Gary Thickbroom

A practical guide to diagnostic transcranial magnetic stimulation: Report of an IFCN committee

Transcranial magnetic stimulation (TMS) is an established neurophysiological tool to examine the integrity of the fast-conducting corticomotor pathways in a wide range of diseases associated with motor dysfunction. This includes but is not limited to patients with multiple sclerosis, amyotrophic lateral sclerosis, stroke, movement disorders, disorders affecting the spinal cord, facial and other cranial nerves. These guidelines cover practical aspects of TMS in a clinical setting. We first discuss the technical and physiological aspects of TMS that are relevant for the diagnostic use of TMS. We then lay out the general principles that apply to a standardized clinical examination of the fast-conducting corticomotor pathways with single-pulse TMS. This is followed by a detailed description of how to examine corticomotor conduction to the hand, leg, trunk and facial muscles in patients. Additional sections cover safety issues, the triple stimulation technique, and neuropediatric aspects of TMS.

Transcranial magnetic stimulation and synaptic plasticity: experimental framework and human models

Interest in the therapeutic potential of non-invasive human brain stimulation has been boosted by an improved understanding of the mechanisms of synaptic plasticity and the stimulus protocols that can induce plasticity in experimental preparations. A range of transcranial magnetic stimulation (TMS) protocols are available that have the potential to mimic these experimental protocols in the human. Repetitive TMS emulates aspects of activity-dependent plasticity, and theta-burst refinements may be able to take into account excitatory and inhibitory networks, paired associative stimulation can extend network considerations to incorporate sensorimotor integration, inhibitory networks may be targeted with short-interval paired stimulation and finally even the precision of spike-timing dependent plasticity may be accessible through I-(indirect)wave dynamics. This review will provide a synthesis of current concepts of activity- and time-dependent plasticity and their homeostatic regulation based on experimental studies, and relate these concepts to the promising range of TMS interventions that are available to target human brain plasticity.

The muscle silent period following transcranial magnetic cortical stimulation

Transcranial magnetic stimulation (TMS) of the motor cortex during tonic muscle contraction produces a motor evoked potential followed by a silent period in the electromyogram. We sought to characterize the TMS induced silent period and to compare it to the silent period induced by supramaximal peripheral nerve stimulation. TMS was delivered to the motor cortex using a 9 cm diameter circular coil and the surface electromyogram was recorded from the contralateral abductor pollicis brevis muscle in six normal subjects. Increasing TMS stimulus intensity from 10 to 50% above threshold resulted in an increase in the duration of the silent period from a mean of 50 ms to 185 ms. Increasing the level of tonic muscle contraction from 5% of maximum to maximum resulted in a decrease in silent period duration from a mean of 155 ms to 133 ms. In contrast, the duration of the silent period following supramaximal median nerve stimulation showed greater shortening under similar conditions, from a mean of 160 ms at 5% of maximum contraction to 99 ms at 75% of maximum contraction. The TMS induced silent period was present during a TMS induced increase in the reaction time for a ballistic movement, the onset of movement being delayed until the end of the silent period. Peripheral nerve stimulation did not produce a delay in movement onset. The present findings favour a cortical origin for the TMS induced silent period, probably on the basis of intracortical inhibition, rather than peripheral inhibition of spinal motoneurones which is considered to be the basis for the silent period following peripheral nerve stimulation.

Transcranial magnetic stimulation mapping of the motor cortex in normal subjects: The representation of two intrinsic hand muscles

The TMS-mapped representations of two intrinsic hand muscles, abductor pollicis brevis (APB) and abductor digiti minimi (ADM), were quantified using a transcranial magnetic stimulation (TMS) mapping technique in 10 right handed and 6 left handed subjects. A 50 mm diameter figure eight coil was used. Stimulus sites were located using a latitude/longitude based coordinate system, stimulus intensity was threshold-adjusted and stimuli were applied during controlled low-level (10%) voluntary contraction of the target muscles. Maps of the corticomotor representation were generated by fitting a continuously defined three dimensional function to the data obtained from stimulation at specific scalp sites, and projecting this function onto a two dimensional surface using a radial projection. It was found that the mapped representations of APB and ADM were large and overlapping but that there was a statistically significant separation of the two areas, the APB area being more laterally placed than the ADM area. The TMS-mapped representations of the two muscles showed no significant interhemispheric differences and were similar in left and right handed subjects. Rotation of the magnetic coil through 90 degrees resulted in medial shift and elongation of the TMS-mapped representations but there was no change in the relative positions of the two areas. The TMS-mapped representations were found to be very reproducible when mapping was repeated after intervals of up to 181 days. The present technique of TMS mapping allows the representation of individual hand muscles in the primary motor cortex to be reliably and reproducibly mapped and should prove useful for further studies of the physiology and pathophysiology of the motor cortex in man.

Functional reorganisation of the corticomotor projection to the hand in skilled racquet players

Abstract. While it is known that relatively rapid changes in functional representation may occur in the human sensorimotor cortex in short-term motor-learning studies, there have been few studies of changes in organisation of the corticomotor system associated with the long-term acquisition of motor skills. In the present study, we have used transcranial magnetic stimulation (TMS) to investigate the corticomotor projection to the hand in a group of elite racquet players, who have developed and maintained a high level of skill over a period of many years, and have compared the findings with those in a group of social players and a group of non-playing control subjects. Increased motor-evoked-potential (MEP) amplitudes and shifts in the cortical motor maps for the playing hand were found in all of the elite players and cortical motor thresholds were reduced in some players, whereas in the social players all parameters were within the normal range. The findings in the elite players are interpreted as being indications of a process of functional reorganisation with the motor cortex or corticomotor pathway that are associated with the acquisition and retention of complex motor skills.

Isometric force-related activity in sensorimotor cortex measured with functional MRI.

Abstract Isometric force-related functional magnetic resonance imaging (fMRI) signals from primary sensorimotor cortex were investigated by imaging during a sustained finger flexion task at a number of force levels related to maximum voluntary contraction. With increasing levels of force, there was an increase in the extent along the central sulcus from which a fMRI signal could be detected and an increase in the summed signal across voxels, but these parameters were related in such a way that the signal from each voxel was similar for each level of force. The results suggest that increased neuronal firing and recruitment of corticomotor cells associated with increased voluntary isometric effort are reflected in an expansion of a relatively constant fMRI signal over a greater volume of cortex, rather than an increase in the magnitude of the response in a particular circumscribed region, possibly due to perfusion of an increase in oxygen-enriched blood over a wider region of the cortex.

Repetitive paired-pulse TMS at I-wave periodicity markedly increases corticospinal excitability: A new technique for modulating synaptic plasticity

OBJECTIVE We hypothesised that facilitatory I-wave interaction set up by paired-pulse transcranial magnetic stimulation delivered with I-wave periodicity (iTMS) may reinforce trans-synaptic events and provide a means for modulating synaptic plasticity and cortical excitability. Our objective was to determine whether prolonged iTMS can increase corticospinal excitability, and whether this form of stimulation can have lasting aftereffects. METHODS Paired stimuli of equal strength with a 1.5 ms inter-stimulus interval were delivered for 30 min at a rate of 0.2 Hz. Motor threshold and motor evoked potential (MEP) amplitude to single-pulse TMS was compared before and after intervention. RESULTS Paired-pulse MEP amplitude increased linearly throughout the period of iTMS, and had increased five-fold by the end of the stimulation period. Single-pulse MEP amplitude was increased a mean of four-fold for 10 min after stimulation. Motor threshold was unaffected. CONCLUSIONS iTMS is an effective method for increasing excitability of the human motor cortex, and probably acts by increasing synaptic efficacy. SIGNIFICANCE Reinforcement of trans-synaptic events by iTMS may provide a means to investigate and modulate synaptic plasticity in the brain.

Physiological studies of the corticomotor projection to the hand after subcortical stroke

OBJECTIVE The mechanisms which lead to recovery of motor function after a stroke are poorly understood. Functional reorganization of cortical motor centres is thought to be one of the factors which may contribute to recovery. We have investigated the extent of reorganization which occurs at the level of the primary motor cortex after a lesion of the corticospinal pathway. METHODS Transcranial magnetic stimulation was used to map the topography of the primary corticomotor projection to the abductor pollicis brevis muscle and study changes in cortical motor thresholds and corticospinal conduction in a group of 20 subjects with subcortical infarcts of varying duration (1 week to 15 years) and varying degrees of motor deficit. RESULTS There was a broad correlation between motor evoked potential (MEP) amplitude and motor thresholds on the one hand and the severity of motor deficit and site and extent of the lesion on the other. Shifts in the cortical motor maps were found in both early and late cases, irrespective of the site of the lesion, but were more frequent in the longer standing cases. Shifts were usually along the mediolateral axis but anteroposterior shifts were found in some late cases. CONCLUSION Our findings indicate that there is functional reorganization of the corticomotor projection in subjects who regain a degree of motor control following a subcortical lesion sparing the motor cortex.

Changes in corticomotor excitation and inhibition during prolonged submaximal muscle contractions

Changes in motor evoked potential (MEP) amplitude, post‐MEP silent period duration, and interpolated twitch torque were measured using transcranial magnetic (TMS) and electrical (TES) stimulation during a 20% maximum voluntary contraction of the elbow flexors sustained to exhaustion. TMS‐ and TES‐induced MEP amplitude increased progressively over the contraction period up until the point of exhaustion. The TMS‐induced silent period was prolonged only during the second half of the contraction period, the time course being different from that of the MEP responses, whereas the TES‐induced silent period did not change. The findings indicate that corticomotor excitability increases during a sustained submaximal voluntary contraction and that, as fatigue develops, there is a progressive buildup of intracortical inhibition. This may represent a mechanism whereby corticomotor output is maintained at an appropriate level to preserve optimal motor unit firing frequencies during a fatiguing contraction.

Differences in sensory and motor cortical organization following brain injury early in life

There have been a number of physiological studies of motor recovery in hemiplegic cerebral palsy which have identified the presence of novel ipsilateral projections from the undamaged hemisphere to the affected hand. However, little is known regarding the afferent projection to sensory cortex and its relationship to the reorganized cortical motor output. We used transcranial magnetic stimulation (TMS) to investigate the corticomotor projection to the affected and unaffected hands in a group of subjects with hemiplegic cerebral palsy, and also performed functional magnetic resonance imaging (fMRI) studies of the patterns of activation in cortical motor and sensory areas following active and passive movement of the hands. Both TMS and fMRI demonstrated a normal contralateral motor and sensory projection between the unaffected hand and the cerebral hemisphere. However, in the case of the affected hand, the TMS results indicated either a purely ipsilateral projection or a bilateral projection in which the ipsilateral pathway had the lower motor threshold, whereas passive movement resulted in fMRI activation in the contralateral hemisphere. These results demonstrate that there is a significant fast‐conducting corticomotor projection to the affected hand from the ipsilateral hemisphere in this group of subjects, but that the predominant afferent projection from the hand is still directed to the affected contralateral hemisphere, resulting in an interhemispheric dissociation between afferent kinesthetic inputs and efferent corticomotor output. The findings indicate that there can be differences in the organization of sensory and motor pathways in cerebral palsy, and suggest that some of the residual motor dysfunction experienced by these subjects could be due to an impairment of sensorimotor integration at cortical level as a result of reorganization in the motor system. Ann Neurol 2001;49:320–327