Herbert H. Jasper

INTRACELLULAR OSCILLATORY RHYTHMS IN PYRAMIDAL TRACT NEURONES IN THE CAT.

Abstract Intracellular micro-electrode records from pyramidal tract neurones during spindle bursts in cerveau isole pyramidal cat preparations, or with light barbiturate anaesthesia, has shown a close relationship between spindle waves and much larger oscillations in membrane potential of PT cells. Intracellular oscillations are composed of excitatory (depolarizing) and inhibitory (polarizing) components of 5–17 mV amplitude. Excitatory components correspond to the surface negative spindle wave or recruiting response, and are most prominent in stable cells with a high resting MP and low rate of spontaneous firing. Inhibitory phases of intracellular oscillation, most prominent in partially depolarized active cells are not so clearly reflected in the form of surface spindle waves. The inhibitory phase may arrest spontaneous firing and decrease the probability of intracellular invasion of antidromic impulses. Although intracellular oscillations and occasionally a burst of spindle waves may be evoked by antidromic volleys, such stimuli are far less effective than intralaminar thalamic stimulation in controlling spindle bursts. Axon collateral inhibition, though present and long lasting in PT neurones, does not seem to be the most important mechanism generating spontaneous spindle bursts in the cortex. Spindle bursts are most likely composed of synchronized alternating excitatory and inhibitory post-synaptic potentials distributed over the extent of the soma-apical dendritic membrane of pyramidal cells, the more superficially located synapses being largely responsible for the surface negative excitatory waves. Surface positive waves may be also excitatory and slow surface negative waves may be associated with long lasting polarizing waves in PT neurones. Multiple intracortical, thalamo-cortical, and cortico-thalamic reverberating rhythmic systems, normally loosely linked and capable of a degree of independent action, must be involved in the generation of the variety of waves and rhythms of the EEG. Pacemaker neuronal systems in the thalamus probably provide the timing for many cortical rhythms, even though intracortical axon collateral or other self re-exciting circuits may participate in generating rhythmically repeated discharge, and may become at times independent of thalamic control.

Effects of distraction upon simultaneous auditory and visual evoked potentials

Abstract Evoked potentials have been recorded from implanted electrodes in visual and auditory cortex, and in medial and lateral geniculate bodies in cats in response to simultaneous high intensity “click” and “flash” test stimuli. During continuous test stimuli at 1/sec, auditory or visual distraction was introduced in the form of the “squeaking” of a rat, or the presence of a live rat in the cage with the cat. The changes in simultaneously recorded evoked potentials during auditory or visual distraction may be summarized as follows: 1. 1. Evoked potentials in the unanaesthetized, freely-moving animal were highly variable with the animal at rest after it had become accustomed to the experimental situation. 2. 2. Decrease in evoked potentials at both cortical and geniculate levels occurred after prolonged continuous stimulation with habituation to the test stimuli. 3. 3. Distraction with either visual or auditory stimuli caused a marked increase in regularity of evoked responses, with an increase in average amplitude and a marked decrease in their variability. There was also a “sharpening” of their form due to suppression of later components of the evoked potential complex implying improved synchronization or less dispersion of responding elements. Such effects were not selective, affecting visual and auditory systems alike though to different degrees, regardless of the form (visual or auditory) of the distraction. 4. 4. In relatively alert animals, prior to distraction there was a marked reduction in evoked potential amplitudes in both auditory and visual systems with either visual or auditory distraction. There was an accompanying dispersion and increased variability of evoked responses suggesting desynchronization and/or occlusive blockage, or masking of specific responses to afferent volleys with excessive non-specific “activation”. 5. 5. No consistent selective action upon one modality or the other could be demonstrated as might be expected for an attentive process. 6. 6. It is concluded that increased alertness facilitates and sharpens cortical and geniculate response to sensory test volleys, decreases their variability, and increases their amplitude if previously habituated (dishabituation). Excessive non-specific activation causes decreased evoked potentials probably due to occlusive blockage or possibly with the participation of inhibitory processes.

The identity of spreading depression and “suppression”

Abstract 1. 1. That type of electrical change characterized by the appearance of reduced electrical activity at the point of cortical stimulation, thence to appear in successive fashion in contiguous areas of cortex, requiring minutes for such spread, has been identified in the literature with “suppression of electrical activity”, a property ascribed only to certain “suppressor areas”. Experimental evidence herein presented has shown that this phenomenon is actually due to the spreading depression of Leao and cannot be distinguished from it by any presumed criteria of differentiation. 2. 2. Spreading depression can be produced at times, under ill defined conditions, by strychnine as well as other methods of stimulation (chemical, electrical or mechanical) from any area of the cortex in cat and monkey. 3. 3. The mechanism by which the changes of electrical activity known under the general heading of spreading depression are produced, is essentially cortico-cortical; further, it does not require neural continuity, but only neural contiguity. 4. 4. The type I or type II spreading depression of electrical activity is accompanied by a decrease in cortical excitability, as judged by decrease in cortically induced movements and by a depression of strychnine spikes and sensory evoked potentials. 5. 5. Stress has been laid upon the importance of considering mechanisms functioning independently of neuro-anatomical connections, as being of significance in function either normal or abnormal. In particular, possible relationships between the phenomenon of spreading depression and the spread by contiguity of a focal epileptic discharge have been suggested.

Electrical signs of epileptic discharge

Abstract 1. 1. The only form of electrical activity which is though to characterize a local epileptogenic lesion of the cortex is the random spike discharge. 2. 2. The local spike discharge must become repetitive at a fairly rapid frequency before sufficient activation occurs to cause a change in behaviour or awareness of the patient. 3. 3. The spread of epileptic activation is manifest by an enhancement of the background spontaneous rhythms before the form of its activity is changed to a multiple spike pattern indicating violent local autonomous activation of this distant cortical area. Specific regions may produce a depression in background activity at the onset of an attack. 4. 4. Large areas of the cortex may be activated by electrical signs of epileptic activity, with little obvious change in the patient, these areas being the anterior frontal region and large portions of the temporal and parietal lobes. Spread to subcortical structures seems likely when changes in level of consciousness and behaviour automatisms are associated with epileptic discharge. 5. 5. The cerebral cortex alone, isolated from connections to subcortical structures, is capable of maintaining epileptic after-discharge, so that long reverberating circuits are not required for this process. 6. 6. Rhythmic epileptic activity of large areas of the cortex synchronized in one hemisphere or bilaterally synchronous from homologous regions of the two hemispheres, most probably has its pacemaker in the thalamus since from the thalamus, such rhythmic bilateral disturbances can be induced by local electrical stimulation. Other subcortical projection systems may also be involved. 7. 7. Local cortical epileptic discharge may also be initiated by local thalamic stimulation of the more directly projecting thalamic nuclei. 8. 8. Subcortical rhythmic systems, projecting to large areas of both hemispheres can also be actuated by local cortical epileptic discharge, most readily in certain portions of frontal and temporal regions. 9. 9. The clinical pattern of an epileptic seizure is not closely related to the form of associated E E G disturbance but rather to the functional area of the brain primarily involved and the functional characteristics of the neuronal circuits involved in the path of spread.

Surgical therapy in patients with temporal lobe seizures and bilateral EEG abnormality.

Clinical, pathological and follow‐up data on 29 patients with independent bitemporal EEG abnormality and in whom unilateral temporal lobectomy has been carried out, have been analyzed and compared to similar data on patients with EEG abnormality limited to one temporal lobe. Repeated pre‐operative EEG studies showed that in some cases the amplitude and amount of epileptiform discharge was predominant on one side (Group A), while in others it was about equal on the two sides (Group B).

Studies of the regulatory functions of the limbic cortex

Abstract 1. 1. Stimulation of the anterior limbic area, and infra-limbic area, can produce three general types of changes in electrical activity. These responses have in common: that they can occur in all areas of cortex bilaterally at the same time; that they occur immediately when elicited by electrical stimulation; and that they act via cortico-subcortical mechanisms. The types of changes in electrical activity affected are: 1.1. (a) Attenuation. 1.1.1. (i) Decrease in voltage without change in pattern. 1.1.2. (ii) Decrease in voltage with decreased number of bursts or with simplification of burst patterns. 1.2. (b) Augmentation of bursts. 1.3. (c) Activation or “arousal” responses. 1.3.1. (i) with decreased voltage. 1.3.2. (ii) with increased voltage. Subcortical mechanisms by which these effects may be produced have been suggested. 2. 2. The anterior limbic cortex (“24s”) cannot be accurately described as a “suppressor area” on the basis of its electrical properties. This is based upon two facts: 2.1. (i) That type of electrical response called “suppression” in the literature, and attributed to this area as a localizable property has been shown to be the phenomenon of spreading depression which has no such local characteristics. 2.2. (ii) Attenuation of cortical electrical activity (which differs markedly from the “suppressor” response described in the literature) can be evoked by stimulation of this area; but so also can the contrasting types of responses in electrical activity herein called augmentation and activation. The term “regulatory” seems to describe the functional properties of anterior limbic cortex better than “suppressor”. 3. 3. It has been suggested that intimate relationships exist between phylogenetically old areas of the brain, i.e. the “mesocortex” of the anterior limbic regions, the thalamic reticular system, and the reticular formations in hypothalamus, subthalamus and brain stem; all possessing important regulatory control of cortical electrical activity and function.

Evaluation of EEG and Cortical Electrographic Studies for Prognosis of Seizures following Surgical Excision of Epileptogenic Lesions

In the attempt to throw some light on the value of electroencephalographic and cortical electrographic studies of patients with seizures due to focal epileptogenic lesions and treated by surgical excision prognosis based upon electrographic results has been compared with follow‐up studies in 71 selected cases.

Studies of Non-Specific Effects upon Electrical Responses in Sensory Systems

Publisher Summary Electrical responses in specific sensory systems show wide variations due apparently to the modulating action of “extrasensory” or “unspecific” mechanisms. The chapter presents a summary of some observations related to these variations and their physiological and psychological significance. Two experiments that have contributed to an understanding of the significance of changes in sensory evoked potentials in relation to attention and behavior are described in the chapter: studies of changes in acoustic evoked potentials from the primary auditory cortex in the cat as affected by electrical stimulation of the amygdaloid nucleus and studies of the effects of distraction upon evoked potentials simultaneously recorded from visual and auditory systems in response to combined click and flash stimulation in the unanesthetized cat.

Physiopathological mechanisms of post-traumatic epilepsy.

Some, of the probable physiopathological mechanisms of post‐traumatic epilepsy have been reviewed and an hypothesis concerning an additional mechanism involving the decrease in inhibitory controls which might ensue with rupture of axon collaterals has been presented. Disruption of finely regulated vascular supply producing periodic or chronic functional ischaemia is considered of likely importance in chronic epileptogenic lesions which follow penetrating wounds of the brain. Mechanical distortion of dendrites caught in a glial cicatrix may also be of importance, as suggested by Ward, though it is not proven. Defects in the blood‐brain barrier and alterations in the buffering action of glial cells upon the maintenance of extracellular electrolyte balance may be also of importance. Finally it is proposed that the delicate collaterals which branch at right angles from axons of pyramidal cells may be particularly susceptible to the shearing forces of closed head injuries. Their rupture would result in a marked reduction in inhibitory controls permitting the recruitment of excessive synchronous discharge in large assemblies of neurones which is characteristic of the epileptic process.

General Summary of “Basic Mechanisms of the Epileptic Discharge”

The excellence of the papers presented at this Symposium is a tribute to the insight of our chairman, Dr. Ward, not only as to the selection of contributors but as to the timeliness of this subject, Mechanisms of the Epileptic Discharge. I am not sure that Dr. Ward was so wise, however, in his choice of the person to attempt a summary of all of this material, but I shall do the best I can not to summarize but to comment on certain aspects of the material presented. I can assure you that I am not going to present another paper, however, which would be the easy solution. The presentations of material by the speakers, as well as the papers given by the discussants have provided us with much new information and ideas for a reconsideration of basic mechanisms of epileptic discharge. The deliberate exclusion of neurochemical aspects of this problem has served to make it possible to concentrate on the electrophysiological or neurophysiological aspects alone. This has been shown to be more than enough for one symposium. In general, it is apparent that the rapid progress which has been made during recent years in the furtherance of our understanding of epileptic mechanisms has been due to the expanded use of microelectrodes to analyse the behaviour of single neurones during epileptic discharge. Without this information, records taken with gross electrodes, either form the surface of the brain or within the depths, have given only one limited aspect of the synchronous electrical manifestations of epileptic discharge. They have missed the more revealing characteristics of individual neurone firing. Dr. Li has provided us with a beautiful demonstration of the characteristics of neuronal membranes, and muscle membranes, which become unstable in their equilibrium and may oscillate to cause abnormal discharges of an epileptiform character. Li has rightly emphasized that the basic disorder of nerve cells which become epileptic lies in the instability of the nerve cell membrane and that these membrane potentials, when recorded intracellularly with microelectrodes, show wide fluctuations and