers in using the qEEG for clinical applications.

What This Unit Covers

This unit covers the early antecedents of electrophysiology, the network and neuron theories, Hans Berger and his German contemporaries, Edgar Douglas Adrian, Bryan Matthews, William Grey Walter, North American EEG research, North American sleep and epilepsy research, neurophysiological research on thalamocortical relationships, and the point at which the EEG became mainstream.

It then turns to Mary A. B. Brazier, the development of fast Fourier transforms, Frank Duffy's contribution to computerized brain mapping, and the work of E. Roy John, Leslie S. Prichep, Roberto Pascual-Marqui, Hershel Toomim, J. Peter Rosenfeld and Elsa Baehr, Joel F. Lubar, Judith O. Lubar, Jay Gunkelman, Robert Thatcher, Thomas F. Collura, and Juri Kropotov.

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Early Antecedents

Luigi Galvani

Luigi Galvani (1791) was an Italian physician and anatomist at the University of Bologna who reported electrical currents in animals (Swartz & Goldensohn, 1998). Observing that a frog's leg twitched when touched by metal instruments, he proposed that living tissue stored a vital animal electricity. His rival Alessandro Volta argued the current came from the contact of dissimilar metals rather than the tissue itself, a dispute that helped launch the science of electrophysiology. Galvani's name survives in the term galvanism, the stimulation of muscle by electric current.

Galvani's findings were confirmed by Giovanni Aldini (1794) and Freiherr (baron) von Humboldt (1797). Aldini, Galvani's nephew, staged dramatic public demonstrations in which he applied current to the bodies of executed criminals, producing grimaces and twitching limbs that captivated audiences and helped inspire Mary Shelley's Frankenstein. Von Humboldt, the Prussian naturalist, took a more cautious experimental approach, performing hundreds of careful trials, including on his own body, to separate genuine bioelectricity from the effects Volta described.

The Galvanometer

The galvanometer, primarily credited to Leopoldo Nobili in Florence, was further developed by William Thompson in England in 1858, enabling the reliable measurement of ongoing electric currents and their changes in intensity. However, it failed to detect instantaneous electrical events (Niedermeyer & Schomer, 2011). Nobili is pictured below.

Emil du Bois-Reymond

Emil du Bois-Reymond (1849) was a German physiologist in Berlin and a founder of experimental electrophysiology who reported electrical conduction in muscles and peripheral nerves (Schomer & Lopes da Silva, 2011). Building sensitive galvanometers, he was the first to detect the electrical basis of the nerve impulse, establishing that nerves signal through measurable changes in electrical potential. Together with Carlo Matteucci in Bologna, he spearheaded the development of electrophysiology in the study of the nervous system. The improvement of nonpolarizable electrodes for physiological research is also attributed to du Bois-Reymond.

Du Bois-Reymond introduced the term negative variation to describe the unexpected drop in current intensity during muscle contraction, a term later used in early EEG research and the concept of contingent negative variation (Niedermeyer & Schomer, 2011).

Hermann von Helmholtz

Hermann von Helmholtz accurately gauged nerve conduction speed, correcting previous overestimations. The idea of the "action current" was put forward by L. Hermann, providing insight into Du Bois-Reymond’s observed negative variations during muscle contraction.

Julius Bernstein put forth a membrane theory of nerve tissue, eventually expounded upon in the late 1930s and onward by A. L. Hodgkin and A. F. Huxley in England. These advancements set the stage for the first observation of EEG-like electrical brain activity (Niedermeyer & Schomer, 2011).

Richard Caton

Richard Caton (1875) was an English physician in Liverpool who discovered electrical potentials in vivisected animals and reported his findings to the British Medical Journal. He recorded spontaneous electrical potentials from the exposed cortical surface of monkeys and rabbits. He was the first to measure evoked potentials (EPs), which are EEG responses to stimuli (Schomer & Lopes da Silva, 2011).

He also reported the first observations of the shift of the cortical gradient to electro-negative during activation.

Caton's initial findings, presented on August 24, 1875, were published as a short report in the British Medical Journal, followed by a more comprehensive report in 1877 on experiments involving over 40 animals.

Caton observed other intriguing phenomena, such as the positive polarity of the gray matter's external surface compared to the deeper cerebral structures. He also noted a connection between the brain's electrical currents and its functions, observing a negative variation in the electric current when the gray matter was functionally active. Consequently, Caton's pioneering work also contributed to understanding evoked potential. However, making firm statements about his findings, such as discovering the "steady potential" or "DC potential" may be premature without supporting evidence. Caton's galvanometer only had a limited frequency response range from 0 to 6 Hz, as pointed out by Geddes (1987).

Caton's ground-breaking research earned him some renown, and he served as the physiology chair at the University College of Liverpool from 1884 to 1891. Beyond the laboratory he was also a civic leader, becoming dean of the medical faculty and, in 1907, Lord Mayor of Liverpool. Though his later career did not primarily focus on brain's electrical activity, his pioneering work in the field remains a significant milestone. More details about Caton's life and work can be found in Mary Brazier's 1961 account (Niedermeyer & Schomer, 2011).

Gustav Fritsch and Eduard Hitzig

Gustav Fritsch and Julius Eduard Hitzig (1870) discovered that cortical stimulation elicits a localized motor response (Schomer & Lopes da Silva, 2011). The insight traced back to Fritsch's observation of contralateral muscle contractions while tending a brain wound during the Prussian–Danish War of 1864. Working in Fritsch's Berlin home, they applied weak electrical currents to the exposed cortex of a dog and saw specific muscle groups twitch depending on which region they stimulated. This was the first direct evidence that the cortex is electrically excitable and that motor functions are anatomically localized, a cornerstone of the brain mapping that underlies quantitative electrophysiology today.

D. Ferrier and G. F. Yeo expanded on this in 1880 by conducting electrical stimulations of the cerebrum in apes and a patient with a brain tumor. These findings shook the scientific community, many of whom believed the cerebrum was a single, uniform organ hosting mental functions.

During the era of Caton's pioneering work in the 1870s, Eastern European scientists had also begun independently studying the brain's electricity. The discoveries around the cortex's response to electrical stimulation inspired further exploration of its spontaneous electrical activity, particularly in those laboratories. Despite significant ethnic and national differences, it's worth noting that most of 19th-century Poland was under Czarist Russian rule (Niedermeyer & Schomer, 2011).

Vasili Yakovlevic Danilewsky

Vasili Yakovlevic Danilewsky (1877) was a physiologist at Kharkov University who, working independently of Caton, also detected electrical activity in the animal brain. He concluded his doctoral thesis, Investigations in the Physiology of the Brain, at the age of 25, studying both electrically stimulated and spontaneous brain activity in animals and exploring the relationship between the EEG and states of consciousness (Brazier, 1959).

Although his aspiration of correlating spontaneous brain activity with psychic and emotional processes went unmet, Danilewsky remained committed to brain physiology, publishing a comprehensive human physiology textbook in 1915 (Niedermeyer & Schomer, 2011).

Adolf Beck

Adolf Beck (1891) was a Polish physiologist at the Jagiellonian University in Krakow and an assistant to Napoleon Cybulski. Using nonpolarizable electrodes, he published studies of spontaneous electrical potentials detected from the brains of dogs and rabbits. He was the first to document alpha blocking, the desynchronization in which sensory stimulation replaces rhythmic oscillations with faster, lower-amplitude activity (Coenen et al., 1998). Working with rabbits and dogs, Beck noticed that rhythmic oscillations ceased when the eyes were exposed to light, an observation that laid the groundwork for Berger’s later report of this effect in humans.

Beck's work gained prominence due to its publication in the Centralblatt (Niedermeyer & Schomer, 2011).

Ernst Fleischl von Marxow

Ernst Fleischl von Marxow (1883) was an Austrian physiologist in Vienna who recorded visual cortical potentials, the cortical potentials evoked by visual stimuli, but did not describe rhythmic oscillation (Niedermeyer, 1993). To establish priority while continuing his work, he deposited a sealed letter with the Imperial Academy of Sciences in 1883, detailing his research on brain electrical activity across animal species.

Despite his assertion of priority over Beck's 1890 data, Fleischl von Marxow overlooked the earlier work of Caton and Danilewsky. His research was not top-notch, but his broad skillset, including linguistics, sports, and mountaineering, was noteworthy.

Napoleon Cybulski

Napoleon Cybulski and Jelenska-Macieszyna (1914) recorded experimental seizures (Swartz & Goldensohn, 1998). Cybulski, a Polish physiologist at the Jagiellonian University and a co-discoverer of adrenaline, mentored Adolf Beck and, using a photographic galvanometer, captured some of the earliest photographic records of seizure activity in the cortex, including EEG proof of an epileptic seizure electrically triggered in dogs.

Two Russian physiologists, Pavel Kaufman and Vladimir Pravdich-Neminsky, continued this research. New technologies emerged, including the d’Arsonval galvanometer and the capillary electrometer. Significantly, Willem Einthoven introduced the string galvanometer in 1903, a sensitive device that revolutionized electrocardiography.

Kaufman theorized that epileptic seizures correlate with abnormal electrical discharges and explored cortical electrical stimulation. He later adopted the name Rostoutsev and primarily worked at the University of Baku during World War I (Niedermeyer & Schomer, 2011).

Vladimir Pravdich-Neminsky

Vladimir Pravdich-Neminsky (1912) was a Ukrainian physiologist who, using Einthoven's string galvanometer, produced the first photographic recordings of brain electrical activity in a mammal. His 1912 publications, which featured the first EEG images, predated Cybulski's. Recording from the brain, the dura, or the intact dog skull, he photographed dogs' EEG and event-related potentials, demonstrated a regular 12-14 Hz rhythm that slowed significantly during asphyxiation, and introduced the term electrocerebrogram (Schomer & Lopes da Silva, 2011).

The remarkable advancements made by Eastern European neuroscientists in electrophysiologic neurophysiology during the 50 years before World War I are truly awe-inspiring. However, focusing solely on EEG history only scratches the surface. To fully appreciate their neuroscientific institutions, it's crucial to recognize pioneers in related electrophysiologic fields.

Ivan Sechenov, considered the founder of this esteemed group of neurophysiologists, explored the electrical activity of the frog's spinal cord and oblongata, paving the way for Pavlovian thought. Nikolai Wedensky, his successor as chair and professor of physiology at St. Petersburg, is known for the Wedensky inhibition concept. Vladimir Larionov, also based in St. Petersburg, conducted excellent studies on the auditory cortex in dogs (Niedermeyer & Schomer, 2011).

Alexander Forbes

Alexander Forbes and Catharine Thacher (1920) reported using a vacuum tube to amplify the faint currents recorded by the string galvanometer. Forbes was an American physiologist at Harvard whose vacuum-tube amplification increased sensitivity roughly fiftyfold, making it possible to display fast electrical potentials that earlier instruments missed. Forbes and Thacher amplified nerve action currents rather than the EEG, which did not yet exist as a human technique, but electronic amplification became the foundation on which EEG instrumentation was built over the following two decades (Swartz & Goldensohn, 1998).

Vladimir Bechterev

The most distinguished Russian neuroscientist and clinical neurologist was Vladimir Bechterev. Holding the psychiatry chair in St. Petersburg, he combined clinical work with rigorous psychophysiological methods. Trained by prominent figures like Du Bois-Reymond, Flechsig, and Wundt and having worked at Charcot’s clinic in Paris, Bechterev made significant contributions to brain functional anatomy, experimental psychology, and clinical neurology. His "associative reflexology" work remains influential.

However, between Bechterev and Nobel laureate Ivan Pavlov, the Soviet regime chose Pavlov. His theory of conditioned reflexes overshadowed all Soviet neurophysiology, aligning closely with the ideology of dialectic materialism. Despite Pavlov's criticism of the regime, his concept dominated and stifled the growth of traditional neurophysiology. This ideopolitically-driven neuroscience approach led to a swift collapse in global leadership in EEG and related fields and a concerning decline in dogmatically governed neurophysiology.

While electroencephalographic (EEG) research thrived in Eastern Europe, it was dormant in Western and Central Europe, which is surprising given the overall good health of neurophysiology in these regions. The work of Ernst Fleischl von Marxow appears like an odd outcrop in this vast field (Niedermeyer & Schomer, 2011).

Network vs. Neuron Theories

Western neurophysiologists closely followed the debate between network theories, supported by Joseph von Gerlach and Camillo Golgi, and neuron theories, championed by Santiago Ramón y Cajal (pictured below).

Despite resistance from the "reticularists," the neuron theory eventually triumphed. Similarly, proponents of cerebral localization clashed with those opposing it. Researchers such as Friedrich Goltz and H. Rothmann conducted experiments that targeted the entire brain rather than localized areas, contrasting the emerging interest in cortical localization inspired by the work of Fritsch, Hitzig, Ferrier, and Yeo.

Sir Charles Sherrington

Sir Charles Sherrington (1906) proposed the concept of a synapse to describe the junction across which neurons communicate and published The Integrative Action of the Nervous System. The Cambridge classicist Arthur Woollgar Verrall proposed the Greek-derived term (Tansey, 1997). Sherrington also introduced the term neuron. He made significant contributions to understanding muscle action, movement, proprioception, reflexes, and spinal nerves (Schomer & Lopes da Silva, 2011). He shared the 1932 Nobel Prize in Physiology or Medicine with Edgar Adrian for their discoveries on the function of neurons.

Sherrington's work in Liverpool and Oxford profoundly influenced the development of modern Western reflexology, and his groundbreaking book covered a range of topics from reflexology to decerebrate rigidity, focusing largely on physical processes and sparingly addressing mental functions.

His concept of inhibition was a major contribution. Yet, this neurophysiology master had little connection to electrophysiology, focusing primarily on ablation techniques and largely ignoring EEG methods.

Sherrington proposed the "enchanted loom" metaphor for the human brain in a passage in Man on His Nature, first published in 1940 and quoted here from the 1942 printing, in which he poetically described the change in cortical activity as we awaken:

"The great topmost sheet of the mass, that where hardly a light had twinkled or moved, becomes now a sparkling field of rhythmic flashing points with trains of traveling sparks hurrying hither and thither. The brain is waking and with it the mind is returning. It is as if the Milky Way entered upon some cosmic dance. Swiftly the head mass becomes an enchanted loom where millions of flashing shuttles weave a dissolving pattern, always a meaningful pattern though never an abiding one; a shifting harmony of subpatterns." (p. 178)

Current sleep research shows that the cortical networks are considerably more active during sleep than Sherrington imagined.

His students, including Edward Liddell and Derek Denny-Brown, held similar views. Meanwhile, in Cambridge, Edgar Douglas Adrian emerged as a strong proponent of electrically oriented neurophysiology, a topic we'll discuss later in relation to Hans Berger's work (Niedermeyer & Schomer, 2011).

Hans Berger

Hans Berger (1873–1941), the pioneer of the human EEG, was a German neurologist and psychiatrist at the University of Jena who published the first human EEG recording in 1929. Driven by a lifelong quest to find the physical basis of "psychic energy" and mental phenomena, he worked for years in relative obscurity before publishing fourteen scientific papers from 1929 to 1938 (Schomer & Lopes da Silva, 2011).

Berger's first human recording, on July 6, 1924, came from a 17-year-old patient with a skull defect left by a neurosurgical procedure. His son Klaus became a frequent subject of the later scalp recordings, and Klaus's tracings appear among the published samples below.

Berger showed that these potentials were not due to scalp muscle contractions. He discovered the alpha rhythm, the first EEG rhythm, and named it the alpha wave. The eponym Berger rhythm was applied by Adrian and Matthews, who titled their 1934 confirmation paper "The Berger Rhythm." He identified sleep spindles, which are short bursts of 12-15 Hz activity during stage 2 sleep.

Berger viewed the EEG as analogous to the ECG because it generates an electrical signal that can be amplified and displayed. He introduced the German term Elektrenkephalogramm. He believed that the EEG had diagnostic and therapeutic promise in measuring the impact of clinical interventions.

He demonstrated that alterations in state, whether sleep and wakefulness, eyes open and closed, drug and no drug, or illness and health, are associated with changes in the EEG. He associated the beta rhythm with alertness. He described interictal activity (EEG potentials between seizures) and recorded a complex partial seizure (impaired awareness and repetitive behaviors called automatisms) in 1933. Finally, he performed the first qEEG, which measures the signal strength of component EEG frequencies (Hassett, 1978; Robbins, 2000; Swartz & Goldensohn, 1998).

Berger practiced as a neuropsychiatrist, a combined specialty of neurology and psychiatry in Germany, Austria, and many other countries at that time. These departments consisted of neurological and psychiatric wards, with training requiring rotation between the two. Pure neurology was just beginning to become its own discipline in German-speaking countries, thanks to the work of Wilhelm Erb, Max Nonne, and Otfrid Foerster, who lived during the same period as Berger.

Berger was not a leader in either neurology or psychiatry, and his name would have been lost if not for his pioneering EEG work. He was described as meticulous, conscientious, somewhat detached with patients, strict, authoritarian, and disinterested in faculty politics. He did his EEG work in a small, primitive lab, initially focused on cerebral circulation using plethysmographic methods in patients with skull defects. From 1902 to 1910, he studied the electrical activity of the dog's cerebrum using a capillary electrometer, with disappointing results. He started studying the human EEG in 1920.

While cumbersome in their original German, Berger's writings are critical for every electroencephalographer to understand, and this is made easier through Gloor’s English translation. Berger's work was titled, "On the Electroencephalogram of Man," which may not have helped its slow acceptance due to lack of appeal. His focus on linguistics is evident in his rejection of the term "electrocerebrogram" due to its mix of Greek and Latin elements, proposing instead the term "Elektrenkephalogramm."

Berger's electrophysiological instrumentation evolved over time. He initially used a string galvanometer starting in 1910, later switching to the Siemens double-coil galvanometer in 1926, allowing for sensitivity up to 130 μV/cm. He recorded human EEG tracings with nonpolarizable pad electrodes, resulting in one to three minutes of data on photographic paper. His bipolar recording technique used fronto-occipital leads for his one-channel EEG tracings, along with a simultaneous ECG recording and time marker. He obtained an oscillograph in 1932 but could not acquire more amplifiers for multichannel recordings.

Berger began studying human EEG in 1924, primarily on patients with large skull defects, common after World War I in Germany. He initially believed these defects would aid in obtaining recordings, but later realized that good results could be obtained through an intact skull and scalp. Between 1926 and 1929, he successfully recorded alpha waves with a double-coil galvanometer. His initial findings were questioned, and he experienced doubts about his results.

Berger's first 1929 report highlighted the alpha rhythm and alpha blocking response, along with smaller beta waves, using various types of electrodes. His findings were only accepted after confirmation from Adrian in Cambridge in 1934. During the 1930s, Berger's research on human EEG provided valuable insights into various aspects of consciousness, sleep, the effect of hypoxia on the brain, various brain disorders, and early indications of epileptic discharges.

Berger's mandatory retirement in 1938 hindered his further EEG research. Standard histories long attributed that retirement to a poor relationship with the Nazi regime and cast Berger as one of its victims, but archival evidence recovered after the fall of the Berlin Wall has overturned that account, as the reappraisal at the end of this section describes (Fields, 2024; Zeidman et al., 2014). After a bout of illness, Berger developed severe depression, which remained undiagnosed, and he died by suicide in 1941 at the age of 68. His insecurity may have been fueled by the competition from a group of EEG researchers at the Institute of Brain Research at Berlin-Buch.

Berger was complex, both as a person and as a researcher. He did not stand out clinically but was dedicated in his EEG work. His primary research motivation was to understand the nature of "mental energy", which he believed could transmit thoughts and emotions between individuals. Influenced by the Danish physiologist Alfred Lehmann, he considered this mental energy a product of metabolic energy, with EEG waves acting as messengers of mental activities.

Despite not having a formal scientific background, Berger made significant strides in EEG research, and his contribution is considered the greatest in the history of electroencephalography, despite his initial assumptions about EEG not being entirely correct (Niedermeyer & Schomer, 2011).

Berger's German Contemporaries

The Institute of Brain Research in Berlin-Bush was home to various eager neuroscientists under the directorship of Oskar Vogt, a renowned neuroanatomist and neuropathologist, until his dismissal by the Nazi government in 1936 due to his ties with a similar institute in Moscow and his refusal to expel Jewish co-workers. The institute had several departments, notably the Department of Physiology and the Department of Electrophysiology, led by M. H. Fischer and A. E. Kornmüller, respectively. They worked closely with physicist and electronic engineer J. F. Toennies, who developed the first ink-writing biological amplifier for recording brain potentials.

While in New York in 1932, Toennies designed the differential amplifier, which was crucial for EEG amplification, in parallel with Brian Matthews, Adrian's collaborator. Toennies' work provided the Berlin group with superior EEG research tools compared to Hans Berger's. Kornmüller saw the value of using more electrodes for recordings and focused on the differences between various cerebral regions. His early experimental work, particularly on epileptiform spikes, is considered more significant than his later clinical EEG studies.

Oskar Vogt (pictured below) conceived the cortex as divided into about 200 regions with clear demarcations, influencing Kornmüller's EEG work. Richard Jung joined the group in 1937 after Vogt's removal.

Vogt's replacement, Hugo Spatz, significantly altered the research goals. Toennies, in New York, constructed the first cathode follower for high-resistance electrode recording, marking the advent of microelectrode recording.

M. H. Fischer and H. Löwenbach

M. H. Fischer and H. Löwenbach (1935) provided the first demonstration of epileptiform spikes, the sharp EEG transients with a duration of less than 70 ms that signal abnormal, hypersynchronous neuronal firing (Swartz & Goldensohn, 1998). Their work helped establish the link between distinctive EEG waveforms and seizure activity that made the EEG a diagnostic tool for epilepsy.

Post World War II, Kornmüller's work declined due to his fixation on an unproven theory about glia as the generator of slow brain potentials. Meanwhile, Jung became one of the leading electroneurophysiologists of his era (Niedermeyer & Schomer, 2011).

Edgar Douglas Adrian

Edgar Douglas Adrian (1889–1977), Baron of Cambridge and also known as Lord Adrian, was a preeminent electrophysiologic neurophysiologist of the 20th century who is closely linked to the discovery of the EEG. He and Bryan Matthews (1934), his fellow British physiologist at Cambridge, confirmed Berger's observations by recording their own EEGs using a cathode-ray oscilloscope. Adrian had just received the 1932 Nobel Prize in Physiology or Medicine for his work on the nerve impulse, shared with Sir Charles Sherrington for their discoveries regarding neurons. His endorsement therefore carried great weight, and their demonstration to the Physiological Society at Cambridge in May 1934, at which Adrian displayed his own alpha rhythm, turned skepticism into widespread acceptance (Schomer & Lopes da Silva, 2011).

Using himself as a subject, he demonstrated his own alpha rhythm and the blocking effect of eye opening to his peers, despite his colleague Bryan Matthews having a low-voltage EEG without an alpha rhythm. Interestingly, Adrian's recordings from the head ganglion of a water beetle mimicked his alpha rhythm and responded similarly to light, causing confusion among observers.

By the time Adrian corroborated Berger's findings, he was already an esteemed neurophysiologist known for showing single sensory nerve fiber potential and unit activity analysis, leading to the Adrian–Bronk law.

Adrian provided evidence supporting the all-or-none law: action potentials initiated at the axon hillock either occur or not. When they occur, they have the same amplitude and speed. His co-worker, Detlef Bronk, later became president of Johns Hopkins University (Niedermeyer & Schomer, 2011).

Bryan Matthews

Bryan Matthews was both a physiologist and a gifted instrument engineer whose oscillograph and differential amplifier designs became foundational hardware for recording bioelectric signals. The differential amplifier he refined still lies at the heart of modern EEG and neurofeedback systems, where it cancels shared noise and isolates the small signals of interest.

William Grey Walter

W. G. Walter (1940s) was an American-born British neurophysiologist in Bristol who named the delta and theta waves and discovered the contingent negative variation (CNV). This slow cortical potential may reflect expectancy, motivation, intention to act, or attention (Schomer & Lopes da Silva, 2011). He also built some of the first autonomous robots, his "tortoises," to show that lifelike behavior could emerge from simple feedback circuits.

Walter located an occipital lobe source for alpha waves and demonstrated that delta waves could help find brain lesions like tumors. In 1946, he described electrical responses to photic stimulation (visual stimulation at a specific flash frequency).

He improved Berger's electroencephalograph and pioneered EEG topography (Bladin, 2006). EEG topography maps electrical activity across the brain surface.

Although he was a basic scientist with a Ph.D. rather than a clinician, Walter pioneered clinical electroencephalography in England, and his discovery of foci of slow activity (delta waves) sparked significant clinical interest in the method. However, that academic rather than clinical background may also have spurred an aversion to EEG among England’s neurologists, leaving the method mainly in the hands of lab-based Ph.D. electroencephalographers. Walter, an innovative thinker and persuasive writer, founded a highly effective school in Bristol at the Burden Institute (Niedermeyer & Schomer, 2011).

The British EEG Society was established in 1942, and the American EEG Society began in 1947.

North American EEG Research

Around 1935, North America began to eclipse Europe as the focal point for the growing field of EEG research. Discoveries were emerging from the US, attracting European researchers. Hans Berger, a notable figure in this field, almost made a trip to the US in 1939, but his plans were interrupted by the outbreak of World War II.

Before Berger's involvement, the US didn't contribute significantly to the early development of EEG studies. A 1918 incident highlighted this lack of awareness. Donald McPherson, a Harvard Medical School student, identified rhythmic EEG activity in a cat's brain, but Alexander Forbes, a renowned physiologist, dismissed his findings as false.

The US's ascendancy in EEG research is often tied to the contributions of Hallowell Davis, Frederic A. Gibbs, Erna Gibbs from Harvard, and Herbert Jasper from Brown University. According to O’Leary and Goldring (1976), Hallowell Davis became aware of Berger's 1929 paper through his graduate student, A. J. Derbyshire. After initial unsuccessful attempts to replicate alpha rhythms, Davis was finally found to have a notable alpha rhythm. This marked the start of human EEG studies in the US in 1934, a precursor to the rapid increase of such research. Hallowell Davis is pictured below.

However, animal EEG experimentation in the US had begun earlier, spearheaded by researchers like Bartley and Newman in the early 1930s. Their studies, along with those by Davis and Saul, Travis and Dorsey, Travis and Herren, Bishop and Bartley, Bartley, and Gerard, laid the groundwork for future development. The work of Ralph W. Gerard in introducing a concentric needle electrode for animal brain experiments and his partnership with Franklin Offner, a pioneering electronic engineer, played a significant role in the evolution of EEG and related equipment.

The commencement of human EEG studies in the US can be traced back to Harvard, Brown University, and the University of Iowa. Key contributors included Hallowell and Pauline Davis, Frederic and Erna Gibbs, and William G. Lennox at Harvard; Herbert H. Jasper at Brown; and Lee Travis at Iowa, who established a significant school of study (Niedermeyer & Schomer, 2011).

The Gibbs–Gibbs–Lennox Period

Erna Gibbs, Frederic A. Gibbs, Hallowell Davis, and William G. Lennox, working at Harvard Medical School, inaugurated clinical electroencephalography in 1935 by identifying abnormal EEG rhythms associated with epilepsy, including interictal spike waves and the 3-Hz spike-and-wave activity in absence seizures, which involve periods of less than 15 s during which a client blanks out (Brazier, 1959). This 3-Hz pattern became a reliable diagnostic signature, helping move the EEG from the research laboratory into the hospital. Erna and Frederic Gibbs collaborated closely on their research, including developing a scale for rating beta spindles.

In 1934, research on epileptic patients marked a pivotal point in clinical electroencephalography. Frederic Gibbs joined the Harvard team from Johns Hopkins University and partnered with established epileptologist William G. Lennox. Interestingly, Lennox had initially focused on cerebral circulation research.

Erna L. Gibbs, a German immigrant who began as Lennox's technical assistant, later became Frederic Gibbs's wife and a pioneering EEG technician and co-author. Their cerebral blood flow studies were milestones in the field, though EEG ultimately captivated Lennox more.

The first study of petit mal epilepsy by Gibbs and Davis in 1935, featuring twelve children, remains influential in EEG literature, primarily for its linking petit mal absences with 3/sec spike-wave complexes. This discovery eclipsed subsequent findings of grand mal and psychomotor seizure EEG patterns by the same team, even though it was later found that spike waves could occur without petit mal.

Despite their groundbreaking work, the EEG recordings produced were technically inferior. In 1935, Frederic Gibbs and his wife visited Hans Berger in Germany and studied Jan F. Toennies' "polyneurograph" instrument and Matthew's instrumentation in England. Gibbs then commissioned Albert Grass, from the Massachusetts Institute of Technology, to construct a three-channel preamplifier. By the end of 1935, the Grass Model I, featuring three channels and an ink writer, was in use.

The Gibbs–Gibbs–Lennox period in the 1930s arguably marked the most exhilarating phase in EEG history, especially regarding breakthroughs in understanding epileptic seizures. The advent of EEG partitioned epileptology into two historical periods, causing a monumental leap in understanding epilepsy. Building on Fischer's 1931 animal studies, the Gibbses and Lennox applied the knowledge to human epileptology, paving the way for future work (Niedermeyer & Schomer, 2011).

North American Sleep and Epilepsy Research

Other EEG pioneers in North America, like Hallowell and Pauline Davis, made significant contributions to understanding the normal EEG and its variants. They were among the first to investigate the human sleep EEG. In terms of sleep studies, A. L. Loomis, E. N. Harvey, and G. A. Hobart were the first to methodically research human sleep EEG patterns and stages. At Brown University, Herbert Jasper studied the EEG of children's behavior disorders, later focusing on epileptology at McGill University in collaboration with Wilder Penfield.

John R. Knott and Charles E. Henry, disciples of Lee Travis, emerged as critical figures in America's EEG work. D. Lindsley became a pioneer in researching maturational EEG aspects and directed top-tier neurophysiologic EEG research at UCLA.

Robert Schwab and Warren McCulloch also played significant roles, with McCulloch gaining recognition for his thinking that far exceeded the bounds of EEG and neurophysiology. Clinical EEG research began exploring beyond epileptology with Grey Walter’s discovery of the delta focus linked to brain tumors. By the end of the 1930s, North America had led in the field of EEG, while Europe had lagged behind.

During WWII (1939-1945), EEG research and clinical activities suffered, especially in Europe, though it was still used for localizing brain injuries and epileptogenic foci. Post-war, the gap between North America and Europe widened, with the latter's EEG research hitting a nadir.

Post-war revitalization began in England and France while Germany was struggling. W. Grey Walter, V. J. Dovey, and H. Shipton at the Burden Institute discovered the paroxysmal response to certain flickering light frequencies, a method later used by Henri Gastaut in France to establish an individual threshold for paroxysmal responses.

In 1947, the American EEG Society was founded, and the First International EEG Congress was held in London, with a follow-up in Paris in 1949. EEG activities in Germany were minimal during this time, but research efforts in Japan and Switzerland started to stand out.

In the US, Frederic A. Gibbs, Erna Gibbs, and B. Fuster made significant strides in understanding temporal lobe epilepsy. Their findings necessitated the inclusion of sleep in EEG evaluations, causing American EEG labs to be more sophisticated than their European counterparts. Erna and Frederic Gibbs are pictured below.

Despite international acclaim, Frederic Gibbs held a modest academic rank at Harvard, reflecting a generally negative attitude towards EEG within neurologic departments. Herbert H. Jasper, by then at the Neurologic Institute of McGill University, emerged as Gibbs's key competitor (Niedermeyer & Schomer, 2011).

Neurophysiological Research: Thalamocortical Relationships

Frederic Bremer

Frederic Bremer (1935) was a Belgian neurophysiologist who used the EEG to show how sensory signals affect vigilance and studied the sleep-wake cycle. Using his cerveau isolé and encéphale isolé brainstem preparations, he showed that lower brainstem structures help sustain cortical arousal. His work is sometimes credited with dividing the EEG into standard bandwidths, but the band names came from others: Berger named alpha and beta in 1929, and Walter named delta in 1936 and theta, with Vivian Dovey, in 1944.

Per Andersen and S. A. Andersson

Per Andersen and S. A. Andersson (1968) proposed that thalamic pacemaker circuits project synchronous rhythms in the classical alpha band, 8 to 13 Hz, to the cortex through thalamocortical connections. Andersen was a Norwegian neuroscientist at the University of Oslo whose laboratory became the birthplace of long-term potentiation (LTP), the lasting strengthening of synapses that underlies learning and memory. Terje Lømo first observed the effect there in 1966, and Bliss and Lømo characterized it fully in a landmark 1973 paper (Bliss & Lømo, 1973).

Horace W. Magoun and Cortical Electrogenesis

By the late 1940s, two new developments arose: invasive EEG techniques exploring deep brain regions and automatic frequency analysis. Also notable were neurophysiologists' studies on thalamocortical relationships, with researchers like Morison and Dempsey significantly impacting our understanding of cortical electrogenesis.

Horace W. Magoun's research on the brainstem reticular formation, carried out at Northwestern University and the University of California, had a transformative effect on neuroscience, highlighting the association between consciousness and reticular formation. However, his name is less recognized today.

The 1940s witnessed the influential role of EEG in neurophysiology, though by its end, the focus had shifted towards single neurons, and "macro-EEG" interest faded (Niedermeyer & Schomer, 2011).

The EEG Becomes Mainstream

The 1950s saw EEG becoming commonplace. Almost every university hospital had at least one EEG machine, and by the decade's end, they were in many hospitals and private practices. Specialized EEG labs began to appear, catering to children or adults. Psychiatrists appreciated the neurophysiological insights the EEG provided, but despite clear correlations between central nervous system diseases and EEG results, many neurologists remained wary or antagonistic towards EEG. At the same time, neurosurgeons showed interest as long as EEG helped identify focal cerebral lesions.

Herbert Jasper and the International 10-20 System

Frederic A. Gibbs and Herbert H. Jasper (1936) showed that the interictal spike was the defining indicator of epilepsy (Schomer & Lopes da Silva, 2011). Jasper went on to standardize electrode placement, work that led to the International 10-20 System and allowed recordings to be compared across laboratories worldwide.

The International 10-20 System positions electrodes at distances of 10% and 20% along measured lines that run between bony landmarks on the skull, such as the nasion at the bridge of the nose and the inion at the back of the head (Jasper, 1958). Because the spacing is proportional rather than fixed, the same sites land over comparable brain regions on heads of different sizes. Each location carries a letter for the underlying region, such as F for frontal or O for occipital, with odd numbers marking the left hemisphere and even numbers the right. This shared map is why a recording made in one laboratory can be meaningfully compared with one made anywhere else.

Herbert Jasper and Wilder Penfield's work on epilepsy reached a new zenith in Montreal, establishing it as a hub for the neurosurgical treatment of focal epilepsies.

Their collaboration led to the influential book "Epilepsy and the Functional Anatomy of the Human Brain." Controversy, however, surrounded the "centrencephalic" concept of primary generalized epilepsy that they proposed, which was heavily debated, later proven shaky, and largely dismissed by the late 1960s.

Previously at Harvard, Frederic Gibbs moved to the University of Illinois School of Medicine, bolstering Chicago's status as a global leader in the neurologic sciences. Despite their rivalry, the Chicago group under Gibbs and the Montreal group under Jasper and Gloor both made significant advancements in epileptologic electroencephalography. A. Earl Walker, a master from the Chicago school, brought depth EEG, electrocorticography, epilepsy surgery, and a scientifically oriented epileptology to Johns Hopkins in Baltimore, solidifying his legacy in neurosurgery and epileptology.

Computational wave analysis techniques in EEG began with Hans Berger's early attempts in 1932, aided by physicist Dietsch's application of Fourier analysis. Grass, Gibbs, and Knott made further advancements. By the 1950s, automatic frequency analyzers emerged but were largely underused.

In the same decade, EEG technology advanced with the introduction of the microelectrode technique, allowing for the recording of single neurons. The invention of the cathode follower by Toennies made it technically possible to record from single cells. Extracellular microelectrode recording became more prevalent, and a decade later, intracellular microelectrode technology allowed for deeper biochemical insights.

Nathaniel Kleitman and William C. Dement

Nathaniel Kleitman (1953) was a Russian-born physiologist at the University of Chicago who has been recognized as the "Father of American sleep research" for his seminal work on sleep-wake cycle regulation, circadian rhythms, the sleep patterns of different age groups, and the effects of sleep deprivation. To test whether human rhythms could be reset, he famously spent a month deep in Kentucky's Mammoth Cave in 1938. Kleitman described the basic patterns of sleep cycles and the transitional states that connect them (Schomer & Lopes da Silva, 2011).

He discovered the phenomenon of rapid eye movement (REM) sleep with his graduate student Eugene Aserinsky. Below is a sample of brainwave activity during REM sleep.

William C. Dement (1950s), another of Kleitman's students, described the EEG architecture and phenomenology of sleep stages and the transitions between them in 1955, associated REM sleep with dreaming in 1957, and documented sleep cycles in another species, cats, in 1958, which stimulated basic sleep research. He established the Stanford University Sleep Research Center, the first international sleep laboratory, in 1970. He has contributed to research on sleep deprivation and the diagnosis and treatment of sleep disorders like apnea and narcolepsy (Schomer & Lopes da Silva, 2011). Widely regarded as the father of sleep medicine, Dement spent decades raising public and clinical awareness of how untreated sleep disorders harm health.

Kleitman and Dement advanced polysomnography by incorporating eye movement and the EEG during an entire night's sleep. These measurements enabled the study of sleep stages and behaviors like dreaming, and through the 1950s Kleitman and his team at the University of Chicago remained the pioneers of research on sleep organization and REM sleep.

However, as sleep research became more reliant on polygraphic recording, it gradually diverged from EEG research, creating a widening gap between the two fields from the 1960s onwards (Niedermeyer & Schomer, 2011).

José Manuel Rodriguez Delgado's contributions to the field of electroencephalography (EEG) were significant and pioneering, albeit controversial. Delgado, a Spanish physiologist, was among the first to perform electrical brain stimulation in both animals and humans. His work in the 1960s and 1970s was groundbreaking, focusing on the electrical stimulation of specific brain areas to understand and potentially treat mental illnesses and epilepsy.

Some of his notable experiments include evoking complex behaviors in primates through brain stimulation, investigating aggressive behavior in animals, and inducing emotional responses in humans. Delgado's work with the "stimoceiver," a device he invented, allowed for two-way communication with the brain and laid the groundwork for future neuromodulation techniques.

Despite facing severe criticism and controversy, especially concerning the ethical implications and the precision of electrical stimulation effects, Delgado's contributions are acknowledged as paving the way for new modulation techniques like deep brain stimulation (Lorusso et al., 2022).

Although Delgado's work was influential in neurophysiology and the development of EEG techniques, he did not directly contribute to the fundamental development of these technologies. Instead, his work utilized these technologies to explore and manipulate brain functions in novel ways.

Samuel Sutton's work in discovering and understanding the P300 component of the event-related potential (ERP) is a major contribution to cognitive psychophysiology. Sutton and colleagues first reported the P300 slow cortical potential in 1965. They discovered the P300 in a "guessing paradigm," where participants were uncertain about the nature of the test stimulus. They observed that a large positive peak, later known as the P300 wave, occurred at about 300 ms after stimulus onset (Bashore & Molen, 1991).

The P300 (P3) wave is an event-related potential (ERP) component elicited in decision-making. It is also known as an “expectancy wave,” as it defines a degree of uncertainty in the decision-making process.

This discovery was significant because it was one of the first demonstrations that ERPs could reflect cognitive or psychological processes, such as the subject's uncertainty or the task relevance of stimuli, rather than merely the sensory attributes of the stimuli. This revelation has profoundly impacted the field, providing a noninvasive means for studying physiological correlates of cognitive processing in humans.

Sutton's work on the P300 component has influenced a broad range of areas, including basic behavioral research, psychophysiological research, and experimental psychopathology. The P300 wave has been associated with cognitive information processing, including memory, attention, and executive function. The significance of the P300 lies in its ability to provide insights into the functional neuroanatomy of cognitive processes and its potential as a diagnostic tool in various neurological and psychiatric conditions (Bruder, 1992).

Reduced P300 amplitude is an indicator of the broad neurobiological vulnerability that underlies disorders such as alcohol dependence, drug dependence, nicotine dependence, conduct disorder, and adult antisocial behavior.

For example, P300 amplitude is reduced in patients diagnosed with alcohol use disorder (AUD) and their alcohol-naive children.

The P300 wave's discovery has also been pivotal in brain-computer interface (BCI) technology, particularly in developing P300-based BCIs for assisting individuals with motor impairments.

Mary A. B. Brazier

Mary A. B. Brazier (1904-1995) was a British-American neurophysiologist who became one of the foremost authorities on the electrical activity of the brain. After moving from London to Boston on a Rockefeller Fellowship in 1940, she directed the EEG laboratory at Massachusetts General Hospital and, beginning in 1948, pioneered the use of correlation techniques and early digital computers to analyze EEG signals, work that anticipated modern quantitative EEG.

She later joined the Brain Research Institute at the University of California, Los Angeles, and served as president of the International Federation of Societies for Electroencephalography and Clinical Neurophysiology. Brazier also became the field's preeminent historian, and her account of the first half-century of brain electrical recording remains a standard reference (Brazier, 1961). She arranged the English translation of Adolf Beck's pioneering thesis, helping secure the place in this history that Beck holds today.

The Development of Fast Fourier Transforms

The peak of clinical and experimental EEG work was around 1960, but the 1960s saw a shift towards automated data analysis and computerization. James Cooley and John Tukey introduced fast Fourier transforms, foundational for power spectral analysis.

The Fast Fourier Transform (FFT) is a highly efficient algorithm for computing the Discrete Fourier Transform (DFT) and its inverse. This algorithm is widely recognized as a major breakthrough in digital signal processing, and its development is most commonly attributed to Cooley and Tukey, who published a landmark paper on the topic in 1965.

Before the development of the FFT, the calculation of the DFT was computationally intensive. This made the application of Fourier analysis unfeasible for large datasets. The FFT algorithm significantly reduced the computational burden, making it practical for larger datasets.

Cooley and Tukey's FFT algorithm leverages the symmetries and periodicities inherent in the computation of the DFT to reduce the number of necessary computations. It breaks down a DFT of any composite size N = N1*N2 into many smaller DFTs of sizes N1 and N2, recursively, to significantly reduce the number of multiplications and additions. This "divide and conquer" technique provides a dramatic speed-up for large datasets.

It is worth noting that while Cooley and Tukey are most commonly associated with the FFT, the basic principles behind the algorithm have been independently discovered and rediscovered many times throughout history. However, Cooley and Tukey's publication made the technique widely known and led to its broad adoption in the scientific and engineering communities.

The development of the FFT has had far-reaching impacts in numerous fields, including engineering, physics, mathematics, and computer science. It is extensively used in signal processing, image analysis, solving partial differential equations, and even in data compression.

Predictions of full automation in EEG interpretation proved false as EEG complexity required expert human interpretation. Despite this, computerized frequency analysis benefited psychophysiological research and neuropharmacological assessments.

The 1970s witnessed advancements in evoked potential techniques, enhancing their reliability and utility. However, during this period, the once close relationship between EEG and epileptology declined. This trend was later reversed in the 1980s due to a resurgence of interest in EEG for presurgical evaluations of seizure surgery candidates.

The advent of neuroimaging technologies like CT and MRI in the 1970s and 1980s seemed to overshadow EEG, but EEG remained crucial for identifying functional changes around CNS lesions. There's a concern that the focus on structural diagnosis may overlook functional understanding, a trend that needs to be halted (Niedermeyer & Schomer, 2011).

Frank Duffy's Contribution to Computerized Brain Mapping

Erwin Roy John and Frank H. Duffy (1970s) collaborated in developing quantitative electroencephalography and its use in the assessment of disorders. John, a neuroscientist at New York University, created neurometrics, in which a client's EEG is compared to a normative database, and he contributed to the study of memory by proposing that it is distributed across the brain rather than stored in one place. Duffy, at Harvard, developed Brain Electrical Activity Mapping (BEAM), a method for displaying qEEG data as color topographic maps of the cortex.

Computerized brain mapping, associated primarily with Frank Duffy, a prominent neurologist and pioneer in neurophysiology also noted for his contributions to pediatric neurology, revitalized topical EEG diagnosis. Simultaneously, from the late 1960s onwards, novel strides were made in newborn EEG exploration.

In the 1970s and 1980s, Duffy developed techniques for computerized analysis of electroencephalography (EEG) data, leading to the emergence of the qEEG as a valuable tool in clinical and research settings. The qEEG involves using computer algorithms to analyze the electrical patterns of the brain, transforming raw EEG data into color-coded maps that provide a visual interpretation of brain activity. These brain maps can aid in the diagnosis of neurological conditions, the monitoring of disease progression, and the evaluation of treatment efficacy.

Duffy's work has been instrumental in advancing the understanding of various neurological and developmental disorders, including epilepsy, attention deficit hyperactivity disorder (ADHD), and autism (Duffy & Eksioglu, 2003). His research has shown that the qEEG can reveal distinct patterns of brain activity associated with these conditions, which may not be evident in traditional EEG readings.

Additionally, Duffy and his colleagues were among the first to use the qEEG to study brain development in infants and children (Duffy et al., 2003). This pioneering work has provided critical insights into the dynamic changes in brain function that occur throughout early development and the effects of developmental disorders on this process.

In summary, Frank Duffy's work in computerized brain mapping and quantitative EEG has significantly advanced the field of neurophysiology, particularly in pediatric neurology. His contributions have enhanced our understanding of brain function in health and disease and continue to influence current research and clinical practice.

E. Roy John

E. Roy John was a leading pioneer in the field of quantitative electroencephalography. His work spanned many decades and covered a wide range of topics, including the development of novel analytical techniques, the use of the qEEG in clinical and research applications, and the application of the qEEG in neuropsychiatric disorders (John et al., 1980; John & Prichep, 2006).

John was one of the earliest advocates for using computers in EEG analysis. His work in the 1960s and 1970s led to the development of some of the first computer systems used for automated EEG analysis, a fundamental shift in how EEG data was analyzed and interpreted.

John also developed the concept of neurometrics, which involves using qEEG measures to quantify deviations from normal brain function (John et al., 1988). Neurometrics is based on the idea that brain dysfunction can be quantified in terms of deviations from normative data in qEEG measures. This concept has had a significant impact on the clinical use of QEEG, including its use in diagnosing and treating neuropsychiatric disorders (John et al., 2007).

John's work has led to the use of the qEEG in a variety of clinical applications. For example, he and his colleagues have shown that the qEEG can predict a coma's outcome, helping clinicians make more informed decisions about treatment and prognosis.

John has also been instrumental in applying the qEEG to the study of various neuropsychiatric disorders, including ADHD, schizophrenia, and Alzheimer's disease. His research has shown that QEEG can reveal abnormalities in brain function that are not evident from standard clinical assessments.

Overall, E. Roy John's contributions to the qEEG have been instrumental in its development and widespread use in clinical and research settings. His work has transformed how we understand and assess brain function and dysfunction.

Leslie S. Prichep

Leslie S. Prichep was E. Roy John's principal collaborator at New York University and a central figure in the development of neurometrics, the comparison of an individual's EEG to an age-regressed normative database. With John and their colleagues, she helped build and validate the reference data and the statistical methods that let clinicians express a client's brain activity as deviations from expected values, a quantitative approach that aids in diagnosing a range of neurological and psychiatric disorders (John et al., 1988; Prichep, 2005). Her research extended quantitative EEG to the differential diagnosis of dementia, depression, and other disorders, and later to traumatic brain injury and the assessment of concussion.

Prichep has played a major role in demonstrating the qEEG's clinical utility. She has conducted extensive research using the qEEG in various contexts, including assessing brain function in psychiatric disorders, predicting treatment outcomes, and identifying biomarkers for various neurological conditions (Prichep et al., 2006).

Prichep's research has been fundamental in identifying qEEG-based biomarkers for a range of neuropsychiatric disorders. For example, she has identified qEEG patterns that can assist in the diagnosis of conditions such as ADHD and depression.

She has also worked extensively on the use of the qEEG to assess traumatic brain injury, demonstrating that the qEEG can reveal brain abnormalities even when conventional imaging methods such as MRI or CT are normal (Prichep et al., 2013).

Prichep's work has greatly expanded our understanding of how the qEEG can be used to assess brain function and dysfunction. Her research has demonstrated the clinical utility of the qEEG and its potential for improving the diagnosis and treatment of various neuropsychiatric conditions.

Roberto Pascual-Marqui

Roberto Pascual-Marqui has made significant contributions to the field of qEEG, particularly in developing and applying techniques to analyze brain electrical activity. His research has helped enhance our understanding of how the brain functions in various physiological and pathological states.

Pascual-Marqui is perhaps best known for developing LORETA, a method used for localizing sources of brain activity based on EEG recordings (Pascual-Marqui et al., 1994). This technique uses scalp-recorded electrical activities to generate a 3D image of electrical activity within the brain. It is considered a significant advancement in EEG analysis because it helps identify the source of electrical activity with a high degree of precision.

Later, Pascual-Marqui developed a standardized version of LORETA, known as sLORETA, which improved the resolution of the original algorithm and removed the localization bias present in LORETA (Pascual-Marqui, 2002).

Pascual-Marqui also contributed to developing methods to assess functional and effective connectivity using qEEG data (Pascual-Marqui et al., 2011). His work included the use of linear and non-linear methods to understand how different brain regions interact, which is fundamental to understanding many neurological and psychiatric conditions.

Hershel Toomim

Hershel Toomim made significant contributions to biofeedback, particularly in the development of hemoencephalography (HEG).

His work focused on noninvasive monitoring of brain functioning using light in the wavelength region of 650 to 1000 nanometers, which can penetrate human tissue, including bone. In 1994, Toomim discovered that it was possible to measure and teach individuals to control the amount of oxygenated blood flowing in the prefrontal regions of the brain using an optical device. This method, termed hemoencephalography or HEG, represents a form of neurofeedback based on blood flow biofeedback.

HEG, as developed by Toomim, allows for the training of brain functions by providing feedback on cortical circulatory changes. This technique uses a biofeedback device that emits red light into the skull and detects changes in the returning refracted light, representing variations in cortical circulation. Toomim's discovery and subsequent research have been particularly influential in treating conditions like attention deficit hyperactivity disorder (ADHD) and other cognitive deficits, showing promise in improving attention, executive control, and other cognitive functions through neurofeedback training.

Toomim also developed the first standardized and calibrated systems spanning the measures of electromyography (EMG), temperature, galvanic skin response (GSR), and EEG.

J. Peter Rosenfeld and Elsa Baehr

J. Peter Rosenfeld and Elsa Baehr have made significant contributions to the field of neurofeedback and alpha asymmetry protocols, particularly in the context of treating mood disorders such as depression. Using operant conditioning programs, Rosenfeld and colleagues designed experiments demonstrating that cortical asymmetry (A-score) could be modified in subjects. This work laid the foundation for neurofeedback protocols to treat mood disorders (Hammond & Baehr, 2009).

Baehr, Rosenfeld, and colleagues conducted studies where depressed patients were trained to change their frontal alpha asymmetry to resemble non-depressed persons. This clinical application showed that alpha asymmetry neurofeedback training could be an effective adjunct to psychotherapy in treating certain mood disorders (Baehr et al., 1997).

Their research also includes follow-up studies assessing the long-term effectiveness of alpha asymmetry neurofeedback in treating mood disorders. These studies reported that patients who underwent neurofeedback maintained normal scores over time and showed reduced depression symptoms (Baehr et al., 2001).

Further extending their work, Baehr and colleagues explored the use of alpha asymmetry protocols in conditions like premenstrual dysphoric disorder (PMDD), showing the versatility of this approach in different clinical scenarios (Baehr et al., 2004).

Joel F. Lubar

Joel Lubar (1970s) was a psychologist who collaborated with Barry Sterman to extend sensorimotor rhythm biofeedback from epilepsy to attention disorders. He demonstrated that SMR training could improve attention and academic performance in children diagnosed with attention deficit hyperactivity disorder at the University of Tennessee. He was best known for this pioneering work in using neurofeedback to treat ADHD (Lubar, 1989; 1991; Lubar & Shouse, 1977).

He developed a treatment protocol that uses the qEEG to identify abnormal brainwave patterns and then trains individuals to modify these patterns through neurofeedback.

Lubar documented the importance of theta-to-beta ratios (the ratio of power in the theta and beta bands) in ADHD and developed theta suppression-beta enhancement protocols to decrease these ratios and improve student performance. His research has demonstrated the effectiveness of this approach in reducing symptoms of ADHD (Lubar, 2020).

Lubar contributed significantly to developing and refining qEEG techniques used in neurofeedback (Lubar, 1997). His work helped establish the scientific foundation for using neurofeedback in treating various neurological and psychiatric conditions (Monastra et al., 2001).

Judith O. Lubar

Judith O. Lubar was a psychologist at the University of Tennessee who, working alongside Joel Lubar, helped turn the laboratory findings on attention into a workable clinical treatment. As first author of a landmark 1984 study, she reported that enhancing SMR or beta activity while suppressing theta in a clinical setting improved school grades and achievement scores in six children with attention deficit disorders trained twice weekly for 10 to 27 months (Lubar & Lubar, 1984). The study reported no follow-up data, so its gains cannot be described as lasting beyond the training period.

Their protocol paired neurofeedback with academic tasks and showed changes in the EEG power spectrum that matched the behavioral improvements. This work moved EEG biofeedback for ADHD beyond isolated case studies and helped establish the clinical model that thousands of practitioners later adopted.

Jay Gunkelman

Jay Gunkelman's (Moss & Gunkelman, 2002) involvement in applied psychophysiology and biofeedback dates back to 1972 with the grant funding of the first state hospital-based biofeedback laboratory. Since the mid-1970s, he has specialized in the classical clinical EEG and is one of the world's most experienced EEG and qEEG specialists. Over his career, he has personally reviewed an extraordinary volume of clinical EEG and qEEG records, an experience base that informs his teaching and consultation.

He was instrumental in developing biofeedback and neurofeedback efficacy standards that have served as the foundation for the AAPB reference Evidence-Based Practice in Biofeedback and Neurofeedback. Known for his deep EEG knowledge and his ability to distill complex concepts into understandable terms, Jay has been one of the field's most influential educators and prolific authors, giving lectures, conducting workshops, and mentoring new professionals in the clinical and research application of the qEEG. The field is more inclusive and vibrant because of his tireless advocacy, especially on behalf of students and international colleagues.

Gunkelman has vast experience in interpreting qEEG patterns and has shared his insights and approaches to analysis on various platforms. His pragmatic approach has assisted countless clinicians and researchers in interpreting qEEG data and using it effectively (Gunkelman, 2020).

Gunkelman has applied his expertise to neurofeedback. He has played a critical role in demonstrating the application of the qEEG in this field, which has contributed to the understanding and effective use of neurofeedback techniques.

Robert Thatcher

Robert Thatcher is a key figure in the qEEG, with many significant contributions to its development and its practical applications.

Thatcher has been instrumental in creating normative databases for the qEEG, which provide reference standards for different age groups and conditions. These databases are used to compare individual patient data with normative values, which can assist in diagnosing a wide variety of neurological and psychiatric disorders (Thatcher et al., 2014).

Thatcher developed the NeuroGuide software, one of the most widely used tools for qEEG analysis. NeuroGuide incorporates Thatcher's normative database and provides user-friendly tools for qEEG analysis, including various measures of brain connectivity and functionality (Thatcher, 2010).

Thatcher has conducted extensive research on the application of the qEEG in assessing traumatic brain injury. His work has shown that the qEEG can reveal subtle abnormalities that are not visible in conventional imaging studies, which can contribute to diagnosing and treating TBI (Thatcher et al., 1989).

Thatcher has also contributed to understanding brain connectivity (Thatcher et al., 2005). His work has shown that the qEEG can be used to assess the functional connections between different brain regions, which can aid in understanding various brain disorders.

Robert Thatcher's work has significantly advanced our understanding of the qEEG and its clinical applications. His normative databases and analytical software development have played a critical role in enabling clinicians and researchers to apply the qEEG in a practical setting. His work on traumatic brain injury and brain connectivity has opened up new areas of research and has contributed to improved patient care.

Thomas F. Collura

Collura has significantly contributed to developing neurofeedback technologies, particularly in creating accessible and practical systems for the qEEG and neurofeedback. He founded BrainMaster Technologies, a company that produces hardware and software for neurofeedback, biofeedback, and qEEG analysis.

Collura has been influential in advancing z-score neurofeedback, a form of neurofeedback training that involves comparing a patient's brainwave patterns to a normative database and providing feedback based on the statistical difference, or z-score. His work has supported the practical application of this approach in a clinical setting (Collura, 2008; Collura, 2020; Collura et al., 2010).

Collura has contributed significantly to the field as an educator and mentor (Collura, 2013). He has delivered numerous workshops and lectures on the qEEG and neurofeedback and has also written extensively on these subjects. This has helped promote understanding and use of these methods among clinicians and researchers.

In summary, Collura's contributions have substantially impacted the field of qEEG and neurofeedback, both through his practical work in developing technologies and his theoretical work in promoting understanding of these techniques. His work in z-score neurofeedback, in particular, has greatly expanded the potential applications of neurofeedback in treating a wide range of conditions.

Juri Kropotov

Juri Kropotov has been instrumental in the development of qEEG normative databases. His work in this area has provided important reference data that can be used to compare individual patient data, contributing to the diagnosis and assessment of various neurological and psychiatric conditions (Kropotov, 2020).

Kropotov has significantly contributed to our understanding of ERPs (Kropotov et al., 2005). His work has demonstrated how ERP components can be used to gain insight into various cognitive processes and how deviations from normal ERP patterns can indicate the presence of certain disorders.

Kropotov has also conducted extensive research on the application of the qEEG in psychiatry, demonstrating its utility in understanding and diagnosing a wide range of psychiatric conditions, including ADHD, schizophrenia, and post-traumatic stress disorder.

Kropotov has significantly contributed to neurofeedback, demonstrating the efficacy of qEEG-guided neurofeedback in treating various conditions. His work has helped establish the scientific basis for using neurofeedback in clinical practice.

Overall, Kropotov's work has greatly advanced our understanding of the qEEG and its applications in clinical practice and research. His work in developing normative databases, understanding ERPs, applying the qEEG in psychiatry, and advancing neurofeedback has significantly impacted the field.

Cutting-Edge Topics in Quantitative Electrophysiology

The methods that now define the leading edge of the field arrived only in the last three decades, and they are still developing.

Quantitative Electrophysiology Timeline

The path from a twitching frog leg to a color-coded brain map ran through five nations, two world wars, and a succession of instruments that each made visible what the one before it had missed. The entries below place the people described in this chapter in sequence, so that you can see how discovery, instrumentation, and computation advanced together.

Assignment

From your perspective, which EEG researcher contributed most to qEEG development? Why?

Glossary

References

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Baehr, E., Rosenfeld, J., & Baehr, R. (1997). The clinical use of an alpha asymmetry protocol in the neurofeedback treatment of depression: Two case studies. Journal of Neurotherapy, 2, 10-23. https://doi.org/10.1300/J184V02N03_02.

Baehr, E., Rosenfeld, J., & Baehr, R. (2001). Clinical use of an alpha asymmetry neurofeedback protocol in the treatment of mood disorders: Follow-up study one to five years post therapy. Journal of Neurotherapy, 4, 11-18. https://doi.org/10.1300/J184V04N04_03.

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