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Biomedical subjects

Mark Hallett

Publications and source records attributed to Mark Hallett.

At least 73 records · Page 4Linked to original sources
PubMed2004

Exercise-induced dystonia as a preceding symptom of familial Parkinson's disease.

Paroxysmal exercise-induced dystonia can occur with Parkinson's disease (PD), and in rare cases, this can also be the presenting symptom. We report on 2 second cousins (no known consanguinity) who presented with paroxysmal exercise-induced dystonia who later developed clinical features of PD. Although autosomal recessive inheritance was suggested, and the dystonic features further suggest parkin as a possible cause, sequencing for parkin mutations was negative and this family may represent a genetic variant of PD. Further genotype-phenotype studies in this and similar families may give clues to pre-symptomatic symptoms in PD and may reflect a particular phenotype of interest for genetics studies in the future.

Aged↗
PubMed2004

Levodopa in the treatment of Parkinson's disease: current controversies.

Levodopa is the most effective symptomatic agent in the treatment of Parkinson's disease (PD) and the "gold standard" against which new agents must be compared. However, there remain two areas of controversy: (1) whether levodopa is toxic, and (2) whether levodopa directly causes motor complications. Levodopa is toxic to cultured dopamine neurons, and this may be a problem in PD where there is evidence of oxidative stress in the nigra. However, there is little firm evidence to suggest that levodopa is toxic in vivo or in PD. Clinical trials have not clarified this situation. Levodopa is also associated with motor complications. Increasing evidence suggests that they are related, at least in part, to the short half-life of the drug (and its potential to induce pulsatile stimulation of dopamine receptors) rather than to specific properties of the molecule. Treatment strategies that provide more continuous stimulation of dopamine receptors provide reduced motor complications in MPTP monkeys and PD patients. These studies raise the possibility that more continuous and physiological delivery of levodopa might reduce the risk of motor complications. Clinical trials to test this hypothesis are underway. We review current evidence relating to these areas of controversy.

Antiparkinson Agents↗
PubMed2004

Identifying true brain interaction from EEG data using the imaginary part of coherency.

OBJECTIVE: The main obstacle in interpreting EEG/MEG data in terms of brain connectivity is the fact that because of volume conduction, the activity of a single brain source can be observed in many channels. Here, we present an approach which is insensitive to false connectivity arising from volume conduction. METHODS: We show that the (complex) coherency of non-interacting sources is necessarily real and, hence, the imaginary part of coherency provides an excellent candidate to study brain interactions. Although the usual magnitude and phase of coherency contain the same information as the real and imaginary parts, we argue that the Cartesian representation is far superior for studying brain interactions. The method is demonstrated for EEG measurements of voluntary finger movement. RESULTS: We found: (a) from 5 s before to movement onset a relatively weak interaction around 20 Hz between left and right motor areas where the contralateral side leads the ipsilateral side; and (b) approximately 2-4 s after movement, a stronger interaction also at 20 Hz in the opposite direction. CONCLUSIONS: It is possible to reliably detect brain interaction during movement from EEG data. SIGNIFICANCE: The method allows unambiguous detection of brain interaction from rhythmic EEG/MEG data.

Algorithms↗
PubMed2004

Perceived effort in force production as reflected in motor-related cortical potentials.

OBJECTIVE: The perceived effort in force production was investigated in a series of experiments where subjects performed isometric force tasks with the index finger while the nominal force, the rate of force development and signal gain were controlled and rating of effort for each task was obtained. The hypotheses tested were that: (1) force-related perceived effort may selectively influence the amplitude of motor-related cortical potentials (MRCP); and (2) the MRCP may directly reflect the intensity of perceived effort associated with force production. METHODS: The force trace was displayed on a computer monitor using various control-gains so that the perceived effort matched or was at odds with actual muscular effort applied to the load cell to accomplish the task. The MRCP were extracted from continuous EEG records using averaging techniques. RESULTS: The findings showed that: (1) perceived effort proportionally increased with the increment of rate of force development and force error, but not with the actual force level; (2) the amplitude of the MRCP increased when a large amount of force was accompanied by an increased rate of force development; (3) the amplitude of early components of MRCP preceding the force initiation (MP-100 to 0) increased as a function of anticipated effort, whereas, the amplitude movement-monitoring potentials (MMP) accompanying the force production increased as a function of actual force level. CONCLUSIONS: The findings from this study provide additional insight clarifying the distinct patterns of EEG activity exhibited under various degrees of perceived effort associated with force output. The findings support the hypothesis that the early components of MRCP may reflect the perceived effort associated with achieving the required force level. SIGNIFICANCE: The results from this study may be considered in the larger context of physical activity in terms of importance of perceived effort during prescribed exercise in rehabilitation programs.

Adult↗
PubMed2004

Neuronal activity in the basal ganglia and thalamus in patients with dystonia.

OBJECTIVE: To explore the role of abnormal neuronal activity in the basal ganglia and thalamus in the generation of dystonia. METHODS: Microelectrode recording was performed in the globus pallidus internus (GPi), ventral thalamic nuclear group ventral oral posterior/ventral intermediate, Vop/Vim) and subthalamic nucleus (STN) in patients with primary dystonia (n=11) or secondary dystonia (n=9) during surgery. Electromyogram (EMG) was simultaneously recorded in selected muscle groups. Single unit analysis and cross-correlations were carried out. RESULTS: Three hundred and sixty-seven neurons were obtained from 29 trajectories (GPi: 13; Vop/Vim: 12; STN: 4), 87% exhibited altered neuronal activity including grouped discharges in GPi (n=79) and STN (n=37), long-lasting neuronal activity (n=70) and rapid neuronal discharge (n=86) in Vop/Vim. There were neurons in Vop, GPi and STN firing at the same frequency as EMG during dystonia (mean: 0.39 Hz, range 0.12-0.84 Hz). Significant correlations between neuronal activity and EMG at the frequency of dystonia were obtained (GPi: r2=0.7 (n=31), Vop/Vim: r2=0.64 (n=18) and STN: r2=0.86 (n=17)). CONCLUSIONS: Consistent with previous findings of abnormalities observed in Vop/VIM and GPi in relation to dystonia, the present data further show that the altered activity in GPi, specifically in dorsal subregions of GPi, Vop/Vim and STN is likely to be directly involved in the production of dystonic movement. Dystonia-related neuronal activity observed in motor thalamus and basal ganglia nuclei of GPi and STN indicates a critical role of their interactions affecting both indirect and direct pathways in the development of either generalized or focal dystonia. SIGNIFICANCE: These data support a central role of the basal ganglia in producing dystonic movements.

Adolescent↗
PubMed2004

Regional cerebral blood flow correlates of the severity of writer's cramp symptoms.

UNLABELLED: Writer's cramp is a type of idiopathic focal dystonia with incompletely understood pathophysiology. Recent studies provide evidence that one element might be a sensory processing defect. We performed a PET study with O(15) H(2)O to find out in which brain areas activity correlates with the severity of writer's cramp symptoms. METHODS: We studied 10 patients with writer's cramp and 10 age- and gender-matched control subjects. There were seven conditions, each repeated twice: rest, writing, tapping with index finger for 2, 3, 4, and 5 min. For each scan, we obtained EMG recordings from the flexor digitorum superficialis (FDS), extensor indicis proprius (EIP) muscles, and a subjective score of severity of dystonia. Scans were realigned, normalized, smoothed, and analyzed using SPM99. Analysis included both intra- and intergroup comparisons and a correlation analysis where we used EMG recordings and subjective dystonia score as covariates. RESULTS: Random effect analysis of the writing task showed overactivity of the primary sensory cortex and no significant underactivity. Correlation analysis of dystonia patients showed activation of SI when we used the subjective dystonia score as a covariate, and activation of both the SI and primary motor cortex when the normalized EMG score of FDS was used. CONCLUSION: While some overactivity of MI is not surprising, overactivity of SI is more dramatic and suggests a primary deficit in processing sensory feedback. Writer's cramp may arise in part as a dysfunction of sensory circuits, which causes defective sensorimotor integration resulting in co-contractions of muscles and overflow phenomena.

Adult↗
PubMed2004

A shared neural network for simple reaction time.

Simple reaction time, a simple model of sensory-to-motor behavior, has been extensively investigated and its role in inferring elementary mental organization has been postulated. However, little is known about the neuronal mechanisms underlying it. To elucidate the neuronal substrates, functional magnetic resonance imaging (fMRI) signals were collected during a simple reaction task paradigm using simple cues consisting of different modalities and simple triggered movements executed by different effectors. We hypothesized that a specific neural network that characterizes simple reaction time would be activated irrespective of the input modalities and output effectors. Such a neural network was found in the right posterior superior temporal cortex, right premotor cortex, left ventral premotor cortex, cerebellar vermis, and medial frontal gyrus. The right posterior superior temporal cortex and right premotor cortex were also activated by different modality sensory cues in the absence of movements. The shared neural network may play a role in sensory triggered movements.

Adult↗
PubMed2004

Motor evoked potentials.

Noninvasive electrical stimulation of the human brain first was attempted in the 1950s. In the early 1980s, the first clinical application method of transcranial electrical stimulation was developed. Investigators in the mid-1980s showed that it was possible to stimulate the nerve and the brain using external magnetic stimulation (transcranial magnetic stimulation [TMS]), with little or no pain. TMS now is used commonly in clinical neurology to study central motor conduction time. Depending on the stimulation techniques and parameters, TMS can excite or inhibit brain activity, allowing functional mapping of cortical regions and creation of transient functional lesions. It now is used widely as a research tool to study aspects of human brain physiology, including motor function and the pathophysiology of various brain disorders.

Brain↗
PubMed2003

Effects of botulinum toxin on motor system excitability in patients with writer's cramp.

OBJECTIVE: To investigate botulinum toxin (BTX) effects on central and peripheral motor excitability in writer's cramp. METHODS: Using transcranial magnetic stimulation over the motor cortex and brainstem and peripheral electrical stimulation, the authors investigated measures of motor cortical and peripheral motor excitability on the affected and unaffected side before and 2 to 4 weeks after BTX A injection into the affected muscles in six patients with writer's cramp. The following motor excitability measures were studied: resting and active motor threshold, cortical silent period, intracortical inhibition and facilitation using the double-pulse technique, recruitment curves, motor evoked potentials following magnetic brainstem stimulation, and maximum M-response amplitude following supramaximal peripheral nerve stimulation. RESULTS: BTX injection improved function and reduced the M response. No other measures of motor system excitability showed significant changes following BTX injection, and there was no difference in these measures between sides. CONCLUSIONS: BTX A effects on motor system excitability seem to be based mainly on its peripheral mechanisms of action. There was no difference in the motor system excitability between the clinically affected and unaffected sides in this group of patients.

Adult↗
PubMed2003

How self-initiated memorized movements become automatic: a functional MRI study.

We used functional magnetic resonance imaging (fMRI) and dual tasks to investigate the physiology of how movements become automatic. Normal subjects were asked to practice some 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. Our secondary task was a letter-counting task where subjects were asked to identify the number of times a target letter from the letter sequences was seen. Only the performances that achieved high accuracy in both single and dual tasks were considered automatic. The fMRI results before and after automaticity was achieved were compared. Our data showed that for both conditions, sequential movements activated similar brain regions. No additional activity was observed in the automatic condition. There was less activity in bilateral cerebellum, presupplementary motor area, cingulate cortex, left caudate nucleus, premotor cortex, parietal cortex, and prefrontal cortex during the automatic stage. These findings suggest that most of the motor network participates in executing automatic movements and that it becomes more efficient as movements become more automatic. Our results do not provide evidence for any area to become more activated for automatic movements.

Adult↗
PubMed2003

Anti-ganglioside antibodies in idiopathic and hereditary cerebellar degeneration.

Cerebellar degeneration has been associated with gluten sensitivity and celiac disease. Patients with celiac disease may have neuropathy and antibodies to gangliosides. The authors investigated the presence of antiganglioside antibodies in 22 patients with hereditary and nonhereditary ataxia and found 64% reactive in a novel agglutination test.

Aged↗
PubMed2003

Evaluation of essential tremor with multi-voxel magnetic resonance spectroscopy.

The pathologic substrate of essential tremor (ET) remains unknown. The authors studied 10 patients with ET and 10 volunteers using a multislice MR spectroscopy imaging sequence. Left and right cerebellar hemisphere NAA/CR and NAA/Cho ratios were significantly smaller in the ET patients than healthy subjects. The authors' data suggest that the decreased NAA/Cr and NAA/Cho ratios within the cerebellum may represent an abnormality in neuronal function.

Adult↗
PubMed2003

Interference with vision by TMS over the occipital pole: a fourth period.

We investigated the effect of single-pulse transcranial magnetic stimulation (TMS) over the occipital pole on a forced-choice visual letter-identification task. Magnetic stimuli were applied on the midline but with the initial current directed pseudorandomly toward either left or right hemisphere; visual stimuli were presented randomly in either left or right hemifield; magnetic-visual stimulus onset asynchrony varied randomly between 12 values: -500 ms and from -50 ms to +50 ms in 10 ms steps. The data revealed the existence of a hitherto unknown fourth task-interfering TMS effect that was maximal at -10 ms and specific for magnetic stimulus polarity and visual stimulus location. This -10 ms effect cannot be explained by reflex blinking (as the -50 ms effect can) and direct disruption of letter-induced activity (as the +20 ms and +100 ms effects can), but it could be explained by direct disruption of pre-letter activity or indirect disruption of letter-induced activity.

Adult↗
PubMed2003

Contribution of the ipsilateral motor cortex to recovery after chronic stroke.

It has been proposed that the intact (ipsilateral) motor cortex play a significant role mediating recovery of motor function in the paretic hand of chronic stroke patients, but this hypothesis has not been tested experimentally. Here, we evaluated the effects of transcranial magnetic stimulation (TMS) on motor performance of the paretic hand of chronic stroke patients and healthy controls. We hypothesized that, if activity in the intact hemisphere contributes to functional recovery, TMS should result in abnormal motor behavior in the paretic hand. We found that stimulation of the intact hemisphere resulted in delayed simple reaction times (RTs) in the contralateral healthy but not in the ipsilateral paretic hand, whereas stimulation of the lesioned hemisphere led to a marked delay in RT in the contralateral paretic hand but not in the ipsilateral healthy hand. RT delays in the paretic hand correlated well with functional recovery. Finger tapping in the paretic hand was affected by TMS of the lesioned but not the intact hemisphere. These results are consistent with the idea that recovered motor function in the paretic hand of chronic stroke patients relies predominantly on reorganized activity within motor areas of the affected hemisphere.

Adult↗
PubMed2003

Sensory training as treatment for focal hand dystonia: a 1-year follow-up.

In a prior study, 10 patients with focal hand dystonia learned braille reading as sensory training for 8 weeks. Practice time was 30 to 60 minutes daily. They improved both their spatial acuity using the Grating Orientation Discrimination Task (GOT) and their dystonia using the Fahn scale. Three patients continued training for 1 year. Patients showed further improvement in the GOT, writing a standard paragraph, and self-rating scales. Sensory training lasting longer than 8 weeks may lead to continued improvement.

Discrimination Learning↗
PubMed2003

Effect of ethanol on the central oscillator in essential tremor.

We investigated the effects of ethanol and diazepam on the central, mechanical, and mechanical reflex components of tremor in patients with essential tremor (ET). A double-blind crossover study (ethanol or diazepam) was conducted on 2 separate days. Dose of ethanol or diazepam was calculated in each individual according to height, weight, and age in 10 patients with ET. The postural tremor amplitude at the wrist was recorded using a three-dimensional accelerometer placed on the dorsum of the hand. Electromyogram (EMG) was recorded with surface electrodes placed on the forearm extensors and flexors. To separate central and mechanical (reflex) components, a 500-g weight was placed on the dorsum of the hand during a second tremor measurement. Tremor recordings were done at baseline and 30, 60, 90, and 120 minutes after drug ingestion. Ethanol and diazepam blood levels were measured at baseline and after 20, 40, 80, and 120 minutes. Blood ethanol and diazepam levels were highest after 40 and 80 minutes. The amplitude of the central component 60 minutes after ingestion of ethanol was decreased significantly (P = 0.029) compared with diazepam. Our findings suggest that the improvement in tremor after ethanol ingestion was due, at least in part, to an effect on a central oscillator.

Biological Clocks↗
PubMed2003

Power grip disinhibits the ipsilateral sensorimotor cortex: a TMS and fMRI study.

Electrophysiological studies have shown that forceful activation of the hand muscles (power grip) is accompanied by an increased excitability of the ipsilateral corticospinal system. This increase in excitability may be due to spinal or cortical mechanisms. Here we show with fMRI that this phenomenon is at least in part mediated at a cortical level. We used TMS to show that the increased ipsilateral excitability during a forceful maneuver leads to enhanced stimulus-response curves. fMRI was used to compare the activation during a repetitive hand movement with or without an accompanying power grip on the opposite site. The power grip reduced movement-related activation in the ipsilateral sensorimotor cortex. Peak deactivation was located in the left postcentral gyrus extending into the adjacent precentral gyrus. This finding suggests that a forceful activation of the hand muscles disinhibits a distinct functional representation in the ipsilateral sensorimotor cortex. Consequently, the excitability of the corticospinal system increases and less neuronal excitatory activity is needed to perform a given task. The results may be important for a variety of studies as they suggest that fMRI may show decreased hemodynamic response under conditions in which other neurophysiological methods have shown increased functional activity.

Brain Mapping↗