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Biomedical subjects

John C Rothwell

Publications and source records attributed to John C Rothwell.

At least 73 records · Page 4Linked to original sources
PubMed2004

The after effects of motor cortex rTMS depend on the state of contraction when rTMS is applied.

OBJECTIVE: To test whether the after effects of 5 Hz focal rTMS over the primary motor cortex are modulated by the state of muscle contraction when the rTMS is applied. METHODS: Ten healthy volunteers gave informed consent to the studies. Fifty stimuli at active motor threshold intensity were applied at 5 Hz to the forearm motor area during 10% MVC isometric wrist flexion, 10% MVC wrist extension and at rest. Short interval intracortical inhibition (SICI: interstimulus intervals of 2-5 ms) and intracortical facilitation (interstimulus intervals of 7 and 10 ms) were recorded at rest before and after rTMS from flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles with surface electrodes. RESULTS: rTMS during wrist flexion decreased SICI in the FCR whereas SICI was increased if rTMS was given during wrist extension. The opposite was true in ECR: SICI was increased if rTMS was applied during wrist flexion, whereas it was reduced if rTMS was given during wrist extension. rTMS applied at rest produced a small overall decrease of SICI in FCR and ECR but this was not individually significant in the FCR. The 10 s wrist flexion without any rTMS did not have any effect on SICI. CONCLUSIONS: The after effects of motor cortex rTMS can be selectively modulated by the pattern of muscle contraction.

Adult↗
PubMed2004

Action, arousal, and subjective time.

Saccadic chronostasis refers to the subjective temporal lengthening of the first visual stimulus perceived after an eye movement. It has been quantified using a duration discrimination task. Most models of human duration discrimination hypothesise an internal clock. These models could explain chronostasis as a transient increase in internal clock speed due to arousal following a saccade, leading to temporal overestimation. Two experiments are described which addressed this hypothesis by parametrically varying the duration of the stimuli that are being judged. Changes in internal clock speed predict chronostasis effects proportional to stimulus duration. No evidence for proportionality was found. Two further experiments assessed the appropriateness of the control conditions employed. Results indicated that the chronostasis effect is constant across a wide range of stimulus durations and does not reflect the pattern of visual stimulation experienced during a saccade, suggesting that arousal is not critical. Instead, alternative processes, such as one affecting the onset of timing (i.e., the time of internal clock switch closure) are implicated. Further research is required to select between these alternatives.

Adult↗
PubMed2004

Effect of transcranial DC sensorimotor cortex stimulation on somatosensory evoked potentials in humans.

OBJECTIVE: To study the after-effect of transcranial direct current stimulation (tDCS) over the sensorimotor cortex on the size of somatosensory evoked potentials (SEPs) in humans. METHODS: SEPs were elicited by electrical stimulation of right or left median nerve at the wrist before and after anodal or cathodal tDCS in 8 healthy subjects. tDCS was applied for 10 min to the left motor cortex at a current strength of 1 mA. RESULTS: Amplitudes of P25/N33, N33/P40 (parietal components) and P22/N30 (frontal component) following right median nerve stimulation were significantly increased for at least 60 min after the end of anodal tDCS, whereas P14/N20, N20/P25 (parietal components) and N18/P22 (frontal component) were unaffected. There was no effect on SEPs evoked by left median nerve stimulation. Cathodal tDCS had no effect on SEPs evoked from stimulation of either arm. CONCLUSIONS: Anodal tDCS over the sensorimotor cortex can induce a long-lasting increase in the size of ipsilateral cortical components of SEPs. SIGNIFICANCE: tDCS can modulate cortical somatosensory processing in humans and might be a useful tool to induce plasticity in cortical sensory processing.

Adult↗
PubMed2004

Functional MRI of the immediate impact of transcranial magnetic stimulation on cortical and subcortical motor circuits.

Recent studies indicate that the cortical effects of transcranial magnetic stimulation (TMS) may not be localized to the site of stimulation, but spread to other distant areas. Using echo-planar imaging with blood-oxygenation-level-dependent (BOLD) contrast at 3 Tesla, we measured MRI signal changes in cortical and subcortical motor regions during high-frequency (3.125 Hz) repetitive TMS (rTMS) of the left sensorimotor cortex (M1/S1) at intensities above and below the active motor threshold in healthy humans. The supra- and subthreshold nature of the TMS pulses was confirmed by simultaneous electromyographic monitoring of a hand muscle. Suprathreshold rTMS activated a network of primary and secondary cortical motor regions including M1/S1, supplementary motor area, dorsal premotor cortex, cingulate motor area, the putamen and thalamus. Subthreshold rTMS elicited no MRI-detectable activity in the stimulated M1/S1, but otherwise led to a similar activation pattern as obtained for suprathreshold stimulation though at reduced intensity. In addition, we observed activations within the auditory system, including the transverse and superior temporal gyrus, inferior colliculus and medial geniculate nucleus. The present findings support the notion that re-afferent feedback from evoked movements represents the dominant input to the motor system via M1 during suprathreshold stimulation. The BOLD MRI changes in motor areas distant from the site of subthreshold stimulation are likely to originate from altered synaptic transmissions due to induced excitability changes in M1/S1. They reflect the capability of rTMS to target both local and remote brain regions as tightly connected constituents of a cortical and subcortical network.

Adult↗
PubMed2004

Consistent chronostasis effects across saccade categories imply a subcortical efferent trigger.

Saccadic chronostasis refers to the subjective temporal lengthening of the first visual stimulus perceived after an eye movement, and is most commonly experienced as the "stopped clock" illusion. Other temporal illusions arising in the context of movement (e.g., "intentional binding") appear to depend upon the volitional nature of the preceding motor act. Here we assess chronostasis across different saccade types, ranging from highly volitional (self-timed saccades, antisaccades) to highly reflexive (peripherally cued saccades, express saccades). Chronostasis was similar in magnitude across all these conditions, despite wide variations in their neural bases. The illusion must therefore be triggered by a "lowest common denominator" signal common to all the conditions tested and their respective neural circuits. Specifically, it is suggested that chronostasis is triggered by a low-level signal arising in response to efferent signals generated in the superior colliculus.

Adult↗
PubMed2003

Shaping the excitability of human motor cortex with premotor rTMS.

Recent studies have shown that low-frequency repetitive transcranial magnetic stimulation (rTMS) to the left dorsal premotor cortex has a lasting influence on the excitability of specific neuronal subpopulations in the ipsilateral primary motor hand area (M1(HAND)). Here we asked how these premotor to motor interactions are shaped by the intensity and frequency of rTMS and the orientation of the stimulating coil. We confirmed that premotor rTMS at 1 Hz and an intensity of 90% active motor threshold (AMT) produced a lasting decrease in corticospinal excitability probed with single-pulse TMS over the left M1(HAND). Reducing the intensity to 80% AMT increased paired-pulse excitability at an interstimulus interval (ISI) of 7 ms. Opposite effects occurred if rTMS was given at 5 Hz: at 90% AMT, corticospinal excitability increased; at 80% AMT, paired-pulse excitability at ISI = 7 ms decreased. No effects were seen if rTMS was applied at the same intensities to prefrontal or primary motor cortices. These findings indicate that the intensity of premotor rTMS determines the net effect of conditioning on distinct populations of neurones in the ipsilateral M1(HAND), but it is the frequency of rTMS that determines the direction of the induced change. By selecting the appropriate intensity and frequency, premotor rTMS allows to induce a predictable up- or down-regulation of the excitability in distinct neuronal circuits of human M1(HAND).

Adult↗
PubMed2003

A short latency vestibulomasseteric reflex evoked by electrical stimulation over the mastoid in healthy humans.

We describe EMG responses recorded in active masseter muscles following unilateral and bilateral electrical vestibular stimulation (EVS, current pulses of 5 mA intensity, 2 ms duration, 3 Hz frequency). Averaged responses in unrectified masseter EMG induced by unilateral EVS were examined in 16 healthy subjects; effects induced by bilateral (transmastoid) stimulation were studied in 10 subjects. Results showed that unilateral as well as bilateral EVS induces bilaterally a clear biphasic response (onset latency ranging from 7.2 to 8.8 ms), that is of equal amplitude and latency contra- and ipsilateral to the stimulation site. In all subjects, unilateral cathodal stimulation induced a positive-negative response termed p11/n15 according to its mean peak latency; the anodal stimulation induced a response of opposite polarity (n11/p15) in 11/16 subjects. Cathodal responses were significantly larger than anodal responses. Bilateral stimulation induced a p11/n15 response significantly larger than that induced by the unilateral cathodal stimulation. Recordings from single motor units showed that responses to cathodal stimulation corresponded to a brief (2-4 ms) silent period in motor unit discharge rate. The magnitude of EVS-induced masseter response was linearly related to current intensity and scaled with the mean level of EMG activity. The size of the p11/n15 response was asymmetrically modulated when subjects were tilted on both sides; in contrast head rotation did not exert any influence. Control experiments excluded a possible role of cutaneous receptors in generating the masseter response. We conclude that transmastoid electrical stimulation evokes vestibulomasseteric reflexes in healthy humans at latencies consistent with a di-trisynaptic pathway.

Adult↗
PubMed2003

Patients with focal arm dystonia have increased sensitivity to slow-frequency repetitive TMS of the dorsal premotor cortex.

We used PET to examine the pattern and time course of changes produced by repetitive transcranial magnetic stimulation (rTMS) over the dorsal premotor cortex (PMd) in healthy subjects and in patients with primary focal dystonia. Subjects received 1800 stimuli of subthreshold 1 Hz rTMS or sham stimulation to the left PMd. Afterwards, we measured regional cerebral blood flow (rCBF) as a marker of synaptic activity at rest and during performance of freely selected random finger movement. In both groups of subjects, real rTMS caused widespread bilateral decreases in neuronal activity in prefrontal, premotor, primary motor cortex, and left putamen. Conversely, rCBF in the cerebellum increased. Effects were equivalent at rest and during movement, indicating that the pattern of movement-related activation did not change. rTMS-induced changes in neuronal activity lasted for at least 1 h except in the medial aspect of the left globus pallidus. Conditioning effects on neuronal activity were larger in the patients than in the healthy subjects: there was a greater decrease of rCBF in lateral and medial premotor areas, putamen, and thalamus, including the stimulated premotor cortex, and a larger increase in cerebellar rCBF. Our findings indicate that, in healthy subjects and patients with dystonia, a single session of rTMS can produce powerful and widespread changes in regional synaptic activity as indexed by rCBF. Since the greater effects of premotor rTMS were not related to any differences in task performance, increased responsiveness of the motor system to rTMS reveals a physiological trait that characterizes patients with focal arm dystonia.

Adult↗
PubMed2003

The ipsilateral human motor cortex can functionally compensate for acute contralateral motor cortex dysfunction.

What promotes motor recovery from stroke? To date, studies of recovery from stroke have shown alterations in function in various cortical areas, including the contralesional (unaffected) motor cortex (M1). However, whether these changes contribute to recovery or are mere epiphenomena remains unclear. We therefore sought evidence that the ipsilateral M1 can compensate for dysfunction of the contralateral M1. We recorded the change in force production during a finger-tapping task in response to acute disruption of M1 function by repetitive transcranial magnetic stimulation (rTMS). Neither control (occipital) nor ipsilateral M1 rTMS lead to a change in tapping force. RTMS over contralateral M1 had a short-lived effect and induced changes in ipsilateral M1 excitability around the time that these behavioral effects abated, consistent with delayed compensation by the ipsilateral M1. Simultaneous bilateral M1 stimulation, designed to prevent compensation by the ipsilateral M1, had a large and prolonged effect on tapping force. This is the first demonstration that the ipsilateral primary motor cortex is capable of functionally significant compensation for focal contralateral cortical dysfunction in the adult human and provides a rational basis for interventional treatments aimed at promoting functional compensation in unaffected cortical areas after stroke.

Biomechanical Phenomena↗
PubMed2003

Manual chronostasis: tactile perception precedes physical contact.

When saccading to a silent clock, observers sometimes think that the second hand has paused momentarily. This effect has been termed chronostasis and occurs because observers overestimate the time that they have seen the object of an eye movement. They seem to extrapolate its appearance back to just prior to the onset of the saccade rather than the time that it is actually fixated on the retina. Here, we describe a similar effect following an arm movement: subjects overestimate the time that their hand has been in contact with a newly touched object. The illusion's magnitude suggests backward extrapolation of tactile perception to a moment during the preceding reach. The illusion does not occur if the arm movement triggers a change in a continuously visible visual target: the time of onset of the change is estimated correctly. We hypothesize that chronostasis-like effects occur when movement produces uncertainty about the onset of a sensory event. Under these circumstances, the time at which neurons with receptive fields that shift in the temporal vicinity of a movement change their mappings may be used as a time marker for the onset of perceptual properties that are only established later.

Humans↗
PubMed2003

Different patterns of electrophysiological deficits in manifesting and non-manifesting carriers of the DYT1 gene mutation.

A mutation in the DYT1 gene on chromosome 9q34 causes early-onset primary torsion dystonia with autosomal dominant inheritance but low phenotypic penetrance. The aim of the present study was to assess the functional consequences of the DYT1 gene, by comparing the electrophysiology of cortical and spinal circuits in clinically affected and unaffected carriers of the DYT1 gene mutation. We assessed intracortical inhibition (ICI), intracortical facilitation (ICF), the cortical silent period (SP) and spinal reciprocal inhibition (RI) in 10 manifesting DYT1 gene carriers (MDYT1), seven non-manifesting DYT1 gene carriers (NMDYT1) and 13 healthy controls. The MDYT1 subjects had abnormalities similar to those seen in previous studies of non-genetically characterized individuals with primary dystonia. They had reduced ICI, shorter SP and absent presynaptic phase of RI compared with the healthy controls. NMDYT1 subjects also had a significant reduction in cortical inhibition (ICI and SP), but their spinal RI was not different from controls. We conclude that clinical expression of dystonia depends on widespread electrophysiological deficits, and the presence of the DYT1 gene mutation itself leads only to a subset of these changes. This is consistent with the hypothesis that additional environmental/genetic insults may be needed to reveal clinical symptoms in DYT1 gene carriers.

Adult↗
PubMed2003

Differential effect of muscle vibration on intracortical inhibitory circuits in humans.

Low amplitude muscle vibration (0.5 ms; 80 Hz; duration 1.5 s) was applied in turn to each of three different intrinsic hand muscles (first dorsal interosseus, FDI; abductor pollicis brevis, APB; and abductor digiti minimi, ADM) in order to test its effect on the EMG responses evoked by transcranial magnetic stimulation (TMS). Recordings were also taken from flexor and extensor carpi radialis (FCR and ECR, respectively). We evaluated the amplitude of motor evoked potentials (MEPs) produced by a single TMS pulse, short interval intracortical inhibition and facilitation (SICI and ICF) and long interval intracortical inhibition (LICI). TMS pulses were applied 1 s after the start of vibration with subjects relaxed throughout. Vibration increased the amplitude of MEPs evoked in the vibrated muscle (162 +/- 6 % of MEP with no vibration; mean +/- S.E.M.), but suppressed MEPs in the two non-vibrated hand muscles (72 +/- 9 %). Compared with no vibration (test response reduced to 51 +/- 5 % of control), there was less SICI in the vibrated muscle (test response reduced to 92 +/- 28 % of control) and more in the non-vibrated hand muscles (test response reduced to 27 +/- 5 % of control). The opposite occurred for LICI: compared with the no vibration condition (test response reduced to 33 +/- 6 % control), there was more LICI in the vibrated muscle (test response reduced to 17 +/- 3 % control) than in the non-vibrated hand muscles (test response reduced to 80 +/- 11 % control) even when the intensity of the test stimulus was adjusted to compensate for the changes in baseline MEP. There was no effect on ICF. Cutaneous stimulation of the index finger (80 Hz, 1.5 s duration, twice sensory threshold) had no consistent differential effect on any of the parameters. We conclude that vibratory input from muscle can differentially modulate excitability in motor cortical circuits.

Adult↗
PubMed2003

Effects on the right motor hand-area excitability produced by low-frequency rTMS over human contralateral homologous cortex.

Repetitive transcranial magnetic stimulation (rTMS) has long lasting effects on cortical excitability at the site of stimulation, on interconnected sites at a distance and on the connections between them. In the present experiments we have used the technique of transcallosal inhibition between the motor cortices to examine all three effects in the same protocol. Ten healthy subjects received 900 rTMS stimuli at 1 Hz from a figure of eight coil over the left motor hand area. The intensity of rTMS was above the threshold for inducing short latency interhemispherical inhibition with a single stimulus (equivalent to 115-120 % resting motor threshold). Before and after the rTMS we evaluated: (1) in the left hemisphere, the amplitude of motor-evoked potentials (MEPs), and contralateral and ipsilateral cortical silent periods (CSP, ISP); (2) in the right hemisphere, MEP, CSP, ISP and short-interval intracortical inhibition and intracortical facilitation (SICI/ICF), and (3) interhemispherical inhibition (IHI) from the left-to-right hemisphere using a paired-pulse method. There were two main effects after rTMS to the left hemisphere: first, the amplitude of MEPs from the right hemisphere increased; second, there was a reduction in the IHI from the left-to-right hemisphere at interstimulus intervals of 7 and 10 ms but not at longer intervals (15-75 ms). Control experiments showed that these effects were not due to afferent inputs produced by the muscle twitches induced during the rTMS. The data are compatible with the notion that rTMS to the left hemisphere leads to reduced interhemispherical inhibition of the right hemisphere and a consequent increase in corticospinal excitability in that hemisphere.

Adult↗
PubMed2003

Acute remapping within the motor system induced by low-frequency repetitive transcranial magnetic stimulation.

Repetitive transcranial magnetic stimulation (rTMS) of human primary motor cortex (M1) changes cortical excitability at the site of stimulation and at distant sites without affecting simple motor performance. The aim of this study was to explore how rTMS changes regional excitability and how the motor system compensates for these changes. Using functional brain imaging, activation was mapped at rest and during freely selected finger movements after 30 min of 1 Hz rTMS. rTMS increased synaptic activity in the stimulated left M1 and induced widespread changes in activity throughout areas engaged by the task. In particular, movement-related activity in the premotor cortex of the nonstimulated hemisphere increased after 1 Hz rTMS. Analyses of effective connectivity confirmed that the stimulated part of M1 became less responsive to input from premotor and mesial motor areas. Conversely, after rTMS our results were consistent with increased coupling between an inferomedial portion of left M1 and anterior motor areas. These results are important for three reasons. First, they show changes in motor excitability to central inputs from other cortical areas (as opposed to peripheral or exogenous inputs used in previous studies). Second, they suggest that maintenance of task performance may involve activation of premotor areas contralateral to the site of rTMS, similar to that seen in stroke patients. Third, changes in motor activations at the site of rTMS suggest an rTMS-induced remodeling of motor representations during movement. This remapping may provide a neural substrate for acute compensatory plasticity of the motor system in response to focal lesions such as stroke.

Adult↗
PubMed2003

High-frequency transcranial magnetic stimulation of the supplementary motor area reduces bimanual coupling during anti-phase but not in-phase movements.

Previous electrophysiological and neuroimaging studies have provided evidence that the supplementary motor area (SMA) has an important role in the control of bimanual coordination. The present experiment investigated the effects of high-frequency repetitive transcranial magnetic stimulation (rTMS) over the SMA region on kinematic variables during cyclical bimanual coordination, with a particular focus on the quality of coordination. Subjects performed metronome-paced trials of in-phase and anti-phase bimanual index-finger movements at near-maximal cycling frequency. During movement execution, rTMS (20 Hz, 0.5 s, 120% hand motor threshold) was applied over one of three positions in the sagittal midline 2.0, 4.0 and 6.0 cm anterior to the primary motor leg area. Sham rTMS was included as a control condition. After rTMS, the mean relative phase error between hands increased, but only in the anti-phase trials. The maximum increase in phase error occurred immediately after rather than during the rTMS train. The effect was largest after stimulation 4 or 6 cm anterior to the leg area of the primary motor cortex. We did not observe any changes in the variability of relative phase or in cycle duration or movement amplitude. Findings are discussed in light of recent functional models on the role of the SMA in bimanual movement control.

Adult↗
PubMed2003

Changes in finger coordination and responses to single pulse TMS of motor cortex during practice of a multifinger force production task.

We investigated the changes in finger coordination and in finger force responses to transcranial magnetic stimulation (TMS) applied over the motor cortex associated with a single practice session of an accurate ramp force production task. Subjects pressed with their index, middle and ring fingers onto three force transducers fixed to a rigid platform that was balanced on a narrow pivot under the middle finger. The task was to produce a smoothly increasing ramp of total force from 0 to 25 N over 4 s following a visual target. Subjects performed three brief series of trials without TMS (12 trials each) in the beginning, in the middle, and in the end of the experiment. The main part of the experiment involved 173 trials, and in each of them at random times in the ramp a suprathreshold TMS pulse was applied over the hand area of the contralateral motor cortex in order to evoke a twitch in the finger flexor muscles. At the end of the experiment the subjects also performed 12 constant force production trials, and TMS was unexpectedly applied in each trial. During the ramp force trials the amplitude of the response to TMS was largely independent of the force exerted at the time of stimulation, whereas in static holding trials the amplitude of the response increased with higher levels of background contraction. Over time subjects improved their overall tracking performance: the variance of the force trajectory (VarF(TOT)), as computed over sets of unperturbed trials, declined by 60% after the first 100 trials, but there was little additional improvement after the second 100 trials. Variance in the force finger space related to the total moment with respect to the pivot also showed a decline during the first half of practice and minimal further changes during the second half. In contrast, finger force variance that did not affect either total force or total moment showed no changes after the first 100 trials and a decline during the second 100 trials. This variance component quantified per finger was significantly larger than those related to the total force and total moment. The mean size of the TMS-induced phasic force increment decreased by 12% over the course of the 200 trials. The forces evoked in the index and ring fingers gradually became more equal, reducing the total moment with respect to the pivot and improving balance. We speculate that development of a relatively low twitch force with low total moment on the pivot made it easier for subjects to continue tracking after the TMS pulse. Such changes could well be correlated with the degree of corticospinal involvement in the task. The results suggest task specific, practice-related plastic changes in neural structures involved in the responses to TMS.

Adult↗
PubMed2003

Pallidotomy and incidental sequence learning in Parkinson's disease.

Converging evidence from animal research and human brain imaging studies, points to an important role of cortical-striatal motor circuitry in the incidental learning of serial order information. To date, attempts to address this role through the study of patients with striatal disorder have proved inconclusive. The present study examined the impact of a therapeutic lesion of the globus pallidus in patients with Parkinson's disease. The lesion, which blocks a primary output of the putamen to the motor cortices, eliminated incidental learning relative both to controls and unoperated patients. The finding offers support for models proposing that context detection within the striatum is a central process in serial order learning. An unexpected effect of the lesion was to significantly reduce the response time to random stimuli relative to an ordered series, the opposite of the normal pattern. It is speculated that this may reflect an unconscious alerting response to novelty, a process suggested to involve the ventral striatum and its cortical targets. Research on Parkinson's disease patients undergoing functional basal ganglia surgery may shed further light on the mechanisms and neuronal substrate of serial order learning in humans.

Aged↗