Sidney Goldring

Human Motor Cortex: Sensory Input Data from Single Neuron Recordings

Recordings were made from single neurons in the hand area of the human motor cortex while peripheral physiologic stimuli were applied. Such cells responded only to active and passive hand movements. Tactile and autditory (click) stimuli were itneffective. The majority of cells were activated only by movements of the contralateral hand, but a significant number (4 of 16) could be excited if a given movement was made by either hand. Of the cells responding to active movement, some showed an increased discharge before onset of the voluntary action. Such cells were excited by the same movement executed passively, a result that indicates sensory feedback from receptors activated by that movement.

Contribution to steady potential shifts of slow depolarization in cells presumed to be glia

Abstract The relationship between cortical steady potential (SP) shifts and slow depolarization (SD) in cells presumed to be glia was analyzed in 129 adult cats during direct cortical and thalamic stimulation. 1.1. Four hundred and seventy presumed glial cells were encountered; of these 214 showed SD with either direct cortical (119), thalamic (86) or peripheral (9) stimulation. Some cells showed SD occurring concurrently with barbiturate spindles. The mean resting potential of cells that showed SD was 65.6 mV (±13.3 mV). 2.2. SD produced by low frequency (6–10/sec) stimulation mirrors the configuration of cortical SP shifts. By contrast, neurons do not show sustained membrane depolarization at these frequencies. At high frequency (about 50/sec) stimulation, both presumed glial cells and neurons show sustained membrane depolarization. The configurations of the neuronal and presumed glial membrane changes are different, but both occur concomitantly with the SP shifts recorded at the surface. 3.3. During direct cortical stimulation SP shift amplitude diminishes gradually from the surface downward; a polarity reversal of SP shift is not seen even though the primary potentials that follow each stimulus do reverse (about 0.5 mm sub-surface). Similarly, an SD amplitude gradient exists between the surface and the deep layers, SD being very small or absent in the deeper layers. The stronger the surface stimulus, the deeper in cerebral cortex can an SP shift and SD be obtained. 4.4. With low frequency thalamic (VA) stimulation, SP shift and SD also have a similar distribution, but it is different from that seen with direct cortical stimulation. There is no SD gradient, SD occurring at all levels. Similarly the SP shift is evident throughout the cortical thickness. With high frequency stimulation, distribution of SP shift and SD differ. The presumed glial cells continue to show SD in the cortical depth, but SP shifts can be bigger, smaller or even reverse in polarity in the lower cortical layers. 5.5. The effect of sodium pentobarbital on SP shift and SD is the same. Following intravenous injection of amounts that cause the ECoG to become isoelectric, both an SP shift and SD can still be elicited by direct cortical stimulation. At this time, repetitively evoked primary potentials are absent or reversed in polarity. By contrast, smaller amounts of pentobarbital abolish both the SP shifts and SD induced by thalamic stimulation. 6.6. The results indicate that cells presumed to be glia as well as neurons account for stimulus-bound cortical SP shifts. It is suggested that with low frequency stimulation of cortex or thalamus (VA) the SP shift reflects predominantly glial SD. At high frequency the SP shifts are a blend of glial and neuronal depolarization.

Comparative study of sensory input to motor cortex in animals and man

Abstract The sensory input to motor cortex was studied in cat, squirrel monkey and man. In all three, transcortical recording of evoked responses was used to identify the inputs, and observations were made in both the anesthetized and waking states. In the cat, the input to motor cortex could only be identified in the waking state. The response has a long latency (compared to that in the somatosensory area: S1) and can be evoked by ipsilateral as well as contralateral somesthetic stimulation and by auditory stimuli but not by visual excitation. In the squirrel monkey, an input can be demonstrated in both anesthetized and waking states. Under anesthesia, it has the same feature as that projecting to S1 (activation from restricted contralateral receptive field only); in the waking state, there is both an S1 type input and a long latency ipsilateral and polysensory input similar to that observed in the cat. In man, the input varies from one subject to the next. Some show no contralateral sensory input to motor cortex; others show only an S1 type projection, or a response of slightly longer latency. Both absence and presence of input can be seen in either the anesthetized or waking subject. Ipsilateral somesthetic stimulation evokes either no response or a very small potential of non-local origin. A response to click is not seen. The study did not provide an explanation for the differences in sensory input that occur between individuals. The findings suggest that human motor cortex plays a less important role in integration of disparate sensory inputs from the periphery than does motor cortex of lower animals.

Comparative study of cerebral cortical potentials associated with voluntary movements in monkey and man

Eight monkeys (Macaca mulatta) were taught to squeeze and release a handgrip. The movement simulated the brisk squeeze of a hand dynamometer performed by 7 human subjects. Monkey. During the performance of the voluntary movements, slow cortical potentials (motor potentials or MPs) were studied with monopolar, surface bipolar, transcortical and intracortical recordings. A survey of the dorsal expanse of cerebral cortex showed that the contralateral motor hand area, somatosensory hand area and area 6 adjacent to the supplementary motor area became active with movement. MPs also were seen in the motor and somatosensory cortex medial to the hand area, but we concluded that those potentials were probably related to adventitious movements in the arm and leg. That area 6 became active with movement was further verified with extracellular unit recording; the behavior of area 6 units was compared with that recorded from units in the motor hand area. Using simultaneous transcortical recordings a sequence of cortical activation was observed in those areas generating an MP. The motor hand area became active first, followed in turn by area 6 and the somatosensory hand area. The monosynaptic cortico-cortical connections of the motor hand area were studied with autoradiographic and horseradish peroxidase techniques and compared to the distribution of the MP. The hand area demonstrated reciprocal connectivity with portions of the somatosensory hand area, the supplementary motor area in area 6 and the cortex adjacent to the intraparietal sulcus. The distribution of the MPs correlated with the connectivity to the supplementary motor and somatosensory areas. Our physiologic studies did not adequately investigate the area adjacent to the intraparietal sulcus. Man. Motor potentials were studied using surface bipolar recordings with closely spaced electrodes (inter-electrode distances 1 cm or 2 cm). Recordings were made directly from the cortex in one subject studied under local anesthesia during an operation for epilepsy, and epidurally in 6 subjects in whom epidural electrode arrays had been inserted for the purpose of localizing an epileptogenic focus. Similar to the findings in the animals, MPs were recorded from the contralateral motor and somatosensory hand area with activity in motor cortex appearing first; area 6 just anterior to the motor hand area probably also generated a response. In addition, a locally generated potential not seen in monkey was recorded anterior to area 6. This difference in response distribution is viewed as possibly relating to the different significance which the seemingly comparable hand movements have for the animal and human subjects. No response was seen in motor and somatosensory hand area with ipsilateral movements. We have no information for the anteriorly recorded response with ipsilateral movement.

Pediatric Epilepsy Surgery

Summary: The use of implantable arrays of epidural electrodes has made it possible to carry out extraoperative electrocorticography (ECoG) and functional localization in the awake child. This has permitted cortical excisions that are determined by criteria similar to those obtained during surgical procedures performed under local anesthesia in adults. In addition, the method also permits simultaneous ECoG and video monitoring during the childs symptomatic seizures, providing additional important localizing information that is impractical to obtain in operations under local anesthesia. We report our experience with 75 children, ages 5 months to 15 years, whom we have managed with epidural electrode arrays. The method of extraoperative ECoG is described and illustrative cases are presented to demonstrate its feasibility and utility in children. In addition, we call attention to gliomas as a common cause of chronic focal seizures in children. Of 49 children undergoing resection and followed for from 1 to 14 years (mean of 5.8 years), 32 (65%) are either seizure free or have had a significant reduction in seizure frequency that has unambiguously improved their quality of life. The results are analyzed further by relating the surgical outcome to each of the pathologic entities that caused the seizures. This analysis reveals the variety of neurological conditions that commonly cause intractable focal seizure disorder in children and distinguishes those pathologic entities in which the seizure disorder is apt to respond to surgical intervention from those that will not.

Management of Seizure Disorders: Selected Aspects. Part II.

This article discusses the management of seizure disorders, stressing selected aspects including (1) the pharmacology of drugs used in the control of seizures, especially the usefulness of measuring concentrations of anticonvulsants in blood in guiding therapy; (2) the treatment of prolonged seizures, particularly status epilepticus, in infants and children; (3) the use of the ketogenic diet as an adjunct in the therapy of epilepsy; and (4) the place of surgical treatment in the control of seizures resistant to medical management.

Cortical D.C. changes incident to midline thalamic stimulation

Abstract 1. 1. Cortical D.C. changes occur incident to stimulation of the mid-line thalamus of rabbit and cat. 2. 2. At stimulating frequencies which elicit recruiting a negative D.C. shift ordinarily occurs in the rabbit. In the cat there is no shift or a minor positive one may occur. 3. 3. In the rabbit with high frequency stimulation a negative D.C. shift results which may obtain an amplitude of 1.5 mV. and persist for several seconds into the post-stimulatory period. In the cat there is also a negative shift, but it is usually less manifest than the rabbit. 4. 4. The D.C. shift with low frequency stimulation results from summation of after-effect. At high frequency stimulation the D.C. shift is accounted for by summation of transients as well as summation of after-effects and is regarded as a steady state of activity in dendrites. 5. 5. Prolonged stimulation (10–15/sec) may introduce other effects which occasion the return of the D.C. shift to the pre-stimulatory base line and post-stimulatory positivity. 6. 6. The after-effect following the initial response of a recruiting series is associated with increased excitability. The negative D.C. shift following brief repetitive stimulation and the positive one following prolonged (10–15 sec.) stimulation are associated with decreased excitability for a test recruiting series. 7. 7. Intense repetitive stimulation in the relay nuclei of the thalamus may occasion cortical paroxysm on a base line indicative of positive D.C. shift, whereas corresponding stimulation in the mid-line thalamus has been shown to relate to negative D.C. shift. At present no explanation can be offered for this difference.

Correlation between steady transcortical potential and evoked response

In 9 cats and 3 rabbits we investigated the effects of veratrine hydrochloride, weak strychnine, 1 per cent novocaine and 1 per cent KCl upon the steady potential, evoked response, and spontaneous ECG of the somatic receiving area. Under 10−4 veratrine cyclic intense negative shifts of steady potential commence to recur immediately after its application to the cortical surface. In the negative troughs there is depression of evoked response; upon the plateaus between, the initial positive phase is markedly exaggerated and lengthened. Barbiturate spindles also change through exaggeration of their positively directed components. The SP shift which accompanies and follows barbiturate spindles of normal cortex is negative; after veratrine it becomes positive. With time spontaneous spikes of positive polarity appear upon the plateaus of veratrinized cortex, and recur after the steady potential has stabilized again. Such spikes, as well as evoked responses, acquire prolonged after-positivities with time. With 10−3 strychnine we noted exaggeration of the negatively directed components of evoked responses and of barbiturate spindles. The action of veratrine was observed to supercede that of strychnine; that is, after its application the previous effects of strychnine upon the evoked response and upon the barbiturate spindles disappeared, to be succeeded by typical veratrine effect. One per cent novocaine occasions at first an increase in amplitude and duration of the initial positive phase of the evoked response comparable with the earliest noted effect of veratrine. However, no steady potential shifts occur, and this initial effect of novocaine is followed by one of depression of the amplitude of the evoked response. After novocaine is washed off and replaced by veratrine a typical veratrine effect develops with marked exaggeration of the positive component of the evoked response. Veratrine spikes and SP negative shifts also occur. KC1 gives SP negative shifts, occasions only depression in amplitude of the evoked response. Followed by vetratrine, the effect of veratrine on the evoked response while still evident is reduced.

Summation of certain enduring sequelae of cortical activation in the rabbit

Abstract In 32 rabbits, carried under high cord transection and infiltration of sensitive areas with novocaine, steady potential (SP) was studied using transcortical recording from the visual cortex by calomel half-cells and a “chopper” system. From immediately adjoining silver-silver chloride wire electrodes the usual ECG was recorded. Strychnine in different concentrations was applied to the surface of the cortex in some animals; in others primary visual responses were elicited by single and repetitive stimuli at different intensities applied to the contralateral optic nerve and the homolateral geniculate nucleus. 1. 1. Relatively long enduring (1–4 sec.) after-effects detected by the chopper method commonly followed the strychnine spikes and primary visual responses. 2. 2. Clusters of strychnine spikes produced somewhat longer and higher amplitude after-effects than single ones, suggesting summation. Trains of 2–3 primary visual responses evoked by very brief electrical stimulation did not summate, however. 3. 3. Repetitive stimulation of optic nerve for 2–10 sec. led to complex summations. Early in experiments the predominant polarity of the summated after-effect resulting from repetitive stimulation of the nerve was negative regardless of stimulus strength. Later under identical conditions of stimulation but following any major long-lasting SP shift, the summated after-effect was positive. 4. 4. Repetitive stimulation of the lateral geniculate nucleus caused somewhat different changes. At a stimulus strength maximal for the primary visual response the negative summation was replaced by a positive one, which was frequently accompanied by paroxysm. As with the optic nerve, following any major SP shift the summated after-effect changed and was positive at any stimulus strength. At this time repetitive stimulation of the lateral geniculate nucleus at maximum for the primary visual response resulted in a marked positive shift in SP which was most always accompanied by a sustained after discharge in the ECG. As the after-discharge continued to increase in voltage, the surface-positivity became more marked, and the latter did not disappear in a negative shift until the termination of the paroxysm. This pattern of SP shift with paroxysm was observed many times, and the only exception we have observed relates to the occasional appearance of fast spiky paroxysm associated with negativity in SP. 5. 5. It was concluded that relatively long-enduring positive and negative after-effects of primary visual response and of strychnine spikes occur more or less concomitantly, and the dominant polarity as detected in the records is determined by the algebraic summation of the opposing disturbances. 6. 6. Although summation of positive after-effects may account for the accumulation of positivity during paroxysm, and the summation of the opposing after-effects for the subsequent negative change that develops rapidly as paroxysm disappears, significant exceptions occur suggesting the existence of yet undiscovered factors. One such exception occurs when significant positive shift precedes the development of paroxysm.

Experimental modification of dendritic and recruiting processes and their DC after-effects☆

Abstract The study concerns agents that modify evoked cortical potentials of rabbit and cat in a predictable way and at the same time change the DC accompaniments of the activation process. Recruiting, surface-activated (dendritic) and subcortically activated (radiation) potentials were studied, both as responses to single stimuli and in repetitive series. In one set of experiments a variety of agents (1 per cent procaine, 0.01 per cent veratrine, 0.1 per cent GAB, and boiling water as a control) were applied to the cortical surface. In another, modifications were induced by the increasing injection of a barbiturate into artificially respired cats (immobilized with Flaxedil), leading to very deep anesthesia. Of the agents applied to the cortical surface all occasioned reversal (transcortical lead) of the ordinarily negative sign of the recruiting transient to positive, the summated after-effects evident during stimulation being augmented at the same time. Reversal in sign occurred in the transcortical lead even though the negative potentials remained in a lead from a superficial intracortical position to the subcortical white matter. Thus, the reversal could be attributed to a block in activity very close to the cortical surface, with continuation of activity of usual sign in the deeper cortical fraction. Dendritic and radiation activated responses behaved similarly. In the cat prior to the intravenous injection of Nembutal (0.15 – 0.3 g.), the negative dendritic response shows a short-lived negative after-effect followed by a longer lasting positive one. With repetitive stimulation the positive after-effect disappears, the negative one increasing and showing summation. Intravenous Nembutal occasions the disapperance of the positive after-effect which follows the response to a single stimulus and also augments the negative one which then lasts for a much longer time. With deepening anesthesia and repetitive stimulation transients no longer follow each of successive stimuli, a series of shocks then giving rise to a summation of negative after-effect alone. This is comparatively large and outlasts the stimulus series by several seconds. During deepening anesthesia the recruiting response fails earlier than the dendritic and radiation activated ones, the latter two being lost nearly simultaneously.