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Biomedical subjects

Mark Hallett

Publications and source records attributed to Mark Hallett.

At least 55 records · Page 3Linked to original sources

Task-dependent intracortical inhibition is impaired in focal hand dystonia.

We tested whether task-dependent modulation of inhibition within the motor cortex is impaired in patients with dystonia. Paired-pulse transcranial magnetic stimulation (TMS) at an interstimulus interval of 2 msec was used to measure the effect of two different tasks on short ISI intracortical inhibition (SICI) in dystonic and normal subjects. In two experiments, SICI of the fourth dorsal interosseus (4DIO) and abductor pollicis brevis (APB) muscles were measured before and at the end of the training task. In the first experiment, subjects performed a nonselective task consisting of abducting the thumb, where the APB acted as agonist and the 4DIO as synergist. In the second experiment, the function of the 4DIO was changed as the subjects were asked to consciously inhibit this muscle while abducting the thumb (selective task). Therefore, while the APB was activated in both tasks, the 4DIO was activated in the nonselective task but was in the inhibitory surround in the selective task. We found that performance of the selective but not the nonselective task resulted in increased SICI in the 4DIO of normal but not in dystonic subjects. We conclude that task-dependent SICI is disturbed in patients with dystonia.

Dystonic Disorders↗

Resolution and reproducibility of BOLD and perfusion functional MRI at 3.0 Tesla.

Visual and somatosensory activation studies were performed on normal subjects to compare the spatial discrimination and reproducibility between functional MRI (fMRI) methods based on blood oxygen level-dependent (BOLD) and perfusion contrast. To allow simultaneous measurement of BOLD and perfusion contrast, a dedicated MRI acquisition technique was developed. Repeated experiments of sensory stimulation of single digits of the right hand showed an average variability of activation amplitude of 25% for BOLD data, and a significantly lower variability of 21% for perfusion data. No significant difference in the variability of the locus of activity was observed between the BOLD and perfusion data. In somatotopy experiments, digits II and V were subjected to passive sensory stimulation. Both the BOLD and perfusion data showed substantial overlap in the activation patterns from the two digits. In a retinotopy study, two stimuli were alternated to excite different patches of V1. Again there was substantial overlap between the activation patterns from both stimuli, although the perfusion performed somewhat better than the BOLD method. Particularly for the visual studies, the overlap in activation patterns was more than expected based on the fine-scale retinotopic mapping of cortical activity, suggesting that both BOLD and perfusion contrast mechanisms contribute substantially to the point-spread function (PSF).

Adult↗

Electrophysiological studies of myoclonus.

As myoclonus is often associated with abnormally increased excitability of cortical structures, electrophysiological studies provide useful information for its diagnosis and classification, and about its generator mechanisms. The electroencephalogram-electromyogram polygraph reveals the most important information about the myoclonus of interest. Jerk-locked back-averaging and evoked potential studies combined with recording of the long-latency, long-loop reflexes are useful to investigate the pathophysiology of myoclonus further, especially that of cortical myoclonus. Recent advances in magnetoencephalography and transcranial magnetic stimulation have contributed significantly to the understanding of some of the cortical mechanisms underlying myoclonus. Elucidation of physiological mechanisms underlying myoclonus in individual patients is important for selecting the most appropriate treatment.

Action Potentials↗

Cortical reorganization and associated functional motor recovery after virtual reality in patients with chronic stroke: an experimenter-blind preliminary study.

OBJECTIVE: To investigate the effects of virtual reality (VR) on cortical reorganization and motor recovery. DESIGN: Nonparametric pre- and posttest design with experimenter blinded. SETTING: University medical center. PARTICIPANTS: Five patients with hemiparesis (age, 59.8+/-3.4y) were recruited. INTERVENTION: Five patients received VR for 60 minutes a day, 5 times a week for 4 weeks. VR was designed to provide a virtual rehabilitation scene where the intensity of practice and sensory feedback could be systematically manipulated to provide the most appropriate, individualized motor retraining program. MAIN OUTCOME MEASURES: Cortical activation and associated motor recovery were measured before and after VR using functional magnetic resonance imaging and standardized motor tests, respectively. Nonparametric tests were used at P less than .05. RESULTS: Prior to VR, the bilateral primary sensorimotor cortices (SM1s), contralesional premotor cortex, and contralesional or ipsilesional supplementary motor area were activated. After VR, the altered activations disappeared and predominantly the ipsilesional SM1 was activated (P<.05). Motor function was improved (P<.05). CONCLUSIONS: This is a novel demonstration of VR-induced neuroplastic changes and associated motor recovery in chronic stroke.

Adult↗

Temporal activation pattern of parietal and premotor areas related to praxis movements.

OBJECTIVE: We sought to determine the cortical physiology underlying praxis movements in normal subjects using electroencephalography (EEG). METHODS: Eight normal subjects were instructed to perform six types of self-paced tool-use pantomime and communicative gesture movements with the right hand. We recorded 64-channel EEG using a linked ear reference and electromyogram (EMG) from right thumb and forearm flexors. RESULTS: Data revealed early slow wave components of the movement-related cortical potential (MRCP) beginning over the left parietal area about 3s before movement onset, similarly for both movement types. At movement onset, maximal amplitude was present over central and bilateral sensorimotor areas. Event-related desynchronization (ERD) in the beta band was seen over the left parietal and sensorimotor cortices during preparation, later spreading to the homologous area of the right hemisphere. Alpha ERD was mainly in the left sensorimotor cortex about 1.5s before movement onset. Beta ERD in mesial frontal areas was greater during preparation for tool use compared to communicative gesture movements. Mesial frontal beta event-related synchronization (ERS) developed more rapidly after communicative gestures than tool-use. CONCLUSIONS: The dynamics of parietal and frontal activities indicates the timing of these areas in the production of praxis. The posterior parietal cortex contributes to the early slow wave negativity of the MRCP. SIGNIFICANCE: Planning self-paced praxis movements begins as early as 3s before movement in the left parietal area and subsequently engages frontal cortical regions.

Adult↗

Asymmetric spatiotemporal patterns of event-related desynchronization preceding voluntary sequential finger movements: a high-resolution EEG study.

OBJECTIVE: To study spatiotemporal patterns of event-related desynchronization (ERD) preceding voluntary sequential finger movements performed with dominant right hand and nondominant left hand. METHODS: Nine subjects performed self-paced movements consisting of three key strokes with either hand. Subjects randomized the laterality and timing of movements. Electroencephalogram (EEG) was recorded from 122 channels. Reference-free EEG power measurements in the beta band were calculated off-line. RESULTS: During motor preparation (-2 to -0.5s with respect to movement onset), contralateral preponderance of event-related desynchronization (ERD) (lateralized power) was only observed during right hand finger movements, whereas ERD during left hand finger movements was bilateral. CONCLUSIONS: For right-handers, activation on the left hemisphere during left hand movements is greater than that on the right hemisphere during right hand movements. SIGNIFICANCE: We provide further evidence for motor dominance of the left hemisphere in early period of motor preparation for complex sequential finger movements.

Adult↗

Cortical reorganization induced by virtual reality therapy in a child with hemiparetic cerebral palsy.

Virtual reality (VR) therapy is a new, neurorehabilitation intervention aimed at enhancing motor performance in children with hemiparetic cerebral palsy (CP). This case report investigated the effects of VR therapy on cortical reorganization and associated motor function in an 8-year-old male with hemiparetic CP. Cortical activation and associated motor development were measured before and after VR therapy using functional magnetic resonance imaging (fMRI) and standardized motor tests. Before VR therapy, the bilateral primary sensorimotor cortices (SMCs) and ipsilateral supplementary motor area (SMA) were predominantly activated during affected elbow movement. After VR therapy, the altered activations disappeared and the contralateral SMC was activated. This neuroplastic change was associated with enhanced functional motor skills including reaching, self-feeding, and dressing. These functions were not possible before the intervention. To our knowledge, this is the first fMRI study in the literature that provides evidence for neuroplasticity after VR therapy in a child with hemiparetic CP.

Activities of Daily Living↗

Cortical reorganization associated lower extremity motor recovery as evidenced by functional MRI and diffusion tensor tractography in a stroke patient.

PURPOSE: Recovery mechanisms supporting upper extremity motor recovery following stroke are well established, but cortical mechanism associated with lower extremity motor recovery is unknown. The aim of this study was to assess cortical reorganization associated with lower extremity motor recovery in a hemiparetic patient. METHODS: Six control subjects and a 17 year-old woman with left intracerebral hemorrhage due to an arterio-venous malformation rupture were evaluated. The motor function of the paretic (left) hip and knee had recovered slowly to the extent of her being able to overcome gravity for 10 months after the onset of stroke. However, her paretic upper extremity showed no significant motor recovery. Blood oxygenation level dependent (BOLD) functional MRI at 1.5 Tesla was used to determine the acutual location of cortical activation in the predefined regions of interest. Concurrently, Diffusion Tensor Imaging (DTI) in combination with a novel 3D-fiber reconstruction algorithm was utilized to investigate the pattern of the corticospinal pathway connectivity between the areas of the motor stream. All subjects' body parts were secured in the scanner and performed a sequential knee flexion-extension with a predetermined angle of 0-60 degrees at 0.5 Hz. RESULTS: Controls showed anticipated activation in the contralateral sensorimotor cortex (SM1) and the descending corticospinal fibers stemming from motor cortex. In contrast to control normal subjects, the stroke patient showed fMRI activation only in the unaffected (right) primary SM1 during either paretic or nonparetic knee movements. DTT fiber tracing data showed that the corticospinal tract fibers were found only in the unaffected hemisphere but not in the affected hemisphere. CONCLUSIONS: Our results indicate that an ipsilateral motor pathway from the unaffected (right) motor cortex to the paretic (right) leg was present in this patient. This study raises the potential that the contralesional (ipsilateral) SM1 is involved in cortical reorganization associated lower extremity motor recovery in stroke. This study is the first neuroimaging evidence that the combined fMRI and DTI fiber tracing can significantly expand the explanatory power of probing cortical reorganization underlying motor recovery mechanism in stroke.

Adolescent↗

Finger and face representations in the ipsilateral precentral motor areas in humans.

Several human neuroimaging studies have reported activity in the precentral gyrus (PcG) ipsilateral to the side of hand movements. This activity has been interpreted as the part of the primary motor cortex (M1) that controls bilateral or ipsilateral hand movements. To better understand hand ipsilateral-PcG activity, we performed a functional MRI experiment in eight healthy right-handed adults. Behavioral tasks involved hand or lower face movements on each side or motor imagery of the same movements. Consistent with the known M1 organization, the hand contralateral-PcG activity was centered at the "hand-knob" portion of the PcG; face contralateral-PcG activity was localized ventrolateral to it. Hand ipsilateral-PcG activity was identified in most subjects. However, converging results indicated that this ipsilateral PcG activity was situated in Brodmann's area 6 in both hemispheres. The hand ipsilateral-PcG zones were active not only during hand movements but also face movements. Moreover, the hand ipsilateral-PcG zones revealed substantial imagery-related activity, which also failed to differentiate the hand and face. Statistical analyses confirmed poor effector selectivity of the hand ipsilateral PcG activity during both movement and imagery tasks. From these results, we conclude that the hand ipsilateral-PcG activity in healthy adults probably corresponds to a part of the ventral premotor cortex. In contrast, available evidence suggests that M1 contributes to controlling the ipsilateral hand in children and patients after stroke recovery. It appears that within the human PcG, there are two parallel systems potentially capable of controlling ipsilateral hand movements: ventral premotor cortex and M1. These two systems may be differentially influenced by developmental or pathologic changes.

Acoustic Stimulation↗

Transcranial magnetic stimulation of deep brain regions: evidence for efficacy of the H-coil.

OBJECTIVE: Standard coils used in research and the clinic for noninvasive magnetic stimulation of the human brain are not capable of stimulating deep brain regions directly. As the fields induced by these coils decrease rapidly as a function of depth, only very high intensities would allow functional stimulation of deep brain regions and such intensities would lead to undesirable side effects. We have designed a coil based on numerical simulations and phantom brain measurements that allows stimulation of deeper brain regions, termed the Hesed coil (H-coil). In the present study we tested the efficacy and some safety aspects of the H-coil on healthy volunteers. METHODS: The H-coil was compared to a regular figure-8 coil in 6 healthy volunteers by measuring thresholds for activation of the abductor pollicis brevis (APB) representation in the motor cortex as a function of distance from each of the coils. RESULTS: The rate of decrease in the coil intensity as a function of distance is markedly slower for the H-coil. The motor cortex could be activated by the H-coil at a distance of 5.5 cm compared to 2 cm with the figure-8 coil. CONCLUSIONS: The present study indicate that the H-coil is likely to have the ability of deep brain stimulation and without the need of increasing the intensity to extreme levels that would cause a much greater stimulation in cortical regions. SIGNIFICANCE: The ability of non-invasive deep brain stimulation potentially opens a wide range of both research and therapeutic applications.

Adult↗

The influence of normal human ageing on automatic movements.

There is evidence that aged normal subjects have more difficulty in achieving automaticity than young subjects. The underlying central neural mechanism for this phenomenon is unclear. In the present study, functional magnetic resonance imaging (fMRI) was used to investigate the effect of normal ageing on automaticity. Aged healthy subjects were asked to practice self-initiated, self-paced, memorized sequential finger movements with different complexity until they could perform the tasks automatically. Automaticity was evaluated by having subjects perform a secondary task simultaneously with the sequential movements. Although it took more time, most aged subjects eventually performed the tasks automatically at the same level as the young subjects. Functional MRI results showed that, for both groups, sequential movements activated similar brain regions before and after automaticity was achieved. No additional activity was observed in the automatic condition. While performing automatic movements, aged subjects had greater activity in the bilateral anterior lobe of cerebellum, premotor area, parietal cortex, left prefrontal cortex, anterior cingulate, caudate nucleus and thalamus, and recruited more areas, including the pre-supplementary motor area and the bilateral posterior lobe of cerebellum, compared to young subjects. These results indicate that most healthy aged subjects can perform some complex motor tasks automatically. However, aged subjects appear to require more brain activity to perform automatically at the same level as young subjects. This appears to be the main reason why aged subjects have more difficulty in achieving automaticity.

Adult↗

Corticospinal disinhibition during dual action.

When attempting to perform two tasks simultaneously, the human motor as well as the cognitive system shows interference. Such interference often causes altered activation of the cortical area representing each task compared to the single task condition. We investigated changes in corticospinal inhibition during dual action by transcranial magnetic stimulation (TMS). Single-pulse TMS was applied to the left motor cortex, triggered by right leg movement (tibialis anterior muscle) while the right abductor digiti minimi (ADM) muscle was moderately activated (10-20% of the maximal voluntary contraction). The background electromyography (EMG) activity of ADM was measured before and during the leg movement. The silent period (SP) and amplitude of motor evoked potential (MEP) following magnetic stimulation in active ADM were compared for the conditions with and without leg movement. The mean area of the rectified EMG activity of ADM did not alter, while the SP was significantly shortened during leg movement compared to that without leg movement. MEP amplitude was comparable between the two conditions. These results suggest that corticospinal inhibition tested by the SP duration is reduced during the movement of another body part, presumably in order to help maintain muscle force by compensating interference-related alteration in motor cortical activation.

Adult↗

Effect of transcranial magnetic stimulation on bimanual movements.

Transcranial magnetic stimulation (TMS) of the motor cortex can interrupt voluntary contralateral rhythmic limb movements. Using the method of "resetting index" (RI), our study investigated the TMS effect on different types of bimanual movements. Six normal subjects participated. For unimanual movement, each subject tapped either the right or left index finger at a comfortable rate. For bimanual movement, index fingers of both hands tapped in the same (in-phase) direction or in the opposite (antiphase) direction. TMS was applied to each hemisphere separately at various intensities from 0.5 to 1.5 times motor threshold (MT). TMS interruption of rhythm was quantified by RI. For the unimanual movements, TMS disrupted both contralateral and ipsilateral rhythmic hand movements, although the effect was much less in the ipsilateral hand. For the bimanual in-phase task, TMS could simultaneously reset the rhythmic movements of both hands, but the effect on the contralateral hand was less and the effect on the ipsilateral hand was more compared with the unimanual tasks. Similar effects were seen from right and left hemisphere stimulation. TMS had little effect on the bimanual antiphase task. The equal effect of right and left hemisphere stimulation indicates that neither motor cortex is dominant for simple bimanual in-phase movement. The smaller influence of contralateral stimulation and the greater effect of ipsilateral stimulation during bimanual in-phase movement compared with unimanual movement suggest hemispheric coupling. The antiphase movements were resistant to TMS disruption, and this suggests that control of rhythm differs in the 2 tasks. TMS produced a transient asynchrony of movements on the 2 sides, indicating that both motor cortices might be downstream of the clocking command or that the clocking is a consequence of the 2 hemispheres communicating equally with each other.

Adult↗

Surround inhibition in human motor system.

In sensory systems, a neural mechanism called surround inhibition (SI) sharpens sensation by creating an inhibitory zone around the central core of activation. In the motor system, the functional operation of SI remains to be demonstrated, although it has been hypothesized to contribute to the selection of voluntary movements. Here we test this hypothesis by using transcranial magnetic stimulation of the human motor cortex. The motor evoked potential of the little finger muscle is suppressed or unchanged during self-paced, voluntary movements of the index finger, mouth or leg, despite an increase in spinal excitability. This result indicates that motor excitability related to little finger movement is suppressed at the supraspinal level during these movements, and supports the idea that SI is an organizational principle of the motor system.

Adult↗

Changes in brain anatomy in focal hand dystonia.

No consistent cerebral anatomical abnormality has ever been reported in primary focal hand dystonia (FHD). The present voxel-based morphometry study showed a significant bilateral increase in gray matter in the hand representation area of primary somatosensory and, to a lesser extent, primary motor cortices in 36 patients with unilateral FHD compared with 36 controls. The presence of anatomical changes in the perirolandic cortex for the unaffected hand as well as that for the affected hand suggests that these disturbances may be, at least in part, primary.

Adult↗

Disturbed surround inhibition in focal hand dystonia.

Disturbances in surround inhibition could account for various movement disorders. Here we test the functional operation of surround inhibition in focal hand dystonia. Transcranial magnetic stimulation was set to be triggered by self-initiated voluntary flexion of the index finger. During this movement, motor-evoked potential amplitudes from the little finger muscle were significantly suppressed in healthy subjects but enhanced in dystonia patients. This result supports the idea that disturbed surround inhibition is a principal pathophysiological mechanism of dystonia.

Aged↗