Biomedical subjects

Gary W Thickbroom

Publications and source records attributed to Gary W Thickbroom.

At least 19 recordsLinked to original sources

PubMed2006

Reduced functional activation after fatiguing exercise is not confined to primary motor areas.

We have previously shown that following a period of unimanual fatiguing exercise, there is a reduction in primary sensorimotor cortex (SM1) activation with movement of either the fatigued or the non-fatigued hand by Benwell et al. (Exp Brain Res 167:160-164, 2005). In the present study we have investigated whether this reduction is confined to motor areas or is more widespread. Functional imaging was performed before and after a 10-minute fatiguing exercise of the left hand (30% of maximum handgrip strength) in seven normal subjects (4 M, mean age 25 years). The activating task was a handgrip against a low resistance (1 kg) in response to a visual cue (chequerboard reversal every 2 +/- 0.5 s). We compared activation in SM1, supplementary motor area (SMA), cerebellum (CB) and primary visual cortex (V1) before and after the fatiguing exercise. After exercise, contralateral SM1 activation was reduced by 33% (P < 0.05) compared to baseline for the fatigued hand and by 49% for the non-fatigued hand (P < 0.05). A similar pattern was seen for the bilateral SMA and ipsilateral CB following exercise (45 vs. 50% for SMA; 30 vs. 35% for CB; fatigued versus non-fatigued). Activation was also reduced in V1 but to a lesser extent than in motor areas (19 vs. 24%; fatigued versus non-fatigued). These results show that although the reduced functional activation during the recovery period after fatiguing exercise is more marked in motor areas, it also extends to non-motor areas such as the visual cortex, suggesting that there are more widespread changes in cerebral haemodynamic responses after fatigue.

Adult↗

PubMed2006

Motor cortex reorganisation in Parkinson's disease.

Transcranial magnetic stimulation mapping of the motor cortical projection to the hand was performed in a group of patients with Parkinson's disease (PD) of variable duration to determine whether there is evidence of cortical reorganisation. Map shifts were found in the majority of PD cases (12/15), in untreated early cases as well as treated cases of longer duration, and there was a correlation between inter-side difference in the severity of PD symptoms (Unified Parkinson's Disease Rating Scale) and interhemispheric map displacement (r=0.60; P=0.018). These findings indicate that there is reorganisation of the corticomotor representation of the hand in PD, even at a relatively early stage of the disease, and suggest a dynamic process of reorganisation in the motor cortex due to an increase in the pallidal inhibitory inputs to the thalamo-cortical projections.

Aged↗

PubMed2006

Paired-pulse rTMS at trans-synaptic intervals increases corticomotor excitability and reduces the rate of force loss during a fatiguing exercise of the hand.

Previous studies have shown that the motor evoked potential (MEP) amplitude increases as force declines during a fatiguing muscle contraction, indicating that there is an increase in corticomotor excitability. In spite of this there is a progressive reduction in voluntary motor drive, as shown by an increase in the interpolated twitch force as fatigue develops. The aim of this study was to determine whether, by further increasing corticomotor excitability using a paired-pulse rTMS protocol designed to induce I-wave facilitation (iTMS), force loss during a sustained voluntary contraction could be reduced. We designed a cross-over study incorporating a 15-min period of iTMS (ISI 1.5 ms; 0.2 Hz; approximately AMT), following which MEP amplitude (first dorsal interosseous muscle) increased to 194 +/- 38% of baseline (P < 0.05), compared to a control period of stimulation that did not increase MEP amplitude (single-pulse TMS; 0.2 Hz; approximately 1.2 AMT). Eight right-handed healthy subjects received both iTMS and control stimulation, in a randomized order, a week apart. We measured percentage force loss at the end of a 10-s maximum right hand key-pinch task, and compared force loss before and after stimulation. There was an improvement in task performance following iTMS, with a reduction in force loss compared to pre-stimulation baseline (11.3 +/- 2.0 vs. 17.6 +/- 2.4%; post vs. pre; P < 0.05). There was no significant difference in force loss before and after control stimulation. The results indicate that by increasing corticomotor excitability using paired-pulse rTMS at trans-synaptic intervals, maximum voluntary force can be sustained at a higher level during a brief fatiguing maximal voluntary contraction.

Action Potentials↗

PubMed2006

Central motor drive and perception of effort during fatigue in multiple sclerosis.

OBJECTIVE: To determine if task performance and fatiguability during repeated low-level contractions of an intrinsic hand muscle differ in a group of MS subjects compared with a control group, and what central changes accompany the development of fatigue and the period of recovery, whether these measures are related to subjective ratings of fatigue or perception of effort. METHODS: Force of index finger abduction, rating of perceived effort, and motor evoked potential amplitude and silent period duration were measured during and after a 20-min. intermittent submaximal (40%) contraction of the first dorsal interosseous muscle in 23 clinically definite MS subjects with mild-moderate symptoms, and 15 controls. RESULTS: Rating of perceived effort increased at a greater rate in the MS group than in control subjects during exercise, and this was associated with larger increases in both MEP amplitude and silent period duration. CONCLUSIONS: Submaximal fatiguing exercise is associated with an enhanced central motor drive and increased perception of effort in MS. SIGNIFICANCE: MS subjects can increase central drive during fatiguing exercise to a greater degree than controls, but this is associated with greater perceived exertion. These factors may underlie the more general complaint of fatigue experienced by people with MS.

Adult↗

PubMed2006

Blinded placebo crossover study of gabapentin in primary orthostatic tremor.

Primary orthostatic tremor (OT) is a rare but disabling condition characterized by leg tremor and feelings of instability during stance. Previous studies have reported a reduction in OT symptoms with gabapentin treatment. In this study, we report on the benefits of gabapentin treatment in a double-blind placebo-controlled crossover study of 6 OT patients. First, the maximally effective gabapentin dosage (600-2,700 mg/day) for each patient was determined during an initial dose-titration phase. Patients were then studied 7 days after drug withdrawal and again after two 2-week periods of treatment with either gabapentin or placebo, using force platform posturography to quantify postural sway and tremor. Other medications for OT were continued unchanged. Symptomatic response was assessed by a patient-rated severity scale and quality of life (QOL) questionnaire. All patients reported an increase in symptoms during the washout phase and symptom reduction (50%-75%) during gabapentin treatment. Tremor amplitude was reduced to 79% +/- 11% and sway area to 71% +/- 11% of the placebo state. QOL improved in all patients, no adverse drug effects were noted, and symptomatic benefit was maintained at follow-up (mean = 19 months). The findings confirm that gabapentin is an effective treatment for OT, reducing both tremor and postural instability and improving quality of life, and support its use as add-on or first-line therapy for OT.

Aged↗

PubMed2006

Differential activation of frontal lobe areas by lexical and semantic language tasks: a functional magnetic resonance imaging study.

To determine whether frontal lobe regions, including Broca's area, dorsolateral prefrontal cortex (DLPFC) and supplementary motor area (SMA), are differentially activated during lexical and semantic language tasks, we used functional magnetic resonance imaging in eight healthy right-handed subjects silently performing two semantic tasks (adjective and verb generation) and a lexical retrieval task (noun recall). Activation was observed in Broca's area, DLPFC and SMA for all tasks. Broca's area activation was approximately doubled during the semantic tasks compared with the lexical task (verbs vs nouns: 19.1+/-4.5 vs 8.9+/-1.6 voxels, p=0.02; adjectives vs nouns 24.4+/-7.5 vs 10.1+/-2.8 voxels, p=0.04); however, there were no significant differences in the DLFPC or SMA across tasks. We conclude that Broca's area is more active during tasks that have a semantic content, whereas areas involved in preparatory processing (SMA) and memory retrieval (DLPFC) are engaged equally during both types of task.

Adult↗

PubMed2005

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.

Adult↗

PubMed2005

Short-interval cortical inhibition and corticomotor excitability with fatiguing hand exercise: a central adaptation to fatigue?

The central processes occurring during fatiguing exercise are not well understood, however transcranial magnetic stimulation (TMS) studies have reported increases both in corticomotor excitability, as measured by the motor-evoked potential (MEP) amplitude, and in long-interval intracortical inhibition, as measured by the duration of the post-MEP silent period. To determine whether short-interval cortical inhibition (SICI) is modulated by fatiguing exercise, we used single and paired-pulse TMS to measure MEP amplitude and SICI for the first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles of the hand during, and for 20 min after, a 10-min intermittent maximal voluntary abduction of the index finger designed to fatigue the FDI muscle. For the FDI, the index of SICI increased at the onset of exercise (from 0.25+/-0.05 to 0.55+/-0.11, P < 0.05) and then decreased progressively as force declined. At the beginning of recovery, SICI again increased (0.57+/-0.11, P < 0.05) and remained elevated for the 20-min recovery period. In contrast, SICI for ADM did not change during or after exercise. MEP amplitude for both the FDI and ADM increased above baseline during exercise and then decreased below baseline during the recovery period. These results demonstrate that there are significant changes in SICI during and after a fatiguing exercise protocol that are isolated to the representation of the fatigued muscle. The inter-relationship between the changes in excitation and inhibition suggests the presence of a measured and adaptive process of modulation in central excitation and inhibition acting to increase corticomotor drive to the exercising muscle as fatigue is developing.

Adaptation, Physiological↗

PubMed2005

Primary sensorimotor cortex activation with task-performance after fatiguing hand exercise.

We have compared functional MRI signals in primary sensorimotor cortex (SM1) during a paced motor task of each hand before and after unimanual (right hand) fatiguing exercise. Our aims were to determine whether the degree of activation is different when a motor task is performed after a fatiguing exercise, and whether there are any differences in activation between movement of the fatigued and non-fatigued hands. There was a significant reduction in the number of voxels activated in SM1 in the hemisphere contralateral to movement of both the fatigued hand (38 +/- 5 pre-exercise versus 21 +/- 3 post-exercise; P<0.05) and the non-fatigued hand (32 +/- 4 pre-exercise vs 18 +/- 4 post-exercise; P<0.05). There was no significant difference in the magnitude of the functional magnetic resonance imaging signal before or after exercise, however, the variance increased significantly after exercise (6.0 +/- 0.5 pre-exercise vs 7.3 +/- 0.6 post-exercise; P<0.01). Reduced functional activation in SM1 may reflect increased variability in the activation rather than a reduction in activation of cortical motor networks after fatigue.

Adult↗

PubMed2005

Corticomotor organisation and motor function in multiple sclerosis.

Our objective was to determine whether there are changes in the corticomotor map for the hand in multiple sclerosis, and whether these changes correlate with indices of motor function and measures of corticomotor conduction or excitability. Transcranial magnetic stimulation (TMS) maps, motor evoked potential (MEP) latency and amplitude, motor threshold and EDSS and Purdue-pegboard measurements were made in 26 subjects with relapsing-remitting multiple sclerosis. Correlations were sought between these measurements using the Pearson product-moment correlation with a level of significance of p = 0.05 (two-tailed). Map displacement was positively correlated with MEP latency (p = 3 x 10(-4)) and EDSS (p = 0.007), and negatively correlated with Purdue score (p = 4 x 10(-4)). Purdue scores correlated with all MEP parameters (latency, p = 4 x 10(-10); threshold, p = 4 x 10(-6); amplitude, p = 0.003). We conclude that motor reorganisation is associated with impaired corticomotor conduction and may reflect a process of neural plasticity associated with axonal demyelination in MS. An understanding of motor function in MS should incorporate models of both axonal demyelination and conduction deficits as well as neural plasticity.

Adult↗

PubMed2005

Primary writing tremor: motor cortex reorganisation and disinhibition.

BACKGROUND: Primary writing tremor (PWT) is a task-specific tremor of uncertain origin. There has been debate as to whether PWT represents a variant of essential tremor or a tremulous form of focal dystonia related to writer's cramp. In writer's cramp there is evidence of changes in intracortical inhibition (ICI), as well as cortical motor reorganisation. OBJECTIVE: To study corticomotor organisation and short-latency ICI in a patient with typical task-specific PWT. METHODS: Transcranial magnetic stimulation mapping of the corticomotor representation of the hand and studies of ICI using paired-pulse stimulation were performed in a 47-year-old right-handed woman with a pure task-specific writing tremor. RESULTS: The motor maps for the hand were displaced posteriorly on both sides and reverted to a normal position after treatment with botulinum toxin. Short-latency ICI was reduced for the dominant hand. CONCLUSION: The findings indicate reorganisation and disinhibition of the corticomotor projection to the hand and point to the participation of cortical centres in the origin of PWT.

Botulinum Toxins, Type A↗

PubMed2004

Motor outcome after subcortical stroke correlates with the degree of cortical reorganization.

OBJECTIVE: The contribution of cortical reorganization to motor recovery after a subcortical stroke is uncertain. The purpose of the study was to investigate the relationship between changes in motor cortex organization, and the degree of motor function after a subcortical stroke. METHODS: Transcranial magnetic stimulation mapping of the corticomotor projection to the hand was performed in 27 patients who had suffered a subcortical ischemic stroke resulting in an upper limb motor deficit up to 23 years previously. Corticospinal conduction was assessed by measurements of motor evoked potential latency, amplitude and threshold. Motor function in the upper limb was assessed using the Motor Assessment Scale for Stroke and measurements of grip strength. RESULTS: Motor maps for the hand were displaced on the affected side relative to the unaffected side in 17 patients. In 10 of these patients in whom corticospinal conduction had normalized, there was a strong positive correlation between the magnitude of the map shift and grip strength in the affected hand (r=0.79; P=0.006). In the other seven patients with a map shift, in whom corticospinal conduction was still impaired, there was a tendency for a larger map area to be associated with better motor function, and in the group as a whole there was a correlation between map area and grip strength (r=0.52; P=0.005). CONCLUSIONS: The present findings provide evidence that the cortical plasticity and reorganization that occurs after a subcortical stroke is functionally significant and contributes to motor outcome.

Adult↗

PubMed2004

Temporal aspects of passive movement-related corticomotor inhibition.

We have previously shown that during rhythmic passive movement of the index finger, the amplitude of the motor evoke potential (MEP) of the first dorsal interosseous muscle (FDI) as the index finger moved through mid-range adduction, is significantly reduced compared to rest [Edwards, D. J., Thickbroom, G. W., Byrnes, M. L., Ghosh, S., & Mastaglia, F. L. (2002). Reduced corticomotor excitability with passive movement: A study using Transcranial Magnetic Stimulation. Human Movement Science 21, 533-540]. In the present study we have investigated the time-course of this phenomenon. We found that MEP amplitude was significantly reduced at the mid-range position in the first cycle of movement (50+/-6% of resting baseline values), and did not vary across subsequent cycles (10 cycles in 50 s), but that MEP amplitude returned to baseline values within 1s of cessation of movement. The results suggest that the pattern of afferent discharge set up by the kinematics of the movement acting at spinal or supraspinal levels underlies the inhibition observed, rather than an effect of central origin or a cumulative effect of ongoing cyclic movement.

Adult↗

PubMed2004

Functional MRI near vascular anomalies: comparison of cavernoma and arteriovenous malformation.

BACKGROUND AND PURPOSE: Mapping of eloquent cortex using blood-oxygen-level-dependent (BOLD) contrast functional MRI (fMRI) has rapidly gained acceptance as part of the evaluation of patients being considered for neurosurgical interventions. The BOLD signal measures local susceptibility in the blood, which can change during periods of increased neuronal activation as a result of alteration in blood flow and cerebral oxygen utilisation. Vascular anomalies could influence the BOLD signal via their effects on both blood flow and susceptibility. METHODS: In the present study we have compared the fMRI signal associated with functional activation near arteriovenous malformations and cavernomas in a group of patients referred for pre-surgical mapping of eloquent cortex. RESULTS: The magnitude of the BOLD signal was not different for the cavernoma group and the AVM group (mean percentage signal change 6.3% vs. 5.5%). For subjects with cavernoma, there was an increase in cavernoma volume on the functional images compared to T1-weighted anatomical images (mean 570%), and a BOLD signal was only detected outside the enlarged cavernoma. CONCLUSION: The findings show that susceptibility effects associated with cavernoma, most likely due to hemosiderin deposition, can result in an apparent increase in the separation between the BOLD signal and the cavernoma itself. This could lead to falsely high levels of surgical confidence during neurosurgical resection. Differential patterns of blood flow associated with cavernoma and AVM do not appear to significantly affect the BOLD signal magnitude.

Adolescent↗

PubMed2003

Reversible reorganisation of the motor cortical representation of the hand in cervical dystonia.

Previous work has suggested that there may be a widespread disturbance of motor control mechanisms in patients with cervical dystonia. In the present study, we used transcranial magnetic stimulation to investigate the topography of the corticomotor projection to the abductor pollicis brevis (APB) muscle in 10 subjects with idiopathic torticollis. Threshold-adjusted stimuli were delivered at multiple scalp sites during a low-level voluntary contraction of the APB, and maps were generated of motor evoked potential amplitude versus scalp site. The cortical maps for the APB on the side opposite to the direction of head rotation were displaced laterally or posteriorly in all subjects and reverted to a more normal position after botulinum toxin injection of the cervical muscles in 5 subjects. The findings point to a reversible reorganisation of the corticomotor representation of the hand on the same side as the sternocleidomastoid (SCM) muscle that is involved in producing the dystonia. These results provide further evidence for the involvement of cortical centres and for a more widespread abnormality of motor control mechanisms in focal dystonia. The findings also support the notion that head turning is chiefly mediated by the hemisphere ipsilateral to the direction of the head rotation by means of a corticomotor projection to the contralateral SCM.

Adult↗

PubMed2003

Dual representation of the hand in the cerebellum: activation with voluntary and passive finger movement.

Early electrophysiological studies during sensory stimulation in the anesthetized cat and more recent functional imaging studies during voluntary movement in humans have provided evidence for two separate representations of the body in the anterior and posterior lobes of the cerebellum; however, the functional role of these body maps in motor and sensory processing is not known. The aims of the present study were to determine whether this dual representation is also present during passive movement, and to compare the pattern of activation with that obtained during voluntary movement. Functional MRI measurements were undertaken in 14 subjects who performed right index finger flexion and extension movements at approximately 1 Hz, or had their finger moved passively at the same rate and through the same angle using a pneumatic device. During passive movement, dual activation was detected in the ipsilateral cerebellum, in the anterior lobe, and in the posterior lobe. A similar pattern of activation was observed during voluntary movement; however, the overall magnitude was about doubled. These data provide evidence for a dual ipsilateral representation of the hand in the rostral and caudal cerebellar cortex during passive as well as voluntary movements, with the rostral representation being the dominant one, and indicate that both of these areas are involved in kinesthetic sensory and motor processing.

Adult↗

PubMed2003

A functional MRI protocol for localizing language comprehension in the human brain.

We describe a functional magnetic resonance imaging (fMRI) protocol to separate activation of areas in the brain associated with language comprehension from sensory areas activated as a result of the presentation of the language stimulus, by comparing cortical activation patterns during the presentation of similar or the same language stimulus via two different sensory modalities (auditory and visual), and identifying the regions of activation that are common to both modalities. The protocol can be implemented on any MR scanner capable of functional imaging, and has proven valuable for the reliable identification of the lateralization and location of language centres in patients being considered for neurosurgical procedures. As well, the method has potential for the study of cortical processing of auditory speech and written language in healthy subjects and in subjects suffering from language disorders.

Acoustic Stimulation↗

PubMed2002

Reduced corticomotor excitability with cyclic passive movement: a study using transcranial magnetic stimulation.

Human voluntary movement involves the integration of kinaesthetic information with efferent motor activity during the planning and execution stages of movement. While much is known of the inhibitory and excitatory effects resulting from activation of specific kinaesthetic sensory receptors, in the present study we employed cyclic passive movement of the index finger in order to activate a range of kinaesthetic receptors in a manner that was intended to correspond to how these receptors might be active during a comparable voluntary movement. We intended to identify how this passive movement protocol might affect the excitability of the corticomotor pathway. During 1 Hz cyclic passive movement of the index finger there was an approximately 60% reduction in the amplitude of the motor evoked response from the first dorsal interosseous muscle. The results of the present study demonstrate that passive movement can have a profound effect on the excitability of the corticomotor pathway.

Adult↗