Some recent advances in electroencephalography.

J. Neurol. 212, 185--204 (1976) © by Springer-Verlag 1976

Surveys of Progress Some Recent Advances in Electroencephalography Robert B. Aird and Bill Garoutte Departments of Neurology and Anatomy and the Eleetroencephalography Laboratory, University of California, San Francisco, California 94143 Received December 30, 1975

Key words: Electroencephalography - - Clinical Neurophysiology - - Cortical function Epilepsy. The older literature concerning the development of electroencephalography and the associated neuropathophysiology has been reported in excellent treatises such as those of Hill and Parr (1963), and Gibbs and Gibbs (1950, 1952, 1964), and the symposia edited by Jasper et al. (1969) and by Gastaut et al. (1969). The present routine use of the technique has been well summarized in books by Kooi (1971), Thompson and Patterson (1974) and Goldensohn and Kohle (1975). The present review cannot do individual justice to the thousands of E E G and physiological reports of the past decade. I t has been written as a selective review, following an outline as utilized below and with reference to a number of excellent monographs at appropriate places; these can be used to elaborate specific subjects. The interested basic or clinical scientist will want to consult recent numbers of Electroencephalography and Clinical Neurophysiology, and the newly published Handbook o/EEG and Clinical Neurophysiology (R6mond, 1971--1976). Io

a) Source of EEG Potentials From the earliest days, recorded E E G potentials have been presumed to reflect neuronal activity. As a result of much investigative work, this relationship is now generally accepted (Creutzfeldt and Houchin, 1974). Close correlations were early demonstrated between the abnormal spikes of convulsive activity and groups of neuronal unit potentials. In the resting E E G the correlation seemed less certain. However, multiple electrode recordings from cortex and from thalamus (CYeutzfeldt, 1963; Verzeano et al., 1970; Verzeano, 1973) have shown a clear statistical correlation between unit potentials from numerous neurons and the resting scalp EEG. Starting with laminar analysis of the hippocampus (Green et al., 1960), and extending to laminar analysis of the neocortex (Humphrey, 1968; Plonsey, 1969; Pubols and Pubols, 1971 ; Prince, 1971), investigations have led to the conclusion that large numbers of excitatory and inhibitory post-synaptic potentials (EPSP's or IPSP's) which occur more or less simultaneously produce membrane potential changes on the deep ends of a mass of neurons, and result in E E G potentials at

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their superficial ends. Averaging of the surface cortical potential fields is reflected to the scalp by volume conduction. A close correlation has been demonstrated between maturation of dendrites in the upper cortical layers and the development of E E G waves (Scheibel and Scheibcl, 1964).

b) Rhythmicity o/EEG Activity Four processes have been described which may give rise to rhythmically varying neuronal potentials. Probably all of these processes take part in producing E E G rhythms, but in differing degrees in different situations. 1. Reverberating Circuits Studies by many workers, in vertebrate and invertebrate species, and in many portions of the central nervous system have demonstrated paired groups of neurons which interact reciprocally, by way of action potentials passing back and forth, to produce a continuous train of rhythmical potentials at constant frequency (Tsukahara et al., 1973; Getting and Willows, 1973; Freeman, 1974). 2. Reverberation through Inhibitory Rebound (Exaltation) The papers of Andersen ct al. (1964) and of Eccles (1965) elaborated the model of post-inhibitory rebound rhythmicity which is now generally accepted. This process appears important in the production of thalamo-cortical E E G activity. Further discussion of the thalamo-cortical relationships is included in Andersen and Anderson's monograph on the alpha rhythm (1969). Thalamic spindle activity at 8 to 10 per second seems to result from interrupted sequences of IPSP's lasting 100 to 120 ms. During the IPSP's, the neurons are prevented from firing. Action potential discharges occur only on the potential crests between successive IPSP's. 3. The Relaxation Oscillator Model I t has been hypothesized that random volleys of action potentials impinging upon a collection of neurons might produce summation of EPSP's, sufficient to surpass the threshold of many of the neurons. The resultant discharge would be followed by a refractory period, after which the continuing input repeats the process. Because many neurons are interacting, their individual variability averages out, and the resultant action potential volleys occur rhythmically. Such sequential discharges have been proposed in explanation of the "hypersynchrony" of convulsive discharge. Verzeano et al. (1970) have studied this phenomenon in the amygdala during development of seizure discharge. Single-cell relaxation oscillators, such as in cardiac muscle, which operate as a result of ionic leakage through the cell membrane, with gradual depolarization and eventual rhythmic discharge, have not been described in the mammalian nervous system. 4. Electrical Oscillation of Neuronal Membranes Eccles (1957) derived a frequency in the alpha range from experimentally obtained resistance and capacitance of cat's anterior horn cells. This suggests that neuronal membranes may have an intrinsic electrical resonant frequency, and that the normal perturbation of membrane potentials will tend to induce this or

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harmonically related frequencies. This possible source of the brain's rhythmic activity also remains inferential.

c) Bilateral Synchrony o/EEG Activity I t was early recognized that E E G waves occurred simultaneously on the two sides of the normal brain. Mutani et al. (1973) have reported experiments suggesting t h a t the corpus eallosum plays an important role in this kind of activity. The papers by Gloor (1968, 1972), McNaughton and Andermaun (1970), and the monograph edited by Gastaut et al. (1969) provide further information on this mechanism and confirm the obsolescence of the older "centrencephalic" concept. Finally, experiments by Petsche and Rappelsberger (1970), Petsche et al. (1975) and others have defined the parameters of propagation of E E G activity over the surface of the cortex. This phenomenon also appears to be complex, and depends both on intra-cortical transmission from point to point and on thalamic connections. Multiple electrode recording such as used by Verzeano (1973) seems a likely source of future clarification. The probable presence of electrical synapses (Gap Junctions) within the mammalian cortex provides another important pathway for local synchronization of neuronal activity (Mollg&rd and M~ller, 1975).

d) Slow Potentials Recordedby Direct-CoupledAmplifiers I t was not until the early 1950's that Direct-Coupled (D-C) amplifiers of sufficient stability became available for the recording of slowly-changing potentials from the brain (Goldring et al., 1950; KShler et al., 1952). The initial years of development of this technique have been summed up in a review of O'Leary and Goldring (1964). The slow potential changes noted in response to electrical or physiological stimulation of the cortex appear to be the summation of large numbers of excitatory and/or inhibitory post-synaptie potentials. In addition, changes in the membrane potentials of glia cells occur, and in many instances account for the slow potential changes (Grossman et al., 1969). Cortical laminar analysis of evoked slow potentials fails to show the reversal expected if the potentials arose entirely from radially-oriented dipoles. This suggests that the non-oriented glia m a y be the most important source of these cortical potentials (Castellucei and Goldring, 1970). II. Instrumentation and Procedures

a) FrequencyAnalysis As a logical approach to a rhythmic phenomenon, the analysis of EEG's into component frequencies was first assayed in the 1930's (Loomis et al., 1936 ; Dawson and Walter, 1944). Such analyses continue to the present. Through the use of elegant modern equipment and sophisticated techniques (Matou~ek, 1973), tremendous volumes of data have been collected, but surprisingly little of basic physiological value or of clinical significance has been achieved.

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Electronic frequency analysis, however, does provide a means for comparison of the frequency characteristics of E E G epochs under different physiological or clinical conditions. Unfortunately, in the reduction of large amounts of data by the computer, brief transient wave forms, which may be of primary clinical significance, can be missed. Moreover, none of the ususal methods of frequency analysis distinguish clearly between such obviously important differences as a small amount of high voltage activity and a long run of low voltage activity of the same frequency. The attempt to correlate frequency patterns with psychological or psychiatric disorders is complicated by still other factors. Kennard et al. (1955) and others have concluded that the increased amount of beta activity in the EEG's of many psychiatric patients is occasioned by their anxiety--i.e., was a non-specific response. Rodin et al. (1968) and others (Giannitrapani et al., 1974) have emphasized another problem in such correlations, e.g., the vagueness and inconsistency of psychiatric diagnosis. A technique that shows more promise is the "Compressed Spectral Analysis" (Bickford et al., 1974; Bourne et al., 1975), which makes it possible to view the pattern of E E G variability over several hours, compressed by the computer to one page.

b) Correlation Analysis Beginning with some of the earliest studies, attempts have been made to correlate the time, phase, and amplitudes of E E G rhythms from various parts of the brain. This was done by hand at first, and this is still a valuable method, in view of the great variability of rhythmic patterns. Many types of electronic equipment have been developed to carry out the desired correlations. Time, phase, and amplitude relationships between waves at different locations over the cortex have been most widely studied. The times of occurrence of alpha and other activity have been compared (Garoutte and Aird, 1958; R@mond, 1968; Petsche and Shaw, 1972), from side to side, longitudinally, or both, in order to study the patterns of change from moment to moment. Waves have been correlated with earlier waves from the same location ("auto-correlation"~ Barlow and Estrin, 1971). Finally, by means of several types of computerized analysis, the patterns of all potentials in a single region, or in a linear sample, or even from the entire available cortex, have been displayed to provide large amounts of data on the various possible inter-relationships. I t has been deduced from correlation analyses that EEG rhythms do not depend upon a single mode of production and transmission. The interconnections of the cortex with the thalamus, commissures and brain stem all participate in determining the rhythm, frequency relationships within one hemisphere, and the synchrony between the two hemispheres. Likewise, the effects of lesions, either in the cortex or its subcortical connections, act to modify the cortical E E G patterns. A recent interesting example of these techniques has been devised by Chapman and Evans (1975). Using computerized harmonic analysis of potentials from 102 scalp electrodes, they are able to display the probable potential distribution on the actual surface of the cortex.


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c) Computer Averaging The use of electrical averaging techniques for the detection of physiological transients was initiated by Dawson (1951). His pioneer apparatus stored timelocked electrical information in condensers. The number of condensers (60 "storage bins") was limited by the mechanical restrictions of the rotating armature he used. Electronic sorters and storers that are usually digitized are now available, and use solid-state integrated circuits, magnetic storage and transistorized timing and sorting circuits. With such commercially-available computers, it is possible to store 4000 bins of information in a computer that is small enough to transport by hand, simple enough for routine laboratory use, and inexpensive enough for purchase by most large medical centers. Variations of physiological responses can be averaged out and recorded, thus providing information that often can be used clinically. Some specific applications will be discussed in the section on Evoked Potentials. All averagers lose much of the variation from response to response, without which many important characteristics of variable organic function cannot be recognized. However, additional electronic selection processes can be used to take specific variables into account. For example, the equipment may be adjusted to record only responses which occur in one specific physiological context, rejecting all others.

d) Electrode Placement The international 10---20 system for the placement and numbering of electrodes unfortunately does not include Anterior Temporal electrodes. Most laboratories using the system, therefore, do not routinely record from this region of cortex, which has been shown by many workers to be one of the most common sites of E E G abnormalities. Although a high percentage of Anterior Temporal abnormalities can be detected with Frontal and other adjacent electrodes (Silverman, 1960), this is not uniformly true. Because cortical potentials are attenuated severely with scalp recording from any site (Goldensohn et al., 1970), optimal locations such as the Anterior Temporal regions clearly should not be ignored. In an effort to record the frequent abnormalities to be found in or deep to the Anterior Temporal regions, many laboratories insert naso-pharyngeal electrodes or sphenoidal needles. The Anterior Temporal deficiency and some other problems with the 10--20 system have been outlined in the Handbook o/EEG and Clinical Neurophysiology (MacGillivray et al., 1974). Although not originally adopted with the idea of establishing a rigid system that could not be amended, because of the force of conformity the 10--20 system appears to have attained this status. Naso-pharyngeal recording shows abnormalities from the mesial temporal cortex in a small percentage of temporal lobe patients whose Anterior Temporal scalp recordings are non-contributory. Insulated stiff wire electrodes are inserted through the nasal cavities to contact the superior-lateral aspect of the nasopharynx of either side. The bare electrode tips, when properly plac_ed~ lie.$10s~$o, the medial gyri of the inferior temporal lobe, i.e., within LS.ta~.0o~m ofth6 uncus.The uncus, underlying limbic system structur~s,,and~i~ particular the amygdaloid

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nuclear complex, probably account for the largest single source of convulsive potentials. These may be recorded with naso-pharyngeal leads, often most effectively during light sleep. For more details on the E E G of the amygdalo-hippocampal complex, see the discussion of Temporal Lobe Epilepsy (Section III.c.2). Sphenoidal electrodes are still used on occasion (Townsend, 1968) despite the expense, the necessity of insertion by a medically-qualified person, and the relatively small yield, quoted as 3~o of their 250 patients by Pampiglione and Kerridge (1956). Experience suggests that many different techniques may be of value in special instances, but, when the diagnostic yield is small, their value should be weighed against the difficulties and risks attendant upon their use. As in other medical situations, such limited techniques should not be employed routinely, but reserved for those problem patients whose medical findings warrant their special use.

e) Depth Recording Much clinical and experimental work has been reported in recent years on the use of surgically-placed depth electrodes (Bancaud et al., 1973), usually inserted for the identification of epileptogenic foci. The temporal lobe has been studied in particular (Adams and Rutkin, 1969). Stereotaxic techniques have also been used for depth recording and for the destruction of foci showing abnormal EEG activity (Buser et al., 1973; Ojemann and Ward, 1975). Electrodes placed in various parts of the human brain in search of abnormal electrical activity have provided valuable opportunities for E E G investigation. Because of the practical and ethical restrictions of making a complete survey of deep electrical activity in any patient, the data have at best been partial. Nevertheless, much has been learned, such as the existence of important epileptic foci not suspected from surface recordings, the existence of two or more deep secondary loci, or of bilateral foci (Nashold et al., 1973). All of these are clinically important, since they may diminish the chances of successful removal of a primary lesion. In addition, responses to physiological variables and interesting subcortical interactions have been studied in these patients.

/) Contingent Negative Variation; Readiness Potentials Averaging over a very low frequency range by means of direct-coupled amplifiers has demonstrated responses lasting several seconds from various cortical areas, which appear to be associated with volitional intent to perform a motor act or to respond to a future sensory stimulus. The Contingent Negative Variation is a potential that may endure for several seconds and follows an initial stimulus when a second stimulus is expected by the subject. This potential ordinarily occurs over the central sensory cortical region. When a specific motor response, such as pushing a button, is required at the time of the second stimulus, the Contingent Negative Variation occurs in the precentral motor region (Knott and McCallum, 1973; McAdam, 1974; Cohen, 1974). Moreover, recent studies have shown that if the subject merely thinks about receiving a stimulus, a slow Readiness Potential (Bereitsehaftspotential), may appear in the parietal region (Kornhuber and Deeke, 1965). Thinking about performing a motor action will induce a similar Readiness Potential in the frontal


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cortex (Donchin et al., 1971). These potentials differ in location from the cortical projection areas, and from the potentials associated with the actual movement or sensation.

g) Evoked Potentials Peripheral sensory stimulation evokes a sequence of E E G waves in the cortex. Because they are of low voltage, and as a rule hidden by the spontaneous E E G activity, they usually can be detected only by averaging responses to a large number of identical stimuli (Donchin and Lindsley, 1969). B y computerized averaging, evoked potentials can be recorded in response to somatesensory, visuM, or auditory stimulation (see also Section II.c). The patterns of cortical waves evoked by sensory stimulation are generally similar for various modalities, but differ between individuals. As is so often the case in neurology, the interpreter of Average Evoked Responses finds it necessary to compare the "abnormal" with the presumed "normal" side as a control. In multiple sclerosis, the Visual Evoked Response may provide useful evidence of a lesion in the optic pathways (Halliday et al., 1973) even when the patient does not complain of visual disturbances (Asselman et al., 1975). The identification of auditory evoked responses from all components of the auditory pathway (Jewett, 1970 ; Jewett and Williston, 1971 ; Picton et al., 1974) offers exciting possibilities for the analysis of sensory pathways. Chatrian et al. (1975) demonstrated evoked responses from human cortex after the painful electrical stimulation of dental pulp. They found two response fields. The first was in the expected post-central region and the second in the midline precentrally. The latter is interesting in that it m a y be correlated with the known double projection of pain. Visual and auditory evoked responses can be useful in documenting the intactness of the peripheral sensory pathways in babies and comatose patients who are unable to communicate.

h) Telemetry The wireless transmission of E E G activity from a moving, unrestrained patients has depended on the development of small, light, and stable apparatus capable of accurately reproducing the wave forms. This has become possible with advances in solid state electronics (Vreeland et al., 1971; Geier, 1971). Direct correlations between specific events in the patient's life and convulsive E E G changes have exciting therapeutic possibilities that are not yet fully exploited. The technique remains expensive and difficult. HI. Clinical Correlations

a) Basi~ EEG Patterns of Diagnostic Value The E E G patterns of clinical diagnostic interest were largely defined before 1965. There have been a few new observations , and a great many of the older observations habe been refined and brought into concord with changing clinical concepts. Alpha activity remains as fundamentM as when originally described by Berger. Its symmetry or asymmetry can be useful for localizing abnormalities: the uni-

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lateral absence of alpha, or the lack of change of alpha amplitude with attention, suggests the site of abnormality. Paroxysmal slowing, sometimes of the so-called "triphasic" form, often accompanies metabolic encephalopathies. This pattern has most commonly been associated with liver disease, but may occur with uremia, or with metabolic brain damage of other origins (Bickford and Butt, 1955; Laidlaw and Reed, 1961). The exact chemical abnormalities associated with these E E G changes are only partially understood hyperammonemia may be important in some instances (Foley et al., 1952; Cole et al., 1972). Lateralized spiking potentials (Periodic Lateralized Epileptiform Discharges) may accompany the acute insult of a focal cerebral infarct (Chatrian et al., 1965). Bilateral frontal slow activity often accompanies deep lesions. The E E G patterns of normal and abnormal sleep have been the subject of numerous reports. The various stages of sleep have been thoroughly identified electrophysiologically (Rechtschaffen and Kales, 1968), and many correlations with other physiological events have been documented (Dement and Kleitman, 1957; Peter-Quadens and Schlag, 1974). The EEG analysis of sleep stages, the sequence of sleep stages during normal and abnormal sleep studied by all-night recording, polygraphic testing of patients with narcolepsy and other disorders of sleep mechanism have become routine procedures in many laboratories of clinical neurophysiology (Williams et al., 1974). The observation that narcoleptic patients in their spontaneous sleep episodes go directly from the wake state to the stage of Rapid Eye Movement (REM) sleep, has cast new light on this puzzling syndrome, as well as aiding diagnosis in many instances (Dement et al., 1966). A normal individual on going to sleep usually passes through Stage I I or deeper stages of sleep before returning, after an hour or so, to the REM level. Investigations of the neurophysiology of sleep in experimental animals have shown that REM sleep and Slow Wave Sleep are under the control of different ponto-medullary centers (Petitjean and Jouvet, 1970). Dysfunction of these centers therefore may result in various clinical disturbances of sleep. Striking changes of Slow Potentials (see Section I.d. of this Review) during the sleep cycle have been reported by many authors (Tabushi et al., 1966). Some investigators have suggested that the slow E E G activity of Slow Wave Sleep may derive from glial potentials (Bechtereva, 1974). The presence of excessive generalized slow activity in the waking state in individuals beyond the first decade of life remains a clue to diffuse but non-specific abnormalities. Studies of neonatal and childhood EEG's have been numerous and have established the limits of normality at various stages of early cerebral development (Hagne, 1972; Engel, 1975). The 14- and 6 per second "Positive Spike Phenomenon" seems to have lost its original interest, and now is generally regarded as a relatively common normal variant in childhood (Hughes, 1965; EegOlofsson, 1971). b) Coma and Death With the development of effective methods of maintaining cardiac and pulmonary function, survival of the human body has been considerably extended, even


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when the brain has suffered irreversible damage due to anoxia, metabolic disorders, toxins, t r a u m a or other causes. The anatomical seat of consciousness ("the mind", "the personality") resides in the cerebral cortex in association with thalamie nuclei such as the pulvinar, and possibly the eaudate nucleus. I f the cortex is nonfunctioning, the patient will be in coma, and if it is permanently non-functioning, the patient will be capable of only a vegetative existence, despite the adequate function of other body organs. Such patients often pose intolerable burdens of agony and expense to family, friends, and those caring for their medical needs. " I s the patient dead .~" is the question t h a t must be answered in these instances. The idea has gained considerable, although not universal, acceptance t h a t a "dead brain" means a "dead person", regardless of the physiological state of the heart or other organs. E E G has become one of the most important tools for evaluating the viability, and the prognosis for life, of patients in coma (Fischgold and Mathis, 1959; Bennett et al., 1975). Transplant surgery has greatly accentuated this problem. The extension of the useful life of one person b y transplantation of a kidney or other organ from a recently dead person constitutes one of the modern "miracles" of medicine. However, the definition of death assumes immediate and practical medical importance in this situation, since the removal of a vital organ from a person who is not yet dead must be construed as homicide. The general problem has been investigated in most countries of the world. The Russian experience has been summarized b y Negovskii (1965), and a series of criteria have been proposed in America for the definition of death (Harvard, 1968; Silverman et al., 1969), in which the evaluation of the E E G plays a prominent role. Such criteria are necessarily statistical constructs, and the individual patient's problem must always be evaluated b y clinicians in immediate contact with the patient. After prolonged consideration of this problem, the American Neurological Association at its 1975 meeting came to the conclusion t h a t specific, final criteria for the definition of death were inadvisable and should not be given the sanctity of law. E E G ' s of comatose patients m a y take a number of different forms. They m a y show the slow wave patterns characteristic of sleep. They m a y be fiat ("isoelectrie"), in which case the clinician will often feel justified in presuming cortical death, provided the patient has not been sedated and body temperature is normal. The comatose E E G m a y also appear in a number of interesting patterns whose pathophysiological nature remain unknown. One of the most startling is the "suppression-burst" pattern, first noted as a concomitant of certain encephalitic processes (Cobb and Hill, 1950 ;Radermecher, 1956), but more recently documented in association with diffuse cerebral and cortical damage of m a n y types, such as Jakob-Creutzfeld disease (Lesse et al., 1958) and patients with massive cerebral insult from anoxia (Prior, 1973) or trauma. A similar pattern has been found in normal neonates, particularly if premature. I n such babies, the pattern is usually called trace alternant (Dreyfus-Brisac, 1964). Extrapolating from animal studies, it is exciting to conjecture t h a t the Suppression-Burst pattern m a y result from a relative disorganization or lack of synaptic interconnections in neonates, and for similar reasons as a result of extensive cortical insult in older patients with this pattern.

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Some patients in coma associated with severe cortical damage show an alphalike E E G pattern over all cortical areas. This "alpha-like" activity is completely unresponsive to any physiological stimulation, in contrast to normal alpha. Almost all such patients die within a few days or weeks (Vignaendra et al., 1974). The process through which this pattern develops is completely unknown. Perhaps further studies on this subject will aid in elucidating another unknown, the origin of normal alpha activity.

c) Convulsive Disorders 1. Clinical Neurophysiology The principal application of EEG has been its study of convulsive phenomena. This section will cover recent basic and clinical neurophysiological data on this subject. The high frequency and paroxysmal E E G discharge that characterizes epileptic phenomena has been shown to be due to the hyper-excitability of epileptogenic neuronal populations (Schmidt et al., 1959). E E G spiking is associated with depolarizing neuronal potentials, and with the motor manifestations of seizures. The slow wave component of the E E G sequences recorded from the neighborhood of epileptogenic loci has been shown to be due to hyperpolarizing inhibitory potentials, probably arising from recurrent collaterals (Prince, 1971). This has suggested, among other things, a balanced relationship between excitatory and inhibitory mechanisms which may serve to suppress focal epileptic discharge and thus maintain normal neuronal function (Prince and Wilder, 1967). The discharge of epileptogenic neurons is associated with the depolarization of resting membrane potentials (Paroxysmal Depolarization Shift, or PDS, Matsumoto et al., 1969; Prince, 1971), which results in high frequency neuronal discharge and E E G spikes. Experimental models of epilepsy have suggested that these cortical potentials are synaptic in origin (Schmidt et al., 1959; Morrell, 1969). Ward (1969) has suggested that the PDS occurs in partially deafferented neurons. He has shown that the dendrites of epileptic neurons, both in experimental animals and in humans, possess fewer synapses than normal dendrites. I t is tempting to hypothesize a direct relationship between this anatomical change in the neurons with their presumed decrease in inhibitory synaptic input, and their hyperexcitability as manifested through Paroxysmal Depolarization Shifts. Neurons in cortical isolation experiments become hypersensitive and develop spontaneous epileptiform activity. This also could be due to partial deafferentation. Torres (1972) has shown that ephaptic conduction can occur across the sectioned boundaries of small cortical isolates in only one direction, from the outside to the inside of the isolated slab. This finding suggests that such spread depends upon volume conduction, which is ineffective in small isolated preparations, but effective in larger preparations. The epileptogenicity of isolated masses of neurons, therefore, would appear to depend upon the number of neurons involved and their relations with other abnormal cortical regions, as well as the degree of their hypersensitivity. The importance of independent secondary E E G loci, in the same hemisphere or in the opposite hemisphere ("mirror foci"), has been documented in epilepsy by many workers. Such loci have usually been assumed to result from excessive


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bombardment from a eontralateral primary focus. However, the situation seems to be more complex than this. Aird and Garoutte (1960) showed that a high percentage of mirror loci are neither permanent nor independent. This was true in both epileptic and non-epileptic patients, with chronic and marked primary foci. Other more recent studies have also questioned the importance of independent mirror loci in humans, and now Morrell (1969) has reported experimental evidence suggesting that independent secondary foci require at least two sources of abnormal synaptic input, and that trans-callosal input alone is not enough. Other secondary cortical and subcortical loci have been studied (Wilder et al., 1969). Considering the usual diffuse pathology of most epileptic brains, multiple secondary loci may be common, as demonstrated in E E G studies at surgery and with depth recording (Bancaud et al., 1973). Repetitive epileptic discharge m a y produce secondary effects in still another way. Experimental intermittent electrical stimulation at subconvulsive intensities (Goddard et al., 1969) produces after-discharges of gradually increasing duration in the cerebral region stimulated. This "kindling" effect has been demonstrated in many regions and eventually results in clinical convulsions. The number of intermittent stimulations required to reach this end-point varies widely from region to region. In the most sensitive structure, the amygdaloid nuclear complex, daily subconvulsive electrical stimulation produced clinical convulsions after about 15 days in rats. 2. Temporal Lobe Epilepsy A large proportion of convulsive patients have E E G loci in the temporal lobe (Baldwin and Bailey, 1958 ; Aird et al., 1967), and the resulting syndrome is often confused with other types of convulsive disorders (Aird and Tsubaki, 1958). Feindel and Penfield (1954) demonstrated that the abnormality of temporal lobe epilepsy lies in the amygdaloid-hippocampal complex. Because of the common occurrence of such abnormalities, and the low convulsive threshold of this complex to many kinds of insult (Aird and Woodbury, 1974), E E G studies of patients with convulsive disorders should always include electrodes overlying these cortical regions (cf. Section II.e. on Electrode Placements). On the other hand, abnormalities may not be detectable with surface recording even in the presence of convulsive activity of deep temporal lobe structures documented by depth recording (Baneaud et al., 1973). Depth recording also has revealed that in many patients with temporal lobe seizures the E E G loci are bilateral (l~ashold et M., 1973). Bilateral surgical removal of such foci is inadvisable because of the possibility of inducing the Kltiver-Bucy syndrome. Davidson and Falconer (1975) have recently reviewed their handling of these difficult problems. 3. Provocative Procedures The correlations between clinical and E E G findings have been supported by studies on all races and from all parts of the world for both focal and generalized convulsive disorders of all types (Gastaut et al., 1969, 1975). Provocative procedures, such as hyperventilation, photic stimulation, and the use of neuro-active drugs, continue with minor variations in technique and the use of some new agents.

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Studies of the mechanisms through which hyperventilation causes significant changes in the normal or abnormal E E G have led to two suggestions: 1. Changes in the pH of the internal milieu of cerebral arterioles, as produced by the hypocapnia of deep breathing, results in vasoconstriction. This diminishes the supply of blood and oxygen to the brain, and the hypoxia provokes the E E G changes (Meyer and Gotoh, 1960). 2. The change in p H acts directly on the membranes of neurons, synapses and glia to alter their electrolyte balance and this changes the EEG. The relative contribution of the two mechanisms and their degrees of individual variability remain uncertain. Intermittent photic stimulation probably changes the reactivity of abnormal cortex directly through synaptic mechanisms, perhaps related to Paroxysmal Depolarization Shifts. Corticoreticular connections may also be of significance (Hess et al., 1974). Pentylenetetrazol was used for many years to provoke spiking in convulsive patients, often in combination with intermittent photic stimulation. However, the drug's effects show a broad overlap between normal and convulsive individuals, which greatly limits its diagnostic value. Bemegride has been used in the same way (Danielson and Ellebjerg, 1966), but its use has largely disappeared for similar reasons. Rapid-acting barbiturates, such as Methohexital, have recently become popular. Methohexital rarely causes convulsions, which was one of the major disadvantages of the drugs mentioned in the previous paragraph, and seems to reveal epileptic foci with relatively few false positives (Fenton and Scotton, 1967). Further clinical evaluation seems indicated. Loading doses of anticonvulsant drugs (phenytoin, trimethadione) to normalize the E E G abnormalities associated with epilepsy was suggested early as a diagnostic test. Such procedures are rarely used now because of the dangers of toxicity and their failure to produce a clearly defined end-point. However, it has recently been reported (Ferngren, 1974) that small doses of diazepam, injected intravenously, may change epileptic EEG patterns toward normal and that toxic effects are unlikely if the drug is given carefully. Injections of pyridoxine (Vitamin B-6) has resulted in sudden decreases of epileptiform E E G activity in a few children, presumably in deficiency states. While the yield is small, the injection is safe, and is worth trying as a therapeutic test when there is a possibility of inadequate diet in convulsing children (Hunt et al., 1954; Tower, 1969). Hypoglycemia, either from fasting or after insulin administration, may provoke abnormal E E G potentials (Aird and Adams, 1952; Gastaut et al., 1968) but is rarely used because of its nonspecificity. On the contrary, the patient is often given a drink of sweetened fruit juice before E E G recording, to prevent hypoglycemic E E G changes which may occur in normals as well as abnormals. Sleep as a "provocative" procedure has proved its worth many times over, although the labelling of this normal process as "provocative" is historically rather than physiologically justified. The appearance of focal spiking potentials in light sleep has been known for 25 years (Fuster and Gibbs, 1948). This has been


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particularly noted in the anterior temporal regions, but is not restricted to that location. Sleep-inducing drugs, whether sedatives such as barbiturates (e.g., methohexital, as mentioned above), benzodiazepines, antihistamines, or others, appear to affect the E E G primarily as soporifics without drug-specific provocative effects. On the other hand, some of these agents, and especially the neuro-active drugs (such as diazepam) provoke more than the usual amount of fast activity in the first stage of sleep in some individuals. The focal absence of this fast activity has been correlated with focal abnormalities (Hirt, 1968; Kooi, 1971).

d) Degenerative Diseases o/the Central Nervous System The most striking new information on degenerative diseases is the demonstration that some have viral etiologies. Both K u r u and Creutzfeldt-Jakob disease has been transmitted between chimpanzees after inoculation with brain substance from an affected human (Gibbs et al., 1968). The E E G in Creutzfeldt-Jakob disease, as in most of the so-called degenerative diseases, initially shows excessive slowing that is usually generalized. When the disease reaches incapacitating severity, the E E G may assume a suppression-burst pattern. In subacute sclerosing pan-encephalopathy the E E G does not differ greatly from that mentioned in the previous paragraph, but often shows the suppressionburst pattern prior to death (Farrell et al., 1971). No new E E G observations have been reported recently with multiple sclerosis. The presence of a lesion of the subeortical white matter can often be detected as an E E G slow wave focus and this sometimes is of diagnostic value in demonstrating another unsuspected central nervous system lesion. Except for such lesions, and even rarer epileptiform activity, the E E G in multiple sclerosis is usually normal or shows only mild slowing. Viral encephalitis may induce slow wave E E G changes or suppression-burst patterns. Herpes simplex encephalitis involves the temporal lobes in most patients, and is often associated with gross focal E E G slowing in the temporal regions (Illis and Taylor, 1972; Gupta and Seth, 1973). Reye's disease, which has been demonstrated to follow systemic viral influenza in almost every case, is another "degenerative disease" of the nervous system of c h i l d r e n with a bad prognosis (Reye et al., 1963; Tang et al., 1975). The same early E E G slowing and late suppression-burst patterns commonly occur in these patients. Childhood encephalopathies with dementia may result from several etiological factors, and often show the giant spikes of " H y p s a r r h y t h m i a " on E E G recording (Jeavons et al., 1973). e) The EEG in Patients with Brain Tumors In past years, most neurosurgeons have been less than enthusiastic clinical use of EEG. The procedure does not provide the specific information required for adequate surgical approaches. I t does not vascularity of a lesion as does an arteriogram, nor does it usually

about %he diagnostic define the define the

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extent of a lesion as well as radioactive brain scans. Nevertheless, as an innocuous method for the initial determination of focal abnormality, and for follow-up purposes after therapy (Bancaud et al., 1973), E E G can be valuable. The follow-up value has again been emphasized in connection with the recent developing interest in chemotherapy for brain tumors. IV. Comments about Future Possibilities

Routine clinical E E G recording has by now reached a stable level of acceptance, understanding and usefulness. Applications of E E G techniques to new medical uses, such as chemotherapy for brain tumors, are in the process of development. Ancillary measures, such as specific drug effects, evoked response studies, the direct-coupled recording of slow or steady potentials, and the use of readiness and contingent potentials m a y develop into valuable diagnostic tools. Polygraphic studies, with the addition of electronystagmography, electromyography, electroretinography, skin resistance changes, electrocardiography and other recording procedures to the routine E E G recording will no doubt be used more often for the evaluation of patients with sleep problems and with other undiagnosed neurological or psychiatric disorders. An inherent restriction to the clinical and physiological usefulness of E E G is its statistical nature. Potentials recorded from the scalp represent the average of millions of neuronal potentials. Even an electrode applied directly to the cortex or inserted into the brain depths at surgery records from tens of thousands of neurons. Although microelectrodes can record from a few neurons if placed extracellularly or from a single neuron intracellularly, this is not a practical technique even for corticography during neurosurgical procedures. Early hopes t h a t E E G might show correlations with specific types of pathology have not been realized. The nonspecific and limited responses t h a t neurons and synapses are capable of, as well as the specific problems discussed in the previous paragraph in large part explains this limitation. Another kind of sampling problem arises in the detection of transient neurophysiological phenomena. This problem becomes excessive in brief recording sessions, but is largely overcome by more prolonged periods of recording, the use of m a n y channels which permit longer recording from the recorded scalp areas, and b y telemetry. The spacial limitations of E E G are also considerable. Less than half of the total cortical area is available to scalp recording. This limitation has been only partially overcome by corticography, the use of indwelling electrodes, and depth recording. Fortunately, the main cortical projection areas are available to routine E E G recording. Other limitations of EEG, such as the technical failure to utilize enough electrodes, electrodes inaccurately placed, and errors of interpretation have been mentioned (Goldensohn and Koehle, 1975). Despite all these limitations, EEG, when conscientiously performed, remains the best technique for the evaluation of epilepsy and similar neurophysiological disorders, and m a y be expected to improve with the development of cheaper and more effective equipment for telemetry.


199

T h e use o f c o m p u t e r s for t h e r o u t i n e a n a l y s i s o f E E G t r a c i n g s h a s been a d r e a m of e l e c t r o e n c e p h a l o g r a p h e r s for years. This d r e a m seems no n e a r e r f r u i t i o n t h a n i t was 10 y e a r s ago. T h e h u m a n eye a n d b r a i n h a v e a f a c i l i t y for r e c e p t i o n , analysis a n d s y n t h e s i s of c o m p l e x i n f o r m a t i o n t h a t , while t h e o r e t i c a l l y possible for a m i c r o m i n i a t u r i z e d electronic c o m p u t e r o f billions o f p a r t s , is n o t l i k e l y t o be d e v e l o p e d soon. As someone a p t l y c o m m e n t e d , " T h e h u m a n b r a i n is t h e o n l y c o m p u t e r which can be r e a d i l y m a n u f a c t u r e d w i t h u n s k i l l e d l a b o r " .

References

For additional bibliographies, the reader is referred to the KWIC indices to EEG literature for 1964--1966 (Wineburgh and Walter, 1971:5778 titles) and for 1966---1969 (Walter, 1970: 8026 titles) and to the Indices to Current Literature published every few months in the EEG Journal. Adams, J. E., Rutkin, B.: Treatment of temporal lobe epilepsy by stereotaxie surgery. Confin. neurol. (Basel) 31, 80--85 (1969) Aird, R. B., Adams, J. E. : The localizing value and significance of minor differences of homologous tracings as shown by serial E.E.G. studies. Electroenceph. clin. Neurophysiol. 4, 45---60 (1952) Aird, R. B., Garoutte, B. : Propagation of epileptic discharge as revealed by activated E.E.G. Epilepsia 1, 337--350 (1960) Aird, R. B., Tsubaki, T. : Common sources of error in diagnosis and therapy of convulsive disorders. J. here. ment. Dis. 5, 40(0--406 (1958) Aird, R. B., Venturini, A. M., Spielman, P. 1~I.: Antecedents of temporal lobe epilepsy. Arch. Neurol. 16, 67--73 (1967) Aird, R. B., Woodbury, D. IV[.: The management of epilepsy. Springfield (Ill.): Charles C. Thomas 1974 Andersen, P., Anderson, S. A. : Physiological basis of the alpha rhythm. New York: AppletonCentury-Croft 1969 Andersen, P. J., Eccles, J. C., Sears, T . A . : The ventro-basal complex of the thalamus: Types of cells, their responses and their functional organization. J. Physiol. (Lond.) 174, 370--399 (1964) Asselman, P., Chadwick, D. W., Marsden, C. D. : Visual evoked responses in the diagnosis and management of patients suspected of multiple sclerosis. Brain 98, 261--282 (1975) Baldwin, M., Bailey, P. (eds.) : International colloquium on temporal lobe epilepsy. Springfield (Ill.): Charles C. Thomas 1958 Bancaud, J., Talairaeh, J., Geier, St., Scarabin, J. M.: EEG et SEEG dans tumeurs cerebrales et repilepsie. Paris: Edifor 1973 Barlow, J. S., Estrin, T. : Comparative phase characteristics of induced and intrinsic alpha activity. Eleetroenceph. clin. Neurophysiol. 30, 1--9 (1971) Bechtereva, N. P.: DC changes associated with the sleep-wakefulness cycle. In: Handbook of electroencephalography and clinical neurophysiology (ed. A. R~mond), Vol. 10A, pp. 25--32. Amsterdam: Elsevier 1974 Bennett, D. R., Hughes, J. R., Korein, J., Merlis, J. K., Suter, C. (eds.): Atlas of eleetroencephalography in coma and cerebral death. New York: Raven Press 1975 Bickford, R. G., Butt, H. R. : Hepatic coma : The electroencephalographie pattern. J. clin. Invest. 84, 790--799 (1955) Bickford, R. G., Gose, E., Brimm, J., Roberts, W. : Compressed spectral array (CSA) with spike recognition. Electroenceph. elin. Neurophysiol. $7, 206 (1974) Bourne, J. R., Ward, J. W., Teschan, P. E., Musso, M., Johnston, H. B., Jr., Ginn, H. E.: Quantitative assessment of the electroencephalogram in renal disease. Electroenceph. elin. l~europhysiol. 89, 377--388 (1975) Buser, P., Bancaud, J., Talairach, J. : Depth recording in man in temporal lobe epilepsy. In: Epilepsy: Its phenomena in man (ed. 1K. A. B. Brazier). New York: Academic Press 1973

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Castellucci, V. F., Goldring, S. : Contribution to steady potential shifts of slow depolarization in cells presumed to be glia. Electroenceph. elin. Neurophysiol. 28, 109---118 (1970) Chapman, L. F., Evans, J. W. : Attempted reconstruction of brain surface potential distribution from multilead scalp recordings. Abstract 39, Meeting of the American and Mexican E.E.G. Societies, Mexico City, October 18, 1975 Chatrian, G. E., Canfield, R. C., Knauss, T. A., Lettich, E. : Cerebral responses to electrical tooth pulp stimulation in man. Neurology 25, 745--757 (1975) Chatrian, G. E., Shaw, C. M., Luttrell, C. N.: Focal electroencephalographic seizure discharges in acute cerebral infarction. Electrographic, clinical, and pathological observations. Neurology 15, 123--131 (1965) Cobb, W. A., Hill, D. : The electroencephalogram in subacute encephalitis. Brain 73, 392--404 (1950) Cohen, J. : Cerebral psychophysiology: The contingent negative variation. I n : Bioelectric recording techniques. Part. B: Electroencephalography and human brain potentials (eds. R. F. Thompson, M. M. Patterson), pp. 259--280. New York : Academic Press 1974 Cole, M., Rutherford, R. B., Smith, F. 0.: Experimental ammonia encephalopathy in the primate. Arch. Neurol. 26, 130--136 (1972) Creutzfeldt, O. : Activit6 neuronique du syst~me nerveux central: de quelques aspects de l'activit~ neuronique unitaire corticale et de ses rapports avec l'electroenc6phalogramme. In: Probl6mes de base en 61ectroenc6phalographie (ed. H. Fischgold). Paris: Masson et Cie 1963 Creutzfeldt, O., Houchin, J.: Neuronal basis of EEG waves. In: Handbook of electroencephalography and clinical neurophysiology (ed. A. R4mond), Vol. 2 C, pp. 5--55. Amsterdam: Elsevier 1974 Danielsen, J., Ellebjerg, J. : Comparable E.E.G. activation by Megimide and Metrazol. Epilepsia 7, 228--232 (1966) Davidson, S., Falconer, M. A. : Outcome of surgery in 40 children with temporal lobe epilepsy. Lancet 1975 I, 1260--1263 Dawson, G. D. : A summation technique for detecting small signals in a larger irregular background. J. Physiol. (London) 115, 2 P - - 3 P (1951) Dawson, G. D., Walter, W. G. : The scope and limitation of visual and automatic analysis of the E . E . G . J . Neurol. Neurosurg. Psychiat. 7, 119--130 (1944) Dement, W. C., Kleitman, N. : Cyclic variations in EEG during sleep and their relation to eye movements, body motility, and dreaming. Electroenceph. clin. Neurophysiol. 9, 673--690 (1957) Dement, W. C., Rechtschaffen, A., Gulerie, G. : The nature of the narcoleptic sleep attack. Neurology 16, 18--33 (1966) Donchin, E., Lindsley, D. B. (eds.) : Average evoked potentials. Methods, results, and evaluations. NASA, Washington, D.C. 1969 Donchin, E., Otto, D., Gerbrandt, L. K., Pribram, K. H.: While a monkey waits: Electrocortical events recorded during the foreperiod of a reaction time study. Electroenceph. clin. Neurophysiol. 31, 115--127 (1971) Dreyfus-Brisac, C. : The E.E.G. of the premature infant and the full-term new-born. Normal and abnormal development of waking and sleeping patterns. I n : Neurological and electroencephalographic correlative studies in infancy (eds. P. Kellaway, I. Petersen). New York: Grune and Stratton 1964 Eccles, J. C. : The physiology of nerve cells. Baltimore: The Johns Hopkins Press 1957 Eccles, J. C.: Inhibition in thalamic and cortical neurones and its role in phasing neuronal discharges. Epilepsia 6, 89--116 (1965) Eeg-Olofsson, O. : The development of the EEG in normal children from the age of 1 to 15 years: 14 and 6-per-second positive spike phenomenon. Neurop~diatrie 4, 405--427 (1971) Engel, R. C. H. : Abnormal electroencephalograms in the neonatal period. Springfield (Ill.): Charles C. Thomas 1975 Farrell, D. E., Starr, A., Freeman, J. M. : The effect of body temperature on the "periodic complexes" of subacute sclerosing leucoencephalitis (SSLE). Electroenceph. clin. Neurophysiol. 30, 415--421 (1971) Feindel, W., Penfield, W. : Localization of discharge in temporal lobe automatism. Arch. Neurol. Psychiat. 72, 605--630 (1954)


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Fenton, G. W., Scotton, L.: The use of methohexitone in sleep encephalography. Electroenceph, clin. l~europhysiol. 23, 273--276 (1967) l~erngren, H.G. : Diazepam treatment for[acute convulsions in children. Epilepsia 15, 27--37 (1974) l~isehgold, H., Mathis, P. • Obnubilations, comas et stupeurs. Electroenceph. elin. Neurophysiol., Suppl. 11, 1--124 (1959) Foley, J. M., Watson, C. W., Adams, R. D.: Significance of the electroencephalographie changes in hepatic coma. Trans. Amer. neurol. Ass. 77, 161--165 (1952) freeman, W. J.: Average transmission distance from mitral-tufted to granule cells in olfactory cortex. Electroenceph. clin. Neurophysioh 86, 609--618 (1974) Fuster, B., Gibbs, E. L., Gibbs, F. A.: Pentothal sleep as aid to diagnosis and localization of seizure discharges of psychomotor type. Dis. herr. Syst. 9, 199--202 (1948 I Garoutte, B., Aird, R. B. : Studies on the cortical pacemaker: Synchrony and asynchrony of bilaterally recorded alpha and beta activity. Electroenceph. clin. Neurophysiol. 19, 259--268 (1958) Gastaut, H., Jasper, H., Bancaud, J., Waltregny, A. (eds.): Physiopathogenesis of the epilepsies. Springfield (Ill.): Charles C. Thomas 1969 Gastaut, H., Lugaresi, E., Oller-Daurella, L., Pazzaglia, P., Tassinari, C. A.: Epilepsies. In: Handbook of electroencephalography and clinical neurophysiology (ed. A. R~mond), Vol. 13A. Amsterdam: Elsevier 1975 Gastaut, H., Lyagoubi, S., Mesdjian, E., Saier, J., Ouahchi, S. : Generalized epileptic seizures, induced by "non-eonvulsant" substances. Part 1. Experimental study with special reference to insulin. Epilepsie 9, 311--316 (1968) Geier, S.: A comparative Tele-E.E.G. study of adolescent and adult epileptics. Epilepsia 12, 215--223 (1971) Getting, P. A., Willows, A. O. D.: Burst formation in electrically coupled neurons. Brain Res. 68, 4 2 4 429 (1973) Giannitrapani, D., Kayton, L. : Schizophrenia and EEG spectral analysis. Electroenceph. clin. l~europhysioh 86, 377--386 (1974) Gibbs, C.J., Jr., Gajdusek, D.C., Asher, D.M., Alpers, M.P., Beck, E., Daniel, P. M., Matthews, W. B.: Creutzfeldt-Jakob disease (spongiform encephalopathy): transmission to the chimpanzee. Science 161, 388--389 (1968) Gibbs, F. A., Gibbs, E. L. : Atlas of electroencephalography. Voh 1. Methodology and controls. Cambridge (Mass.): Addison-Wesley Press 1950 Gibbs, F . A . , Gibbs, E. L.: Atlas of electroencephalography. Voh 2. Epilepsy. Cambridge (Mass.): Addison-Wesley Publishing Co. 1952 Gibbs, F. A., Gibbs, E. L. : Atlas of eleetroencephalography. Vol. 3. Neurological and psychiatric disorders. Reading (Mass.): Addison-Wesley Publishing Co. 1964 Gloor, P.: Generalized cortico-retieular epilepsies. Some considerations on the pathophysiology of generalized bilaterallysynchronous spike and wave discharge. Epilepsia 9,249--263 (1968) Gloor, P.: Generalized spike and wave discharge: A consideration of cortical and subcortical mechanisms of their genesis and synchronization. In: Synchronization of E.E.G. activity in epilepsies (eds. H. Petsche, YI. A. B. Brazier). New York-Vienna: Springer 1972 Goddard, G. V., McIntyre, D. C., Leech, C. K.: A permanent change in brain function resulting from daily electrical stimulation. Exp. Neurol. 25, 295--330 (1969) Goldensohn, E. S., Koehle, R.: EEG interpretation: problems of overreading and underreading. Mount Kisco, New York" Futura Publishing Co. 1975 Goldensohn, E. S., Zablow, L., Stein, B.: Interrelationships of form and latency of spike discharge from small areas of human cortex. Eleetroenceph. clin. Neurophysiol. 29, 321--322 (1970) Goldring, S., Ulett, G., O'Leary, J. L., Greditzer, A. : Initial survey of slow potential changes obtained under resting conditions and incident to convulsant therapy. Electroenceph. clin. Neurophysiol. 2, 297--308 (1950) Green, J. D., Maxwell, D. S., Schindler, W. J., Stumpf, C. : Rabbit EEG "theta" rhythm: Its anatomical source and relation to activity in single neurons. J. Z~europhysiol. 28, 403--420 (1960) Grossman, R. G., Whiteside, L., Hampton, T. L.: The time course of evoked depolarization of cortical glial cells. Brain Res. 14, 401--415 (1969)

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Gupt~, P. C., Seth, P.: Periodic complexes in herpes simplex encephalitis. A clinical and experimental study. Electroenceph. clin. Neurophysiol. 85, 67--74 (1973) Hagne, I. : Development of the EEG in normal infants during the first year of life. Acta paediat. seand. 282, 5--24 (1972) Halliday, A. M., McDonald, S. I., Mnshin, J. : Visual evoked responses in diagnosis of multiple sclerosis. Brit. reed. J. 1973 IV, 661--664 Harvard Medical School: Report of the Ad Hoc Committee to examine the definition of brain death. J. Amer. med. Ass. 205, 337--340 (1968) Hess, R. F., Harding, G. F. A., Drasdo, N. : Seizures induced by flickering light. Amer. J. Optom. Physiol. Opt. 51, 517--529 (1974) Hill, D., Parr, G. (eds.): Electroeneephalography - - A symposium on its various aspects. New York: MacMillan 1963 Hirt, H. R.: Zur diagnostischen Bedeutung der pathologischen Beta-Aktivit~t im EEG des Kindes und des Jugendliehen. Fortschr. Neurol. Psychiat. 86, 412---433 (1968) Hughes, J. R. : A review of the positive spike phenomenon. In: Applications of electroeneephalography in psychiatry (ed. W. E. Wilson). Durham (N.C.) : Duke University Press 1965 Humphrey, D. R. : Re-analysis of the antidromic cortical response. II. On the contribution of cell discharge and PSPs to the evoked potentials. Electroeneeph. clin. Neurophysiol. 25, 421---442 (1968) Hunt, A. D., Stokes, J., McCrory, W. W., Stroud, H. H.: Pyridoxine dependency: Report of a case of intractable convulsions in an infant controlled by pyridoxine. Pediatrics 18, 140---145 (1954) Illis, L. S., Taylor, F. M. : The electroencephalogram in herpes-simplex encephalitis. Lancet 1972 I, 718--721 Jasper, H. H., Ward, A. A., Pope, A (eds.) : Basic mechanisms of the epilepsies. Boston: Little, Brown, and Co. 1969 Jeavons, P. M., Bower, B. D., Dimitrakoudi, M. : Long-term prognosis of 150 cases of "West syndrome". Epilepsia 14, 153--164 (1973) Jewett, D. L. : Volume-conducted potentials in response to auditory stimuli as detected by averaging in the cat. Electroenceph. clin. Neurophysiot. 28, 609--618 (1970) Jewett, D. L., Williston, J. L. : Auditory-evoked far fields averaged from the scalp of humans. Brain 94, 681--696 (1971) Kennard, M. A., Rabinovitsch, S., Fister, W.: The use of a frequency analyzer in the interpretation of the EEGs of patients with psychological disorders. Electroenceph. olin. Neurophysiol. 7, 29--38 (1955) Knott, J. R., McCallum, W. C. (eds.): Event-related slow potentials of the brain: their relation to behavior. Electroeneeph. clin. Neurophysiol., Suppl. 88, 1--390 (1973) K6hler, W., l~leff, W. D., O'Connel, D. W. : An investigation of cortical currents. Proc. Amer. Philosoph. Soc. 96, 290--330 (1952) Kooi, K. A. : Fundamentals of electroencephalography. New York: Harper and Row 1971 Kornhuber, H. H., Deeke, L.: Hirnpotential-Jtmderungenbei Wilkiirbewegungenmad passiven Bewegmagen des Menschen: Bercitschaftspotential und reafferent potentiale. Pflfigers Arch. ges. Physiol. 284, 1--17 (1965) Laidlaw, J., Read, A.E.: The electroencephalographic diagnosis of manifest and latent "Delirium" with particular reference to that complicating hepatic cirrhosis. J. Neurol. Neurosurg. Psychiat. 24, 58--70 (1961) Lesse, S,, Hoefer, P.F.A., Austin, J. H. : The electroencephalogram in diffuse encephalopathies. Arch. Neurol. Psyehiat. 79, 359--375 (1958) Loomis, A. L., Harvey, E. N., Hobart, G. : Electrical potentials of the human brain. J. exp. Psychol. 19, 249--279 (1936) MacGillivray, B. B., Binnie, C. D., Osselton, J. W. : Traditional methods of examination in clinical EEG. In: Handbook of eleetroencephalography and clinical neurophysiology (ed. A. R6mond), Vol. 3C, pp. 3--126. Amsterdam: Elsevier 1974 Matou§ek, hi. : Review of various methods of E.E.G. analysis. In: Handbook of eleetroeneephalography and clinical neurophysiology (ed. A. R~mond), Vol. 5A, pp. 5---32. Amsterdam: Elsevier 1973

Some Recent Advances in EIectroencephalography

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Dr. Bill Garoutte Professor Department of Neurology University of California San Francisco CA 94143, USA

Some Recent Advances in Paediatrics.

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Some recent advances in cardiac pathology.

Neuro-otology- some recent clinical advances.

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Recent Advances in Surgery.

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Recent advances in epilepsy.

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Recent advances in epilepsy.

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Recent advances in tin dioxide materials: some developments in thin films, nanowires, and nanorods.

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