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Biomedical subjects

G W Thickbroom

Publications and source records attributed to G W Thickbroom.

At least 19 recordsLinked to original sources

Spatial differences in the sites of direct and indirect activation of corticospinal neurones by magnetic stimulation.

Transcranial magnetic stimulation (TMS) over the human motor cortex evokes multiple descending volleys possibly through activation of different elements within the brain. We have investigated whether such elements can be distinguished spatially. Using a figure of eight coil, TMS was delivered over multiple scalp sites during a low level voluntary contraction of the left first dorsal interosseous muscle. At near-threshold intensity, early or late surface electromyograph (EMG) components (relative to anodal response latency) could be preferentially evoked with the coil aligned in a medio-lateral (ML), antero-posterior (AP), or postero-anterior (PA) orientation. The optimal location of the earliest component with ML coil orientation was 8 mm medial and 5 mm anterior compared to a later component with AP orientation. The optimal location for the same latency EMG component mapped using two different coil orientations (AP and ML) was not significantly different. The optimal location of two different late components, one obtained with AP and the other with PA coil orientations, was similar. It is argued that the earliest TMS-evoked component results from direct activation of corticospinal cell axons while later components result from activation of these cells trans-synaptically (indirectly), and that consequently there is a substantial spatial separation between these activation sites.

Adult

Effects of magnetic stimulation over supplementary motor area on movement in Parkinson's disease.

Movement execution can be delayed by transcranial magnetic stimulation delivered over primary motor cortical areas, resulting in transient inhibition of cortico-motor output. Inhibition or disruption of higher-order motor planning and preparatory processes, such as are thought to occur in the supplementary motor area (SMA), would allow an examination of processes at other stages of the motor control system. In this study, six subjects with Parkinson's disease and six healthy control subjects performed a non-cued sequential finger movement task. At various times relative to movement, high-intensity single-pulse magnetic stimulation was delivered over the region of the SMA, with minimal current spread to primary motor areas. When magnetic stimulation was given at early stages during the movement for parkinsonian subjects, movement times were significantly increased, indicating disrupted movements. Supplementary motor area stimulation had no effect when delivered during later stages of the movement or immediately prior to movement onset, and had no apparent effect on control subjects at any time. It is therefore suggested that the SMA is important in motor planning and preparatory processes, since SMA stimulation has no effect on movements in their later stages when planning may be complete, but may disrupt movements in their early stages, when preparation for later stages may still be in progress. Further, possible instability of motor planning/preparation processes in Parkinson's disease is suggested, since these processes appeared more susceptible to disruption by magnetic stimulation in parkinsonian subjects than controls.

Aged

The audiogenic startle response in Tourette's syndrome.

We report the results of a study in which we examined the auditory startle responses (ASR) of 8 patients with Tourette's syndrome and 15 normal controls, none of whom reported or manifested exaggerated startle responses clinically. The ASR in two patients failed to habituate with repetition, a finding not present in any of the controls. There was no correlation between the presence or absence of exaggerated ASRs and the severity of the patients' tics. This study demonstrates that some patients with Tourette's syndrome have exaggerated audiogenic startle responses that may be clinically asymptomatic.

Acoustic Stimulation

Comparison of the magnetically mapped corticomotor representation of a muscle at rest and during low-level voluntary contraction.

This study has compared the topography of the corticomotor representation of an intrinsic hand muscle in the relaxed state and during a low-level voluntary contraction using transcranial magnetic stimulation. It was found that the optimum cortical stimulus site and the surrounding area of excitable cortex were shifted approximately 6 mm medially as a result of performing a voluntary contraction. This difference may be due to a combination of factors involving the spatial distribution of excitable intracortical fibres, the effects of muscle afferent activity on motor cortex excitability, and task-dependent modifications of corticomotor output.

Adult

An investigation of the late excitatory potential in the hand following magnetic stimulation of the motor cortex.

Magnetic stimulation of the motor cortex gives rise to a motor evoked potential (MEP) followed by a silent period (SP) during which a late excitatory potential (LEP) may occur in the surface EMG. To elucidate the mechanism of the LEP we investigated the effect of muscle contraction, stimulus intensity and stimulation site on the LEP recorded from the abductor pollicis brevis muscle. The amplitude of the LEP increased with increasing levels of muscle contraction and decreased with increasing stimulus intensity. There was no direct relationship between the amplitude of the LEP and the MEP, but there was an inverse relationship between LEP amplitude and SP duration. The latency of the LEP was unaffected by the level of muscle contraction, but increased with increasing stimulus intensity. Topographic mapping with stimulation at multiple scalp sites yielded a LEP at sites partially encircling but not including the centre of the APB motor area. These results are consistent with the LEP being due to reflex alpha motoneurone firing as a result of gamma motoneurone activation or with a period of disinhibition at cortical level allowing breakthrough of voluntary activity.

Adult

The origin of the soleus late response evoked by magnetic stimulation of human motor cortex.

Transcranial magnetic stimulation (TMS) of the human motor cortex elicits a primary motor evoked potential (MEP) in the soleus muscle at a latency of approximately 30 msec, which may be followed by a late potential with a variable latency of 80-120 msec (soleus late response, SLR). While the MEP is thought to arise from stimulation of the corticospinal tract, the origin of the SLR is uncertain. In the present study we have investigated the properties of the SLR in order to elucidate its origin. An SLR was evoked at a latency of 100-120 msec in 5 out of 10 normal subjects in the relaxed state and at a latency of approximately 100 msec in all subjects when tibialis anterior (TA) was slightly facilitated. The SLR was largest with 5-10% TA contraction, decreased in size with increasing levels of TA contraction and was negligible in all subjects when the foot was immobilised. The latency of the SLR fell by 23 msec when the foot was passively dorsiflexed 20 degrees. A similar response to the SLR, at a latency of 77 msec, was present in all subjects following electrical stimulation of the peroneal nerve. Our findings suggest that the SLR is a soleus stretch reflex resulting from dorsiflexion of the foot due to preferential activation of TA following cortical stimulation.

Adolescent

Topography of excitatory and inhibitory muscle responses evoked by transcranial magnetic stimulation in the human motor cortex.

Transcranial magnetic stimulation of the motor cortex produces a motor-evoked potential (MEP) in the electromyogram followed by a silent period (SP) which is thought to be due to cortical inhibition. In this study, the topography and size of the cortical areas from which an MEP and SP are evoked in the abductor pollicis brevis muscle (APB) of the hand were compared. The SP area was found to be large, encompassing and surrounding the MEP area. These findings infer the existence of an inhibitory surround limiting the excitatory area for APB in the human motor cortex.

Adult

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.

Adult

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.

Adult

Saccade onset and offset lambda waves: relation to pattern movement visually evoked potentials.

The lambda (lambda) wave is an occipital EEG potential which occurs when saccadic eye movements are made against an illuminated contrast background. There is some disagreement concerning the presence of sub-components to the lambda-wave, and its relationship to visually evoked potentials. In the present study, lambda-waves were recorded with saccades of different durations (30-110 ms) and compared to VEPs associated with pattern movements of similar durations and velocity. It was found that the lambda-wave consisted of a saccade onset component with positive sub-components at 59 and 100 ms after saccade onset, and a saccade offset component with a positive potential at 74 ms after saccade offset. With small saccades of 30 ms duration or less, these components superimposed to form a single lambda-wave. In the case of pattern movement VEPs, a movement onset component of latency 110 ms following movement onset, and a movement offset component at 89 ms after movement offset, were identified. The similar behaviour of the lambda-wave and VEP under these conditions supports the view that the lambda-wave is a visually evoked potential resulting from movement of the visual field across the retina during a saccadic eye movement.

Adult

Premotor negativity associated with saccadic eye movement and finger movement: a comparative study.

The topography and time course of the premotor negativity (PMN) associated with horizontal saccadic eye movement and with thumb movement has been compared in a group of normal subjects. It was found that the time of onset, slope and distribution of the PMN was essentially the same for both types of movement. This finding suggests that the PMN may reflect primarily a non-movement-specific increase in attention or arousal processes common to both types of movement rather than activity in specific cortical areas concerned with the programming and execution of the movements.

Adult

Computer quantitation of gallium 67 lung uptake in crocidolite (blue asbestos) workers of Western Australia.

Pulmonary inflammation has been evaluated in 43 crocidolite-exposed asbestos (ASB) workers and 12 control subjects, using a quantitative index of gallium uptake (GI). The GI was compared with chest roentgenographs (CXRs) graded by the ILO classification. The ASB workers included 15 with asbestosis (CXR greater than or equal to 1/0), 19 with a normal CXR (CXR 0/0), and 9 with equivocal CXR changes (CXR 0/1). In individuals with asbestosis the GI was 3.6 +/- 0.3 (mean +/- SEM), P less than 0.01 compared with exposed patients without asbestosis. In exposed patients with equivocal CXR changes (0/1) the GI was 3.1 +/- 0.3, and in exposed patients with a normal CXR (0/0) the GI was 2.4 +/- 0.2. The GI for subjects without lung disease was 1.2 +/- 0.2, P less than 0.01 compared with exposed patients without asbestosis. The scans were scored independently by two observers, and the correlation coefficient of the two sets of GI was 0.95. These data demonstrate that subjects with crocidolite-induced asbestosis and exposed patients with equivocal CXR changes or a normal CXR have significantly increased GI.

Asbestos

Presaccadic spike potential: a computer model based upon motor unit recruitment patterns in the extraocular muscles.

Details are presented of a computer model of the presaccadic 'spike' potential based upon the discharge properties of motor units in the extraocular muscles. The model provides support for the hypothesis that the spike potential represents the summated electrical activity from the near-synchronous recruitment of motor units in the extraocular muscles by the presaccadic burst of motoneurone activity.

Action Potentials

Crossed facilitation and post-contraction depression of abductor pollicis brevis motor neurons.

Crossed facilitation of abductor pollicis brevis (APB) motor neurons by voluntary contraction of the contralateral APB was investigated using F response analysis. The integrated F response EMG showed a mean 4-fold increase during contraction. This enhancement was maintained until the onset of subjective fatigue and then declined. After isometric or isotonic contraction of the ipsilateral APB there was a significant depression of F responses with a progressive return to baseline values over a 6 minute period. The significance of the findings is discussed.

Adult

Presaccadic spike potential. Relation to eye movement direction.

The spike potential (SP) which precedes horizontal saccadic eye movement has been shown to arise in the agonist lateral and medial rectus muscles of the two eyes. To determine whether other extra-ocular muscles also generate an SP, recordings were carried out in normal subjects performing vertical and oblique as well as horizontal saccades. An SP was recorded before saccades in all directions. The potential was highest in amplitude with horizontal or oblique abducting saccades and was higher in amplitude with vertical upgoing than downgoing saccades.

Action Potentials

Averaging, spatio-temporal mapping and dipole modelling of focal epileptic spikes.

A computer-based technique is described for the acquisition, spatio-temporal mapping and dipole modelling of epileptic spike events. Spike acquisition is operator-controlled and subsequent data processing is performed off-line. Preliminary averaging and topographical display of wave forms provide complementary information on the spike field. The method promises to be a useful adjunct to conventional EEG in spike analysis.

Brain

Presaccadic 'spike' potential: investigation of topography and source.

Approximately 15-30 ms before a saccade, a large-amplitude, relatively short duration potential whose source has not previously been determined with certainty, can be recorded from the scalp in man. We have measured the surface topography of this potential during horizontal saccades in normal subjects and have found it to be maximal near the eye on the side ipsilateral to the direction of the saccade. Dipole modelling predicts a source near the eye ipsilateral to the direction of gaze, and the application of source derivation supports such an origin. Measurements of the potential close to the orbits in normal subjects and in patients with a unilateral abducens nerve palsy, exenterated orbit or ocular prosthesis suggest that it is a summation potential derived from the ipsilateral lateral rectus and contralateral medial rectus muscles. It is hypothesized that the potential may arise as a result of the synchronized recruitment of motor units in the extraocular muscles prior to the commencement of the saccade.

Adult