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Biomedical subjects

J C Rothwell

Publications and source records attributed to J C Rothwell.

At least 289 records · Page 16Linked to original sources

The physiology of idiopathic dystonia.

Dystonia is mysterious and its pathophysiology is uncertain. The fundamental motor abnormality is an abnormality of muscle command signals, such that the wrong agonists may be activated for too long, there is abnormal co-contraction of agonist and antagonists, and there is excessive and misdirected action of synergists and postural fixators. The result is action dystonia. In addition, muscle spasms may occur spontaneously. The peripheral motor apparatus, the corticomotoneurone pathway, and (as far as is known) the proprioceptive feedback machinery, are all intact in primary dystonia. However, a defect of interneuronal machinery has been identified in both the brainstem and spinal cord. In blepharospasm there is hyperexcitability of the lower brainstem interneurones responsible for the R2 component of the blink reflex. In the dystonic arm there is loss of the later phases of Ia reciprocal inhibition from extensors to flexors. Both deficits may be due to loss of normal basal ganglia inputs onto interneurones. The known sites of focal lesions that may cause symptomatic dystonia all impair basal ganglia output. However, whether such abnormal interneuronal function is sufficient to explain dystonia is not known. Among many unanswered questions are 1) are the cortical instructions for movement specified correctly, and 2) what is responsible for the spontaneous dystonic spasms?

Dystonia↗

Disturbance of sequential movements in patients with Parkinson's disease.

The following sequences of two single movements were examined in 10 patients with Parkinson's disease and compared with the performance of 9 normal subjects of similar age. Isometric opposition of thumb and fingers to a force of 30 N ('squeeze'), followed by isotonic elbow flexion ('flex') through 15 degrees with the same arm. 'Squeeze' with the left hand followed by 'flex' with the right elbow. Isotonic opposition of thumb and fingers ('cut') through 90 degrees followed by isotonic 'flex' with the same arm. Isotonic elbow 'flex' followed by isometric 'squeeze' with the same arm. All movements were self-paced. Subjects were given instructions to move as rapidly as possible and to start the second movement immediately after the end of the first. Patients were slower than normal when each single movement was performed separately. There was a further decrease in speed when two movements were executed sequentially. This was due to an increase in movement duration of each of the component movements, especially the second, and to an increase in the pause between the first and second movements. In both normals and patients, there was no correlation between the times taken to perform the first and second movements of any of the four sequences that were studied. Because of this we suggest that the two components of the sequence remained under the control of two separate motor programs. When performing the sequential tasks, normal subjects automatically chose an interval between the onsets of the two separate movements of about 230 ms, even in tasks in which the duration of the first movement was less than 200 ms. If normal subjects were instructed to begin the second movement with an interonset interval of less than 200 ms, the speed of the second movement was much slower. Patients with Parkinson's disease automatically chose a much longer interonset interval of 400-500 ms. In addition, they exhibited difficulty in switching from the first to the second movement in the sequence. We suggest that the problems exhibited by patients with Parkinson's disease when they try to perform two rapid sequential movements can be seen as a deficit in the capacity to switch from one motor program to another within an overall motor plan.

Adult↗

Knowledge of motor commands and the recruitment of human motoneurons.

This study examined the extent to which subjects can direct internal motor commands to specific pools of motoneurons. These commands were subthreshold for muscle activity and were presumably not associated with any change in background afferent activity. Percutaneous stimuli were delivered to the motor cortex using the technique of Merton and Morton (1980) while the discharge of the first-recruited motor units from two intrinsic hand muscles was recorded with selective needle electrodes. In the absence of movement or detectable electromyographic activity subjects learned to focus their internal command upon one of the pair of hand muscles such that a liminal cortical stimulus activated motoneurons in the 'focused' but not the 'unfocused' muscle. This ability was not acquired for pairs of muscles in the forearm. When the cortical stimuli activated only one motor unit in a muscle, the same unit was the first recruited during a voluntary contraction. These results suggest that motor commands can be precisely monitored and fractionated for individual intrinsic muscles of the human hand without recourse to afferent feedback. This ability may be useful for organizing and learning fine manipulative tasks.

Humans↗

Motor cortex stimulation in intact man. 1. General characteristics of EMG responses in different muscles.

This paper is the first of two papers describing our five-year experience with the technique of electrical stimulation of the human motor cortex. In this first paper we illustrate the basic distribution and behaviour of electromyographic responses in limb muscles to anodal stimulation of the motor cortex in intact, awake human subjects. These responses may be recorded at short latency, with estimates of conduction velocities from the brain to the spinal cord suggesting transmission in rapidly conducting pathways, such as the corticomotoneuronal component of the corticospinal tract. The site at which the stimulus activates these motor pathways to produce responses at such short latency is likely to be at, or adjacent to the origin of these major descending motor pathways in the cerebral cortex. The best stimulating sites for activation of arm or leg muscles corresponds to the known somatotopic arrangement of the cerebral cortex. The electromyographic response characteristics are different in the contracting, as compared with the relaxed muscle; the EMG response latency shortens, its size becomes larger and its threshold is lowered when the muscle is voluntarily made to contract. The mechanisms that are responsible for these characteristics are examined in the following paper.

Adult↗

Motor cortex stimulation in intact man. 2. Multiple descending volleys.

Using an isometric strain gauge, we measured the twitch force produced in the first dorsal interosseous (FDI) muscle by a single anodal shock to the contralateral scalp. At high intensities of stimulation this twitch can greatly exceed the force produced by supramaximal stimulation of peripheral nerve. This indicates that a single cortical shock can cause repetitive firing of some or all FDI motoneurons. Such repetitive firing was demonstrated using a collision technique in which a supramaximal ulnar nerve stimulus was given at the wrist shortly after a cortical shock. The antidromic volley from the peripheral nerve stimulation failed to obliterate completely the response to cortical stimulation. Additional EMG activity was visible in the normally silent period between ulnar M and F waves. This activity must have been due to the presence of repetitive volleys of activity set up in spinal motoneurons by the cortical shock. Such activity summates with the twitch produced by the ulnar M wave to produce a very large force twitch of the muscle. Multiple firing of some motoneurons can be observed in some individuals at cortical stimulation intensities below that necessary to evoke activity in all the motoneurons in the FDI pool. Multiple firing probably was caused by repetitive excitatory inputs impinging on spinal motoneurons. These could be demonstrated using poststimulus time histogram techniques on single motor units. Low intensities of cortical stimulation produced a single short duration (mean 1.8 ms) peak of increased motor unit firing 20 to 30 ms after the shock. At high intensities, this was followed by extra peaks some 4 to 5 ms later. H reflex testing showed that the threshold of the initial descending volley, produced by the cortical stimulus was uninfluenced by a voluntary contraction. These results are discussed with reference to the D and I waves recorded from pyramidal tract after anodal stimulation of the exposed cortex in animals.

Biomechanical Phenomena↗

Some experiences of techniques for stimulation of the human cerebral motor cortex through the scalp.

Stimulation of the motor cortex transcranially has shown a rough somatotopy of stimulation sites on the scalp corresponding to the homunculus and preferential activation of contralateral hand muscles, as well as very short latencies of signals in the cervical spinal cord. The responses are also facilitated by background activation of the muscles. We are reporting a set of patients studied using electrical and magnetic stimulation transcranially. We observed that the latency of electromyogram activation is much shorter in active than contracting muscles and that the muscle twitch produced by cortical stimulation can exceed the force produced by supramaximal stimulation of the peripheral nerve. Our findings suggest that this may be due to multiple firing of motor neurons. Another observation is that magnetic stimulation is not as subject to a reduction in the response latency with facilitation, and response latencies with magnetic stimulation were 2 ms longer than with electrical stimulation. The implications of these findings are discussed.

Adult↗

Activation of the human diaphragm from the motor cortex.

1. Rapidly conducting corticofugal pathways were activated by percutaneous electrical stimulation of the motor cortex in normal subjects. The electromyographic response produced in the diaphragm was assessed with recordings via a gastro-oesophageal catheter and the mechanical response was measured as a change in transdiaphragmatic pressure. 2. The mean latency from the cortical stimulus to the muscle action potential in the diaphragm was 12.3 ms. The latency to the diaphragm from stimulation of the cervical spinal cord at the C4 level was 8.0 ms. The mean 'central conduction time' to the phrenic motor nucleus of 4.3 ms (range 4.0-4.6 ms) was similar to that for the deltoid (mean 4.4 ms; range 4.0-4.8 ms) recorded in the same subjects. 3. The largest twitch contractions of the diaphragm were evoked by cortical stimuli near the vertex during inspiration. The amplitude and duration of the electromyographic and mechanical responses often exceeded those produced by a supramaximal stimulus to both phrenic nerves simultaneously. 4. These results provide the first direct evidence that there is a rapidly conducting oligosynaptic pathway from the motor cortex to the human diaphragm.

Action Potentials↗

Evidence favouring presynaptic inhibition between antagonist muscle afferents in the human forearm.

1. A single motor-threshold electrical stimulus to the radial nerve in the spiral groove produced three phases of inhibition in the H reflex of relaxed wrist and finger flexor muscles. The first phase of inhibition occurred with a conditioning-test interval of -1 to 3 ms and represents disynaptic Ia reciprocal inhibition of flexor motoneurones by afferent input from extensor muscles. The second phase occurred with a conditioning-test interval of 5-40 ms. The characteristics of the second inhibitory phase have been investigated in the present study. 2. The threshold intensity of radial nerve stimulation required to produce the second phase of inhibition was 0.7 X motor threshold and was the same as that required to produce the first (disynaptic) phase of inhibition. 3. The time course of the effect of a radial nerve stimulus on the size of e.m.g. response to transcranial electrical stimulation of the motor cortex also was studied. The results were compared to those obtained with H reflex testing. The time course and depth of the first phase of inhibition were identical with both test inputs. The second phase of inhibition, however, was seen only with the H reflex test stimulus. When the corticospinal volley was timed to arrive at the cervical cord 30 ms after the radial nerve afferent volley, the flexor muscle response was facilitated rather than inhibited. 4. A single stimulus (2-3 X sensory threshold) to the superficial (cutaneous) branch of the radial nerve at the wrist failed to produce inhibition of the flexor H reflex. Instead, the H reflex was facilitated when the median nerve Ia volley (for the H reflex) was timed to arrive at the cervical cord between 30-40 ms after the radial nerve cutaneous afferent volley. In contrast to results using mixed nerve stimulation in the spiral groove, there was no difference between the effect of this cutaneous input on the cortically evoked e.m.g. response and the H reflex. 5. We conclude that the second phase of flexor H reflex inhibition is produced by activity in large-diameter (group I) extensor muscle afferents which acts on the H reflex pathway at a premotoneuronal site.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Simple and complex movements off and on treatment in patients with Parkinson's disease.

The performance of a 15 degrees elbow flexion and a 30N hand squeeze was studied in nine normal subjects and in five patients with Parkinson's disease. The patients were studied when immobile after 12-18 hours withdrawal from antiparkinsonian drug therapy (OFF) and when more mobile after drugs (ON). Subjects performed each movement separately (simple movements) and both movements either simultaneously or sequentially (complex movements). The duration of both movements and the time between the onset of each movement in the sequential task (interonset latency) were measured. The patients OFF therapy had longer movement times than normal for both movements; these improved after levodopa but still were not normal. When the patients performed complex movements there was an extra slowness, over and above that seen for simple movements, in both movements of the simultaneous task and in the second movement of the sequential task. In addition, the interonset latency in the sequential task was longer than normal. After levodopa there was a more striking improvement in the movement times of complex movements than there had been for simple movements. The interonset latency in the sequential task was shorter than before therapy though still was not the same as in normal subjects. It is suggested that the basal ganglia are not only involved in the execution of simple motor programmes, but also play some role in the superimposition and sequencing of motor programmes.

Adult↗

The physiology of orthostatic tremor.

This article describes the physiological findings in a patient with orthostatic tremor. The tremor primarily affected the legs, was alternating between antagonist muscle groups, and had a remarkably rapid frequency of 16 Hz. It was present only during certain postures and appeared to be of central origin. A tremor of the same frequency was also recorded in the arms during particular movements, but was cocontracting. We suggest that orthostatic tremor may be generated by spontaneous oscillation in those central structures responsible for organizing the motor programs for standing.

Electromyography↗

Electrophysiology of the corticomotoneurone pathways in patients with movement disorders.

The corticomotoneurone pathways were examined in 21 patients with movement disorders, using the technique of percutaneous electrical stimulation of the motor cortex. Conduction in these pathways was assessed by measuring the latency to onset of electromyographic activity in the muscles of the upper limb after cortical stimulation. In all patients [five with primary (idiopathic) torsion dystonia and two with secondary (symptomatic) hemidystonia, seven with Huntington's disease, four with essential tremor, and three with Parkinson's disease] central motor conduction was normal. This and other evidence suggests that the origin of the disorder of movement in these conditions lies in the delivery of abnormal motor commands to a normal corticomotoneuronal system.

Adult↗

Simple and complex movements in a patient with infarction of the right supplementary motor area.

The role played by the supplementary motor area (SMA) in the higher-level organization of motor behaviour (motor programming) has been highlighted by the study of cerebral blood flow during voluntary movements in normal humans. We present a detailed physiological investigation from a patient with a right SMA lesion and show that the right SMA plays a role in programming simultaneous and sequential movements in both arms, though the contralateral arm was the more severely impaired. In addition, we obtained evidence to suggest that the precentral motor cortex may be more responsive to peripheral perturbations when the modulating influence of the SMA is absent. In view of the similarity of the physiological findings in this subject to those in patients with Parkinson's disease, we suggest that the defect of motor programming in Parkinson's disease is likely to reflect functional deafferentation of the SMA.

Aged↗

Habituation and conditioning of the human long latency stretch reflex.

The effects of stretch repetition rate, prior warning stimuli and self administered stretch were examined on the size of the short and long latency components of the stretch reflex electromyographic EMG response in flexor pollicis longus and the flexor muscles of the wrist and fingers. Stretches of constant velocity and extent were given every 10 s, 5 s, 2 s, or 1 s to either the wrist or thumb during a small background contraction of the flexor muscles. The size of the long latency component of the stretch reflex (measured as the area under the averaged rectified EMG responses) declined dramatically at faster repetition rates, especially in the wrist and finger flexors. The size of the short latency component was relatively unaffected. The size of the electrically elicited H-reflex in forearm muscles also failed to habituate under the same conditions. If each individual trial of a series was examined, the long latency component of the stretch reflex EMG could be seen to decrease in size over the first three to six stretches if stretches were given every 1 s, but not if stretches were given every 10 s. When stretches were given every 5 s to either wrist or thumb, an electrical stimulus applied to the digital nerves of the opposite hand 1 s before stretch reduced the size of the long latency component of the reflex EMG response. The short latency component was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Motor strategies involved in the performance of sequential movements.

The present study analyses the strategies adopted by normal subjects when they are asked to make two separate movements as rapidly as possible one after the other. Five subjects performed the following sequential movements in their own time. 1) Squeeze an isometric force transducer between fingers and thumb to a force of 30 N and then flex the elbow of the same arm through 15 degrees. 2) Squeeze the transducer with one hand and then flex the elbow of the other arm. 3) Perform an isotonic opposition of finger and thumb and then flex the elbow of the same arm. 4) First flex the elbow through 15, 30 or 45 degrees and then squeeze the transducer. 5) Flex and then extend the elbow as rapidly as possible. In tasks 1-4 there was no correlation between the times taken to complete the two separate components of the sequence. Because of this we suggest that the two movements remained under the control of two separate motor programmes. In contrast, in task 5, the times taken for the two components were correlated and hence we suggest that in this case a single programme was used to perform the sequence. In tasks 1-3, in which the mean duration of the first movement was some 135-162 ms, there was a mean pause of about 85 ms before the start of the second movement. Subjects tended to chose a minimum inter-onset latency between the start of the first and the start of the second movement of a sequence of some 230 ms. The reason for this appeared to be that if subjects were encouraged to decrease their inter-onset latencies to less than 200 ms, the speed of the second movement decreased sharply. However, if the duration of the first movement was prolonged as in task 4, the second movement could be delayed, although there now was little or no pause between the two movements. We conclude that when a single motor programme is run, it is followed by a "relative refractory period". If a second programme is run within this period, it cannot be executed without loss of speed. Switching from one motor programme to another is achieved with an optimal minimum delay of 200 ms. Sequential movements which are controlled by a single programme do not share this limitation.

Adult↗

Performance of simultaneous movements in patients with Parkinson's disease.

Ten right-handed patients with Parkinson's disease and 9 normal subjects performed five different types of movements as rapidly as possible in their own time: isotonic elbow flexion through an angle of 15 deg ('flex'); isometric squeezing of a force transducer between thumb and fingers ('squeeze'); isotonic finger flexion ('cut'); simultaneous performance of both 'flex' and 'squeeze'; simultaneous performance of 'flex' and 'cut'. The patients performed the separate movements of 'flex', 'squeeze' and 'cut' more slowly than normals. However, a more striking deficit was seen when a 'flex' and a 'squeeze' had to be performed at the same time, and with the same arm. There was an additional increase in movement times over and above that seen in the separate movements alone. If the patients used both arms ('flex' with the right, 'squeeze' with the left), rather than one, or when a 'flex' and a 'cut' had to be combined in the same arm, only a slight increase in movement times was observed. In normals, however, the speed of individual movements of 'flex', 'squeeze' or 'cut' was the same irrespective of whether they were performed separately or simultaneously. In any one subject, movement times for the separate components of 'flex' and 'squeeze' varied independently during the performance of the simultaneous movement. Because they remain independent, we suggest that when 'flex' and 'squeeze' are performed at the same time, two separate motor programmes are superimposed to produce the combined movement. In Parkinson's disease there may be a deficit in superimposing two separate motor programmes which leads to the pronounced slowness of simultaneous movements with the same arm. Comparison of movement times for a 'flex' (but not for a 'squeeze') in the separate and simultaneous movements showed that the degree of clinical akinesia was more closely related to the additional slowness in simultaneous movements than to the slowness seen when the movements were performed separately. The degree of disturbance in superimposing separate motor programmes may determine the amount of clinical akinesia in patients with Parkinson's disease.

Adult↗

The effect of percutaneous motor cortex stimulation on H reflexes in muscles of the arm and leg in intact man.

The technique of electrical stimulation of the brain via scalp electrodes has been used to activate corticospinal pathways in intact man. The intensity of stimulation was adjusted to be below the threshold necessary to evoke a direct electromyographic response when the muscles being tested were totally relaxed. Changes in spinal cord excitability were measured using H-reflex (monosynaptic) testing. By this means it was found that subthreshold scalp stimulation can produce a descending corticospinal volley even in the absence of a direct muscle response. The time course of changes in spinal cord excitability was evaluated by evoking test H reflexes at different intervals relative to the scalp stimulus. In wrist and finger flexor muscles of seven subjects, a single subthreshold scalp shock produced an initial peak facilitation of the H reflex which on average lasted for 2.5 ms. The end of the initial facilitation was marked by a return of the H reflex towards basal levels and on one occasion by a frank inhibition. It is suggested that the initial facilitation is produced by arrival at the motoneurones of monosynaptic excitatory post-synaptic potentials (e.p.s.p.s) and is truncated by the subsequent arrival of disynaptic inhibitory post-synaptic potentials (i.p.s.p.s). The initial facilitation was followed by a second phase of facilitation of the H reflex. The second phase was weaker, more variable and longer lasting (from 5 to 20 ms) than the first phase. The threshold of scalp stimulus intensity required to produce an effect on the H reflex was the same for the first and second phases of facilitation. Several possible explanations are discussed for the mechanism responsible for the late and long-lasting facilitation. In two subjects wrist and finger extensor muscles were studied. The time course of H-reflex changes was similar to that of the flexors except that the initial facilitation was followed by a frank inhibition in both subjects. In one subject thenar muscles and tibialis anterior were studied and behaved similarly to wrist and finger flexor muscles. Effects on the soleus H reflex was studied in seven subjects. In five of these subjects, in contrast to the other muscles studied, the initial event was an inhibition of the H reflex. This inhibition also could be seen preceding the usual period of facilitation in averaged rectified surface electromyogram (e.m.g.) records when scalp stimuli were given during weak voluntary activation of soleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Arm↗

Scaling of the size of the first agonist EMG burst during rapid wrist movements in patients with Parkinson's disease.

Rapid wrist flexion movements were studied in a group of 10 patients with Parkinson's disease both on and off their normal drug therapy, and were compared with the same movements made by a group of eight normal individuals. When normal subjects made movements through 60 degrees, the first agonist burst of EMG activity in the wrist flexor muscles was longer and larger than that seen in movements of 15 degrees. If a large opposing load of 2.2 Nm was added, this also increased the size and duration of the first agonist EMG burst. Although the movements made by the patients were slower than those of normals, the size and duration of the first agonist EMG burst changed with movement size and added load in the normal way. This shows that patients can produce large, long bursts of EMG activity, but that there is a failure to match these parameters appropriately to the size of movement required. The effect of levodopa therapy on the movements was not dramatic. Although patients produced faster wrist movements when on medication than when off, the change was relatively small compared with the change seen in their overall clinical rating. Changes in the velocity of movements at a single joint are not a good reflection of the overall clinical state of patients with Parkinson's disease.

Adult↗

Associated postural adjustments in Parkinson's disease.

Postural activity in muscles of the back and legs associated with voluntary forward elevation of the arm at the shoulder with the subject standing was examined in 14 patients with Parkinson's disease and nine normal individuals. The time of onset of EMG activity in each of the postural muscles, relative to the onset of activity in the prime mover, was the same for both patient and normal groups and did not depend on load. The amplitude of the EMG bursts and their frequency of occurrence, was less in patients off drug treatment and immobile, than when mobile on therapy. We conclude that the timing of associated postural adjustments is normal in Parkinson's disease, although their size may be decreased.

Adult↗