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Biomedical subjects

J C Rothwell

Publications and source records attributed to J C Rothwell.

At least 109 records · Page 6Linked to original sources

Common 3 and 10 Hz oscillations modulate human eye and finger movements while they simultaneously track a visual target.

1. A 10 Hz range centrally originating oscillation has been found to modulate slow finger movements and anticipatory smooth eye movements. To determine if an interaction or linkage occurs between these two central oscillations during combined visuo-manual tracking, frequency and coherence analysis were performed on finger and eye movements while they simultaneously tracked a visual target moving in intermittently visible sinusoidal patterns. 2. Two different frequencies of common or linked oscillation were found. The first, at 2-3 Hz, was dependent on visual feedback of target and finger tracking positions. The second, at around 10 Hz, still occurred when both target and finger positions were largely obscured, indicating that this common oscillation was generated internally by the motor system independent of visual feedback. Both 3 and 10 Hz oscillation frequencies were also shared by the right and left fingers if subjects used these together to track a visual target. 3. The linking of the 10 Hz range oscillations between the eyes and finger was task specific; it never occurred when eye and finger movements were made simultaneously and independently, but only when they moved simultaneously and followed the target together. However, although specific for tracking by the eyes and fingers together, the linking behaviour did not appear to be a prerequisite for such tracking, since significant coherence in the 10 Hz range was only present in a proportion of trials where these combined movements were made. 4. The experiments show that common oscillations may modulate anatomically very distinct structures, indicating that single central oscillations may have a widespread distribution in the central nervous system. The task-specific manifestation of the common oscillation in the eye and finger suggests that such mechanisms may have a functional role in hand-eye co-ordination.

Adult↗

Impact of deep brain stimulation on upper limb akinesia in Parkinson's disease.

Recent pathophysiological models of Parkinson's disease have led to new surgical approaches to treatment including deep brain stimulation (DBS) and lesioning of basal ganglia structures. Various measures of upper limb akinesia were assessed in 6 patients with bilateral DBS of the internal pallidum and 6 with DBS of the subthalamic nucleus. Stimulation improved a number of aspects of motor function, and particularly movement time, and force production. Time to initiate movements, and to perform repetitive movements also improved but less dramatically. Processes indicating preparatory motor processes showed no significant change. Few significant differences were found between the internal pallidum and subthalamic nucleus groups. In general, the effects of DBS closely parallel previous reports of the effects of dopaminergic medication. It is suggested that disrupted pallidal output in Parkinson's disease interferes with the rate, level, and coordination of force production but has little effect on preparatory processes. The similarity of the effects of subthalamic nucleus and internal pallidum stimulation suggests this disrupted outflow is the most important determinant of upper limb akinesia in Parkinson's disease. The effects of DBS were similar to the effects of unilateral pallidal lesions reported elsewhere.

Brain↗

Direct demonstration of interhemispheric inhibition of the human motor cortex produced by transcranial magnetic stimulation.

Electromyographic (EMG) responses evoked in hand muscles by a magnetic test stimulus over the motor cortex can be suppressed if a conditioning stimulus is applied to the opposite hemisphere 6-30 ms earlier. In order to define the mechanism and the site of action of this inhibitory phenomenon, we recorded descending volleys produced by the test stimulus through high cervical, epidural electrodes implanted for pain relief in three conscious subjects. These could be compared with simultaneously recorded EMG responses in hand muscles. When the test stimulus was given on its own it evoked three waves of activity (I-waves) in the spinal cord, and a small EMG response in the hand. A prior conditioning stimulus to the other hemisphere suppressed the size of both the descending spinal cord volleys and the EMG responses evoked by the test stimulus when the interstimulus interval was greater than 6 ms. In the spinal recordings, the effect was most marked for the last I-wave (I3), whereas the second I2-wave was only slightly inhibited, and the first I-wave (I1) was not inhibited at all. We conclude that transcranial stimulation over the lateral part of the motor cortex of one hemisphere can suppress the excitability of the contralateral motor cortex.

Adult↗

Effects of voluntary contraction on descending volleys evoked by transcranial electrical stimulation over the motor cortex hand area in conscious humans.

The spinal volleys evoked by electric anodal and cathodal stimulation over the cerebral motor cortex hand area were recorded from a bipolar electrode inserted into the cervical epidural space of two conscious human subjects. We measured the size of volleys elicited by electric stimulation at active motor threshold and at 3% of maximum stimulator output above this value with subjects at rest and during maximum voluntary contraction of the contralateral first dorsal interosseous muscle. Surface EMG activity was recorded at the same time. Electrical anodal stimulation evoked a single negative wave that we termed D-wave in analogy with data in experimental animals. Cathodal stimulation evoked a single negative wave with a latency of 0.2 ms longer than the D-wave recruited by anodal stimulation. At both intensities tested, voluntary contraction did not modify the amplitude of the descending waves. We conclude that changes in cortical excitability induced by voluntary activity do not modify the corticospinal volley evoked by electric stimulation and that the D-waves evoked by both anodal and cathodal electric stimulation are probably initiated several nodes distant to the cell body.

Adult↗

Dynamic changes in corticospinal excitability during motor imagery.

We investigated temporal changes in the amplitudes of motor-evoked potentials (MEPs) induced by transcranial magnetic stimulation over the left motor cortex during motor imagery. Nine subjects were instructed to imagine repetitive wrist flexion and extension movements at 1 Hz, in which the flexion timing was cued by a tone signal. Electromyographs (EMGs) were recorded from the first dorsal interosseous, flexor carpi radialis and extensor carpi radialis muscles of the right hand, and magnetic stimulation was delivered at 0, 250, 500 and 750 ms after the auditory cue. On average, the evoked EMG responses were larger in the flexor muscle during the phase of imagined flexion than during extension, whilst the opposite was true for the extensor muscle. There were no consistent changes in the amplitudes of MEPs in the intrinsic hand muscle (first dorsal interosseous). The EMG remained relaxed in all muscles and did not show any significant temporal changes during the test. The H-reflex in the flexor muscle was obtained in four subjects. There was no change in its amplitude during motor imagery. These observations lead us to suggest that motor imagery can have dynamic effects on the excitability of motor cortex similar to those seen during actual motor performance.

Adult↗

Afferent input and cortical organisation: a study with magnetic stimulation.

Previously, we had described a technique for investigating probable GABAergic cortical inhibitory circuits in conscious man using transcranial magnetic stimulation. This type of inhibition has been termed intracortical inhibition. During voluntary contraction, activity in the circuits responsible for this inhibition is reduced. The mechanism by which this reduction in activity is brought about is unknown. However, evidence exists to suggest that afferent input may be, at least in part, responsible for the reduction in inhibition. The experiments described here were designed to investigate this possibility further. The results of these experiments showed that afferent input, produced by electrical peripheral-nerve stimulation, reduced the level of intracortical inhibition. Also, motor imagery, which activates similar brain regions as overt movement, but does not result in afferent input, failed to produce significant changes in intracortical inhibition. We conclude from these results that afferent input is capable of altering activity in cortical inhibitory circuits. The relevance of these findings to the mechanisms involved in cortical reorganisation is discussed.

Adult↗

Human handedness and asymmetry of the motor cortical silent period.

We performed transcranial magnetic stimulation of the motor cortex in 22 left-handed and 25 right-handed subjects during active contraction of a small hand muscle. Motor evoked potentials had the same latency, amplitude and threshold on both sides of the body, whilst the silent period duration was shorter in the dominant hand. Silent periods elicited by nerve and brainstem stimulation were the same in both hands. Since the latter part of the cortical silent period is due mainly to withdrawal of corticospinal input to spinal motoneurones, we speculate that the results are compatible with the suggestion that tonic contractions of the non-dominant hand are associated with a greater involvement of the corticospinal tract than those of the dominant hand. It also seems likely that there is an asymmetry in the excitability of cortical inhibitory mechanisms with those responsible for the cortical silent period being less excitable in the dominant motor cortex.

Adult↗

Intracortical origin of the short latency facilitation produced by pairs of threshold magnetic stimuli applied to human motor cortex.

Under certain conditions, EMG responses evoked by pairs of transcranial magnetic stimuli over the motor cortex are larger than the sum of the responses to each stimulus given alone. This occurs with interstimulus intervals of around 1.3, 2.5 and 4.3 ms and could be due to interaction between the responses to each stimulus at either the cortex or spinal cord. We recorded the descending volleys set up by such pairs of stimuli from the cervical epidural space of five patients implanted with chronic stimulators for pain control. Interstimulus intervals of 1, 1.2, 1.4 and 2 ms were used to investigate the first peak of facilitation. Enhanced EMG responses occurred after pairs of stimuli at 1, 1.2 and 1.4 ms, and these were accompanied by larger and more numerous descending volleys than expected from the sum of each stimulus alone. We conclude that facilitatory interaction between the stimuli can occur within the cerebral cortex. This may involve elements that produce repetitive I-wave activity in response to a single stimulus.

Adult↗

Human anticipatory eye movements may reflect rhythmic central nervous activity.

To investigate the possibility that rhythmic activity originating in the central nervous system may modulate human eye movements, anticipatory eye movements were generated by tracking an intermittently obscured sinusoidally moving target. Eight subjects tracked intermittently obscured sinusoids of three different frequencies and of two different amplitudes. Eye movements were recorded by an infra-red reflection technique. The eye velocity records were analysed in the frequency domain by power spectral estimates. During periods where the target was obscured, eye movements consisted of a staggered series of anticipatory saccades with intervening smooth anticipatory eye movements or relatively stationary periods. In sections where the intervening smooth components of anticipatory tracking were of high velocity (above 15 deg/s), a superimposed smooth tremulous oscillation at around 10 Hz was sometimes present. Coherence analysis showed that this 10 Hz range oscillation of smooth anticipatory movement was not derived from head tremor and that the same oscillation was present in both eyes. This oscillation was not generally observed during smooth tracking of pseudorandom waveforms. Investigation of anticipatory eye movements has revealed a 10-Hz range oscillation or "tremor" superimposed upon smooth movements that might in other circumstances be inhibited by direct visual feedback. This smooth eye movement oscillation is thought to originate from the central nervous system and may reflect a widespread frequency modulation of motor commands.

Adult↗

The effects of posteroventral pallidotomy on the preparation and execution of voluntary hand and arm movements in Parkinson's disease.

We studied the effect of posteroventral pallidotomy on movement preparation and execution in 27 parkinsonian patients using various motor tasks. Patients were evaluated after overnight withdrawal of medication before and 3 months after unilateral pallidotomy. Surgery had no effect on initiation time in unwarned simple and choice reaction time tasks, whereas movement time measured during the same tasks was improved for the contralesional hand. Movement times also improved for isometric and isotonic ballistic movements. In contrast, repetitive, distal and fine movements measured in finger-tapping and pegboard tasks were not improved after pallidotomy. Preparatory processes were investigated using both behavioural and electrophysiological measures. A precued choice reaction time task suggested an enhancement of motor preparation for the contralesional hand. Similarly, movement-related cortical potentials showed an increase in the slope of the late component (NS2) when the patients performed joystick movements with the contralesional hand. However, no significant change was found for the early component (NS1) or when the patient moved the ipsilesional hand. The amplitude of the long-latency stretch reflex of the contralesional hand decreased after surgery. In summary, the data suggest that pallidotomy improved mainly the later stages of movement preparation and the execution of proximal movements with the contralesional limb. These results provide detailed quantitative data on the impact of posteroventral pallidotomy on previously described measures of upper limb akinesia in Parkinson's disease.

Electroencephalography↗

Sequential bilateral transplantation in Parkinson's disease: effects of the second graft.

Five parkinsonian patients who had received implants of human embryonic mesencephalic tissue unilaterally in the striatum 10-56 months earlier were grafted with tissue from four to eight donors into the putamen (four patients) or the putamen plus the caudate nucleus (one patient) on the other side, and were followed for 18-24 months. After 12-18 months, PET showed a mean 85% increase in 6-L-[18F]fluorodopa uptake in the putamen with the second graft, whereas there was no significant further change in the previously transplanted putamen. Two patients exhibited marked additional improvements after their second graft: 'on-off' fluctuations virtually disappeared, movement speed increased, and L-dopa could be withdrawn in one patient and reduced by 70% in the other. The improvement in one patient was moderate. Two patients with atypical features, who responded poorly to the first graft, worsened following the second transplantation. These findings indicate that sequential transplantation in patients does not compromise the survival and function of either the first or the second graft. Moreover, putamen grafts that restore fluorodopa uptake to normal levels can give improvements of major therapeutic value.

Adult↗

Identification of the cerebral loci processing human swallowing with H2(15)O PET activation.

Lesional and electrophysiological data implicate a role for the cerebral cortex in the initiation and modulation of human swallowing, and yet its functional neuroanatomy remains undefined. We therefore conducted a functional study of the cerebral loci processing human volitional swallowing with 15O-labeled water positron emission tomography (PET) activation imaging. Regional cerebral activation was investigated in 8 healthy right handed male volunteers with a randomized 12-scan paradigm of rest and water swallows (5 ml/bolus, continuous infusion) at increasing frequencies of 0.1, 0.2, and 0.3 Hz, which were visually cued and monitored with submental electromyogram (EMG). Group and individual linear covariate analyses were performed with SPM96. In five of eight subjects, the cortical motor representation of pharynx was subsequently mapped with transcranial magnetic stimulation (TMS) in a posthoc manner to substantiate findings of hemispheric differences in sensorimotor cortex activation seen with PET. During swallowing, group PET analysis identified increased regional cerebral blood flow (rCBF) (P < 0.001) within bilateral caudolateral sensorimotor cortex [Brodmann's area (BA) 3, 4, and 6], right anterior insula (BA 16), right orbitofrontal and temporopolar cortex (BA 11 and 38), left mesial premotor cortex (BA 6 and 24), left temporopolar cortex and amygdala (BA 38 and 34), left superiomedial cerebellum, and dorsal brain stem. Decreased rCBF (P < 0.001) was also observed within bilateral posterior parietal cortex (BA 7), right anterior occipital cortex (BA 19), left superior frontal cortex (BA 8), right prefrontal cortex (BA 9), and bilateral superiomedial temporal cortex (BA 41 and 42). Individual PET analysis revealed asymmetric representation within sensorimotor cortex in six of eight subjects, four lateralizing to right hemisphere and two to left hemisphere. TMS mapping in the five subjects identified condordant interhemisphere asymmetries in the motor representation for pharynx, consistent with the PET findings. We conclude that volitional swallowing recruits multiple cerebral regions, in particular sensorimotor cortex, insula, temporopolar cortex, cerebellum, and brain stem, the sensorimotor cortex displaying strong degrees of interhemispheric asymmetry, further substantiated with TMS. Such findings may help explain the variable nature of swallowing disorders after stroke and other focal lesions to the cerebral cortex.

Adult↗

Inhibitory action of forearm flexor muscle afferents on corticospinal outputs to antagonist muscles in humans.

1. To find out whether muscle afferents influence the excitability of corticospinal projections to antagonist muscles, we studied sixteen healthy subjects and one patient with a focal brain lesion. 2. Using transcranial magnetic and electrical brain stimulation we tested the excitability of corticomotoneuronal connections to right forearm muscles at rest after conditioning stimulation of the median nerve at the elbow. Somatosensory potentials evoked by median nerve stimulation were also recorded in each subject. 3. Test stimuli delivered at 13-19 ms after median nerve stimulation significantly inhibited EMG responses elicited in forearm extensor muscles by transcranial magnetic stimulation, but did not inhibit responses to electrical stimulation. In contrast, magnetically and electrically elicited responses in forearm flexor muscles were suppressed to the same extent. 4. The higher the intensity of the test shocks, the smaller was the amount of median nerve-elicited inhibition. Inhibition in extensor muscles was also smaller during tonic wrist extension, or if the induced electrical stimulating current in the brain flowed from posterior to anterior over the motor strip rather than vice versa. Test responses evoked by magnetic transcranial stimulation in the first dorsal interosseous and in brachioradialis muscles were not inhibited after median nerve stimulation at the elbow. Stimulation of digital nerves failed to inhibit motor potentials in extensor muscles. 5. Test stimuli delivered at 15 and 17 ms after radial nerve stimulation significantly inhibited EMG responses elicited in forearm flexor muscles by magnetic transcranial stimulation. 6. In the patient with a focal thalamic lesion, who had dystonic postures and an absent N20 component of the somatosensory-evoked potentials but normal strength, median nerve stimulation failed to inhibit magnetically evoked responses in forearm extensor muscles. 7. We propose that activation of median nerve muscle afferents can suppress the excitability of cortical areas controlling the antagonist forearm extensor muscles acting on the hand. The inhibitory effect occurs at short latency and might assist spinal pathways mediating reciprocal inhibition by contrasting the co-activation of antagonistic pools of corticospinal cells.

Adult↗