Grouping of brain rhythms in corticothalamic systems

Animal models of the epilepsies

Pathophysiological mechanisms of genetic absence epilepsy in the rat

Anterograde and retrograde tracing experiments have been used to demonstrate the origin and terminal distribution of commissural fibers in the first somatosensory cortex (SI) of the rat. The commissural fibers originate from pyramidal cells of all layers, but predominantly from layers III and V. The fibers terminate in a series of approximately vertical bands. In each of these there are concentrations of terminals extending from the inner portion of the molecular layer to the deep portion of layer III as well as in the superficial part of layer V, and in layer VI. Discrete vertical bands of cortex are reciprocally connected across the midline to give both the origin and terminal regions of the projection a patchy or “columnar” appearance. The commissural fibers arise from and terminate in areas of the cortex that lie between and alongside the aggregations of granule cells that distinguish SI of the rat. No commissural fibers terminate within the aggregations of layer IV cells themselves but the more superficial terminal ramifications may come to overlie these aggregations. A heterotopic projection to the contralateral second somatosensory cortex has been observed and is similar in form to the homotopic projection to SI.



Many commissural fibers have crossed the midline in the corpus callosum by the day of birth but lie in the underlying white matter and do not enter the cortical plate until at least the third postnatal day. During the first postnatal week these fibers grow somewhat diffusely into the maturing cortex and their topographic and laminar pattern of distribution attains its adult characteristics by the end of the first week. Commissural axons, thus, arise from immature cells but the maturation of cell form seems to precede the ingrowth of these axons and the acquisition of commissural synapses.

The organization and postnatal development of the commissural projection of the rat somatic sensory cortex.

Publisher Summary This chapter discusses epilepsy and γ-aminobutyric acid (GABA) mediated inhibition. The inhibitory action of short-chain ω-amino acids (such as β-alanine, GABA, and taurine) on central neurons has been established by the microiontophoretic studies. Additional data that have led to the widespread acceptance of the hypothesis that GABA is the inhibitory transmitter at numerous central sites include (1) the demonstration of high GABA content and glutamic acid decarboxylase (GAD) activity in synaptosome preparations, (2) the evidence for the selective local release of GABA when known inhibitory systems are activated in the cerebral cortex or cerebellum, and (3) evidence from intracellular recordings that the changes in membrane potential and in specific ionic conductances produced by physiological inhibitory inputs are similar to those produced by the iontophoretic application of GABA. The principal sites where GABA produces hyperpolarization of the neuronal membrane, which resembles the physiologically induced inhibitory postsynaptic potential (IPSP) in its dependence on an enhanced chloride conductance, and where naturally induced inhibition and the action of applied GABA are blocked by picrotoxin or bicuculline, are the neocortex, the cerebellum, the hippocampus, and the thalamus.

Epilepsy and gamma-aminobutyric acid-mediated inhibition.

THE PRECISE and constant location of origin of the bilateral, symmetrical patterns of electrical discharge as they occur in man with "idiopathic" or "essential epilepsy" ("petit mal" and "grand mal") has not yet been completely defined. The characteristic electroencephalographic patterns which accompany the "absence" seizure of petit mal have not yet been exactly reproduced in animals. The most distinctive electroencephalographic pattern of idiopathic epilepsy in childhood is the 2.5 to 3.5 cycle-per-second (cps) spike wave associated with the "absence" seizure. This discharge is abrupt in onset, bilateral, nearly synchronous, and of nearly equal amplitude in the two hemisphere. It is often precipitated by hyperventilation and photic stimulation. Two distinct categories of hypotheses of the location of the lesion responsible for originating the bilateral grouped discharges of idiopathic epilepsy, especially in petit mal, have emerged: (1) The "centrencephalic" hypothesis of exclusive origin of the process giving rise to the spike

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Bilateral synchronous spike wave electrographic patterns in the cat. Interaction of bilateral cortical foci in the intact, the bilateral cortical-callosal, and adiencephalic preparation.

RELATIONSHIPS, both general and specific, between ovarian function and seizure susceptibility have long been postulated. Analysis of patients who have the onset of a seizure disorder in the age range 10 to 20 years indicates a prevalence of females among patients subject to "petit mal" 1 and to seizures of other forms. 2 Significant age-related sex differences occur in the incidence of light-evoked electroencephalographic abnormalities with a higher incidence in the female during the years of active ovarian function. 3 Seizures in many females are increased in their frequency in relation to the menstrual cycle. Logothetis et al 4 postulated that a premenstrual exacerbation of seizures might be related to increased estrogenic activity. A lowering of electroshock threshold during estrus in the rat has been related to high levels of circulating estradiol during this phase. 5 The exact relation of circulating estrogenic substances to seizure exacerbations in the human

Effects of Steroids on Cerebral Electrical Activity: Epileptogenic Effects of Conjugated Estrogens and Related Compounds in the Cat and Rabbit

WE HAVE previously reported the results of a series of experiments in the cat concerning the interaction of acute relatively large bilateral epileptogenic foci in homologous areas of cerebral cortex 1,2 (predominantly posterior sigmoid and suprasylvian gyri). In the intact animal, this interaction often resulted in the rapid production of persistent synchronous and symmetrical patterns of bilateral discharge including 21/2 to 31/2 cycles per second (cps) spike-slow wave complexes. Relevant behavioral concomitants of these bilateral discharges resembled some of the clinical phenomena observed in patients with idiopathic petit mal or grand mal seizures during similar bilateral discharges: bilateral facial muscle and forelimb myoclonus, transient suspension or imperfect continuation of a repetitive act, and occasional generalized convulsive seizures. Investigations of the underlying anatomical pathways involved in this interaction of bilateral cortical foci indicated the significant role of the corpus callosum. Synchrony of bilateral discharge failed to occur after total

Symmetrical epileptogenic foci in monkey cerebral cortex. Mechanisms of interaction and regional variations in capacity for synchronous discharges.

UMMARY
This discussion has examined 2 central questions regarding the pathophysiology of petit mal epilepsy. First, what is the locus of the lesion responsible for the bilateral synchronous and symmetrical spike-slow wave discharges and the associated behavioral absence of petit mal epilepsy? We have demonstrated that it is possible to produce an experimental model of petit mal epilepsy in the otherwise intact cat or monkey without the necessity of lesions in the brain stem or diencephalic structures. The essential lesion in this model is solely cortical and bilateral in location. In particular our experiments have involved the production of acute relatively large bilateral and symmetrical cortical epileptogenic foci. The interaction of these foci resulted in the development of synchronous and symmetrical patterns of bilateral discharge resembling the various forms of human primary bilateral synchrony including the 2½-4 c/s spike-slow wave complex. In the monkey, regional variations in capacity for bilateral discharge were noted, related to regional differences in callosal projection. Particularly well regulated bilaterally synchronous and symmetrical bursts of 2½-4 c/s spike-slow wave complexes occurred with bilateral foci in the premotor area of monkey frontal lobe. Studies of behavior and simultaneously recorded electroencephalogram indicated that bilateral synchronous discharges of 3 c/s spike-slow wave complex resulting from bilateral foci in anterior premotor area were closely correlated with short staring spells resembling petit mal (absence) seizures.

Second, irrespective of where the responsible lesion(s) may be located, are the brain stem and diencephalic structures essential for the development of these bilateral symmetrical and synchronous discharges of 2½-3 c/s spike-slow wave complexes which are the hallmark of petit mal epilepsy? From the standpoint of the present model, it is demonstrated that section of the corpus callosum in the cat or of all major commissures in the monkey markedly disrupted the synchrony of discharge of bilateral foci. Alternate pathways for coarse synchrony at low rates of discharge were demonstrated. These results should be compared to the high degree of synchrony of bilateral discharge obtained in the cat or monkey preparation in which large blocks of cerebral cortex in each hemisphere were isolated from subcortical structures but remained connected via the corpus callosum. The spike discharges of bilateral foci in this preparation were synchronized within 10–20 msec, well within the limits noted in the intact animal and in the patient with petit mal epilepsy. The patterns of bilateral discharge in this cortical-callosal preparation included bilateral synchronous bursts of 2½-3 c/s spike-slow wave complexes.

RESUME
Ce travail envisage deux questions essentielles concernant la physiopathologie de l'epilepsie petit mal. Premiere question: Quel est le siege de la lesion responsable des decharges bilaterales, synchrones et symetriques de pointes-ondes qui accompagnent les absences petit mal? Nous avons demontrea ce propos qu'il est possible de reproduire une epilepsie du type petit mal chez un chat ou un singe d'autre part normal independamment de toutes lesions du tronc cerebral ou du diencephale. II suffit de realiser chez ces animaux des lesions corticales bilaterales, notamment des foyeis epileptogenes corticaux aigus, bilateraux et symetriques, assez etendus. L'interaction de ces foyers aboutit a la production de decharges bilaterales synchrones et symetriques ressemblant aux differents types de synchronic bilaterale primaire observee chez FHomme, y compris la pointe-onde a 2½-4 c/s. Chez le singe on observe des variations regionales dans la capacitye de produire des decharges bilaterales qui dependent des differences regionales dans les projections commissurales calleuses; c'est ainsi que les bouffees de pointes-ondes bilaterales synchrones et symetriques a 2½-4 c/s particulierement regulieres, accompagnees de troubles du comportement evoquant une absence, surviennent sous l'effet de foyers bilateraux dans l'aire premotrice des lobes frontaux.

Deuxieme question: Quel que soit le siege des lesions responsables, le tronc cerebral et le diencephale sont-ils indispensables pour le developpement des decharges bilaterales synchrones et symetriques de pointes-ondes a 2½-4 c/s qui sont caracte-ristiques des epilepsies petit mal?

En ce qui concerne nos propres experiences, il apparait que la section du corps calleux du chat ou celle de toutes les grandes commissures chez le singe altere considerablement la synchronic des decharges de foyers bilateraux. Ces resultats contrasted avec le haut degre de synchronic des decharges bilaterales obtenues dans les larges etendues de cortex cerebral qui, dans chaque hemisphere, sont isolees des structures sous-corticales mais demeurent interconnectees a travers le corps calleux. Dans de telles preparations cortico-callosales, les decharges de pointes des complexes pointes-ondes recueillies dans les foyers bilateraux sont synchronises dans des limites de 10–20 msec qui correspondent a celles observees chez l'animal intact ou chez le sujet humain presentant une epilepsie petit mal.

An Experimental Model of Some Varieties of Petit Mai Epilepsy Electrical‐Behavioral Correlations of Acute Bilateral Epileptogenic Foci in Cerebral Cortex

Elliott M. Marcus

Papers

Bilateral synchronous spike wave electrographic patterns in the cat. Interaction of bilateral cortical foci in the intact, the bilateral cortical-callosal, and adiencephalic preparation.

Effects of Steroids on Cerebral Electrical Activity: Epileptogenic Effects of Conjugated Estrogens and Related Compounds in the Cat and Rabbit

Symmetrical epileptogenic foci in monkey cerebral cortex. Mechanisms of interaction and regional variations in capacity for synchronous discharges.

An Experimental Model of Some Varieties of Petit Mai Epilepsy Electrical‐Behavioral Correlations of Acute Bilateral Epileptogenic Foci in Cerebral Cortex

The laminar distribution of fibers of the corpus callosum: a comparative study in the rat, cat, rhesus monkey and chimpanzee.