Search PubMed⌕ Search

Biomedical subjects

J C Rothwell

Publications and source records attributed to J C Rothwell.

At least 37 records · Page 2Linked to original sources
PubMed2004

Effects of transcranial direct current stimulation over the human motor cortex on corticospinal and transcallosal excitability.

Weak transcranial direct current stimulation (tDCS) can induce long lasting changes in cortical excitability. In the present study we asked whether tDCS applied to the left primary motor cortex (M1) also produces aftereffects distant from the site of the stimulating electrodes. We therefore tested corticospinal excitability in the left and the right M1 and transcallosal excitability between the two cortices using transcranial magnetic stimulation (TMS) before and after applying tDCS. Eight healthy subjects received 10 min of anodal or cathodal tDCS (1 mA) to the left M1. We examined the amplitude of contralateral motor evoked potentials (MEPs) and the onset latency and duration of transcallosal inhibition with single pulse TMS. MEPs evoked from the tDCS stimulated (left) M1 were increased by 32% after anodal and decreased by 27% after cathodal tDCS, while transcallosal inhibition evoked from the left M1 remained unchanged. The effect on MEPs evoked from the left M1 lasted longer for cathodal than for anodal tDCS. MEPs evoked from the right M1 were unchanged whilst the duration of transcallosal inhibition evoked from the right M1 was shortened after cathodal tDCS and prolonged after anodal tDCS. The duration of transcallosal inhibition returned to control values before the effect on the MEPs from the left M1 had recovered. These findings are compatible with the idea that tDCS-induced aftereffects in the cortical motor system are limited to the stimulated hemisphere, and that tDCS not only affects corticospinal circuits involved in producing MEPs but also inhibitory interneurons mediating transcallosal inhibition from the contralateral hemisphere.

Adult↗
PubMed2004

The physiological basis of transcranial motor cortex stimulation in conscious humans.

Transcranial stimulation of the human motor cortex can evoke several different kinds of descending activity depending on the type of stimulation, the intensity of stimulation and the area of the cortex being stimulated. Thus, transcranial magnetic stimulation preferentially activates different structures than transcranial electrical stimulation. In addition, the response to magnetic stimulation depends on the direction of the induced current in the brain, the waveform of the stimulating current, and the shape of the coil. Stimulation of the lower limb area of motor cortex recruits different elements than stimulation of the upper limb area. These differences occur because different structures in the motor cortex have a differential threshold to the different techniques of stimulation. We have had the opportunity to perform a series of direct recordings of the corticospinal volley evoked by the different techniques of transcranial stimulation from the epidural space of conscious patients with chronically implanted spinal electrodes. These recordings provide insights about the physiological basis of the excitatory and inhibitory phenomena produced by transcranial stimulation.

Efferent Pathways↗
PubMed2004

Inhibitory interactions between pairs of subthreshold conditioning stimuli in the human motor cortex.

OBJECTIVE: These experiments examined short interval paired-pulse paradigms for intracortical inhibition (ICI) and facilitation (ICF). We tested whether pairs of subthreshold conditioning stimuli interact, and whether they showed rapid periodicity similar to that observed in subthreshold I-wave interaction. METHODS: Transcranial magnetic stimulation (TMS) was given over left M1 to evoke a motor-evoked potential (MEP) of approximately 1 mV peak-to-peak amplitude in the contralateral first dorsal interosseous (FDI) muscle. Each test shock (TS) was preceded by single or paired subthreshold conditioning stimuli (CS(1) and CS(2)) at short interstimulus intervals (ISIs 1-15 ms). Intensities of CS were set just below thresholds for intracortical inhibition (ICI) or intracortical facilitation (ICF). RESULTS: Each CS(single) alone had no effect on the test MEP, but with two CS, clear inhibition was elicited at certain intervals. With a CS(2)-TS interval of 2 ms, maximum suppression occurred if CS(1) was applied 1-2.5 ms before CS(2). This inhibitory effect tapered off gradually as the CS(2)-CS(1) interval was increased up to 13 ms. When facilitation was present with a CS(single)-TS interval of 10 ms, a small but non-significant extra-facilitation occurred at ISIs between CS(2) and CS(1) of 6-15 ms. CONCLUSIONS: Two subthreshold conditioning stimuli facilitate inhibition that lacks the rapid periodicity typical of I-wave interaction. The data would be compatible with a model in which synaptic inputs converge on a common inhibitory interneurone.

Adult↗
PubMed2004

Comparison of descending volleys evoked by transcranial and epidural motor cortex stimulation in a conscious patient with bulbar pain.

OBJECTIVE: To compare the pattern of activation of motor cortex produced by transcranial magnetic stimulation and epidural electrical stimulation. METHODS: The spinal volleys evoked by transcranial magnetic stimulation and epidural electrical stimulation over the cerebral motor cortex were recorded from an electrode inserted into the cervical epidural space of one conscious subject who also had a cortical epidural electrode over the motor area. The volleys were termed D- and I-waves according to their latency. Magnetic stimulation was performed with a figure-of-eight coil and the induced current flowed either in a postero-anterior (PA) or in latero-medial (LM) direction. RESULTS: At active motor threshold intensity LM magnetic stimulation evoked a D wave whereas PA stimulation evoked an I(1) wave with later I waves being recruited at increasing stimulus intensities. Electrical epidural stimulation evoked both a D wave and I waves. However, the D wave evoked by electrical epidural stimulation had a longer latency than the LM D wave, suggesting either a more proximal site of activation of the pyramidal axon or activation of slightly faster conducting set of corticospinal fibres by LM stimulation. The I3 wave evoked by electrical epidural stimulation also had a longer latency than the PA I3-wave CONCLUSIONS: Epidural stimulation of the motor cortex can produce repetitive excitation of corticospinal neurones. The order of recruitment of the volleys, and the latency of the D and I3 waves may be slightly different to that seen after transcranial magnetic stimulation. SIGNIFICANCE: Our findings suggest that there may be subtle differences in the populations of neurones activated by the two forms of stimulation.

Consciousness↗
PubMed2004

The cortical silent period: intrinsic variability and relation to the waveform of the transcranial magnetic stimulation pulse.

OBJECTIVE: To assess the variability of the duration of the contralateral cortical silent period (CSP) between individuals and to assess the effect of different transcranial magnetic stimulation (TMS) pulse waveforms. METHODS: In Expt. 1, CSP duration, and the motor-evoked potential (MEP) amplitude and area were measured in the first dorsal interosseous muscle (FDI) of 11 subjects on 3 separate occasions using a TMS intensity of 150% active motor threshold (AMT). In Expt. 2, the stimulation intensity was varied between 100% AMT and 150% AMT. In both sets of experiments, 3 types of TMS pulse were used: monophasic posterior-anterior (PA) induced current in the brain, monophasic anterior-posterior induced current (AP), and biphasic PA/AP stimulation. RESULTS: Experiment 1: Between-subject variation in CSP duration was high. In addition, the duration after PA stimulation was significantly shorter than after AP or PA/AP stimulation. However, there was a good correlation between CSP duration and the area, or amplitude, of the MEP. This meant that calculating the ratio of duration/amplitude or duration/area reduced intersubject variability and eliminated differences between TMS pulses. Experiment 2: increasing stimulation intensity increased the mean value of all parameters, but with significantly lower values for PA than other forms of stimulation. The ratios of duration/amplitude or duration/area did not differ between current flow directions and were relatively constant for intensities 130-150% AMT. CONCLUSIONS: Between-subject variation in the duration of the CSP is high. A given intensity of stimulation (expressed in %AMT) produces a shorter CSP for PA stimulation than for AP or PA/AP stimulation. SIGNIFICANCE: If the ratio (CSP duration)/(MEP size) is calculated, then intersubject variability is reduced, and TMS pulse type differences are eliminated.

Adult↗
PubMed2004

Motor unit excitability changes mediating vestibulocollic reflexes in the sternocleidomastoid muscle.

OBJECTIVE: To investigate the patterns of motor unit firing in single motor units from the sternocleidomastoid (SCM) muscles in response to stimuli previously shown to be capable of evoking vestibulocollic reflexes (loud clicks and electrical stimulation) and to relate these to the previously described surface potentials (VEMPs, vestibular evoked myogenic potentials) evoked by the same stimuli. METHODS: Eleven male subjects (30-43-years-old) were studied. Local anaesthetic was used to block the SCM and confirm that the surface potentials (p13n23) arose from it. At another time, fine wire or needle electrodes were used to record single motor unit activity and peristimulus time histograms were constructed. RESULTS: Local anaesthetic block reduced or abolished the p13n23 response in 5 of 6 subjects. A total of 94 histograms of motor unit discharges were recorded. The excitability changes seen were always small. Loud click stimuli given ipsilaterally evoked short latency (mean 14.2 ms, uncorrected for triggering delays), and short duration (mean 3.6 ms) inhibition. Contralaterally, the effect was excitatory (latency 11.9 ms, uncorrected, mean duration 2.3 ms). For electrical stimulation, short latency inhibition occurred ipsilateral to the cathode (average latency 14.0 ms, uncorrected, mean duration 2.9 ms) and excitation occurred contralaterally. CONCLUSIONS: We confirmed that the SCM is the sole or dominant source of the VEMPs recorded from electrodes over it. Short latency, short duration motor unit firing changes are evoked in SCM by loud clicks and electrical stimulation, stimuli known to be capable of evoking vestibulocollic reflexes. VEMPs beginning with a positivity correspond to inhibition of the underlying motor unit firing and those starting with a negativity correspond to an underlying excitation, findings consistent with intracellular recordings of otolith effects. Qualitative explanations of how the surface potentials are generated by these excitability changes and relating to other properties of the surface responses are proposed. SIGNIFICANCE: This study has shown consistent patterns of single motor unit firing which underlie VEMPs evoked by both clicks and short duration galvanic stimulation.

Acoustic Stimulation↗
PubMed2004

Direct recording of the output of the motor cortex produced by transcranial magnetic stimulation in a patient with cerebral cortex atrophy.

OBJECTIVE: To examine the descending motor activity evoked by transcranial magnetic stimulation (TMS) in a chronic alcoholic patient with a slight atrophy of the peri-central cortex and compare with that observed in neurologically intact subjects. METHODS: EMGs from the first dorsal interosseous (FDI) muscle, and descending activity from an electrode implanted in the high cervical epidural space for relief of pain were recorded after TMS of the hand area of motor cortex. A figure-of-8 coil was used to induce either a posterior-anterior (PA) or a latero-medial (LM) flow across the central sulcus. RESULTS: In intact subjects, LM stimulation evoked the earliest volley, which we termed a D wave. This was followed by later, presumed I waves at intervals of about 1.5 ms. At a stimulus intensity of 120% resting threshold (RMT), up to 5 I waves were seen. PA stimulation rarely evoked D waves at intensities up to 120% RMT, but 3 or 4 I waves were visible in all subjects. The patient had an increased resting threshold, and the descending volleys were dominated by a D wave. I waves were unclear, with two possible small peaks at 5.5 and 7.2 ms. CONCLUSIONS: The lack of I waves in the patient was probably due to an impairment of interneuronal circuitry in the context of the brain damage related to chronic alcohol abuse, and is consistent with a trans-synaptic origin of the I waves in humans. The intact D wave is consistent with the assumption that the D wave represents direct stimulation of the axons of intact corticospinal neurones in the subcortical white matter. The patient's increased RMT reflects the fact that usually multiple descending volleys are needed to discharge resting spinal motoneurones.

Alcoholism↗
PubMed2003

Changes in corticospinal motor excitability induced by non-motor linguistic tasks.

The excitability of the corticospinal motor pathways to transcranial magnetic stimulation (TMS) can be differentially modulated by a variety of motor tasks. However, there is emerging evidence that linguistic tasks may alter excitability of the corticospinal motor pathways also. In this study we evaluated the effect of several movement-free, low-level linguistic processes involved in reading and writing on the excitability of the bilateral corticospinal motor pathways in a group of right-handed subjects. The study included two series of tasks, visual searching/matching and imaginal writing/drawing. The tasks were designed to roughly correspond with elemental aspects of the reading and writing, grapheme recognition and grapheme generation, respectively. Each task series included separate blocks with different task targets: letters, digits, semantically easy-to-code (i.e. geometric) shapes, and semantically hard-to-code shapes, as well as control blocks with no task. During task performance, TMS was delivered randomly over the hand area of either the left or right motor cortex and the modulation of the excitability of the corticospinal motor pathways was measured bilaterally through changes of the size of the motor-evoked potential (MEP) induced in the relaxed right and left first dorsal interosseous (FDI) muscles. We found that the size of the MEP in hand muscles increased during visual searching/matching tasks, particularly when targets were letters or geometric shapes, and the increase was significant for the dominant hand (left hemisphere) only. No such consistent effects were seen across subjects during imaginal tasks. This study provides evidence that even the performance of certain low-level linguistic tasks can modulate the excitability of the corticospinal motor pathways, particularly those originating from the left (dominant) hemisphere, despite the absence of overt motor activity. Moreover, in the light of the recently increased awareness of the role of "mirror neurons" in perception, the results suggest that activation of motor circuits used in generation of the written output may be an essential part of the perception of the written material as well. Understanding the patterns of task-dependent changes in excitability of the corticospinal motor pathways will provide insights into the organisation of central nervous system functional networks involved in linguistic processes, and may also be useful for future development of novel approaches to rehabilitation therapy of linguistic and motor functions.

Adult↗
PubMed2003

Changes in pharyngeal corticobulbar excitability and swallowing behavior after oral stimulation.

Faucial pillar (FP) stimulation is commonly used in swallowing rehabilitation, yet its physiological basis remains uncertain. We investigated the effects of intraoral FP stimulation on human corticobulbar excitability and swallowing behavior, to explore the possibility of a central mechanism for functional change. In 10 healthy subjects, corticobulbar projections to pharynx were investigated with transcranial magnetic stimulation, via intraluminal electrodes, before and up to 1 h after 10 min of electrical FP stimulation with three frequencies (0.2, 1, and 5 Hz) or sham and peripheral (median nerve) stimulation. In a second study, swallowing behavior was assessed with videofluoroscopy before and after FP stimulation. FP stimulation at 5 Hz inhibited the corticobulbar projection (-14 +/- 6%, P < 0.02) and lengthened swallow response time (+114 +/- 24%, P = 0.02). By comparison, FP stimulation at 0.2 Hz facilitated this projection (+60 +/- 28%, P < 0.04), without enhancing swallowing behavior. Neither 1-Hz, sham, nor median nerve stimulation altered excitability. Thus changes in corticobulbar excitability to FP stimulation are frequency dependent with implications for the treatment for neurogenic swallowing dysfunction.

Adult↗
PubMed2003

Short-lasting impairment of tactile perception by 0.9Hz-rTMS of the sensorimotor cortex.

To test whether low-frequency repetitive transcranial magnetic stimulation (rTMS) of sensorimotor cortex (SM1) has prolonged effects on somatosensory function, eight subjects were given 900 TMS pulses over the left hand SM1 (0.9Hz, 90% of the resting motor threshold) or at sites 3 cm anterior or posterior to it. Tactile threshold of the right hand was increased for a short duration after rTMS over SM1, but two-point discrimination and median nerve SEPs were unaffected after rTMS at any sites.

Adult↗
PubMed2003

Direct demonstration of reduction of the output of the human motor cortex induced by a fatiguing muscle contraction.

A brief period of strong muscle contraction suppresses the amplitude of EMG responses evoked in relaxed muscle by transcranial magnetic stimulation (TMS) of the contralateral motor cortex. Here we investigate this phenomenon in more detail by recording the descending motor volleys evoked by TMS from electrodes in the cervical epidural space of three conscious patients implanted with chronic electrical stimulators for control of pain. We confirm that fatigue suppresses I waves evoked by TMS. In addition, D waves were suppressed in two of the patients, suggesting that axonal excitability might also be compromised by a period of intense muscle contraction.

Adult↗
PubMed2003

The variability of intracortical inhibition and facilitation.

OBJECTIVE: To assess the variability of transcranial magnetic stimulation paired pulse measurements of cortical excitability between subjects, between sessions and within subjects within sessions. METHODS: In experiment 1, intracortical inhibition and facilitation were assessed with a fixed conditioning stimulus intensity (CSI) of 80% of active motor threshold (AMT) whereas in experiment 2, the effect of different CSIs (60-110% of AMT) was investigated. RESULTS: Experiment 1 revealed that subjects differed significantly in the degree of inhibition and facilitation. Between sessions the variability was substantial as predicted by high within session variability. Experiment 2 allowed determination of individual thresholds for inhibition and facilitation. These thresholds were the best predictor of the amount of inhibition or facilitation at a given CSI. Across subjects we observed a high correlation of the threshold for inhibition (expressed in terms of maximum stimulator output) with AMT (r=0.93). Results for facilitation were more variable. CONCLUSIONS: The variability was high if a single CSI was used to compare the percent intracortical inhibition or facilitation between subjects, or between sessions. Much less variable was the threshold for intracortical inhibition/facilitation, which was highly correlated to AMT. We suggest that the ratio of CSI:AMT is a robust and useful additional measure of the integrity of neuronal circuits underlying intracortical inhibition/facilitation.

Adult↗
PubMed2003

Physiological studies in carriers of the DYT1 gene mutation.

The DYT1 gene mutation is associated with early onset generalised dystonia. However, only 30-40 per cent of gene carriers develop symptoms. We have used electrophysiological tests to search for subclinical effects of the presence of the mutation in non-manifesting cases and compared these with those seen in clinically affected cases and healthy controls. Clinically affected patients had the same pattern of abnormalities in spinal and motor cortical circuits as described previously in non-genetically characterised patients. Non-manifesting cases had some but not all of these defects, suggesting that additional genetic or environmental factors may be needed to produce the full range of physiological deficiencies needed to give rise to clinical symptoms.

Carrier Proteins↗
PubMed2002

Repetitive transcranial magnetic stimulation for Tourette syndrome.

In a single-blinded, placebo-controlled, crossover repetitive transcranial magnetic stimulation (rTMS) trial, 16 patients with Gilles de la Tourette syndrome (GTS) received in random sequence 1 Hz motor, premotor, and sham rTMS, which each consisted of two 20-minute rTMS sessions applied on 2 consecutive days. In the 12 patients who completed the trial, there was no significant improvement of symptoms after any of the rTMS conditions as assessed with the Motor tic, Obsessions and compulsions, Vocal tic Evaluation Survey.

Anxiety↗
PubMed2002

Corticospinal transmission to leg motoneurones in human subjects with deficient glycinergic inhibition.

Normal coordinated movement requires that the activity of antagonistic motoneurones may be depressed at appropriate times during the movement. Both glycinergic and GABAergic inhibitory mechanisms participate in this control. Patients with the major form of hyperekplexia (hereditary startle disease) have impaired inhibition of spinal motoneurones from local glycinergic interneurones and represent an ideal opportunity for studying the role of glycinergic inhibition in the control of antagonistic muscles. In the present study we investigated whether impaired glycinergic inhibition affects the corticospinal control of antagonistic spinal motoneurones in 10 patients with hyperekplexia and whether there are mechanisms that may compensate for the lack of glycinergic inhibition. In healthy subjects transcranial magnetic stimulation (TMS) produced a short-latency inhibition of the soleus H-reflex at rest and during tonic dorsiflexion. This inhibition, which has been shown to be mediated by spinal (glycinergic) inhibitory interneurones, was absent in all four patients in whom this experiment was performed. This confirms that glycinergic transmission is impaired in the patients. During voluntary dorsiflexion subthreshold TMS produced a depression of the ongoing EMG activity in the tibialis anterior (TA) muscle in both healthy subjects and all of the six tested patients. This is consistent with the idea that this EMG depression is caused by activation of cortical (GABAergic) inhibitory interneurones. Cross-correlation analysis revealed normal short-term synchronization of TA motor units accompanied by coherence in the 8-12 Hz and 18-35 Hz frequency bands in the 10 patients. As in healthy subjects, 8-12 Hz coherence accompanied by decreased tendency to discharge synchronously (de-synchronization) was found in recordings from the antagonistic TA and soleus muscles in 2 of the 10 patients. This suggests that glycinergic inhibition is not responsible for de-synchronization of antagonistic motor units, but that other GABAergic-inhibitory mechanisms must be involved. We propose that such mechanisms may compensate for the lack of glycinergic reciprocal inhibition in the hyperekplectic patients and explain why voluntary movements are not more severely affected.

Adult↗
PubMed2002

Short-term reduction of intracortical inhibition in the human motor cortex induced by repetitive transcranial magnetic stimulation.

Ten healthy subjects and two patients who had an electrode implanted into the cervical epidural space underwent repetitive transcranial magnetic stimulation (rTMS; 50 stimuli at 5 Hz at active motor threshold intensity) of the hand motor area. We evaluated intracortical inhibition before and after rTMS. In healthy subjects, we also evaluated threshold and amplitude of motor evoked potentials (MEPs), duration of cortical silent period and short-latency intracortical facilitation. rTMS led to a short-lasting reduction in the amount of intracortical inhibition in control subjects with a high interindividual variability. There was no significant effect on other measures of motor cortex excitability. Direct recordings of descending corticospinal volleys from the patients were consistent with the idea that the effect of rTMS on intracortical inhibition occurred at the cortical level. Since the level of intracortical inhibition can be influenced by drugs that act on GABAergic systems, this may mean that low-intensity repetitive magnetic stimulation at 5 Hz can selectively modify the excitability of GABAergic networks in the human motor cortex.

Adult↗
PubMed2002

Noninvasive in vivo assessment of cholinergic cortical circuits in AD using transcranial magnetic stimulation.

BACKGROUND: A recently devised test of motor cortex excitability (short latency afferent inhibition) was shown to be sensitive to the blockade of muscarinic acetylcholine receptors in healthy subjects. The authors used this test to assess cholinergic transmission in the motor cortex of patients with AD. METHODS: The authors evaluated short latency afferent inhibition in 15 patients with AD and compared the data with those of 12 age-matched healthy controls. RESULTS: Afferent inhibition was reduced in the patients (mean responses +/- SD reduced to 85.7% +/- 15.8% of the test size) compared with controls (mean responses +/- SD reduced to 45.3% +/- 16.2% of the test size; p < 0.001, unpaired t-test). Administration of a single oral dose of rivastigmine improved afferent inhibition in a subgroup of six patients. CONCLUSIONS: The findings suggest that this method can be used as a noninvasive test of cholinergic pathways in AD. Future studies are required to evaluate whether short latency afferent inhibition measurements have any consistent clinical correlates.

Aged↗