Psychological Reports, 1991, 68, 783-801.

O Psychological Reports 1991

CIRCADIAN ASPECTS O F EPILEPTIC BEHAVIOR IN COMPARATIVE PSYCHOPHYSIOLOGY " CHRISTIAN POIREL

McGill University Universib of Quibec

AND

MUSTAPHA ENNAJI

University of Quibec

Summary.-This paper is concerned with some experimental and clinical problems regarding the circadian chronobiology of epilepsy. Rhythmometrically analyzed, the temporal fluctuations of seizure susceptibility tend to indicate that epileptic events are circadian stage-dependent processes whose chronobiologic characteristics are possibly predictable on the basis of mathematical models. As an integrative discipline in physiology and psychology, behavioral chronobiology renders possible the discovery of new regulation processes concerning the central mechanisms of epgepsy. In this respect, the circadian psychophysiological patterns of epilepsy express dynamical biological systems which suggest some intermodulating endogenous processes between vigilance level and seizure susceptibility. Moreover, such chronobiologic studies applied to epileptic behavior suggest the development of new heuristic aspects in the field of comparative psy~hoph~siology.

The chronobiology of epilepsy has had epistemological status in the history of scientific knowledge ever since the beginnings of Aristotelian conceptualism which favoured the principle of a measuring scale in temporally classifying the phenomena of the events of mental life. Referring to logical concepts of time measurement in the field of natural sciences, Aristotle postulated a physiological basis for certain mental disturbances as had previously been suggested by Hippocratic medicine. Regarding biological time from these theoretical perspectives, the following statements are concerned with some considerations referring to the chronobiologic characterization of seizure susceptibility as a circadian rhythm and to the possible chronobiologic linkage between sleep and epilepsy (Webb, 1985). In thls context, we know that such approaches were surmised in the early history of medicine and psychology (Joly, 1964; Temkin, 1971). Over 2,400 years ago the Greek physician Hippocrates took into consideration the presence of daily rhythms in the onset of grand mal seizures (i.e., tonic-clonic convulsions). However, if the first statistical approaches to mental fluctuations of epileptic processes go back to Beau in 1836 and to Fer6 in 1888, the first factual analysis regarding the temporal occurrence of epileptic events should rightly be attributed to Gowers in 1885. In this respect, with -

-

-

--

'This work was supported by the Medical Research Council of Canada 'We are indebted to Prof. F. Halberg, Faculty of Medicine, University of Minnesota, for his inestimable help during the conception of certain as ects of these studies. We thank J. w m o n t , M. Lesley Sinclair, and B. Thkriault for their Relpiul assistance. Requests for reprints should be sent to Prof. C. Poirel, Research Laboratory of Chronobiology and Experimental Psychopathology, University of Quebec, Chicoutimi, PQ, Canada G 7 H 2B1.

784

C. POIREL & M.ENNAJI

reference to 840 subjects, i t was observed that convulsions were nocturnal for 21%, diurnal for 42%, and randomly distributed for 37% Moreover, "Gowers felt that there were two susceptible periods for nocturnal seizures, the onset and the end of sleep, morning attacks being the more common" (Montplaisir, Laverdiere, & Saint Hilaire, 1987). Throughout the twentieth century, several neurological investigations (Langdon-Down & Brain, 1929; Patry, 1931; Hopkins, 1933; Denny-Brown & Robertson, 1934; Griffiths & Fox, 1938; Halberg & Howard, 1958; Janz, 1974; Mikol & Monge-Strauss, 1987) tended to confirm the preliminary observations provided by Gowers and have made it possible to differentiate and classify three circadian chronobiologic aspects of epilepsy. According to the distribution of epileptic seizures over a period of 24 hours, the subjects were referred to as nocturnal, diurnal, or diffuse types. I n this clinical context, the nocturnal type would correspond to patients expressing predominantly generalized responses, the diurnal type to subjects exhibiting more atypical convulsions, and the dzfluse type to those manifesting polysymptomatic seizures (e.g., psychomotor equivalents). For instance, according to this classification, Janz in his position paper (1974) concerning the distribution of grand ma1 seizures over 24 hours (study reviewed by Autret and Gaillard in 1990) estimated that they were nocturnal for 44%, diurnal for 33% (convulsive fits associating epileptic processes occurring at the morning and during the afternoon), and diffuse for 23%. Where these descriptive observations were preferentially conducted in adult patients, the problem of circadian chronobiology of epilepsy was also approached in the light of ontogeny studies regarding the development of brain biological rhythms (Hellbriigge, 1960). I n this context, where chddren were concerned, the first statistical studies referring to behavioral fluctuations of epileptic processes go back to Loiseau and Jallon in 1977. With reference to 486 subjects, it was demonstrated that seizure susceptibility was nocturnal for 56% and diffuse for 44%. From observations by Dalla Bernardina, Bondavalli, and Colamaria, in 1982, with reference to 92 subjects (manifesting seizures with rohndic spikes), it was also observed that convulsions were nocturnal for 43%, diurnal for 32%, and randomly distributed for 25%. I n this psychophysiological context, Autret and Gaillard suggested in 1990 that the tendency to nocturnal susceptibility was particularly accentuated in children exhibiting rolandic spikes. Considering the classical problem of petit mal epilepsy in childhood, distinct behavioral disorder features were also analyzed over 24 hours (Hallek, Reinberg, Schmidt, Levi, & Hellbriigge, 1983). For instance,

'Such electrical discharges on the motor frontal cortex are similar to cortical responses observed during seizures in genetically epileptic mice (Poirel & Ennaji, 1990).

CIRCADIAN ASPECTS OF EPILEPTIC BEHAVIOR

785

circadian variations of restlessness were validated in cases of West Syndrome (childhood myoclonic encephalopathy; hypsarrhythmia) and in petit mai events, but with acrophases (peaks of psychophysiological activity) differing by approximately 12 hours. From another neurological perspective, ocular seizures manifested some circadian rhythmicities in West Syndrome but not in petit ma1 events. Incidence of epileptic seizure exhibited periodicities corresponding approximately to 08 hours in West Syndrome, whereas possible circadian rhythms were suspected in petit mal events. From a psychopbysiological perspective, such clinical comparisons, involving adults and children, tended to take into account the modulating role of sleep or hypovigilance on seizure susceptibility and a possible predictive recurrence of epileptic events over a period of 24 hours. However, in the light of such temporal convergences, the variation in seizure susceptibility as a function of circadian stage remains a complex chronobiologic problem to be elucidated (Webb, 1985). O n the basis of these descriptive clinical studies possibly involving the sleep/wakefulness cycle, some explanatory analyses regarhng brain functioning were also undertaken. Behavioral and physiological investigations in the field of neuroscience (Jasper, Ward, & Pope, 1969; Poirel, 1984; Montplaisir, Laverdiere, Walsh, Saint Hilaire, & Bouvier, 1980; Montplaisir, Laverdiere, & Saint Hilaire, 1987) have established that a moderate level of vigilance (i.e., central activation) is closely related to the sensitization and occurrence of generalized epileptic phenomena (Poirel, 1987). As reported in the history of epilepsy (Joly, 1964; Temkin, 1971), central mechanisms involving subcortical structures were put forward by the first neuroanatomist, Galen, during the Roman classical period (2nd century AD). This was an ancient working hypothesis which will be confirmed by the modern behavioral neurosciences (Penfield & Jasper, 1954; Fromm, Faingold, Browning, & Burnham, 1987) with the centrencephalic notion of vigilance regulation and epileptic pathogenesis (Penfield, 1969). I n this respect, in clinical research, considering the three neurological forms of epileptic seizures: (1) the grand ma1 epilepsies frequently occur during nonREM (rapid eye movement) sleep; for instance, 1 to 2 hours after the beginning of scotofraction and at the end of the rest span (Besset, 1982; Billiard, 1982; Janz, 1962; Montplaisir, et ai., 1987; Sterman, Shouse, & Passouant, 1982); interictal discharges being predominant at the beginning of sleep, during the last part of scotofraction, and towards the end of the afternoon (Mikol & Monge-Strauss, 1987), (2) the petit ma1 epilepsies (i.e., absences) occur clinically during wakefulness (photofraction) and during R E M or nonREM sleep w M e interictal discharges correspond preferentially to nonREM sleep (Sato, Dreifuss, & Perry, 1973), [as for myoclonic activities, such petit mal events can frequently be observed after waking in the

786

C. POIREL & M. ENNAP

morning (Meier Ewert & Broughton, 1967), interictal discharges being facilitated by vigilance states (Touchon, 1982)l. Note that these two forms of epileptic responses are recognized as generalized seizures according to the International Ckzss$cation of Epileptic Seizures ["Commission on Classification and Terminology of the League Against Epilepsy," 1981 (see Fromm, et al., 1987)], and (3) the partial epilepsies occur more frequently during the day (Billiard, 1982; Montplaisk, et al., 1987); however, interictal discharges are more frequent during nonREM sleep (Montplaisir, et al., 1987). Analyzed together, the different circadian manifestations of generalized or partial epilepsies (e.g., for interictal discharges) show that seizure susceptibility tends to be functionally associated with cerebral states of electrical synchronization (i.e., brain processes of hypovigilance). Events of neuronal firing and mechanisms of spread of the paroxysmal discharges would be facilitated by hypovigilant states and their circadian fluctuations (episodes of normal sleep during rest span but also episodes of diffuse drowsy states during the activity span). For instance, neurophysiologic mechanisms of sleep involve a generalized synchronization of neuronal discharges on the cerebral cortex. Vast populations of neurons exhibit electrical synchronization (e.g., high voltage during slow-wave sleep) with momentary functional states which tend to fire synchronous activities. Moreover, the role played by some hypovigilance fluctuations would not be incompatible with the leading importance of state transitions for facilitating seizure susceptibility (Halasz, 1972; Passouant, 1977). Such functional conditions during rest span appear to be particularly favorable to triggering the pyramidal neurons and to releasing striate motor discharges expressing an epileptic behavior.

PATTERNS OF HYPOVIGILANCE AND MANIFESTATIONS RELATEDTO EPILEPSY Among psychophysiological states directly related to epilepsy, benign epilepsy of childhood with rolandic spikes (BERS), electrical status epilepticus during sleep (ESES), and the Lennox-Gastaut syndrome ("petit mal variant" analyzed by Vizioli in 1970) present some nocturnal characteristics and some functional relationships with the rest/actiuify cycle. For instance, BERS may occur during all stages of sleep, ESES occurs at the beginning of sleep and during nonREM sleep, while Lennox-Gastaut syndrome presents more frequent reactional episodes during inactive wakefulness and drowsiness over 24 hours. However, the convulsive modalities of this syndrome may be greatly activated by nonREM sleep. Among psychophysiological events indirectly related to epilepsy, parasomnias represent nonREM sleep phenomena including recurrent manifesta'See also International League Against Epilepsy. Proposal for classification of epilepsies and epileptic syndromes. Epilepsia, 1985, 26, 268-278.

CIRCADIAN ASPECTS O F EPILEPTIC BEHAVIOR

787

tions of simple or complex aberrant behavioral responses (e.g., sleepwalking, night-terrors, nightmares). Such nocturnal behavioral disorders with epileptiform characteristics (e.g., sudden onset, altered states of consciousness, retrograde amnesia) occur most frequently in the first third of scotofraction (Montplaisir & Demers, 1983). As for the nocturnal paroxysmal dystonia (intense motor responses affecting limbs and trunk), such an event always occurs in relation to arousal from stages 3 and 4 nonREM sleep (Lugaresi & Cirignotta, 1982). Among- ultradian or circadian manifestations directly or indirectly related to epilepsy, certain clinical events are open to consideration on the basis of psychosomatic disorders. These would include, for instance, the problems of temporal fluctuations of transitory phenomena such as auras, acute psychotic events, epileptic furor, hysterical seizures, fainting attacks, migraine episodes, vasovagal seizures, and other allied phenomena which are all still under discussion (Poirel, 1990). Such psychophysiological events appear also to be modulated by the vigilance level but with special reference to emotional fluctuations. Such functional modalities between emotional level and reactional behavior would respond, at least theoretically, to the psychological conceptualization of a "continuum of vigilance" (functional linear relationship among vigilance, overarousal, and emotionality). ' I n this context, there is a possibility that variability of this continuum could respond to endogenous circadian processes (Poirel, 1990). FROMBRAINCHRONOBIOLOGY TO CHRONOPSYCHOLOGY: RHYTHMOMETRIC CONSIDERATIONS FOR STUDYOF EPILEPSY I n establishing the new science of chronobiology, Halberg (1960, 1969) made it possible to discover the biological time structure of living tissues and organisms, at different levels of biological organization and physiological integration. Thus, time processes may be investigated from traditional biometric studies to new rhythmometric analyses at several levels of resolution and for a broad spectrum of rhythmicities (Halberg, Carandente, Corntlissen, & Katinas, 1977; Halberg, 1983). Considering the experimental field of animal models for epilepsy, Halberg, Bittner, and Gully began in 1955 to investigate the influence of daily photoperiodicity upon the susceptibility to sound-induced convulsions in mice. From some observations carried out over 24 hours, it was generally hypothesized that such psychophysiological variations could respond to circadian processes (Poirel, 1975, 1984). Since then, our research unit has been analyzing various periodicities encountered in comparative psychopathology Psychophysiological aspects referrin to clinical problems of hysteriform motor disturbances and ystcm-epilepsy (emotiondy chargedB conwbions). Studies concerning emotional chronobiology in comparative ethology (Poirel, 1975, 1988).

788

C. POIREL & M. ENNAJI

(Poirel, 1974, 1982; Poirel & Larouche, 1987, 1989; Sechter & Poirel, 1985) and has attempted to study the cerebral mechanisms underlying circadian modifications in the onset or severity of tonic-clonic convulsions (Poirel & Dantzer, 1971; Poirel, 1987). Considering, for instance, the field of comparative chronopsychology (Poirel, 1975, 1990), behavioral rhythms can be detected and described as algorithmically-formulatable recurring psychophysiological changes, with a waveform validated by inferential statistical computer methods. With the rhythmometric procedures now available in chronobiology, it is possible (1)to analyze the temporal structure of psychophysiological functions and (2) to correlate some changes in different kinds of seizure susceptibility with marker rhythms such as vigilance. Moreover, the periodicities considered at different levels of cerebral integration show circadian systems to be intermodulated, involving functional networks, with time structures that are interdependent (Sechter & Poirel, 1985). In this context, several murine circadian variations of seizure susceptibility (i.e., atypical convulsions, tonic-clonic responses, tonic events expressing dominant cholinergic mechanisms, clonic events expressing dominant adrenergic processes) may be analyzed and compared with vzgzlance patterns on the basis of descriptive studies (circadian chronograms of seizure susceptibility) and on the basis of mathematical models involving cosinor-rbythmometry procedures (Halberg, 1966, 1969; Halberg, et al., 1977). Such quantitative analyses make it possible: (1) to detect rhythms on the basis of the assumption of "no-rhythm" or zero-amplitude of the cosine function fitted by least-squares to the data (Nelson, Tong, Lee, & Halberg, 1979) and (2) to vahdate rhythmometrically the phase displacement (phase concordance, phase opposition, phase relation) regarding two or more variation curves on the basis of the comparison of cosinor parameters, a comparison involving "inferential statistical test of amplitude and/or acrophase s i d a r i t y in two or more rhythms" (Halberg, et al., 1977; Bingham, Arbogast, Corn6lissenGudlaume, Lee, & Halberg, 1982). Thus, within the field of psychopbysiology, the rhythmometric data concerning vigilance and epilepsy suggest that chronobiology should be considered when exploring for possible mechanisms underlying tonic-clonic convulsions and when studying possible brain processes regulating the timing of behavioral integrations. CIRCADIAN PARADIGMS IN EXPERLMENTAL EPILEPSYAND PSYCHOPHYSIOLOGICAL ASPECTSOF TEMPORALREGULATION OF SEIZURESUSCEPTIBILITY In central neurophysiology it is known that a moderate level of vigilance is related closely to the sensitization and occurrence of generalized epileptic phenomena (Jasper, et al., 1969; Poirel & Dantzer, 1971; Poirel, 1975). In our studies we have extended that knowledge by demonstrating the circadian relationships between epileptic behavior and vigilance (Poirel, 1982, 1987).

CIRCADIAN ASPECTS OF EPILEPTIC BEHAVIOR

789

The following aspects summarize some chronobiologic data from studies undertaken with murine models of epilepsy (Poirel, 1967, 1990). According to some chronobiologic experimental procedures discussed by Webb (1985), "to determine the interrelationship between two systems within a circadian framework," displacement designs involving several photoperiodicity regimens had been used: (I) to establish murine circadian patterns of seizure susceptibhty (Poirel, 1967, 1984; Poirel & Dantzer, 1971) and (2) to confirm the circadian fluctuations in epileptic behavior relative to vigilance level rather than to clock hours (Poirel, 1975, 1982; Sechter & Poirel, 1985). Chronobiologic comparisons concerning the circadian fluctuations of vigilance and epilepsy (Fig. l ) showed a phase opposition between the two psychophysiological functions considered. Correlation analyses between the two variation curves suggested for psychophysiology the functional possibility of an inverse relationship between the level of central activation and the susceptibility to tonic-clonic seizures. To verify the circadian form of these variation curves, we experimentally modifiedparameters of photoperiodic entrainment (e.g., with light-darkchanges). The new re-entrained rhythm curves obtained confirmed the amplitude, form, and phase relations between the circadian rhythms shown in the diagram of Fig. 1. Correlation analyses between the new variation curves obtained expressed the same significant tendencies with a remarkable stability of interrelationship between the two psychophysiological systems considered (Poirel, 1975; Sechter & Poirel, 1985). Using different desynchronization programmes (with new synchronizers rescheduling psychophysiological functions of their established time givers), it was possible to show that circadian rhythms differently phased to clock hours manifest identical phase relationships. Considering chronobiologic relationships between vigilance and seizure susceptibility (tonic-clonic activity), there exists for different circadian modalities of displacement designs an identical phase relation corresponding to approximately 180' [for instance, 174' considering acrophase data ( 4 = -307'; 4 = -133') as indicated in Fig. 11. The working hypotheses emanating from chronobiology were verified and confirmed within the field of brain neurophysiology. Considering several investigations concerned with experimental stimulation of meso-diencephalic structures (e.g., "reticular activating system"), susceptibhty to tonic-clonic seizures decreases significantly with the progressive increase in central activation (Poirel & Dantzer, 1971; Poirel, 1982). Such psychophysiological analyses converge with rhythmometry investigations (e.g., phase opposition between circadian fluctuations of vigilance and epileptic susceptibility) involving the hypothesis suggested by chronobiology that central hyperactivation negatively influences seizure susceptibility.

790

C. POIREL & M. ENNAJI

As reviewed in the field of comparative neuroscience (Frornm, et al., 1987; Gloor, 1979; Penfield, 1969; Poirel, 1982), the convergent results ernanating from chronobiology and psychophysiology may take into consideration the functional role played by the reticular structures on seizure susceptibility. SCOTOFRACTION

PHOTOFRACTION

(Y) 3.00

p: W

2.00

t

3 P

I

0

0

>

g

1.00

E2

P

Qc d

0.00 MOTOR ACTIVITY

-1 .oo 0

1

160°

20"'

M

= 2.1 03 M = 1.458

3

4

04"'

080°

2

OOoO

A = 0.729 A = 1.722

(P (P

=

5

6

12W (H)

-133.2 (SEIZURE SUSCEPTIBILITY)

= -307.7 (VIGILANCE LEVEL)

CIRCADIAN PARAMETERS OF VIGILANCE AND EPILEPSY

FIG.1. Circadian paradigm for susceptibilit to tonic-clonic seizures (murine model described by Poirel, 1975, 1990). Results are plottedYin a plane Cartesian coordinate system with chnobiologic characteristics of circadian profiles (e.g., waveforms) for striate motor activit vigilance level, and tonic-clonic responses. Time references are expressed in hours along the a61 scissa (H) with conventiondv 160° for point of origin (OO).Period is experimentally determined by the photo eriodicity regllnen (photofraction 16°0-0400; scotofraction 04°0-1600). The compurcr arc indicated along the ordinate 0. White and black dots refer to means plotte!by data concerning the vigilance level and the seizure susceptibility. Chmnobiologic analyses of circadian processes of vigilance and epile sy as com uted b the cosinor-rbytbmomehy procedures involve the cosine function modef)corresponing to tKe equation: y = M + Acos (wt + 6). Circadian parameters are characterized by the MESOR (rhythm-adjusted level M), the Amplitude (A) of variation (a measure of extent of predictable change around the MESOR), and the Acrophase (6)corms onding to the best-fitting cosine curve (a measure of timing of over-all high values in the rhytkn). Angular frequency corresponds to w = 21~124hr. Period, MESOR, Amplitude, and Acrophase express the temporal structure of the behavioral integration investigated. Rhythmometric variation curves correspond to y = 1.45 + 1.72 cos (wt - 307.70) and y = 2.10 + 0.72 cos (wt - 133.20), respectively. The two rhythms are detected by the zero-amplitude test. The time interval expressing a ase opposition (psychophysiological phase relations) between the two variation curves is v a l i k e d b rhe amplitude-rrrophase test. Chmnobiologic data of striate motor activity are biometrically vddated by the Friedman nonparametric test (after Poirel, 1984, 1990).

CIRCADIAN ASPECTS O F EPILEPTIC BEHAVIOR

79 1

I n this respect, considering behavioral electrophysiology of central axis during sleep/wakefulness cycle (i.e., restlactivity cycle), we know that the mesodiencephalic activation (i.e., the "reticular activating system" with ascending and long descending pathways) traditionally exerts its influence both upon the cerebral cortex (processes of electrical desynchronization associated with hypervigilance states or with REM sleep episodes) and the spinal motor system (activation processes of alpha motoneurons commanding striate motor activity). processes of sleep involve a generalized For instance, ne~roph~siologic reduction of neuronal asynchronism in the cerebral cortex and the diminution of muscular tonus. I n this context, two complementary hypotheses were stated (Poirel, 1975, 1987): -a stage of moderate central activation could launch an epileptic attack, because during sleep vast populations of neurons exhibit electrical synchronization (i.e., high-voltage recorded on EEGs, e.g., functional links between slow-wave sleep and generalized seizure discharges); -the motor effects of these cortical discharges would be accentuated at the behavioral level, because striate muscles are in a physiological state of prolonged rest during sleep. Such psychophysiological relationships may be illustrated from a chronobiologic perspective (Fig. 1). For instance, towards 00 hour, the maximal susceptibility of epileptic responsiveness is corresponding to the lowest level of vigilance and to the 24-hr. terminal cycle of striate motor activity.

BIOLOGICAL TIMEAND NEUROPHYSIOLOGY OF EPILEPTIC DISCHARGES As analyzed by Webb (1982) from a physiological and psychological context: "there is an interaction between time and behavior." If one considers some functional aspects of the biological time structure of neuronal networks (neural tissue) together with some brain devices regulating seizure activity (epileptic excitability), it must be considered that basic mechanisms fundamentally involve: (1)self-sustained processes in neuronal networks (concept of the transmission of self-sustained discharges) and (2) recruitment processes for propagating hypersynchrony phenomena (concept of paroxystic hypersynchrony). If such mechanisms are classically analyzed for possible pathogenesis of epilepsy (Wyler, 1974; Wyler & Ward, 1980), in the light of time dzmension, ultradian processes of synchronization should also be considered when exploring pathophysiology of convulsive events at a functional level of integration networks. With regard to this chronobiologic interpretation, the two functional modalities of transmission of the epileptic activities implicate: (1) processes of specific hodologic "conduction" (Jasper, et al., 1969; Jinnai & Mukawa, 1987), involving neuronal pathways (time range in milliseconds), and (2) processes of diffuse "propagation" (Jasper, et al., 1969; Okumura, 1958) involving neuronal mass (time range in seconds). Such staggered modes of transmission refer to different functional levels

792

C. POIREL & M.ENNAJI

of resonance involving a broad spectrum of ultradian rhythmicities regarding different kinds of neural tissue integration (Poirel, 1975), i.e., neurophysiologic processes portrayed clinically by the "march of symptoms" classically described by Penfield and Jasper (1954). Thus, during the hypovigilance states (e.g., slow-wave sleep episodes), neuronal electrogenesis activir~esrend to enter into functional synchrony (these cortical states physiologically facilitate some processes of isorhythmicity and hypersynchrony, with resonance phenomena leading to widespread neuronal firing). More generally, the drowsy states and the lowest levels of vigilance favour electrical discharges in phase-concordance (pulsatory phenomena of high amplitude during the slow-wave sleep). Thus, such pathophysiologic aspects permit the underlining of the epileptogenic facilitation role of resonance processes and beat phenomena bound to neuronal isorbytbmicity and paroxystic hypersynchrony (Moruzzi, 1950; Jasper, et al., 1969; Gastaut, 1987). As reported elsewhere (Poirel, 1982, 1990), the neuronal quiescence of the cerebral cortex during slow-wave sleep or during- states of diffuse vigilance may lead to "epileptogenic conditions," with possible precipitation of convulsive fits or sudden occurrence of electrical discharges during an EEG recording (e.g., bursts of spikes, bursts of high amplitude waves, and neuronal firing of somatic motor areas in the cerebral cortex). Both the quantitative neurochemical and E E G parameters that characterize the psychophysiology of sleep and wakefulness [e.g., nonREM sleep time organization and tonic-clonic event facatation, fluctuations of cholinergic and adrenergic integrations and motor patterns of convulsive responses, neurotransmitter receptor rhythms and seizure susceptibility, "Basic Rest Activity Cycle" (BRAC) and ultradian rhythmicities of discharges] may become extremely important in determining characteristics of the circadian manifestations for different lunds of epilepsy. In this respect, chronobiologic analyses of neuronal networks may contribute to the elucidation of some ultradian mechanisms (e.g., reference to biological oscillators) regarding the pathogenesis of epileptic events.

Fluctuations of Hypovigilance and Circadian Bimodality of Epilepsy Responsiveness I n 1982, Broughton referred to: "The substantial evidence for an early afternoon sag in vigilance essentially 180' out of phase from the early morning nadir. . . ." There is a possibility that such a daily bimodal sleep tendency expressing an endogenous about 2/day (circasemidian) rhythm of sleep propensity (Broughton, 1975, 1988) corresponds to two spaced hypovigilance states optimizing the distribution of epileptic events (Poirel, 1990). Considering the brain processes regulating seizure activity and response

CIRCADIAN ASPECTS OF EPILEPTIC BEHAVIOR

793

enhancement (i.e., tonic-clonic events), we know that the basic mechanisms fundamentally involve some "recruitment" rhythm phenomena in the propagation of generalized convulsions. Such processes appear to be directly or indirectly modulated by the fluctuations of vigilance states. That is why certain bimodaldistributions of human idiopathic generalized epilepsies (Halberg & Howard, 1958; Mikol & Monge-Strauss, 1987) [e.g., circadian bimodalities of epileptic cortical activities (electrical discharges on EEGs) with a high peak of discharges at the awakening and a lower one towards the end of the afternoon] could respond to circasemidian vigilance processes corresponding to a "daily bimodal sleep tendency" described by Broughton in 1988. In this respect, the major peak of deep nonREM sleep (i.e., slow-wave events) occurs in the first part of night, and the secondary deep sleep episode appears during the afternoon (sometimes approximately 12.5 hours later; see Gagnon and De Koninck cited by Broughton, 1988). Based on psychophysiological considerations (Poirel, 1975, 1987), these two hypovigilance states (referring to a bimodal rhythm of pressure for deep nonREM sleep) could facilitate the bimodal occurrence of electrical cortical discharges and certain dephased clinical motor expressions of generalized epilepsies. '

Circadian Models for Seizure Susceptibility in Comparative Ethology The working hypothesis that overarousal states (i.e., central hyperactivation) negatively influence the onset of generhzed epileptic seizures may be offered by a comparison of the time of epilepsy susceptibility in mice and humans (Poirel, 1975, 1982). Epilepsy experiments regarding several different strains of mice showed the temporal convergences of their circadian acrophases for seizure susceptibility. Thus, rhythmometric relationships between circadian acrophases of vigilance and temporal peaks of seizure susceptibility display experimental models that might allow a better understanding of human epileptic mechanisms. Based on temporal factors, such models could be of clinical importance in eventually preventing the occurrence of tonic-clonic seizures and programming some chronotherapy strategies. In patients with epilepsy such generalized seizures show a phase difference of nearly 180°, relative to those induced experimentally in mice; see Fig. 2 for this approximate relationship. The reversal of the sleep/wakefulness cycle in the two species notwithstanding, the temporal variations in convulsive behavior yet tend to fluctuate synchronistically. The parallel between temporal occurrences of epileptic events (i.e., generalized discharges) 'From another psychophysiological perspective and in the light of circasemidian models, the circadian acm hase of the ultradian BRAC process occurs between the two circasemidian slow-wave sfeep peaks (Broughton, 1388), i.e., towards 03-04 hours during scotofraction and towards 15-16 hours during otofraction. These two tempi minoris resistentiae correspond to hypovi ilance states responsib e for possible occurrence of abnormal adaptive behaviors (e.g., ind u s t r i j accidents) and psychosomatic disorders.

yh

794

C. POIREL & M. ENNAJI

in mice during the diurnal span of the daily cycle and those of humans during the nocturnal portion of a "nychthemeron" with, however, another peak in the last thlrd of photofraction (e.g., electrical discharges on EEGs), tends to legitimate the modulator role of slow-wave sleep on epileptic neuronal firing (e.g., functional modalities of hypovigilance states involving neuronal isosynchrony processes and pulsatory events in phase concordance: basic conditions facilitating the propagation of paroxysmal activities and leading to "epileptic excitability"). -

SCOTOFRACTION (Rest)

-

PHOTOFRACTION (Actlvlry)

I

I

SLEEPTENDENCY I

I

16m

20m

OOm

,

I

I

I

I

I

04m

OBm

12m

16"

20m

DOm

TIME (CLOCK HOURS)

FIG. 2. Diagrammatic representation of circadian fluctuations of psychophysiological functions regarding epilepsy: diagram for chronobiologic profiles of susceptibility to tonic-clonic seizures in mice and in humans. Rhythmologic data analyzed from behavioral observations concerning subline Orl (curve G,) (after Poirel, 1975) and subline Rb (curve G,)(after Poirel, 1987) mice are compared to circadian fluctuations of seizure susceptibility in humans [data pooled from comparative clinical studies (Janz, 1974; Poirel, 1982, 1990)], (curve H). This graph must be considered only as a paradtgm visualizing the approximate circadian fluctuations of generalized events encountered in the mouse (i.e., experimental epilepsy) and in humans (i.e., clinical epiiepy): The vertical broken lines demarcate the alternation of scotofraction and photofraction. For a dlt~onalinformation in neurology, the diagram is showing comparatively: (1) the time variations of electrical epileptic dtscharges (EEDs), (2) the fluctuations of hypovi dance states (SWS) with the first slow wave sleep pulse (towards 22.00 hours), and (3) the timodal slow wave sleep tendency (ST) (after Broughton, 1988). The black dots indicate referential occurrences for partial epilepsies (PE) [after Mikol & Monge-Strauss (1987) and a!apted from Poirel (1982, 1990)l. As suggested by this study, some tem oral convergences should be considered for possible manifest or latent human-seizure susceptibity: for instance, with the photoperiodidty regimen indicated, towards 22.00, 06.00, and 16.00 hours.

During the slow wave sleep pressure (stage corresponding to the nonREM sleep during the night) towards I 6 hours, human subjects are in a

CIRCADIAN ASPECTS OF EPILEPTIC BEHAVIOR

795

physiological state of striate muscular activity where the behavioral responses of epilepsy are not elicited as compared to the motor propitious conditions realized between 04 and 08 hours (stage corresponding to a state of muscular rest). Such circadian dissociations between electrophysiologic activities and behavioral expressions of epilepsy (see Fig. 2) are not only compatible with central and peripheral mechanisms of generalized responses but also confirm the working interpretations previously formulated on the propagation of convulsive impulses (Poirel, 1975, 1990). Seizure susceptibhty paradigms may offer for comparative pathophysiology some worhng hypotheses regarding the functional modulation of epileptic processes by vigilance mechanisms, such complementary studies concerned with chronobiology and psychopbysiology supporting the hypothesis that the highest susceptibility to tonic-clonic events corresponds to the lowest level of central activation. Thus, the temporal occurrences of seizures in mice towards the end of photofraction (i.e., sleep stage for nocturnal species) and in humans towards the end of scotofraction (i.e., sleep stage for diurnal species) tend to confirm the marked influence of drowsy states on the manifestation of neuronal discharges in grand mal seizures of epilepsy.

Occurrence of Epileptic Events and the Concept of Order by Fluctuation If analysis of epileptic entities may constitute a "window to brain mechanisms" (Lockard & Ward, 1980), rhythmologic studies regarding tonic-clonic behaviors may also open a window on different frequency spectra of brain chronophysiology. Such theoretical aspects, involving possibly functional relationships between brain oscillators and epileptogenic pacemakers (Wyler & Ward, 1980; Silva, Amitai, & Connors, 1991), may offer some suggestions regarding intrinsic physiological rhythmicities from cerebral clocks to chaos phenomena. If certain paroxysmal electrical cortical events (EEGs) and epileptic storms may be considered hic et nunc as chaotic behaviors, i.e., "dynamical diseases" according to the formulation of Glass and Mackey in 1988, responding to ultradian micro-activities of high frequency (e.g., epilepsy cortical spikes of 30 cycles/sec. reachng 200 pV in amplitude; epileptogenic impulses in the pyramidal tract corresponding to 1,000 cycles/sec. discharges), certain recurrences of generalized seizures, at apparently irregular intervals, could also respond to chaotic fluctuations over 24 hours. In this context, chronobiologic analyses involving nonhomeostatic variations might contribute to the elucidation of some mechanisms of chaotic systems, those regarding notably the time distribution of partial seizures, atypical convulsive events, or psychomotor

796

C. POIREL & M. ENNAJI

manifestations of epilepsy (i.e., mental substitutes for fits with complex psychomotor phenomena, dreamy states, fugues with amnesia, secondary states of consciousness). Furthermore, theoretical chronobiology and comparative psychophysiology applied to epileptic phenomena and their apparent erratic variations also allow us to draw some heuristic perspectives in clinical neurology and psychiatry. Moreover, such chronobiologic studes are concerned with epistemological considerations regarding the modern concept of time, as well as the conceptualization of rhythms within time (Poirel, 1975, 1982). Such psychophysiological events considered at different levels of resolution suggest that chronobiologic research may facilitate finding answers to some of the epistemological questions regarding the new concepts of "order by fluctuation." Where rhythmometry analyses made it possible to demonstrate intermodulating rhythms with a broad range of frequencies characterizing the biological time structure of organisms (i.e., the dynamical rhythmic structure of life), a major problem which challenges biological research today is that of "chaotic behavior" (i.e., the study of movements of some physical or biological systems which can become chaotic or unpredictable); chronobiologic experiments and physical investigations concerned with "biological oscillators" are made in this direction and lead to discovery of entities of the biological time structure: "the sum of nonrandom and thus predictable time-dependent biologic changes, including, withgrowth, development and aging, a spectrum of rhythms with different frequencies" (Halberg, et al., 1977). Where the field of epileptology involving a "window to brain mechanisms" is concerned with special reference to behavioral sciences, time structure characterizes any biologic entity, including ecosystems and populations as well as individual or grouped organisms, organ systems, organs, tissues, cells and subcellular structures, exhibiting one or several frequencies. I n this respect, chronobiologic analyses may well contribute to the elucidation of some mechanisms of chaotic systems, notably in ecology (concept of chronoecology in behavioral biosciences) and in psychology (clinical and physiological aspects including the mind-body problem). Chronobiology contributes to revolutionizing some classical concepts regarding the functional mechanisms of oscillatory phenomena (e.g., spatiotemporal organization in chemical and cellular systems; logical structure of dynamical systems; adaptive regulation processes in biology and physiological psychology). I n a biological context of order by fluctuation, we now know, at least theoretically, that all organisms exhibit ultradian, circadian, and infradian frequency variations in their adaptive functions and their behavioral integration. As a result, these systematic temporal variations question sharply the classically held physiological concept of homeostasis (Halberg, 1969,

CIRCADIAN ASPECTS O F EPILEPTIC BEHAVIOR

797

1983) as well as the Euclidean principle of the linearity of time (Poirel, 1975, 1982). I n this respect, chronobiology discoveries challenge the traditional view of steady state in biology and behavioral science by demonstrating intrinsic physiological rhythmicities modulated by extraneous or environmental synchronizers. From rhythmometric determinism to chaotic behavior, chronobiology is expected, at least theoretically, to unravel the relationship of time to chaos and rhythmologic fluctuations, as well as to chaos and arrhythmias [e.g., problems referring to rhythmicities and erratic fluctuations submitted to peribdic and aperiodic synchronizers with possible action of attractors; studies regarding nonlinear dissipative systems, chaotic states, and their possible effects on chronobiologic predictability (for instance, in these transitional contexts: burst firing patterns ultradian rhythmicities in neurophysiology; circadian rhythms of mental life in chronopsych~log~, complex phenomena of infradian oscillations with climatic fluctuations in chronoecology (Poirel, 1990)l. Chronobiologic events of epilepsy from neuronal activities to psychological integrations are directly concerned with these complex problems of predictability.

Psychophysiology of Seizure Susceptibility, Psychopathology, and Dreaming From another perspective in psychopathology, it should be recalled that physiological parameters which characterize the BRAC and certain qualitative aspects, such as the afJective content of dreams, may become very important for the possible rhythmicity of different kinds of seizure susceptibility. Such clinical events refer to the possible relationship between dream phenomena and the mental significance of certain epilepsies (e.g., psychotic reactions), the temporal distribution of which may be partly linked to the occurrence of dreams whose endogenous mechanisms may respond to ultradian and circadian processes. For instance, considering some relationships between dreaming- and seizure susceptibility, daytime occurrence of certain epileptic auras might also correspond to recurrent nocturnal dreams. I n psychophysiology, epilepsy events and dream phenomena might "depend upon the same neuronal mechanisms in the temporal cortex" (Penfield & Rasmussen, 1950), e.g., notion of complex epileptic behaviors involving hippocampal vigilance. lo Such 'In this psychophysiological context, note that Freud (1928) had suspected that the epileptic lit was a manifestation of an instinctual defus~on. 'Amon telencephalic structures actlng :IS modulators on vigilance and epilepsy, the limbic sysI m incfuding the amygdala and the h~ pocam us must be taken into considention since the limbic system operates not only upon iRe psycRoghyriological organization of temporni putterns of motor activities but also upon initiation of ep' eptlc processes and related behavioral events. In this respect, ethological studies in comparative psychopathology show that some epileptic manifestations (e.g., atypical convulsions) and some "derived activities" (e.g., behavioral stereotypies) present several circadian rhythms in s nchrony (Poirel, 1975, 1988). Such chronobiologic convergences suggest, at least theoretically, tlat these behavior rhythms would respond to circadian fluctuations of hippocampal vigilance.

798

C. POIREL & M. ENNAJI

possible chronobiologic relationships between dreaming and epilepsy may offer new psychophysiological research perspectives regarding the subjective experience of time and the altered mental states of consciousness. In spite of the remarkable studies by Lockard and Ward (1980) regarding epilepsy and theoretical psychophysiology, we can say with Broughton (1982) that "Epilepsy has provided so much insight into brain mechanisms in general, and into the mechanisms of conscious mental experience in particular, that it has often been referred to in this regard as an "experiment of nature," given this and the many studies of epileptic phenomena in sleep, it is surprising that so little investigation has been done on the relationships between nocturnal epileptic phenomena and dreaming per se" (p. 107). In this theoretical context of functional relationships between vigilance level and seizure susceptibility, brain chronobiologic events should also be considered as "experiments of nature" which make it possible to explore mental activity processes, psychology of time, and possibly the biological space of the stream of consciousness. REFERENCES AUTRET,A., & GAILLARD, PH. Sommeil et pathologie de lPnc6phale (Rapport de neurologie). Paris: Masson, 1990. BEAU,M. Recherches statistiques pour servir H I'histoire de I'tpilepsie et de l'hysttrie. Archives Gktkales de Midecine, 1836, 11, 328-532. BESSET,A . Influence of generalized seizures on sleep organization. In M. B. Sterman, M. N . Shouse. & P. Passouant (Eds.), Sleep and epilepsy. New York: Academic Press, 1982. Pp. 339-346. B u m , M. Epilepsies and the sleep-wake cycle. In M. B. Sterman, M. N. Shouse, & P. Passouant (Eds.), Sleep and epilepsy. New York: Academic Press, 1982. Pp. 269.286 BINGHAM,C., ARBOGAST,B., CORNBLISSEN-GUILLAUME, G., LEE, J. K., & HALBUIC,F Inferential statistical methods for estimating and comparing cosinor parameters. Chronobiologia, 1982, 9, 397-439. BROUGHTON, R. J. Biorhythmic variations in consciousness and psychological functions. Canadian Psvcholonical - Review. 1975.. 16.. 217-239. BROUGHTON, R. J. Human consciousness and sleep/waking rhythms: a review and some neuropsychological considerations. Journal of Clinical Neuropsychology, 1982, 4, 193-218. (a) R. J. Neurology and dreaming. Revue de Psychiatric de I'Universitt d'Ottawa, BROUGHTON, 1982, 7. 101-110. (b) BROUGHTON, R. J. The circasemidian sleep rhythm and its relationships to the circadian and ultradian sleep-wake rhythms. In W. P. Koella, F. O b d , H. Schulz, & I? Visser (Eds.), Sleep 86: the organization and regulation of sleep; various models. Stuttgart: Fischer-Verlag, 1988. Pp. 41-43. DALLABERNARDINA, B., BONDAVALLI, S., & COLAMARIA, V. Benign epile sy of childhood with rolandic spikes (BERS) during slee I n M. B. Sterman, M. N. SEouse, & P. Passouant (Eds.), Sleep and epilepsy. New ~ o r Academic t Press, 1982. Pp. 495-506. DENNY-BROWN, D., & ROBERTSON, E . G . Observations on records of local epileptic convulsions. Journal of Neurology and Psychopathology, 1934, 15, 97-136. FERE,C. De la fr6quence des accts d'Cpilepsie selon les heures. Comptes Rendus de la Soci6ti de BioIogie (Paris), 1888, 40, 740-742. FREUD,S. Dostojewski und die Vatertotung. Gesammelte Schriften, Vienna, 1928 [Cf., S. Freud. The ego and the id. New York: Norton, 1960 (Trans]. by J. Riviere)]. FROMM,G . H., FAINGOLD, C. L., BROWNING,R. A., & BURNHAM,W. M. (Eds.) Epilepsy and the reticular formation. New York: Alan R. Liss, 1987.

CIRCADIAN ASPECTS O F EPILEPTIC BEHAVIOR

799

GASTAUT, H . Foreword. In G. H . Fromm, C. L. Faingold, R. A. Browning, & W. M. Burnham (Eds.), Epilepsy and the reticular formation. New York: Alan R. Liss, 1787. Pp. xi-xii. GLASS,L., & MACKEY,M. C. From clocks to chaos. Princeton, NJ: Univer. of Princeton Press, 1988. GLOOR, I? Generalized epilepsy with spike-and-wave discharge: a reinterpretation of electmgraphic and clinical manifestations. Epilepsia, 1779, 20, 571-588. GOWRS, W. R. Epilepsy and ofher chronic convulsive diseases: their causes, symptoms and treatment. London: William Wood, 1885. G R ~ H SG ., M., & FOX,J. T. Rhythm in epilepsy. Lancet, 1938, 2, 409-416. HMASZ,P. The generalized epileptic spike-wave mechanisms and the sleep-wakefulness system. Acta Physiologia Hungmian Academy of Sciences, 1972, 42, 293-314. HALBERG, F. Some current research methods and results with special reference to the central nervous system; physiopathologic approach. American Journal of Mental Deficiency, 1960, 65, 156-171. HALBERG,F. Resolving power of electronic computers in chronopathology, and analogy to microscopy. Scientia, 1966, 101, 412-419. HALBERG, F. Chronobiology. Annual Review of Physiology, 1967, 3 1, 675-725. HALBERG,F. QUO k d i s basic and clinical chronobiology: promise for health maintenance. American Journal of Anatomy, 1983, 168, 543-574. HALBERG, F,, BITTNER,J. J., & GULLY,R. J. Twenty-four hour susceptibility to audiogenic convulsions in several stocks of mice. Federation Proceedings, 1755, 14, 67-68. HALBERG, F,, CARANDENTE, F., CORNLLISSEN, G . , & KAT~NAS, G . S. Glossary of chronobiology. Chronobiologia, 1977, 4(Suppl. I), 1-189. HALBERG, F., & HOWARD, R. B. 24-hour periodicity and experimental medicine; examples and interpretations. Postgradnate Medicine, 1958, 24, 349-358. HMLEK, M., REINBERG, A,, S C H M ~ TR., , LEVI, F., & HELLBRUGGE, T. Circadian and ultradian rhythms in behavior and seizures in children with petit mal epilepsy. Chronobiologia, 1783, 10, 131. (Abstract) HELLBRUGGE, T. The development of circadian rhythms in infants. Cold Spring Harbor Symposium Quantitative Biology, 1960, 25, 311-323. H O P ~ SH., T i e of appearance of epileptic seizures in relation to age, duration and type of syndrome. Journal of Nervous and Mental Diseases, 1933, 77, 153-162. JANZ,D. The Grand Mal epilepsies and the sleep-waking cycle. Epilepsia, 1962, 3, 69-107. JANZ,D. Epilepsy and the sleep/waking cycle. In P. J. Vinken & G. W. Bruyn (Eds.), Handbook of clinical neurology. Vol. 15. The epilepsies. Amsterdam, The Netherlands: Elsevier, 1974. Pp. 457-490. JASPER,H., WARD,A., & POPE,A. Basic mechanisms ofthe epilepsies. London: Churchill, 1769. JINNAI,D., & MUKAWA, J. Clinical observation in man: Forel-H-Tomy and its place in epilepsy. In G. H . Fromm, C. L. Faingold, R. A. Browning, & W. M. Burnham (Eds.), Epilepsy and the reticular formation. New York: Alan R. Liss, 1987. Pp. 163-191. JOLY,R. Hippocrate, Midecin Grecque. Paris: Gallimard, 1764. LANGDON-DOWN, M., & BRAIN,W. R. Time of day in relation to convulsions in epilepsy. Lancet, 1929, 1, 1029-1032. s ~ : to brain mechanisms. New York: LOCKARD, J. S., & WARD,A. A. (Eds.) ~ ~ i l e a~window Raven Press, 1780. LOISEAU,P., & JALLON, P. Les tpilepsies morphtiques de I'enfance. In W. l? Koella & l? Levin (Eds.), Sleep 1976. Basel: Karger, 1977. Pp. 43-49. LUGARESI,E., & CIRIGNOT~A, F. Nocturnal paroxysmal dystonia. In M. B. Sterman, M. N. Shouse, & P. Passouant (Eds.), Sleep and epilepsy. New York: Academic Press, 1782. Pp. 507-511. MEIEREWERT,K., & BROUGHTON, R. J. Photomyoclonic response of epileptic subjects during wakefulness, sleep, and arousal. Electroencephalography and Clinical Neurophysiology, 1967, 23, 142-151. MLKOL,F., & MONGE-STRAUSS, M. F. Horaires des crises et ripartition nycthtmirale des activitis EEG paroxystiques: ttude chez 197 ipileptiques. Revue Neurologique, 1987, 143, 451-456.

800

C. POIREL & M. ENNAJI

MONTPWSIR, J., & DEMERS,L. Le somnambulisme. L'Union MPdicale du Canada, 1983, 112, 619-623. MONTPLAISIR, J., LAVERDIERE, M., & SAINTHILALRE,J. M. Sleep and epilepsy. In J. Gotman, J. R. Ives, & l? Gloor (Eds.), Long-term monitoring and computer analysis of the EEG epilepsy. Amsterdam, The Netherlands: Elsevier, 1987. Pp. 1-48. MONTPLAISIR, J., LAVERDIERE, M., WALSH, J., SAINTHILAIRE,J. M., & BOUVIER,G . Epilepsie et sommeil. L'Union Midicale du Canada, 1980, 109, 1004-1008. Monuzzr, G. L . ' ~ ~ i l e ~exphimentale. sie (Trans]. by M. Reuchlin) Paris: Hermann, 1950. NELSON,W., TONG,Y. L., LEE, J. K., & HALBERG,F. Methods for cosinor-rhythmometry. Chronobiologia, 1979, 6, 305-323. OKIJMURA,S. [Experimental study of the propagation of convulsive impulses.] Okayama Igakkai Zasshi, 1958, 70, 723-752. Cjapanese]. PASSOUANT, P. Influence des itats de vigilance sur les ipilepsies. In W. l? Koella & P. Levin (Eds.), Sleep 1976. Basel: Karger, 1977. Pp. 57-65. PATRY,F. L. The relation of time of day, sleep and other factors to the incidence of epileptic seizures. American Journal of Psychiatry, 1931, 87, 789-813. PENFIELD,W. Epilepsy, neuro hysiology, and some brain mechanisms related to consciousness. In H . Jasper, A. war{ & A. Pope (Eds.), Basic mechanisms of the epilepsies. Boston, M A : Little Brown. 1969. PD. 791-805. PENFIEU),W., & JASPER,H. Epilepsy and the firnctional anatomy of !he human brain. Boston, MA: Little, Brown, 1954. PENFIELD,W., & RASMUSSEN, TH. The cerebral cortex of man. New York: Macmillan, 1950. POIREL, C. Mise en ividence de variations nycthCmCrales de la susceptibilit6 i la crise audiogene chez la souris Swiss/Albinos. Comptes Rendus de la SociPt6 de Biologie (Paris), 1967, 161, 1461-1465. POIREL,C. Some circadian rhythms in experimental ethology and comparative psychopathology. In L. E. Scheving, F. Halberg, & J. E. Pauly (Eds.), Chronobiology. Tokyo: Igaku Shoin, 1974. Pp. 540-543. POIREL,C. Les rhythmes circadiens en psychopathologie. Paris: Masson, 1975. POIREL,C. Circadian rhythms in behavior and experimental psychopathology. In F. M. Brown & R. C. Graeber (Eds.), Rhythmic aspects of behavior. Hillsdale, N J : Erlbaum, 1982. Pp. 363-398. POIREL,C. Circadian rhythms and temporal structure of the susceptibility to tonic-clonic seizures in the mouse. Brain Research, 1984, 301, 384-388. POIREL,C. Circadian patterns of vigilance and seizure susceptibility in genetically epileptic mice: heuristic aspects in neurology. In J . E. Pauly & L. E. Scheving (Eds.), Advances in chronobiologv. Vol. 2. New York: Alan R. Liss, 1987. Pp. 459-466. POIREL,C. Rhythmometric analyses of circadian variations of grooming behavior in the mouse: research ~ e r s ~ e c t i v eins behavioral chronobiology. Journal of General Psychology, 1988, 115, 187-201. medPOIREL,C. The concept ol chronopsychology and the circadian rhythms in icine. Reyue de MPdecine Psychosomatique, 1990, 31, 81-98. POIREL, C. Circadian chronobiology of epilepsy: murine models of seizure susceptibility and theoretical perspectives for neurology. Chronobiologia, 1990 (in press). P o m , C., & DANTZER, R. Psychophysiological research on the circadian rhythms of epilepsy. La Presse Midicale, 1971, 79, 2175-2177. P o m , C., & ENNAJI,M. Modkles chronobiologiques circadlens en neurologic comp&e. Recherches ~om~iimentaires sur I'Cpilepsie expirimentale. In J. M. L-iger (Ed.), Comptes Rendus dl, CongrPr de Psychiahie ef de Neurologie. Paris: Masson, 1990. Pp. 516-522. P o r w , C., & LMOUCHE, B. Human circadian patterns of memory processes: chronopsychology of rates of forgetting: a rhythmometric study. Psychological Reports, 1987, 61, 3-12. POIREL,C., & LAROUC~IE, B. Circadian patterns of basic emotional reactivity and stress related events revisited in mice treated with lithium: behavioral rhythmometric analyses. Chronobiologia, 1989, 16, 229-239. SATO,S., DREIFUSS,F., & PERRY, J. K. The effect of sleep on spike-wave discharges in absence seizures. Neurology, 1973, 23, 1335-1345. SECI-ITER, D., & POIREL,C. Chronobiologie et psychiah.ie. Paris: Masson, 1985.

CIRCADIAN ASPECTS O F EPILEPTIC BEHAVIOR

801

SILVA,L. R., AMITAI,Y., & CONNORS, B. W. Intrinsic oscillations of neocortex generated by layer 5 pyramidal neurons. Science, 1991, 251, 432-435. STERMAN,M. B., SHOUSE,M. N., & PASSOUANT, P. (Eds.) Sleep and epilepsy. New York: Academic Press, 1982. TEMKIN,0 . The falling sickness, a history of epilepsy from the Greeks to the bey~nningsof modern neurology. Baltimore, MD: Johns Hopkins, 1971. TOUCHON, J. Effect of awakening on epileptic activity in primary generalized myoclonic epilepsy. In M. B. Sterrnan, M. N. Shouse, & P Passouant (Eds.), Sleep and epilepsy. New York: Academic Press, 1982. Pp. 239-248. V ~ z r o u R. , Le Syndrome de Lennox-Gastaut. Paris: Masson, 1970. WEBB,W. B. Foreword. In F. M. Brown & R. C. Graeber (Eds.), Rhythmic aspects of behavior. Hillsdale, NJ: Erlbaum, 1982. Pp. ix-xiii. WEBB, W. B. Circadian biological rhythm aspects of sleep and epilepsy. In A. Martins da Silva, et al. (Eds.), Biorhythms and epilepsy. New York: Raven Press, 1985. Pp. 13-27. WYLER,A. R. Epileptic neurons during sleep and wakefulness. Ewperimentul Neurology, 1974, 42, 593-608. W ~ E RA., R., & WARD,A. A,, JR. Epileptic neurons. In J. S. Lockard & A. A. Ward, Jr. (Eds.), Epikpsy, a window to brain mechanisms. New York: Raven Press, 1980. Pp. 51-68. Accepted April 18, 1991

Circadian aspects of epileptic behavior in comparative psychophysiology.

This paper is concerned with some experimental and clinical problems regarding the circadian chronobiology of epilepsy. Rhythmometrically analyzed, th...
793KB Sizes 0 Downloads 0 Views