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Biomedical subjects

R N Englander

Publications and source records attributed to R N Englander.

9 recordsLinked to original sources

Cerebellar stimulation: regional effects on a thalamocortical system.

Regional effects of electrical stimulation of the cerebellar surface were quantitatively analyzed. Computer controlled stimulus sequences were delivered to ventrolateral thalamus and evoked responses recorded from ipsilateral sensorimotor cortex in the cat. Threshold and excitability profiles were produced with an on-line computer, and their modification by cerebellar stimulation was determined. The results of electrical stimulation of the cerebellar surface were: (1) depressed excitability from paramedian lobule and lobulus simplex; (2) uniquely elevated thresholds from paramedian lobule; and (3) a profound and long-lasting depression of excitability following termination of lobulus simplex stimulation. In comparison with our anticonvulsant drug studies, these data suggest that cerebellar surface stimulation has a far greater capacity to control excitability and threshold responsiveness of thalamocortical systems. Cerebellar electrode placement and temporal pattern of stimulation appear to be important factors in the production of antiepileptic effects.

Animals

Effects of valproate and ethosuximide on thalamocortical excitability.

Sodium valproate and ethosuximide are anticonvulsants employed in the treatment of petit mal epilepsy; both drugs are considered to be thalamically active. Valproate and ethosuximide both decreased the average evoked response following the second of two stimuli delivered to the ventrolateral thalamus at stimulus frequencies in the region of 3 Hz. Ethosuximide, but not valproate, enhanced the average evoked response at high stimulus frequencies an action shared with several convulsant treatments having different modes of action. The clinical effects of valproate and ethosuximide can be related to this differential modulation of thalamocortical excitability.

Animals

Effects of antiepileptic drugs on thalamocortical excitability.

Comparative effects of anticonvulsant drugs on the thalamocortical system were analyzed quantitatively. Paired stimuli were delivered to the ventrolateral thalamus with evoked responses recorded from the ipsilateral sensorimotor cortex in the cat. Threshold and excitability profiles were developed with an on-line computer. Effects of phenytoin and diazepam were generally similar, with depression of excitability and slight elevation of thresholds. Ethosuximide produced a pronounced pair-interval dependent effect of unchanged or increased excitability and lowered threshold at shorter intervals, with depressed excitability and raised threshold at longer intervals. These data demonstrate a marked difference in effect of the petit mal and grand mal agents tested and suggest a basis for the effectiveness of ethosuximide in controlling 3-per-second repetitive activity.

Animals

Stabilization of the thalamocortical motor system by cerebellar stimulation.

Epilepsy typifies instability in a complex control system. We have previously identified parameters of the thalamocortical motor system of the cat which correlate with epileptiform activity and are controlled by common anticonvulsants. This study is concerned with the control of such parameters by cerebellar stimulation, potencially promoting stability within the motor system. Under computer control, stimuli were delivered to both ventrolateral thalamus and cerebellar cortex, with multichannel recording of evoked responses obtained from sensorimotor cortex. Cortical evoked responses were plotted as an excitability curve (mean response amplitude as a function of pulse interval) or a family of threshold curves (mean response amplitude as a function of stimulus amplitude at various fixed intervals). The present study reveals that cerebellar epidural stimulation can reduce both the height and duration of the excitability curve, as well as increase the response threshold and reduce the saturation level of the threshold curve. The degree and direction of these parameter changes are dependent on the frequency, polarity, and amplitude of cerebellar stimulation, with the amount of parameter change exceeding that achieved by monotoxic doses of anticonvulsants. These data suggest that control of parameters related to excitability and threshold in the thalamocortical motor system may be the means by which cerebellar stimulation accomplishes control of clinical seizures.

Animals

Ethosuximide and bicuculline inhibition in petit mal epilepsy.

The mechanisms of petit mal epilepsy remain a mystery despite successful therapy. Previous workers have proposed that paroxysmal activity of cortical inhibitory systems plays a role in absence seizures. In this study, we have compared the effects of bicuculline, a potent convulsive agent and GABA antagonist, with ethosuximide, a drug used to treat petit mal epilepsy, on the thalamocortical motor system of the cat. Under chloralose anesthesia, sequential pairs of pulses were delivered to ventrolateral thalamus (VL) varying either pulse amplitude or interval. The evoked responses were recorded from sensorimotor cortex, analyzed on-line by computer, and plotted as an excitability curve (mean response amplitude as a function of pulse interval), or a family of threshold curves (mean response amplitude as a function of stimulus amplitude at various fixed intervals). Administration of each drug resulted in increased thalamocortical excitability and decreased threshold to stimulation for short pulse-pair intervals, with diminished duration of the excitability curve. Increased alertness was produced by both drugs. Studies with grand mal anticonvulsants demonstrated entirely different effects. Because GABA is thought to be the primary inhibitory transmitter in VL and cerebral cortex, bicuculline would be expected to result in disinhibition. The similarity of the data for ethosuximide suggests that ethosuximide also suppresses inhibition in the thalamocortical motor system and adds further to the accumulating evidence of the role of inhibitory system in petit mal epilepsy.

Animals

Location of human pyramidal tract in the internal capsule: anatomic evidence.

A patient with a small infarct located posteriorly in the internal capsule had 9 years of weakness of the contralateral face, arm, and leg. At necropsy, it was found that degeneration of the corticospinal tract was almost complete in the midbrain and medullary pyramid. This case supports the increasing evidence that the human pyramidal tract is located in the third quarter of the posterior limb of the internal capsule.

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