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J C Rothwell

Publications and source records attributed to J C Rothwell.

At least 55 records · Page 3Linked to original sources
PubMed2002

Direct demonstration of the effects of repetitive transcranial magnetic stimulation on the excitability of the human motor cortex.

The effects of repetitive transcranial magnetic stimulation (rTMS; 20 stimuli at 5 Hz at 120% resting motor threshold intensity using a biphasic stimulus pulse) on the excitability of human motor cortex were investigated in two patients who had an electrode implanted into the cervical epidural space. The corticospinal D wave increased in amplitude with successive stimuli, and reached a maximum after three or five pulses. At this stage, the amplitude of the I waves was unchanged, but after a further 10 stimuli an additional I wave was recruited. Both effects were still evident 2 min after the end of the rTMS. The effects are compatible with a short-term increase in cortical excitability during suprathreshold rTMS.

Aged↗
PubMed2002

Striatal contribution to cognition: working memory and executive function in Parkinson's disease before and after unilateral posteroventral pallidotomy.

The basal ganglia are intimately connected to the frontal cortex via five fronto-striatal circuits. While the role of the frontal cortex in cognition has been extensively studied, the contribution of the basal ganglia to cognition has remained less clear. In Parkinson's disease, posteroventral pallidotomy (PVP) involves surgical lesioning of the internal section of the globus pallidus (GPi, the final output pathway from the basal ganglia) to relieve the motor symptoms of the disorder. PVP in Parkinson's disease provides a unique opportunity to investigate the impact of disruption of striatal outflow to the frontal cortex on cognition. We assessed executive function and working memory after withdrawal of medication in 13 patients with Parkinson's disease before and 3 months after unilateral PVP compared to 12 age- and IQ-matched normals assessed twice with an interval of 3 months. The tests used were: Wisconsin Card Sorting (WCST), Self-Ordered Random Number Sequences, Missing Digit Test, Paced Visual Serial Addition Test (PVSAT), and Visual Conditional Associative Learning Test (VCALT). After PVP, the patients performed significantly better on the Self-Ordered Random Number Sequences and the WCST, an improvement that was also observed in the normals across the two assessment and is therefore likely to reflect practice effects. Relative to the normals, the patients showed significant differential change following PVP on the Missing Digit Test and PVSAT, on which they performed worse after compared to before surgery, while the controls performed better on the second assessment. For the patients, performance on the VCALT also indicated deterioration after PVP, but the changes approached significance. The side of PVP had no effect on the results. The pattern of change observed 3 months after PVP was maintained at 15-month follow-up. The results suggest that striatal outflow to the frontal cortex may be essential for those aspects of executive function that showed deterioration after PVP.

Adult↗
PubMed2002

Two phases of intracortical inhibition revealed by transcranial magnetic threshold tracking.

Intracortical inhibition was investigated in normal human volunteers by paired-pulse transcranial magnetic stimulation, using a new, computer-assisted threshold-tracking method. Motor threshold was defined as the stimulus amplitude required to evoke a motor evoked potential of 0.2 mV (peak-to-peak) in abductor pollicis brevis, and inhibition was measured as the percentage increase in threshold, when the test stimulus was preceded by a subthreshold conditioning stimulus. This method was used to investigate the dependence of intracortical inhibition on conditioning stimulus parameters and on voluntary activity. Interstimulus interval (ISI) was first stepped from 1 to 4.5 ms, as inhibition was measured using conditioning stimuli of fixed amplitude (50-90% resting motor threshold). Maximal inhibition was produced at ISIs of 1 and 2.5 ms. The effect of conditioning stimulus intensity was then assessed at these ISIs. Inhibition occurred at significantly lower conditioning stimulus intensities with ISI=1 ms than with ISI=2.5 ms. Voluntary activity reduced inhibition at both ISIs, but had a much greater effect on inhibition at ISI=2.5 ms. Inhibition during voluntary activity was also examined for single motor units in first dorsal interosseous by generating poststimulus time histograms. Inhibition, indicated by a reduction in the later peaks of increased firing, was observed with ISI=1 ms, but not with ISI=2.5 ms. We conclude that there are two distinct phases of inhibition, occurring at ISI=1 ms and ISI=2.5 ms, differing both in thresholds and susceptibility to voluntary activity.

Adult↗
PubMed2002

Functional connectivity of human premotor and motor cortex explored with repetitive transcranial magnetic stimulation.

Connections between the premotor cortex and the primary motor cortex are dense and are important in the visual guidance of arm movements. We have shown previously that it is possible to engage these connections in humans and to measure the net amount of inhibition/facilitation from premotor to motor cortex using single-pulse transcranial magnetic stimulation (TMS). The aim of this study was to test whether premotor activation can affect the excitability of circuits within the primary motor cortex (M1) itself. Repetitive TMS (rTMS), which is known to produce effects that outlast the train at the site of stimulation, was given for 20 min at 1 Hz over premotor, primary motor, and sensory areas of cortex at an intensity of 80% of the active motor threshold for the motor hand area. The excitability of some corticocortical connections in M1 was probed by using paired-pulse testing of intracortical inhibition (ICI) and intracortical facilitation (ICF) with a coil placed over the motor cortex hand area. rTMS over the premotor cortex, but not other areas, changed the time course of the ICI/ICF for up to 1 hr afterward without affecting motor thresholds or motor-evoked potential recruitment. The cortical silent period was also shortened. The implication is that rTMS at a site distant from the motor cortex can change the excitability of circuits intrinsic to the motor cortex.

Adult↗
PubMed2002

Parietal magnetic stimulation delays visuomotor mental rotation at increased processing demands.

Visuomotor rotation (VMR) is a variant of the classic mental rotation paradigm. Subjects perform a center-out arm reaching movement, with the instruction to point clockwise or anticlockwise away from the direction of a reaction signal by a prespecified amount. Like classic mental rotation (MR) tasks, there is a linear relationship between reaction time (RT) and required angle of rotation (angular disparity). Although functional imaging studies have consistently demonstrated parietal activations centered around the intraparietal sulcus during MR tasks, the involvement of parietal cortex in VMR has not been investigated. The aim of the present experiments was to test in human subjects whether VMR also involves activity in parietal areas. We used short trains of transcranial magnetic stimulation (TMS) to produce a temporary "virtual lesion" of the posterior parietal cortex (PPC) around the intraparietal sulcus during the reaction period of a VMR task. Four pulses of 20-Hz rTMS were applied to the left PPC, right PPC, or vertex (control condition) 100 ms after the presentation of an instruction cue. Reaction times (RTs) were evenly prolonged by right or left parietal TMS compared with vertex stimulation, but only for large angles of rotation, and without affecting the spatial accuracy of the final response. A control experiment showed that parietal rTMS did not impair visual perception or the ability to judge the size of visual angles. The data thus provide evidence for bilateral involvement of the PPC in VMR that increases with processing demands.

Adult↗
PubMed2002

Descending volleys evoked by transcranial magnetic stimulation of the brain in conscious humans: effects of coil shape.

OBJECTIVES: To directly compare the volleys evoked by figure-of-eight and circular magnetic coil stimulation of the motor cortex and to correlate the descending volleys with the EMG responses in distal hand muscles. METHODS: Descending corticospinal volleys were recorded from an electrode inserted into the cervical epidural space of two conscious human subjects after transcranial stimulation of the hand area of the motor cortex. We compared volleys evoked by stimulation with (a) a figure-of-eight coil inducing posterior-anterior or latero-medial currents in the brain, (b) a large circular coil centred at the vertex inducing clockwise currents in the brain, and (c) anodal electric pulses. RESULTS: For a given amplitude of EMG response in the first dorsal interosseous muscle, volleys were larger after stimulation with a circular than a figure-of-eight coil. In addition, the D wave evoked by circular coil stimulation had a longer latency than the anodal D wave, and increased in amplitude when stimulation was given during voluntary contraction. CONCLUSIONS: We conclude that stimulation with a large circular coil activates descending outputs less selectively than figure-of-eight coil stimulation and that it is capable of activating pyramidal neurones at the initial segment region.

Aged↗
PubMed2002

rTMS over the cerebellum can increase corticospinal excitability through a spinal mechanism involving activation of peripheral nerve fibres.

OBJECTIVES: Single-pulse transcranial magnetic stimulation (TMS) over the cerebellum affects corticospinal excitability by a cerebellar and a peripheral mechanism. We have investigated whether any of the long-lasting effects of repetitive TMS (rTMS) over cerebellum can also be attributed to peripheral effects. METHODS: Five hundred conditioning stimuli at 1 Hz were given over either the right cerebellum using a double-cone coil, or over the right posterior neck using a figure-8-coil. Corticospinal excitability was assessed by measuring the amplitude of motor evoked potentials (MEPs) evoked in the right and left hand and forearm muscles. Hoffman reflexes (H-reflex) were also obtained in the right flexor carpi radialis muscle. RESULTS: rTMS over either the right cerebellum or the right posterior neck significantly facilitated MEPs in hand and forearm muscles in the right but not in the left arm (n=8) for up to 30 min after the end of the train. rTMS (1 Hz) of the right neck area increased the amplitude of the H-reflex (n=5). CONCLUSIONS: Much of the persisting effects of rTMS over the cerebellum on corticospinal excitability appear to be mediated through stimulation of peripheral rather than central structures. Moreover, the results show that rTMS over peripheral areas can cause long-lasting changes in spinal reflexes.

Adult↗
PubMed2002

Direct demonstration of long latency cortico-cortical inhibition in normal subjects and in a patient with vascular parkinsonism.

OBJECTIVE: The motor evoked potential to a single suprathreshold transcranial magnetic stimulus (TMS) is suppressed by a preceding stimulus given 100-200 ms before (long latency intracortical inhibition, LICI). The effect is enhanced in patients with Parkinson's disease. Although previous studies have agreed that the effect is cortical, there is disagreement over exactly which cortical mechanisms are involved. The aim of this study was to provide further evidence for cortical involvement in LICI. METHODS: Recordings of corticospinal volleys evoked by the TMS stimulation were made from electrodes inserted into the cervical epidural space of 4 conscious subjects. Three of the patients had received the electrodes for treatment of lumbo-sacral pain; the other patient had vascular parkinsonism, and had the electrode implanted to evaluate its effect on cerebral blood flow. The number and amplitude of the volleys were compared with and without a conditioning stimulus. RESULTS: In 3 pain patients, a conditioning stimulus suppressed the later components of the corticospinal volley (I2 and later waves) when the interval between stimuli was 100-150 ms; at 50 ms the responses were enhanced. Early components of the volley were not affected. Inhibition was much more pronounced and involved all descending volleys except the D wave in the patient with vascular parkinsonism. CONCLUSIONS: LICI, which is conventionally described in EMG recordings, is also evident in recordings of descending corticospinal volleys and appears enhanced in a patient with vascular parkinsonism.

Back Pain↗
PubMed2001

Descending spinal cord volleys evoked by transcranial magnetic and electrical stimulation of the motor cortex leg area in conscious humans.

1. Descending corticospinal volleys evoked after transcranial magnetic or electrical stimulation of the leg area of the motor cortex were recorded from an electrode in the spinal epidural space of six conscious patients who had electrodes implanted for treatment of chronic pain, and from one anaesthetised patient undergoing surgery for a spinal tumour. 2. At threshold, the shortest-latency volley (L1 volley) was evoked by stimulation with an anode 2 cm lateral to the vertex. Anodal stimulation at the vertex also elicited a volley at this latency in two patients, but in the other patients the first volley evoked appeared 1-1.3 ms later (L2 volley), at the same latency as the initial volley evoked by magnetic stimulation. High-intensity stimulation of any type could evoke both the L1 and L2 waves as well as later ones (L3, L4, etc.) that had a periodicity of about 1.5 ms. 3. Voluntary contraction increased the amplitude of the L2 and later volleys, but had no effect on the L1 volley. 4. Intracortical inhibition between pairs of magnetic stimuli resulted in clear suppression of the L4 and later waves. The L2 and L3 waves were unaffected. 5. In the anaesthetised patient the L1 volley occurred 1.7 ms later than the volley produced by transmastoid stimulation of the corticospinal pathways in the brainstem. 6. The L1 volley is likely to be a D wave produced by the direct activation of pyramidal axons in the subcortical white matter; the L2 and later volleys are likely to be I waves produced by the trans-synaptic activation of corticospinal neurones. The implication is that electrical stimulation with an anode at the vertex is more likely to evoke I waves preferentially than stimulation over the hand area. A more secure way to ensure D wave activation of corticospinal fibres from the leg area is to place the anode 2 cm lateral to the vertex.

Adult↗
PubMed2001

Illusory perceptions of space and time preserve cross-saccadic perceptual continuity.

When voluntary saccadic eye movements are made to a silently ticking clock, observers sometimes think that the second hand takes longer than normal to move to its next position. For a short period, the clock appears to have stopped (chronostasis). Here we show that the illusion occurs because the brain extends the percept of the saccadic target backwards in time to just before the onset of the saccade. This occurs every time we move the eyes but it is only perceived when an external time reference alerts us to the phenomenon. The illusion does not seem to depend on the shift of spatial attention that accompanies the saccade. However, if the target is moved unpredictably during the saccade, breaking perception of the target's spatial continuity, then the illusion disappears. We suggest that temporal extension of the target's percept is one of the mechanisms that 'fill in' the perceptual 'gap' during saccadic suppression. The effect is critically linked to perceptual mechanisms that identify a target's spatial stability.

Adult↗
PubMed2001

Interference with performance of a response selection task that has no working memory component: an rTMS comparison of the dorsolateral prefrontal and medial frontal cortex.

It has been suggested that the dorsolateral prefrontal cortex (DLPFC) is involved in free selection (FS), the process by which subjects themselves decide what action to perform. Evidence for this proposal has been provided by imaging studies showing activation of the DLPFC when subjects randomly generate responses. However, these response selection tasks have a hidden working memory element and it has been widely reported that the DLPFC is activated when subjects perform tasks which involve working memory. The primary aim of this experiment was to establish if the DLPFC is genuinely involved in response selection. We used repetitive transcranial magnetic stimulation (rTMS) to investigate whether temporary interference of the DLPFC could disrupt performance of a response selection task that had no working memory component. Subjects performed tasks in which they made bimanual sequences of eight nonrepeating finger movements. In the FS task, subjects chose their movements at random while a computer monitor displayed these moves. This visual feedback obviated the need for subjects to maintain their previous moves "on-line." No selection was required for the two control tasks as responses were cued by the visual display. The attentional demands of the control tasks varied. In the high load (HL) version, subjects had to maintain their attention throughout the sequence, but this requirement was absent in the low load (LL) task. rTMS over the DLPFC slowed response times on the FS task and at the end of the sequence on the HL task, but had no effect on the LL task. rTMS over the medial frontal cortex (MFC) slowed response times on the FS task but had no effect on the HL task. This suggests that a response selection task without a working memory load will depend on the DLPFC and the MFC. The difference appears to be that the DLPFC is important when selecting between competing responses or when concentrating if there is a high attentional demand, but that the MFC is only important during the response selection task.

Attention↗
PubMed2001

Decreased corticospinal excitability after subthreshold 1 Hz rTMS over lateral premotor cortex.

OBJECTIVE: To study whether trains of subthreshold 1 Hz repetitive transcranial magnetic stimulation (rTMS) over premotor, prefrontal, or parietal cortex can produce changes in excitability of motor cortex that outlast the application of the train. BACKGROUND: Prolonged 1 Hz rTMS over the motor cortex can suppress the amplitude of motor-evoked potentials (MEP) for several minutes after the end of the train. Because TMS can produce effects not only at the site of stimulation but also at distant sites to which it projects, the authors asked whether prolonged stimulation of sites distant but connected to motor cortex can also lead to lasting changes in MEP. METHODS: Eight subjects received 1500 magnetic stimuli given at 1 Hz over the left lateral frontal cortex, the left lateral premotor cortex, the hand area of the left motor cortex, and the left anterior parietal cortex on four separate days. Stimulus intensity was set at 90% active motor threshold. Corticospinal excitability was probed by measuring the amplitude of MEP evoked in the right first dorsal interosseous muscle by single suprathreshold stimuli over the left motor hand area before, during, and after the conditioning trains. RESULTS: rTMS over the left premotor cortex suppressed the amplitude of MEP in the right first dorsal interosseous muscle. The effect was maximized (approximately 50% suppression) after 900 pulses and outlasted the full train of 1500 stimuli for at least 15 minutes. Conditioning rTMS over the other sites did not modify the size of MEP. A control experiment showed that left premotor cortex conditioning had no effect on MEP evoked in the left first dorsal interosseous muscle. CONCLUSIONS: Subthreshold 1 Hz rTMS of the left premotor cortex induces a short-lasting inhibition of corticospinal excitability in the hand area of the ipsilateral motor cortex. This may provide a model for studying the functional interaction between premotor and motor cortex in healthy subjects and patients with movement disorders.

Adult↗
PubMed2001

Spontaneously changing muscular activation pattern in patients with cervical dystonia.

The objective of this study was to determine stability of the neck muscle activation pattern in a given dystonic head position in patients with cervical dystonia (CD). We assessed 26 patients with CD and botulinum toxin (BT) treatment failure before surgical denervation. None of them had received BT injections for at least 4 months. To relate dystonic head position to underlying neck muscle activity, we used synchronised video and poly-electromyographic (EMG) recording over a period of 10 minutes. The muscle activation pattern during constant ("stable") maximal dystonic excursions was analysed. EMG data of nine patients was excluded from the analysis, as these patients had a constantly changing head position or marked head tremor. In the remaining 17 patients, who had a fairly stable dystonic position, muscular activation patterns during the recording spontaneously changed in nine (Group A) while in eight it remained stable (Group B). There was no significant difference in demographic variables between the two groups other than a male predominance in Group A. However, the retrospectively determined initial response to BT treatment (before BT treatment failure had occurred) was significantly worse in Group A as compared with Group B. Neck muscle activation patterns can spontaneously change in CD patients despite constant dystonic head position, implying an inherent variability of the underlying central motor program in some patients. This should be considered when BT treatment response is unsatisfactory, and should also be taken into account when interpreting results of EMG recordings of neck muscles in these patients.

Adult↗
PubMed2001

TMS produces two dissociable types of speech disruption.

We aimed to use repetitive transcranial magnetic stimulation (rTMS) to disrupt speech with the specific objective of dissociating speech disruption according to whether or not it was associated with activation of the mentalis muscle. Repetitive transcranial magnetic stimulation (rTMS) was applied over two sites of the right and left hemisphere while subjects counted aloud and recited the days of the week, months of the year, and nursery rhymes. Analysis of EMG data and videotaped recordings showed that rTMS applied over a posterior site, lateral to the motor hand area of both the right and the left hemisphere resulted in speech disruption that was accompanied by activation of the mentalis muscle, while rTMS applied over an anterior site on the left but not the right hemisphere resulted in speech disruption that was dissociated from activation of the mentalis muscle. The findings provide a basis for the use of subthreshold stimulation over the extrarolandic speech disruption site in order to probe the functional properties of this area and to test psychological theories of linguistic function.

Adult↗
PubMed2001

Transcranial magnetic stimulation can be used to test connections to primary motor areas from frontal and medial cortex in humans.

Surface EMG responses (MEPs) were recorded from the relaxed first dorsal interosseous (FDI) of 16 normal subjects following transcranial magnetic stimulation (TMS) over the hand area of the primary motor cortex. These test responses were conditioned by a subthreshold stimulus applied 2-15 ms beforehand over a range of anterior or medial sites. Stimuli applied 3-5 cm anterior to the hand motor area (site A) or 6 cm anterior to the vertex on the nasion-inion line (site B) inhibited the test responses at short latency. The largest effect was seen when the interstimulus interval was 6 ms and the intensity of the conditioning stimulus was equal to 0.9x active motor threshold (AMT) at the hand area. Increasing the intensity to 1.2x AMT produced facilitation. Suppression of surface EMG responses was mirrored in the behavior of single motor units. Conditioning stimuli had no effect on responses evoked in the active FDI muscle by transcranial electric stimulation of motor cortex nor on forearm flexor H reflexes even though MEPs in the same muscle were suppressed at appropriate interstimulus intervals. We conclude that low-intensity TMS over presumed premotor areas of frontal cortex can engage corticocortical connections to the primary motor hand area.

Adult↗
PubMed2001

The effect on corticospinal volleys of reversing the direction of current induced in the motor cortex by transcranial magnetic stimulation.

Descending corticospinal volleys were recorded from a bipolar electrode inserted into the cervical epidural space of four conscious human subjects after monophasic transcranial magnetic stimulation over the motor cortex with a figure-of-eight coil. We examined the effect of reversing the direction of the induced current in the brain from the usual posterior-anterior (PA) direction to an anterior-posterior (AP) direction. The volleys were compared with D waves evoked by anodal electrical stimulation (two subjects) or medio-lateral magnetic stimulation (two subjects). As reported previously, PA stimulation preferentially recruited I1 waves, with later I waves appearing at higher stimulus intensities. AP stimulation tended to recruit later I waves (I3 waves) in one of the subjects, but, in the other three, I1 or D waves were seen. Unexpectedly, the descending volleys evoked by AP stimulation often had slightly different peak latencies and/or longer duration than those seen after PA stimulation. In addition the relationship between the size of the descending volleys and the subsequent EMG response was often different for AP and PA stimulation. These findings suggest that AP stimulation does not simply activate a subset of the sites activated by PA stimulation. Some sites or neurones that are relatively inaccessible to PA stimulation may be the low-threshold targets of AP stimulation.

Adult↗
PubMed2001

Motor cortex excitability following short trains of repetitive magnetic stimuli.

Trains of repetitive transcranial magnetic stimuli (rTMS) appear to have effects on corticospinal excitability that outlast the duration of the train. In order to investigate the mechanism of this effect in more detail we applied short periods of rTMS consisting of up to 20 stimuli at 5 Hz, 10 Hz or 20 Hz (rTMS) to the motor cortex at an intensity equal to resting threshold in 11 healthy, relaxed subjects. Spinal excitability, as judged by effects on the H-reflex or on transcranial anodal facilitation of the H-reflex, was not affected by the rTMS. However, cortical excitability, as judged by the effect on the size of EMG responses evoked by a suprathreshold TMS pulse, was decreased for up to 1 s after the end of rTMS. Post-train suppression was more powerful following longer trains or higher frequencies of rTMS. The predominant suppression contrasts with previous reports of facilitation, particularly after high-frequency rTMS. A second set of experiments, however, showed that this could be converted into facilitation if the intensity of rTMS was increased. We conclude that the after-effects of rTMS depend on its frequency, intensity and duration. The results are consistent with a model in which inhibition and facilitation build up gradually during the course of a conditioning train. Inhibition reaches its maximum effect after only a small number of stimuli, whereas facilitation takes longer. The threshold for evoking inhibition is lower than that for facilitation. Thus if moderate intensities of conditioning train are applied, inhibition is predominant after short trains, whereas facilitation dominates after long trains.

Adult↗