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Biomedical subjects

J C Rothwell

Publications and source records attributed to J C Rothwell.

At least 19 recordsLinked to original sources

Exploring Theta Burst Stimulation as an intervention to improve motor recovery in chronic stroke.

OBJECTIVE: To explore the effects of a single session of repetitive Transcranial Magnetic Stimulation, given as Theta Burst Stimulation, on behavioural and physiological measures of hand function in chronic stroke patients. METHODS: Six chronic stroke patients with incomplete recovery of the hand were tested under three conditions: excitatory TBS over the stroke hemisphere (iTBS(SH)), inhibitory TBS (cTBS(IH)) over the intact hemisphere and sham stimulation. Behavioural outcomes included simple and choice reaction time paradigms. Physiological effects were assessed using single pulse TMS on both sides. Changes were sought for up to 40min after TBS. RESULTS: Immediately after iTBS(SH) simple reaction times in the paretic hands were decreased and, compared to sham stimulation, remained significantly shorter throughout the testing period. The amplitude of the MEPs at rest and during background contraction and the area under the Input-Output curves were also increased on the stroke side after iTBS(SH). cTBS(IH) suppressed the MEPs evoked in the healthy hands but did not change motor behaviour or the electrophysiology of the paretic hands. No side effects were encountered. CONCLUSIONS: TBS seems safe in chronic stroke patients. iTBS over the stroke hemisphere transiently improved motor behaviour and corticospinal output in the paretic hands. SIGNIFICANCE: Excitatory TBS may represent a useful rTMS protocol to apply to the stroke hemisphere in future longer term therapy trials.

Adult↗

Origin of facilitation of motor-evoked potentials after paired magnetic stimulation: direct recording of epidural activity in conscious humans.

A magnetic transcranial conditioning stimulus given over the motor cortex at intensities below active threshold for obtaining motor-evoked potentials (MEPs) facilitates EMG responses evoked at rest in hand muscles by a suprathreshold magnetic stimulus given 10-25 ms later. This is known as intracortical facilitation (ICF). We recorded descending volleys produced by single and paired magnetic motor cortex stimulation through high cervical epidural electrodes implanted for pain relief in six conscious patients. At interstimulus intervals (ISIs) of 10 and 15 ms, although MEP was facilitated, there was no change in the amplitude or number of descending volleys. An additional I wave sometimes was observed at 25 ms ISI. In one subject, we also evaluated the effects of reversing the direction of the induced current in the brain. At 10 ms ISI, the facilitation of the MEPs disappeared and was replaced by slight suppression; at 2 ms ISI, there was a pronounced facilitation of epidural volleys. Subsequent experiments on healthy subjects showed that a conditioning stimulus capable of producing ICF of MEPs had no effect on the EMG response evoked by transmastoidal electrical stimulation of corticospinal tract. We conclude that ICF occurs because either 1) the conditioning stimulus has a (thus far undetected) effect on spinal cord excitability that increases its response to the same amplitude test volley or 2) that it can alter the composition (but not the amplitude) of the descending volleys set up by the test stimulus such that a larger proportion of the activity is destined for the target muscle.

Adult↗

Changes in forearm reciprocal inhibition following pallidal stimulation for dystonia.

The authors recorded forearm H reflex reciprocal inhibition and clinical outcome in eight patients with primary torsion dystonia before and 1, 3, and 6 months after pallidal deep brain stimulation (DBS). There was progressive increase in reciprocal inhibition after surgery, which correlated with clinical improvement. The authors conclude that pallidal DBS for dystonia results in functional reorganization of the nervous system, which includes a long-term increase in spinal inhibition.

Adult↗

Motor system inhibition in dopa-responsive dystonia and its modulation by treatment.

Dopa-responsive dystonia (DRD) causes dystonia-parkinsonism, which is abolished by levodopa. The authors assessed short intracortical inhibition and facilitation, silent period, blink reflex recovery cycle, and reciprocal inhibition in seven patients with DRD on and off treatment. Short intracortical inhibition and blink reflex recovery cycle were reduced, but increased with treatment. Silent period was normal on and off treatment. Third phase of reciprocal inhibition was reduced on and off treatment. A discrete pattern of motor inhibitory dysfunction occurs in DRD.

Blinking↗

Arm function after stroke: neurophysiological correlates and recovery mechanisms assessed by transcranial magnetic stimulation.

Transcranial Magnetic Stimulation has been used for over 20 years to investigate recovery of motor function in stroke patients. In particular, it has been used to quantify the extent of damage to the corticospinal output, reorganisation of the cortical representation of the affected body parts and excitability of intracortical and cortico-cortical circuitries in both hemispheres. In this review, we provide a detailed account of most of the published data with particular reference to methodological issues that affect their interpretation.

Arm↗

Task-specific hand dystonia: can too much plasticity be bad for you?

Patients with occupational hand dystonias have task-specific involuntary co-contraction and overflow of activity to inappropriate muscles. This interferes with highly skilled movements such as handwriting (writer's cramp) or playing a musical instrument (musician's cramp). Transcranial stimulation methods that probe mechanisms of synaptic plasticity in the motor cortex show an abnormal modifiability of sensorimotor circuits in patients with writer's cramp, probably because homeostatic control of the range of modification is deficient. We argue that during skilled motor practice, this leads to an excessive tendency to form associations between sensory inputs and motor outputs (abnormal potentiation) and to a failure to weaken already existing associations (deficient depotentiation). Deficient homeostatic control might be an important mechanism that triggers maladaptive reorganization and produces symptoms of occupational hand dystonias.

Animals↗

Dopaminergic drugs restore facilitatory premotor-motor interactions in Parkinson disease.

OBJECTIVE: To explore the impact of dopaminergic therapy on facilitatory premotor-motor interactions in patients with Parkinson disease (PD). METHODS: Ten patients with PD and 10 age-matched healthy volunteers received repetitive transcranial magnetic stimulation (rTMS) over the left dorsal premotor cortex (5 Hz, 1,500 stimuli, 90% of active motor threshold). Patients were studied while "on" and "off" medication. Motor evoked potentials (MEPs) were recorded from the right first dorsal interosseus muscle before and after rTMS to quantify changes in motor cortical excitability. The after-effects of rTMS on motor function were assessed using the Unified Parkinson's Disease Rating Scale and the kinematics of ballistic wrist flexions. RESULTS: MEPs evoked from the ipsilateral motor cortex were increased after premotor rTMS in relaxed normal subjects, consistent with an increase in motor cortex excitability. In patients with PD, the effect of premotor rTMS was modified by medication. When patients were in a practically defined "off" state, premotor rTMS had no effect on MEPs, whereas when they were in the "on" state, premotor rTMS facilitated MEPs. Premotor rTMS had no effect on clinical parkinsonian symptoms or motor performance of ballistic wrist movements, regardless of whether patients were in the "on" or "off" state. CONCLUSIONS: In Parkinson disease, the ability of premotor-motor connections to increase motor cortical excitability is defective but restored to normal by dopaminergic medication. Dopamine deficiency in the basal ganglia may affect the way that frontal motor areas interact with each other.

Adult↗

Theta-burst repetitive transcranial magnetic stimulation suppresses specific excitatory circuits in the human motor cortex.

In four conscious patients who had electrodes implanted in the cervical epidural space for the control of pain, we recorded corticospinal volleys evoked by single-pulse transcranial magnetic stimulation (TMS) over the motor cortex before and after a 20 s period of continuous theta-burst stimulation (cTBS). It has previously been reported that this form of repetitive TMS reduces the amplitude of motor-evoked potentials (MEPs), with the maximum effect occurring at 5-10 min after the end of stimulation. The present results show that cTBS preferentially decreases the amplitude of the corticospinal I1 wave, with approximately the same time course. This is consistent with a cortical origin of the effect on the MEP. However, other protocols that lead to MEP suppression, such as short-interval intracortical inhibition, are characterized by reduced excitability of late I waves (particularly I3), suggesting that cTBS suppresses MEPs through different mechanisms, such as long-term depression in excitatory synaptic connections.

Aged↗

Excitability of motor cortex inhibitory circuits in Tourette syndrome before and after single dose nicotine.

The pathophysiology underlying the involuntary tics of Gilles de la Tourette syndrome (GTS) remains unknown. Here we used transcranial magnetic stimulation (TMS) to examine the excitability of two different inhibitory systems in the human motor cortex: short interval intracortical inhibition (SICI) and short interval afferent inhibition (SAI) in 10 healthy non-smoking controls and eight untreated non-smoking patients with GTS. Compared with the healthy control group, both SICI (measured at a range of conditioning intensities) and SAI were reduced in patients. This is consistent with the suggestion that reduced excitability of cortical inhibition is one factor that contributes to the difficulty that patients have in suppressing involuntary tics. In addition, the reduced SAI indicates that impaired intracortical inhibition may not be limited to the motor cortex but also involves circuits linking sensory input and motor output. A single dose of nicotine reduced tic severity as assessed by blind video scoring in the majority of patients. In addition, it abolished the difference between patients and controls in SICI and SAI. There was no effect of nicotine, and no difference between controls and patients in measures of motor or SICI threshold. This indicates that cholinergic input can modulate the efficiency of SICI and SAI differently in GTS and healthy controls.

Adult↗

Caffeine has no effect on measures of cortical excitability.

OBJECTIVE: To assess the effect of caffeine on motor thresholds, short interval intra-cortical inhibition (SICI), intra-cortical facilitation (ICF) and cortical silent periods in a placebo controlled double-blinded trial. METHODS: In eleven healthy non-smoking subjects the following parameters were measured using transcranial magnetic stimulation (TMS): motor thresholds (rest, RMT and active, AMT), SICI and ICF at different conditioning stimulus intensities (60, 70, 80, 90% AMT), cortical silent periods at 130, 150 and 175% AMT, and size of motor evoked potential at rest at 110, 125 and 150% RMT. Measurements were repeated after one cup of decaffeinated coffee. On another day, measurements were obtained before and after one cup of decaffeinated coffee that contained caffeine (3 mg/kg bodyweight). Caffeine concentrations were measured in serum before and after experiments. Experiments were conducted and data were evaluated blinded to the experimental condition. RESULTS: The results of repeated measurements of all parameters were similar comparing experiments on each day, or when comparing the caffeine arm of the study with the placebo arm. CONCLUSIONS: Caffeine in a concentration similar to that in a strong cup of coffee does not have a major effect on TMS measures of motor cortex excitability. SIGNIFICANCE: In healthy controls, the design of TMS experiments that investigate the parameters assessed in this TMS study does not need to control for caffeine.

Adult↗

Parkinsonism following bilateral lesions of the globus pallidus: performance on a variety of motor tasks shows similarities with Parkinson's disease.

OBJECTIVES: The authors report the results of detailed investigations into the motor function of a patient who, after a heavy drinking binge and subsequent unconsciousness, respiratory acidosis, and initial recovery, developed parkinsonism characterised by hypophonic speech and palilalia, "fast micrographia", impaired postural reflexes, and brady/akinesia in proximal (but not distal) alternating upper limb movements. METHODS: In addition to brain magnetic resonance imaging (MRI), different aspects of motor function were investigated using reaction time (RT) tasks, pegboard and finger tapping tasks, flex and squeeze tasks, movement related cortical potentials (MRCPs), and contingent negative variation (CNV). Cognitive function was also assessed. The results were compared to those previously reported in patients with Parkinson's disease (PD). RESULTS: Brain MRI showed isolated and bilateral globus pallidus (GP) lesions covering mainly the external parts (GPe). These lesions were most probably secondary to respiratory acidosis, as other investigations failed to reveal an alternative cause. The results of the RT tasks showed that the patient had difficulties in preparing and maintaining preparation for a forthcoming movement. MRCP and CNV studies were in line with this, as the early component of the MRCP and CNV were absent prior to movement. The patient's performance on pegboard and finger tapping, and flex and squeeze tasks was normal when performed with one hand, but clearly deteriorated when using both hands simultaneously or sequentially. CONCLUSIONS: In general, the present results were similar to those reported previously in patients with PD. This provides further indirect evidence that the output of globus pallidus is of major importance in abnormal motor function in PD. The possible similarities of the functional status of GP in PD and our case are discussed.

Acidosis, Respiratory↗

Mirtazapine increases cortical excitability in healthy controls and epilepsy patients with major depression.

BACKGROUND: Epilepsy is often complicated by depression requiring antidepressant treatment. Such treatment might be proconvulsive. OBJECTIVE: To examine the effects of the noradrenergic and specific serotonergic antidepressant mirtazapine on motor cortex excitability in epilepsy patients with depression and in healthy controls, using transcranial magnetic stimulation (TMS). METHODS: Seven clinically depressed epilepsy patients treated with anticonvulsant drugs and six healthy volunteers were studied. Before intake of mirtazapine and 24 hours afterwards (and also three weeks afterwards in the patients), the active and resting motor threshold (AMT, RMT), the size of the motor evoked potential (MEP), the cortical silent period (SP), and intracortical inhibition/facilitation and intracortical facilitatory I wave interactions were determined using single and paired pulse TMS. RESULTS: At baseline, AMT and RMT were higher (p = 0.049 and p = 0.04, respectively) and the ratio SP duration/MEP area greater in patients (p = 0.041). In patients but not in healthy subjects AMT was lower 24 hours after intake of mirtazapine (p = 0.028). Mirtazapine had no significant effect on the MEP size, duration of the SP, or the ratio of SP duration to MEP size in patients. The duration of the SP was longer (p = 0.037) but the ratio of SP duration to MEP size remained similar in healthy subjects after mirtazapine. There were no significant differences in paired pulse measures between the two groups either at baseline or after mirtazapine. CONCLUSIONS: Mirtazapine increased neuronal excitability of pyramidal tract axons in an activated state in both healthy controls and epilepsy patients with major depression.

Adult↗

Longlasting antalgic effects of daily sessions of repetitive transcranial magnetic stimulation in central and peripheral neuropathic pain.

BACKGROUND AND OBJECTIVE: A single session of repetitive transcranial magnetic stimulation (rTMS) over motor cortex had been reported to produce short term relief of some types of chronic pain. The present study investigated whether five consecutive days of rTMS would lead to longer lasting pain relief in unilateral chronic intractable neuropathic pain. PATIENTS AND METHODS: Forty eight patients with therapy resistant chronic unilateral pain syndromes (24 each with trigeminal neuralgia (TGN) and post-stroke pain syndrome (PSP)) participated. Fourteen from each group received 10 minutes real rTMS over the hand area of motor cortex (20 Hz, 10x10 s trains, intensity 80% of motor threshold) every day for five consecutive days. The remaining patients received sham stimulation. Pain was assessed using a visual analogue scale (VAS) and the Leeds assessment of neuropathic symptoms and signs (LANSS) scale, before, after the first, fourth, and fifth sessions, and two weeks after the last session. RESULTS: No significant differences were found in basal pain ratings between patients receiving real- and sham-rTMS. However, a two factor ANOVA revealed a significant "+/- TMS" x "time" interaction indicating that real and sham rTMS had different effects on the VAS and LANSS scales. Post hoc testing showed that in both groups of patients, real-rTMS led to a greater improvement in scales than sham-rTMS, evident even two weeks after the end of the treatment. No patient experienced adverse effects. CONCLUSION: These results confirm that five daily sessions of rTMS over motor cortex can produce longlasting pain relief in patients with TGN or PSP.

Electromyography↗

Subthreshold rTMS over pre-motor cortex has no effect on tics in patients with Gilles de la Tourette syndrome.

OBJECTIVE: A previous study showed no effect of 1Hz repetitive transcranial magnetic stimulation (rTMS) on tics in Gilles de la Tourette Syndrome (GTS). We modified the rTMS protocol in order to investigate some of the possible methodological reasons for the negative outcome in that study. METHODS: In a single blinded placebo-controlled cross-over study in five GTS patients without obsessive compulsive disorder we probed whether longer trains (1800 stimuli) of 1 Hz pre-motor cortex rTMS at 80% of active motor threshold and application to both hemispheres can improve tics in GTS. This was measured with the Yale Global Tic severity rating scale, the MOVES self-rating scale and video analysis. RESULTS: We found no significant effect of either left pre-motor cortex stimulation alone, or left pre-motor followed by right pre-motor cortex stimulation. CONCLUSIONS: These results suggest that the rTMS protocol used in this study is not useful for the treatment of tics in GTS. SIGNIFICANCE: rTMS protocols need to be modified substantially in order to explore their potential for the treatment of tics in GTS.

Adult↗