Biomedical subjects

J C Rothwell

Publications and source records attributed to J C Rothwell.

At least 127 records · Page 7Linked to original sources

PubMed1998

Effects of voluntary contraction on descending volleys evoked by transcranial stimulation in conscious humans.

1. The spinal volleys evoked by single transcranial magnetic or electric stimulation over the cerebral motor cortex were recorded from a bipolar electrode inserted into the cervical epidural space of three conscious human subjects. These volleys were termed direct (D) and indirect (I) waves according to their latency. 2. We measured the size and number of volleys elicited by magnetic stimulation at various intensities with subjects at rest and during 20 or 100 % maximum contraction of the contralateral first dorsal interosseous muscle (FDI). Surface EMG activity was also recorded. 3. Electrical stimulation evoked a D-wave volley. Magnetic stimulation at intensities up to about 15 % of stimulator output above threshold evoked only I-waves. At higher intensities, a D-wave could be seen in two of the three subjects. 4. At all intensities tested, voluntary contraction increased the number and size of the I-waves, particularly during maximum contractions. However, there was only a small effect on the threshold for evoking descending activity. Voluntary contraction produced large changes in the size of EMG responses recorded from FDI. 5. Because the recorded epidural activity is destined for muscles other than the FDI, it is impossible to say to what extent increased activity contributes to voluntary facilitation of EMG responses. Indeed, our results suggest that the main factor responsible for enhancing EMG responses in the transition from rest to activity is likely to be increased excitability of spinal motoneurones, rather than increases in the corticospinal volley. The latter may be more important in producing EMG facilitation at different levels of voluntary contraction.

Aged↗

PubMed1998

Role of spinal premotoneurones in mediating corticospinal input to forearm motoneurones in man.

1. Evidence was sought to support the suggestion that corticospinal input can be relayed to motoneurones (MNs) via a population of interneurones (premotoneurones) in the cervical cord, and that this pathway operates in parallel with the direct monosynaptic pathway. 2. Single motor units were recorded in forearm muscles and post-stimulus time histograms (PSTHs) of their firing pattern were constructed during voluntary activation. Weak transcranial magnetic stimulation of the contralateral motor cortex was used to produce a small facilitation in the PSTH. We then examined how the size of this peak was affected by low threshold electrical stimulation of either the homonymous muscle nerve or the musculo-cutaneous nerve at various interstimulus intervals (ISIs). 3. Homonymous nerve stimulation had the following characteristics: (a) the cortical peak was facilitated when stimuli were timed so that both inputs arrived simultaneously at the MN; (b) the amount of facilitation was only slightly greater than the sum of the effects of each stimulus given alone; and (c) facilitation affected even the earliest bins of the cortically evoked peak. These three features are consistent with a monosynaptic input onto the MN from both sources. 4. Stimulation of the musculo-cutaneous nerve (which has no monosynaptic connections with forearm MNs) had no effect at similar timings. It (a) produced facilitation only at longer intervals corresponding to an extra central delay of 4-6 ms; (b) always gave a significantly larger facilitation than expected from the algebraic sum of the effects of each stimulus given alone; and (c) never affected the earliest bins of the cortical peak. These features are compatible with interaction of peripheral and cortical inputs at a population of premotoneurones. 5. These results confirm the suggestion that premotoneurones mediate part of the cortical command to MNs innervating forearm muscles. 6. Excitation is followed by an inhibition which may almost completely suppress the cortical peak. It is suggested that cortical and musculo-cutaneous volleys also converge onto inhibitory interneurones projecting to the premotoneuronal pool.

Adult↗

PubMed1998

Sensorimotor modulation of human cortical swallowing pathways.

1. Transcranial magnetic stimulation over motor areas of cerebral cortex in man can activate short latency bilateral cortical projections to the pharynx and oesophagus. In the present paper we investigate the interaction between pathways from each hemisphere and explore how activity in these pathways is modulated by afferent feedback from the face, pharynx and oesophagus. 2. Comparison of unilateral and bilateral stimulation (using interstimulus intervals (ISIs) of 1, 5 or 10 ms between shocks) showed spatial summation of responses from each hemisphere at an ISI of 1 ms, indicating that cortical efferents project onto a shared population of target neurones. Such summation was not evident at ISIs of 5 or 10 ms. There was little evidence for transcallosal inhibition of responses from each hemisphere, as described for limb muscles. 3. Single stimuli applied to the vagus nerve in the neck or the supraorbital nerve, which alone produce intermediate (onset 20-30 ms) and long (50-70 ms) latency reflex responses in the pharynx and oesophagus, were used to condition the cortical responses. Compared with rest, responses evoked by cortical stimulation were facilitated when they were timed to coincide with the late part of the reflex. The onset latency was reduced during both parts of the reflex response. No facilitation was observed with subthreshold reflex stimuli. 4. Single electrical stimuli applied to the pharynx or oesophagus had no effect on the response to cortical stimulation. However, trains of stimuli at frequencies varying from 0.2 to 10 Hz decreased the latency of the cortically evoked responses without consistently influencing their amplitudes. The effect was site specific: pharyngeal stimulation shortened both pharyngeal and oesophageal response latencies, whereas oesophageal stimulation shortened only the oesophageal response latencies. 5. Cortical swallowing motor pathways from each hemisphere interact and their excitability is modulated in a site-specific manner by sensory input. The latter may produce a mixture of excitation and inhibition at both brainstem and cortical levels.

Adult↗

PubMed1998

Functional involvement of cerebral cortex in Duchenne muscular dystrophy.

Transcranial stimulation was performed in 4 patients with Duchenne muscular dystrophy and 4 control subjects. The patients' central motor conduction time was normal. The threshold for evoking electromyographic responses using electrical anodal stimulation was the same in both groups, but the threshold for stimulation with a circular magnetic coil at the vertex was higher in the patients. This is compatible with reduced cortical excitability that may be related to the deficiency of brain synaptic dystrophin.

Adolescent↗

PubMed1998

Action tremor and weakness in Parkinson's disease: a study of the elbow extensors.

We have previously shown that action tremor persists during maximal wrist extension in patients with Parkinson's disease, and that this contributes to weakness at this joint by preventing the fully fused contraction of the forearm extensor muscles. Antiparkinsonian medication reduces the action tremor in torque and electromyographic (EMG) records, thereby improving strength at the wrist. In the present experiments, peak torque and action tremor were recorded during maximal extension of the elbow in nine patients with Parkinson's disease while they were on and off antiparkinsonian medication, and in eight age- and sex-matched healthy subjects. Peak torque and mean rectified EMG levels were reduced by 34% and 36%, respectively, during maximal elbow extension when patients off medication were compared to those in the treated state. Action tremor was visible in torque records and had a frequency of approximately 10 Hz both in parkinsonian patients and in normal controls. Activity of a similar frequency was often detected in EMG records, especially in patients off therapy. The absolute amplitude of action tremor in torque (A[torque]) and EMG (A[EMG]) records from the elbow was unaffected by therapy and was little different from that recorded in healthy controls. The relative action tremor in torque ([A(torque)/peak torque] x 100) and EMG ([A(EMG)/mean rectified EMG] x 100) was reduced by treatment, but this was the result of the increase in peak torque and mean rectified EMG. Thus, in contrast to the results at the wrist, antiparkinsonian medication has little effect on the 10-Hz action tremor at the elbow. Increased strength is produced by a different mechanism which allows recruitment of triceps motor units outside of this synchronizing influence.

Aged↗

PubMed1998

The offset cortical potential: an electrical correlate of movement inhibition in man.

Nine normal subjects were asked to make either a brisk isometric pinch of a force transducer held between the forefinger and thumb, or to hold a pinch for approximately 15 s and then release the force suddenly without any overt antagonist contraction. EEG activity was averaged about the onset or offset of EMG activity, and movements were made in the subjects' own time. All subjects found the task simple. The EEG activity preceding offset of contraction (offset cortical potential) was significantly smaller in lateral leads than that seen before onset of contraction. Midline activation was similar in both tasks. We suggest that in the onset task, motor cortex activity related to the act to be performed contributes substantially to the EEG potentials in lateral leads. This activity is absent in the offset task which requires only withdrawal of tonic input to motor cortex. Midline activity, common to both onset and offset tasks, could reflect timing, attentional, or other processes. The results are discussed in relation to previous data from an isotonic relaxation task.

Adult↗

PubMed1998

Physiology and anatomy of possible oscillators in the central nervous system.

Pathologic tremors occur when the normal, continuous pattern of muscle activation is replaced by relatively synchronous bursting. This article discusses the possible roles of stretch reflex and central oscillators in producing tremor. The gain and conduction delay in some reflex arcs places the stretch reflex close to oscillation in some muscles during normal operation. Within the brain, cells in the thalamic relay nuclei and inferior olive contain a set of ionic conductancies in the cell membrane that can interact to produce oscillations in membrane potential. This tendency is exaggerated by hyperpolarizing or depolarizing the cell away from the normal resting potential. The activity of neighboring cells can be coupled (by electrotonic gap junctions in the olive and by recurrent axonal projections from the reticular nucleus in the thalamus), thus a large population of cells can oscillate together and exert a powerful rhythmic influence on motor output.

Cerebral Cortex↗

PubMed1998

Transcranial magnetic stimulation selectively impairs interhemispheric transfer of visuo-motor information in humans.

We investigated the cerebral cortical route by which visual information reaches motor cortex when visual signals are used for manual responses. Subjects responded unimanually to photic stimuli delivered to the hemifield ipsilateral or contralateral to the moving hand. On some trials, trans-cranial magnetic stimulation (TMS) was applied unilaterally over the occiput, with the aim of stimulating extrastriate visual areas and thereby modifying transmission of visual input. In association with the side of a visual stimulus and a motor response, TMS could change inter- or intra-hemispheric transmission needed to convey visual information to motor areas. Reaction time differences following TMS suggested that TMS exerted an inhibitory effect only when visuo-motor information had to be transferred interhemispherically. This result reinforces evidence for an extrastriate pathway of interhemispheric transfer of visuomotor information.

Acoustic Stimulation↗

PubMed1998

Magnetic transcranial stimulation at intensities below active motor threshold activates intracortical inhibitory circuits.

A magnetic transcranial conditioning stimulus given over the motor cortex at intensities below threshold for obtaining electromyographical (EMG) responses in active hand muscles can suppress responses evoked in the same muscles at rest by a suprathreshold magnetic test stimulus given 1-5 ms later. In order to define the mechanism of this inhibitory effect, we recorded descending volleys produced by single and paired magnetic transcranial stimulation of motor cortex through high cervical, epidural electrodes implanted for pain relief in two conscious subjects with no abnormality of the central nervous system. The conditioning stimulus evoked no recognisable descending activity in the spinal cord, whilst the test stimulus evoked 3-4 waves of activity (I-waves). Conditioning stimulation suppressed the size of both the descending spinal cord volleys and the EMG responses evoked by the test stimulus. Inhibition of the descending spinal volleys was most pronounced at ISI 1 ms and had disappeared by ISI 5 ms. It was evident for all components following the I1-wave, while the I1-wave itself was not inhibited at all. We conclude that a small conditioning magnetic stimulus can suppress the excitability of human motor cortex, probably by activating local corticocortical inhibitory circuits.

Aged↗

PubMed1998

Facilitation of muscle evoked responses after repetitive cortical stimulation in man.

The technique of repetitive transcranial magnetic stimulation (rTMS) allows cortical motor areas to be activated by trains of magnetic stimuli at different frequencies and intensities. In this paper, we studied long-term neurophysiological effects of rTMS delivered to the motor cortex at 5 Hz with an intensity of 120% of motor threshold. Each stimulus of the train produced muscle-evoked potentials (MEPs) in hand and forearm muscles, which gradually increased in size from the first to the last shock. After the end of the train, the response to a single-test stimulus remained enhanced for 600-900 ms. In contrast, the train had no effect on the size of the MEPs evoked by transcranial electrical stimulation, while it suppressed H-reflexes in forearm muscles for 900 ms. We conclude that rTMS of these parameters increases the excitability of the motor cortex and that this effect outlasts the train for almost 1 s. At the spinal level, rTMS may increase presynaptic inhibition of Ia afferent fibers responsible for the H-reflex.

Adult↗

PubMed1998

Recovery of swallowing after dysphagic stroke relates to functional reorganization in the intact motor cortex.

BACKGROUND & AIMS: The aim of this study was to determine the mechanism for recovery of swallowing after dysphagic stroke. METHODS: Twenty-eight patients who had a unilateral hemispheric stroke were studied 1 week and 1 and 3 months after the stroke by videofluoroscopy. Pharyngeal and thenar electromyographic responses to magnetic stimulation of multiple sites over both hemispheres were recorded, and motor representations were correlated with swallowing recovery. RESULTS: Dysphagia was initially present in 71% of patients and in 46% and 41% of the patients at 1 and 3 months, respectively. Cortical representation of the pharynx was smaller in the affected hemisphere (5 +/- 1 sites) than the unaffected hemisphere (13 +/- 1 sites; P </= 0.001). Nondysphagic and persistently dysphagic patients showed little change in pharyngeal representation in either hemisphere at 1 and 3 months compared with presentation, but dysphagic patients who recovered had an increased pharyngeal representation in the unaffected hemisphere at 1 and 3 months (15 +/- 2 and 17 +/- 3 vs. 9 +/- 2 sites; P </= 0.02) without change in the affected hemisphere. In contrast, thenar representation increased in the affected hemisphere but not the unaffected hemisphere at 1 and 3 months (P </= 0.01). CONCLUSIONS: Return of swallowing after dysphagic stroke is associated with increased pharyngeal representation in the unaffected hemisphere, suggesting a role for intact hemisphere reorganization in recovery.

Aged↗

PubMed1998

Gut feelings about recovery after stroke: the organization and reorganization of human swallowing motor cortex.

Swallowing problems can affect as many as one in three patients in the period immediately after a stroke. In some cases this can lead to serious morbidity, in particular malnutrition and pulmonary aspiration. Despite this, swallowing usually recovers completely in the vast majority of patients within weeks. This impressive propensity for recovery is likely to relate to how the area of the motor cortex concerned with swallowing is organized and then reorganized after cerebral injury. Recent studies have indicated that swallowing has a bilateral but asymmetric inter-hemisphere representation within motor and premotor cortex. Damage to the hemisphere that has the greater swallowing output appears to predispose that individual to swallowing problems. However, because there is additional substrate for swallowing in the undamaged hemisphere, the capacity for compensatory reorganization in the contralateral motor cortex might be increased, leading to a greater likelihood of recovery. Swallowing might be an excellent system for studying cortical plasticity, and might prove useful in the development of new therapies aimed at accelerating reorganization in the undamaged hemisphere after unilateral cerebral injury.

Adaptation, Physiological↗

PubMed1998

Comparison of descending volleys evoked by transcranial magnetic and electric stimulation in conscious humans.

OBJECTIVES: The present experiments were designed to compare the understanding of the transcranial electric and magnetic stimulation of the human motorcortex. METHODS: The spinal volleys evoked by single transcranial magnetic or electric stimulation over the cerebral motor cortex were recorded from a bipolar electrode inserted into the cervical epidural space of two conscious human subjects. These volleys were termed D- and I waves, according to their latency. Magnetic stimulation was performed with a figure-of-eight coil held over the right motor cortex at the optimum scalp position, in order to elicit motor responses in the contralateral FDI using two different orientations over the motor strip. The induced current flowed either in a postero-anterior or in a latero-medial direction. RESULTS: At active motor threshold intensity, the electric anodal stimulation evoked pure D activity. At this intensity, magnetic stimulation with the induced current flowing in a posterior-anterior direction evoked pure I1 activity. When a latero-medial induced current was used, magnetic stimulation evoked both D and I1 activity. Using electric anodal stimulation, at a stimulus intensity of 9% of the stimulator output above the active motor threshold (corresponding approximately to 1.5 active motor threshold), a small I1 wave appeared only in subject 1. Using magnetic stimulation with a posterior-anterior induced current, at a stimulus intensity of 21% of maximum stimulator output above the active motor threshold (corresponding approximately to 1.8 times threshold in subject 1 and to two times threshold in subject 2), a small D wave appeared in subject 1 but not in subject 2. CONCLUSIONS: Present results demonstrate that, in conscious humans at threshold intensities, electric stimulation evokes D waves and magnetic stimulation (with a posterior-anterior induced current) evokes I waves, while magnetic stimulation (with a latero-medial induced current) evokes both activities.

Differential Threshold↗

PubMed1998

Reduced excitability of the cortico-spinal system during the warning period of a reaction time task.

Seven subjects made a wrist flexion movement as rapidly as possible in response to a cutaneous shock on the opposite hand. In some trials, an auditory warning signal was given 0.5 s beforehand. In random trials, transcranial magnetic stimulation (TMS) was used to elicit EMG responses (MEPs) in forearm flexor and extensor muscles 0-500 ms before the cutaneous shock. H-reflexes were elicited in flexor muscles at the same intervals. The warning stimulus reduced reaction time from about 400 ms to 200 ms. MEPs in the flexor muscles were significantly suppressed from 125 ms after the warning stimulus until the time of the cutaneous shock whilst MEPs in the extensors, and H-reflexes in the flexor were either unaffected, or reduced by a smaller amount at a later time. Responses in relaxed contralateral muscles were unchanged. If the task was changed to a choice reaction, in which the imperative stimulus (but not the warning signal) indicated whether to flex or extend the wrist, then there was no change in the MEPs or H-reflex in the warning period. A similar effect was seen if the duration of the warning period was extended from 0.5 to 2 s in a simple reaction (flexion) task. We conclude that increased excitability of the corticospinal output is not required to speed up reaction times. The time taken to discharge cortical output elements is relatively unimportant compared with the time needed to process the sensory input and link it to the motor output.

Adult↗

PubMed1998

Long-term reorganization of human motor cortex driven by short-term sensory stimulation.

Removal of sensory input can induce changes in cortical motor representation that reverse when sensation is restored. Here we ask whether manipulation of sensory input can induce long-term reorganization in human motor cortex that outlasts the initial conditioning. We report that for at least 30 minutes after pharyngeal stimulation, motor cortex excitability and area of representation for the pharynx increased, while esophagus representation decreased, without parallel changes in the excitability of brainstem-mediated reflexes. Therefore increased sensory input can drive long-term cross-system changes in motor areas of the cerebral cortex, which suggests that sensory stimulation might rehabilitate dysphagia, a frequent consequence of cerebral injury.

Adult↗

PubMed1998

A study of medial pallidotomy for Parkinson's disease: clinical outcome, MRI location and complications.

We have studied the effects of unilateral ventral medial pallidotomy in 26 patients with medically intractable Parkinson's disease with marked drug-induced dyskinesias. Preoperatively, all patients were assessed during one 5-day admission according to the Core Assessment Programme for Intracerebral Transplantation (CAPIT) protocol, including rating in the 'practically defined off' and 'best on' states before and during a single-dose levodopa challenge. Motor performance was assessed with subset categories of the Unified Parkinson's Disease Rating Scale (UPDRS), timed motor tests and a standard dyskinesia rating scale. Pallidotomy was performed under stereotaxic CT guidance with intra-operative extracellular microelectrode recording made from the basal ganglia. All patients were re-assessed 3 months postoperatively and a subgroup (n = 9) have so far also been re-assessed after 1 year. Pre- and postoperative performance scores were compared in order to determine which categories of performance improved postoperatively. Significance was accepted at P < 0.005 in order to take into account the multiple number of comparisons performed. Patient medication was compared pre- and postoperatively and the morbidity associated with surgery was also recorded. The most significant improvement postoperatively was the diminution of 'on' dyskinesias contralaterally (67%, P = 0.0001); however, ipsilateral (45%, P = 0.0006) and axial (50%, P = 0.0008) dyskinesias also improved. Contralateral to pallidotomy, the median 'off' motor UPDRS score improved by 27% (P = 0.001) and a significant improvement was also observed in contralateral rigidity by 25% (P = 0.001). There were trends towards improvement in contralateral tremor (33%, P = 0.016) and bradykinesia (24%, P = 0.013) scores. Ipsilateral rigidity improved by 22% (P = 0.005), but other ipsilateral motor scores did not alter significantly. The 'off' gait/postural instability score and 'off' walking time showed marginally significant improvements by 7% (P = 0.007) and 29% (P = 0.014), respectively. On medication, no significant postoperative improvements in parkinsonism were detected. Anti-parkinsonian medication increased by 11% postoperatively. In the subgroup who were available for assessment 1 year postoperatively, responses were generally maintained. Two (7.7%) of the 26 patients had fatal complications (one cerebral haemorrhage and one haemorrhagic infarct) directly related to surgery. Among the remaining 24 patients, four (15.4% of the total 26) had major complications (two persisting and two transient). Ten patients (38.5%) had minor complications. The majority of the complications (major and minor) occurred in the earlier operated patients and the complication rate subsequently declined with increasing operative experience. The remaining 10 patients (38.5%) had no significant side-effects. One of these 10 patients died from an incidental malignant glioma 6 months postoperatively. These findings confirm that levodopa-induced dyskinesias are dramatically reduced following ventral medial pallidotomy and constitute the principal indication for pallidotomy. Improvements in underlying parkinsonism were of smaller magnitude. Pallidotomy may also offer some patients an opportunity to increase antiparkinsonian medication. Patient selection for medial pallidotomy should, therefore, be based largely on anticipated improvements in levodopa-induced dyskinesias, but this must be balanced against the associated morbidity and mortality.

Aged↗

PubMed1998

Abnormal motor unit synchronization of antagonist muscles underlies pathological co-contraction in upper limb dystonia.

The aim of this study was to examine the pathophysiological mechanisms underlying co-contraction in patients with dystonia (n = 6) and writer's cramp (n = 5). Multi-unit needle and surface EMGs were recorded from extensor carpi radialis (ECR) and flexor carpi radialis (FCR) muscles during motor tasks that elicited dystonia or writer's cramp. The EMGs from ECR and FCR were recorded simultaneously and analysed using cross-correlation analysis. Similar recordings were obtained from healthy age- and sex-matched control subjects (n = 8). Despite co-contraction of the muscles, cross-correlograms from the healthy subjects did not reveal evidence of motor unit synchronization. Cross-correlograms from the dystonic subjects revealed a central peak with a median duration of 37 ms, indicating broad-peak motor unit synchronization. Cross-correlograms from patients with writer's cramp were either flat or modulated by a 11-12-Hz tremor. Frequency-domain analysis of ECR and FCR EMGs demonstrated significant coherence in the patients with dystonia and writer's cramp. These results indicate that co-contraction in dystonia is neurophysiologically distinct from voluntary co-contraction and is produced by abnormal synchronization of presynaptic inputs to antagonist motor neuron pools. ECR and FCR co-contraction in writer's cramp may be a compensatory process under voluntary control.

Adolescent↗

PubMed1998

An open-labelled clinical and electrophysiological study of 3,4 diaminopyridine in the treatment of fatigue in multiple sclerosis.

We studied the electrophysiological parameters of motor performance in eight patients with multiple sclerosis and troublesome fatigue, before and after treatment with 3,4-diaminopyridine. Symptomatic fatigue was evaluated by the Krupp Fatigue Severity Score and motor performance of adductor pollicis by transcranial magnetic stimulation, rapid voluntary movements and a fatiguing exercise test of a sustained 45-s isometric contraction. The motor tests revealed baseline abnormal motor function and substantial central fatigue. After a 3-week course of 3,4-diaminopyridine (25-60 mg/day), six out of the eight patients reported substantial improvement in fatigue and the group showed slightly less fatigue on the exercise test. Other electrophysiological tests of motor function were unchanged. The findings suggest that 3,4-diaminopyridine may play a role in the symptomatic treatment of fatigue in multiple sclerosis. However, the mechanism behind such a benefit in fatigue remains unclear and the discrepancy between subjective and more objective responses underlines the probable multifactorial nature of the pathogenesis of this symptom in multiple sclerosis.

4-Aminopyridine↗