The anatomy and physiology of cerebellar disease.
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Animals↗
Biomedical subjects
B L Day
Publications and source records attributed to B L Day.
"Resetting" of postural tremors at the wrist with mechanical stretches in Parkinson's disease, essential tremor, and normal subjects mimicking tremor.
The response of postural wrist tremors to brief mechanical displacements was compared in two groups of patients, one with classical hereditary essential tremor (n = 18) and another with typical Parkinson's disease (n = 13). These groups were compared with an additional group of normal subjects mimicking wrist tremor (n = 9). The degree to which brief mechanical displacements of the wrist produced by torque pulses of three different sizes could modulate the timing of rhythmic electromyographic bursts in the forearm flexor muscles was quantified by deriving a resetting index, which could range between 0 (no phase resetting) and 1 (complete phase resetting). In all three groups of subjects studied, the resetting index varied significantly with the size of the mechanical perturbation and, in an inverse fashion, with the ongoing tremor amplitude. When due allowance for these factors was made, the difference in mean resetting indexes between the three groups of patients and subjects was reduced to the extent that no definitive statement could be made as to whether brief mechanical perturbations had more effect on essential tremor than parkinsonian tremor. The method is therefore unlikely to be useful in differentiating the common causes of postural wrist tremors.
Adult↗
Voluntary stimulus-sensitive jerks and jumps mimicking myoclonus or pathological startle syndromes.
Five patients who presented with stimulus-induced jerking as part of an apparent myoclonic or pathological startle syndrome are reported. Neurophysiological observations in these patients suggested the jerks were voluntary in origin. These included (a) variable latencies to the onset of stimulus induced jerks, (b) latencies were greater than that seen in reflex myoclonus of cortical or brainstem origin, and were (c) longer than the fastest voluntary reaction times of normal subjects, (d) variable patterns of muscle recruitment within each jerk and, (e) significant habituation with repeated stimulation. It is argued that these features are consistent with a voluntary origin for the jerks and enable them to be distinguished from the stereotyped electrophysiological characteristics of myoclonus of cortical and brainstem origin. Electrophysiological recordings may help identify patients with this form of psychogenic movement disorder.
Adult↗
Primary orthostatic tremor: further observations in six cases.
The clinical and physiological features of six new patients with primary orthostatic tremor are described. We suggest that use of the term primary orthostatic tremor be confined to the clinical syndrome in which unsteadiness when standing is the predominant complaint and accompanied by characteristic electrophysiological findings of a rapid (frequency around 16 Hz), regular leg tremor which is not influenced by peripheral feedback, is synchronous between homologous leg muscles, and in certain postures of the upper limbs, between muscles of the arm and leg. The fast frequency of muscle activity in primary orthostatic tremor of the legs causes unsteadiness when standing (presumably due to partially fused muscle contraction) but only a fine ripple of muscle activity is visible. In contrast, the slower frequency of other leg tremors, for example essential tremor, results in obvious leg movement which is evident in many leg postures, is variable over time and can be reset by a peripheral nerve stimulus. Essential tremor and orthostatic tremor do not respond to the same therapies, suggesting differences in the pharmacological profiles of the two conditions. Accordingly, there are clinical, physiological and pharmacological differences between primary orthostatic and essential tremor. Whether these factors are sufficient to regard these tremors as separate conditions is discussed.
Adult↗
Effect of digital nerve stimuli on responses to electrical or magnetic stimulation of the human brain.
1. Reflexes were elicited in the first dorsal interosseous muscle of seven normal subjects by electrical stimulation of the digital nerves of the index finger at 3 times perceptual threshold while subjects maintained a constant voluntary contraction of the muscle. The average response in the surface-rectified electromyogram (EMG) consisted of an early inhibitory (I1) component followed by a later excitation (E2). 2. Low intensity anodal electrical or magnetic scalp stimuli were given over the motor cortex in order to elicit muscle responses within the period of the I1 and E2 reflex components. 3. Compared with control responses elicited in the absence of digital nerve stimulation, responses to electrical cortex stimulation were suppressed in the I1 period and facilitated during the E2 period of the reflex. In contrast, responses evoked by magnetic stimulation were suppressed during I1 and also for the first 10 ms or so of the E2 response. Magnetically evoked responses were facilitated during the later part of the E2 reflex. 4. Similar effects were seen when the probability of firing of single motor units was studied. 5. In three subjects, small taps were given to the abducted index finger in order to stretch the first dorsal interosseous muscle and evoke reflexes which were of comparable size to the E2 reflex evoked by digital nerve stimulation. In contrast to the experiments in which digital nerve stimuli were given, responses evoked by magnetic stimulation over motor cortex were facilitated at all times during the course of the reflex evoked when the muscle was stretched. 6. We conclude that single electrical stimuli applied to the digital nerves can reduce for a short period the excitability of motor cortex to magnetic stimulation. This occurs at a time when the same stimulus is evoking an excitatory (E2) reflex in the average surface-rectified EMG.
Adult↗
Interhemispheric inhibition of the human motor cortex.
1. Using two magnetic stimulators, we investigated the effect of a conditioning magnetic stimulus over the motor cortex of one hemisphere on the size of EMG responses evoked in the first dorsal interosseous (FDI) muscle by a magnetic test stimulus given over the opposite hemisphere. 2. A single conditioning shock to one hemisphere produced inhibition of the test response evoked from the opposite hemisphere when the conditioning-test interval was 5-6 ms or longer. We shall refer to this as interhemispheric inhibition. However, the minimum latency of inhibition observed using surface EMG responses may have underestimated the true interhemispheric conduction time. Single motor unit studies suggested values 4-7 ms longer than the minimum interval observed with surface EMG. 3. Interhemispheric inhibition was seen when the test muscle was active or relaxed. Increasing the intensity of the conditioning stimulus increased the duration of inhibition: increasing the intensity of the test stimulus reduced the depth of inhibition. 4. The conditioning coil had to be placed on the appropriate area of scalp for inhibition to occur. The effect of the conditioning stimulus was maximal when it was applied over the hand area of motor cortex, and decreased when the stimulus was moved medial or lateral to that point. 5. The inhibitory effect on the test stimulus probably occurred at the level of the cerebral cortex. In contrast to the inhibition of test responses evoked by magnetic test stimuli, test responses evoked in active FDI by a small anodal electric shock were not significantly inhibited by a contralateral magnetic conditioning stimulus. Similarly, H reflexes in relaxed forearm flexor muscles were unaffected by conditioning stimuli to the ipsilateral hemisphere. However, inhibition was observed if the experiment was repeated with the muscles active.
Adult↗
Correlation of phasic muscle strength and corticomotoneuron conduction time in multiple sclerosis.
Central motor conduction times for the adductor pollicis muscle, the twitch force of that muscle to scalp magnetic motor cortex stimulation, and the maximum force of phasic voluntary contraction of the same muscle were measured in 15 patients with multiple sclerosis. Two tests of manual dexterity of the same hand also were studied: the Purdue pegboard test, and the maximal frequency of a scissors movement of the thumb and index finger. The patients had normal strength or minimal weakness of the intrinsic muscles of the hand on clinical examination. The mean central motor conduction times for the adductor pollicis muscle for the patients were longer than normal, the peak twitch force of the adductor pollicis muscle evoked by cortical stimulation and the maximum force of a phasic voluntary contraction of the adductor pollicis muscle were smaller than normal. There were strong correlations between all these measures. Central motor conduction time in the patients was inversely correlated with voluntary phasic force and the twitch force after cortical stimulation. That is, the longer the central motor conduction time, the weaker the force. Prolonged central motor conduction time is likely to be accompanied by conduction block in corticomotoneuron pathways. The correlation of central motor conduction time with voluntary phasic force and the twitch force most likely reflects the degree of conduction block and temporal dispersion rather than delay in conduction per se. These results indicate that objective assessments of phasic muscle strength may reveal correlations with central motor conduction time that are not evident on conventional clinical examination which assesses tonic muscle contraction strength.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Percutaneous electrical stimulation of corticospinal pathways at the level of the pyramidal decussation in humans.
Stimulation over the base of the skull can activate descending motor pathways to produce electromyographic (EMG) responses in muscles of the arm and leg. The evoked EMG responses were larger when the muscles were preactivated by a small voluntary contraction compared to when they were completely relaxed. The latency of these responses in preactivated muscles was approximately midway between that produced by electrical stimulation over the motor cortex, and by electrical stimulation over the cervical enlargements. With horizontally spaced electrodes, the latency difference between cortical and brainstem stimulation was 1.8 milliseconds in all muscles tested. The latency difference between cervical and brainstem stimulation was 3.9 milliseconds for the first dorsal interosseous and 2.6 milliseconds for tibialis anterior muscles. These values suggest that brainstem stimulation occurs at the level of the cervicomedullary junction. With vertically spaced electrodes in the midline, stimulation often occurs at a higher level. The EMG responses from brainstem stimulation differed from those following cortical stimulation in two ways: (1) They were simpler in form, and (2) their onset latency was the same in active as it was in relaxed muscles. This suggests that brainstem stimulation evoked a large descending motor volley in comparison with the multiple volleys that cortical stimulation can produce. Collision experiments between cortical and brainstem volleys indicated that the major part of the responses evoked by brainstem stimulation were conducted via the large-diameter component of the corticospinal tract.
Action Potentials↗
Paroxysmal axial spasms of spinal origin.
A 55-year-old man with a 4 1/2-year history of paroxysmal bouts of involuntary large-amplitude flexion jerks of the trunk and a 1-year history of persistent rhythmic small-amplitude movements of the anterior abdominal wall is described. Clinical and electrophysiological evidence suggested that the paroxysmal myoclonus arose in propriospinal systems intrinsic to the spinal cord.
Cerebral Cortex↗
A therapeutic trial of milacemide in myoclonus and the stiff-person syndrome.
We investigated the therapeutic effects of milacemide in seven patients with myoclonus and three patients with the stiff-person syndrome in an open-label trial. Milacemide was initiated at 800 mg/day and was gradually increased to a maximum dosage of 2,400 mg/day. No significant improvement occurred in the 10 patients.
Acetamides↗
A case of postanoxic encephalopathy with cortical action and brainstem reticular reflex myoclonus.
A patient with postanoxic encephalopathy, with both action- and stimulus-sensitive reflex myoclonus, is described. The action myoclonus was multifocal and cortical in origin. In contrast, reflex myoclonus elicited by somaesthetic and auditory stimulation was generalised. The earliest reflex electromyograph activity was recorded in the sternocleidomastoid; myoclonic activity then spread up the brainstem and down the spinal cord, suggesting that this reflex myoclonus had its origin in the caudal brainstem. Stimulus sensitivity was greatest in the limbs. The bulbospinal motor pathways involved in the generalised reflex myoclonus were rapidly conducting, and this characteristic distinguishes this form of brainstem reflex myoclonus from that described in hyperekplexia.
Aged↗
Further observations on the facilitation of muscle responses to cortical stimulation by voluntary contraction.
The effect of voluntary contraction on the discharge of single motor units following electrical and magnetic stimulation of the motor cortex was examined using the post-stimulus time histogram (PSTH) technique. The latencies of responses in single motor units of the first dorsal interosseous muscle to cortical stimulation were 2-4 msec shorter when the muscle was contracting than when at rest in 9 of 10 units studied. These latency differences are comparable with those recorded by surface electromyography for compound muscle action potentials following cortical stimulation in relaxed and active muscles. The new findings are that the intensity of cortical stimulation required to discharge a resting motor unit to produce a single PSTH peak produced multiple PSTH peaks when the same unit was contracting. The timing of the PSTH peak of relaxed motor unit discharge corresponded to one of the later PSTH peaks (usually the second) when the motor unit was voluntarily activated. These findings are in keeping with our previous suggestions that the longer latency of responses in relaxed muscles is due to the time taken for temporal summation of multiple descending corticospinal volleys at the cortico-motoneurone synapse. Facilitation produced by voluntary contraction occurs at least in part at the level of the spinal cord by lowering motoneurone threshold to enable discharge on the initial descending volley. The higher threshold of relaxed muscles is related to the higher intensities of stimulation needed to recruit multiple descending volleys and discharge resting motoneurones.
Adult↗
New observations on the normal auditory startle reflex in man.
The latency and pattern of muscle recruitment in the startle response elicited by unexpected auditory stimulation was determined in 12 healthy subjects. Reflex EMG activity was recorded first in orbicularis oculi. This was of similar latency to the normal auditory blink reflex and, unlike the generalized startle response, persisted despite the frequent presentation of the test stimulus. It is argued that this early latency activity in orbicularis oculi represents a normal auditory blink reflex and is not part of the generalized auditory startle reflex. With the exception of this early latency activity in orbicularis oculi, the relative latencies of both cranial and distal muscles in the auditory startle response increased with the distance of their respective segmental innervations from the caudal brainstem. Thus the earliest EMG activity was recorded in sternocleidomastoid. The recruitment of caudal muscles was relatively slow and the latencies of the intrinsic hand muscles were disproportionately long. The pattern of recruitment of cranial muscles suggests a brainstem origin for the normal startle response. Studies on the auditory startle reflex in animals are reviewed in the light of this finding.
Acoustic Stimulation↗
The hyperekplexias and their relationship to the normal startle reflex.
The startle response to unexpected auditory and somaesthetic stimulation was studied in 8 patients with hereditary or symptomatic hyperekplexia. It was abnormal in its resistance to habituation and in its exaggerated motor response. Both noise and taps to the face and head elicited a normal early blink response, separate from the subsequent true startle reflex. The earliest reflex EMG activity recorded after the blink was in sternocleidomastoid. EMG activity in masseter, and trunk and limb muscles followed later. This pattern of muscle recruitment suggests a brainstem origin for the abnormal startle responses. In addition, the abnormal startle responses exhibited disproportionately long latencies to the intrinsic hand and foot muscles and relatively slow recruitment of caudal muscles. The pattern of muscle recruitment was similar between patients, irrespective of the absolute latency of the response, and regardless of whether stimulation was auditory or somaesthetic. This suggests that auditory and somaesthetic afferents converge on a common brainstem efferent system, and that this system forms the final common pathway for abnormal startle responses of differing latency. The characteristics of this efferent system differ from those previously described in brainstem reticular reflex myoclonus, but are similar to those described in the normal auditory startle reflex in man. This suggests that the abnormal startle response in hyperekplexia, and the normal startle reflex represent pathological and physiological activity in the same brainstem efferent system.
Acoustic Stimulation↗
Intrahemispheric and interhemispheric spread of cerebral cortical myoclonic activity and its relevance to epilepsy.
Nine patients with cortical myoclonus (due to various pathologies), in whom movement of one limb induced bilateral limb jerks, were investigated. Three of these patients also had bilateral cortical reflex myoclonus when one limb was subjected to an electrical stimulus. The relative latencies to onset of electromyogram (EMG) activity in various ipsilateral and contralateral muscles in action and reflex jerks were studied. Bilateral reflex and action jerks induced by unilateral electrical stimuli or limb movement were not synchronous. EMG activity was usually recorded in the muscles of the stimulated or moved limb, before being recorded in the homologous muscles of the contralateral limb. It is proposed that this difference in relative latency between homologous muscles represents the interhemispheric delay due to the transcallosal spread of excitation from one sensorimotor cortex to the opposite cerebral cortex. The relative latencies of muscles on the same side of the body reflected not only the differences in efferent delays from the motor cortex via spinal cord and peripheral nerves, but also delays due to the spread of myoclonic activity within the sensorimotor cortex itself. This intrahemispheric spread followed a grossly somatotopic pattern. It is suggested that this spread involves cortico-cortical pathways. The additional delay due to spread of activity from hand to leg area of the sensorimotor cortex was about 10 ms in the first active hemisphere, in both generalized reflex and action jerks. The delays due to somatotopic spread of activity in the opposite later activated hemisphere were shorter. The tendency for spread of excitation through callosal and cortico-cortical pathways is an additional pathophysiological abnormality in some patients with cortical myoclonus, and may be important in the generalization of seizures seen in these patients.
Adult↗
Paraesthesias are elicited by single pulse, magnetic coil stimulation of motor cortex in susceptible humans.
A minority of normal humans experience paraesthesias (usually tingling) projected to the contralateral hand in response to individual transcranial magnetic coil (MC) pulses. The cortical source of the paraesthesias was sought by comparing their incidence with that of muscle responses to focal MC stimulation with either a figure 8 MC or with edge stimulation of a tilted round MC in 4 susceptible subjects. In all 4, paraesthesias were best felt with MC stimulation either at, or anterior to sites yielding movement, implying an initial source in precentral gyrus (and possible premotor cortex), rather than parietal cortex. In the two subjects exhibiting the strongest paraesthesias, the threshold for the paraesthesias was less than that for movement in the relaxed arm. The optimal site of the paraesthesias within the hand was usually in the digits, but differed among subjects. Motor responses and paraesthesias following a given stimulus occurred at different sites in the hand, implying that excitation of differing sets of motor cortical neurons subserved sensory and motor responses. In only one subject were the paraesthesias sufficiently reproducible to warrant interacting electrical digital and transcranial MC pulses. The data suggested that central processing of the response to the MC pulse is slowed by an antecedent digital stimulus, but the delay for perception of each type of stimulus does not greatly differ. The central sense of movement (Amassian et al., 1989a) elicited by MC stimulation of motor cortex is compared with the paraesthesias. Both are attributed to brief, high frequency discharge by motor cortical neurons accessing the perceptual system more readily than after excitation of post-central gyrus, which requires prolonged repetitive stimulation (Libet et al., 1964). Given also the normal pattern of muscle responses in the 4 subjects, their paraesthesias are best explained by a heightened sensitivity of the perceptual system to the motor cortical response to MC stimulation.
Action Potentials↗
Stimulation of the human motor cortex through the scalp.
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Animals↗
Changes in the response to magnetic and electrical stimulation of the motor cortex following muscle stretch in man.
1. The effect of muscle stretch on the EMG response from the stretched muscle to transcranial magnetic stimulation of the motor cortex was studied in eight subjects. Muscle stretch was produced by increasing the torque of a motor acting through a lever which was held at constant position by a flexion force of the index and middle fingers. EMG responses were recorded from fine-wire electrodes inserted into flexor digitorum profundus muscle in the forearm. They consisted of a spinal latency component and a long-latency component which could in some subjects be separated into an early and a late phase. 2. In four subjects, four intervals between the stretch and the cortical stimulus were explored using three intensities of cortical stimulation. At all three intensities, when the magnetic cortical stimulus was timed to produce an EMG response in the period of the later part of the long-latency stretch reflex the response was larger than when it was timed to produce a response in the period of the short-latency spinal reflex or when superimposed on the tonic muscle activity used to resist the standing torque of the motor. 3. When the intensity of magnetic cortical stimulation was reduced so that it was just below threshold to produce an EMG response in the short-latency reflex period or on the background tonic EMG activity, it still was capable of producing a response when superimposed on the long-latency stretch reflex. 4. In four subjects the time course of this effect was studied in more detail using only one intensity of magnetic cortical stimulus set to be just above threshold to produce a response in tonically active muscles. The time course of the facilitatory effect was similar to the time course of the later part of the long-latency stretch reflex. From these data it was not possible to determine whether the early part of the long-latency stretch reflex also was accompanied by the facilitatory effect since this component was present in only one of the four subjects. 5. The facilitatory effect persisted after the ulnar and median nerves were totally blocked at the wrist by injections of local anaesthetic. This suggests that inputs from muscle receptors of the stretched muscle contribute to the effect.4=
Adult↗