Showing papers by "Mark Hallett published in 1999"

Feedforward ankle strategy of balance during quiet stance in adults

Abstract: 1. We studied quiet stance investigating strategies for maintaining balance. Normal subjects stood with natural stance and with feet together, with eyes open or closed. Kinematic, kinetic and EMG data were evaluated and cross-correlated. 2. Cross-correlation analysis revealed a high, positive, zero-phased correlation between anteroposterior motions of the centre of gravity (COG) and centre of pressure (COP), head and COG, and between linear motions of the shoulder and knee in both sagittal and frontal planes. There was a moderate, negative, zero-phased correlation between the anteroposterior motion of COP and ankle angular motion. 3. Narrow stance width increased ankle angular motion, hip angular motion, mediolateral sway of the COG, and the correlation between linear motions of the shoulder and knee in the frontal plane. Correlations between COG and COP and linear motions of the shoulder and knee in the sagittal plane were decreased. The correlation between the hip angular sway in the sagittal and frontal planes was dependent on interaction between support and vision. 4. Low, significant positive correlations with time lags of the maximum of cross-correlation of 250-300 ms were found between the EMG activity of the lateral gastrocnemius muscle and anteroposterior motions of the COG and COP during normal stance. Narrow stance width decreased both correlations whereas absence of vision increased the correlation with COP. 5. Ankle mechanisms dominate during normal stance especially in the sagittal plane. Narrow stance width decreased the role of the ankle and increased the role of hip mechanisms in the sagittal plane, while in the frontal plane both increased. 6. The modulation pattern of the lateral gastrocnemius muscle suggests a central program of control of the ankle joint stiffness working to predict the loading pattern.

Modality-specific frontal and parietal areas for auditory and visual spatial localization in humans.

Abstract: Although the importance of the posterior parietal and prefrontal regions in spatial localization of visual stimuli is well established, their role in auditory space perception is less clear. Using positron emission tomography (PET) during auditory and visual spatial localization in the same subjects, modality-specific areas were identified in the superior parietal lobule, middle temporal and lateral prefrontal cortices. These findings suggest that, similar to the visual system, the hierarchical organization of the auditory system extends beyond the temporal lobe to include areas in the posterior parietal and prefrontal regions specialized in auditory spatial processing. Our results may explain the dissociation of visual and auditory spatial localization deficits following lesions involving these regions.

Mesial Motor Areas in Self-Initiated Versus Externally Triggered Movements Examined With fMRI: Effect of Movement Type and Rate

Abstract: Mesial motor areas in self-initiated versus externally triggered movements examined with fMRI: effect of movement type and rate. The human frontomesial cortex reportedly contains at least four cort...

Corticomuscular coherence: a review.

Abstract: Corticomuscular coherence measured between electroencephalography (EEG), magnetoencephalography, or local field potentials and electromyography (EMG) should be helpful in understanding the cortical control of movement EEG-EMG coherence and phase spectra depend on the types of EEG derivation and current source density function of EEG appears to be the most appropriate for computation of EEG-EMG coherence A new model for the interpretation of the phase spectra ("constant phase shift plus constant time lag model") shows that cortical surface negative potentials are phase-locked to EMG firing There are functional differences of EEG-EMG coherence among the alpha, beta, and gamma bands suggesting differences in their possible generator mechanisms Since corticomuscular coherence is a noninvasive measure of corticomotoneuronal function in a specific frequency range, clinical application of this method might be very fruitful in tremor research

Dissociation of the pathways mediating ipsilateral and contralateral motor-evoked potentials in human hand and arm muscles

Abstract: Growing evidence points toward involvement of the human motor cortex in the control of the ipsilateral hand. We used focal transcranial magnetic stimulation (TMS) to examine the pathways of these ipsilateral motor effects. Ipsilateral motor-evoked potentials (MEPs) were obtained in hand and arm muscles of all 10 healthy adult subjects tested. They occurred in the finger and wrist extensors and the biceps, but no response or inhibitory responses were observed in the opponens pollicis, finger and wrist flexors and the triceps. The production of ipsilateral MEPs required contraction of the target muscle. The threshold TMS intensity for ipsilateral MEPs was on average 1.8 times higher, and the onset was 5.7 ms later (in the wrist extensor muscles) compared with size-matched contralateral MEPs. The corticofugal pathways of ipsilateral and contralateral MEPs could be dissociated through differences in cortical map location and preferred stimulating current direction. Both ipsi- and contralateral MEPs in the wrist extensors increased with lateral head rotation toward, and decreased with head rotation away from, the side of the TMS, suggesting a privileged input of the asymmetrical tonic neck reflex to the pathway of the ipsilateral MEP. Large ipsilateral MEPs were obtained in a patient with complete agenesis of the corpus callosum. The dissociation of the pathways for ipsilateral and contralateral MEPs indicates that corticofugal motor fibres other than the fast-conducting crossed corticomotoneuronal system can be activated by TMS. Our data suggest an ipsilateral oligosynaptic pathway, such as a corticoreticulospinal or a corticopropriospinal projection as the route for the ipsilateral MEP. Other pathways, such as branching of corticomotoneuronal axons, a transcallosal projection or a slow-conducting monosynaptic ipsilateral pathway are very unlikely or can be excluded.

Modulation of motor cortex excitability by median nerve and digit stimulation.

Abstract: We investigated the time course of changes in motor cortex excitability after median nerve and digit stimulation. Although previous studies showed periods of increased and decreased corticospinal excitability following nerve stimulation, changes in cortical excitability beyond 200 ms after peripheral nerve stimulation have not been reported. Magnetoencephalographic studies have shown an increase in the 20-Hz rolandic rhythm from 200 to 1000 ms after median nerve stimulation. We tested the hypothesis that this increase is associated with reduced motor cortex excitability. The right or left median nerve was stimulated and transcranial magnetic stimulation (TMS) was applied to left motor cortex at different conditioning-test (C-T) intervals. Motor-evoked potentials (MEPs) were recorded from the right abductor pollicis brevis (APB), first dorsal interosseous (FDI), and extensor carpi radialis (ECR) muscles. Right median nerve stimulation reduced test MEP amplitude at C-T intervals from 400 to 1000 ms for APB, at C-T intervals from 200 to 1000 ms for FDI, and at C-T intervals of 200 and 600 ms for ECR, but had no effect on FDI F-wave amplitude at a C-T interval of 200 ms. Left median nerve (ipsilateral to TMS) stimulation resulted in less inhibition than right median nerve stimulation, but test MEP amplitude was significantly reduced at a C-T interval of 200 ms for all three muscles. Digit stimulation also reduced test MEP amplitude at C-T intervals of 200-600 ms. The time course for decreased motor cortex excitability following median nerve stimulation corresponds well to rebound of the 20-Hz cortical rhythm and supports the hypothesis that this increased power represents cortical deactivation.

Period of susceptibility for cross-modal plasticity in the blind

Abstract: Cross-modal plasticity in blind subjects contributes to sensory compensation when vision is lost early in life, but it is not known if it does so when visual loss occurs at an older age. We used H215O positron emission tomography to identify cerebral regions activated in association with Braille reading, and repetitive transcranial magnetic stimulation to induce focal transient disruption of function during Braille reading, in 8 subjects who became blind after age 14 years (late-onset blind), after a lengthy period of normal vision. Results were compared with those previously reported obtained from congenitally and early-onset blind subjects. As shown by H215O positron emission tomographic scanning, the occipital cortex was strongly activated in the congenitally blind and early-onset blind groups but not in the late-onset blind group. Occipital repetitive transcranial magnetic stimulation disrupted the Braille reading task in congenitally blind and early-onset blind subjects but not in late-onset blind subjects. These results indicate that the susceptible period for this form of functionally relevant cross-modal plasticity does not extend beyond 14 years. Ann Neurol 1999;45:451–460

Functional coupling of human cortical sensorimotor areas during bimanual skill acquisition

Abstract: Bimanual co-ordination of skilled finger movements is a high-level capability of the human motor system and virtually always requires training. Little is known about the physiological processes underlying successful bimanual performance and skill acquisition. In the present study, we used task-related coherence (TRCoh) and task-related power (TRPow) analysis of multichannel surface EEG to investigate the functional coupling and regional activation of human sensorimotor regions during bimanual skill acquisition. We focused on changes in interhemispheric coupling associated with bimanual learning. TRCoh and TRPow were estimated during the fusion of two overlearned unimanual finger-tapping sequences into one novel bimanual sequence, before and after a 30-min training period in 18 normal volunteers. Control experiments included learning and repetition of complex and simple unimanual finger sequences. The main finding was a significant increase in interhemispheric TRCoh selectively in the early learning stage (P < 0.0001). Interhemispheric TRCoh was also present during the unimanual control tasks, but with lower magnitude, even if learning was involved. Training improved bimanual sequence performance (from 58.3+/-24.1 to 83.7+/-15.3% correct sequences). After training, interhemispheric (bimanual) TRCoh decreased again, thereby approaching levels similar to those in the unimanual controls. We propose that the initial increase in TRCoh reflects changes in interhemispheric communication that are specifically related to bimanual learning and may be relayed through the corpus callosum. The present data might also offer a neurophysiological explanation for the clinical observation that patients with lesions of the corpus callosum may show deficits in the acquisition of novel bimanual tasks but not necessarily in the execution of previously learned bimanual activities.

Increased iron in the dentate nucleus of patients with Friedreich's ataxia

Abstract: Friedreich's ataxia (FA) is the most frequently inherited ataxia. To test the hypothesis that iron is increased in the cerebellum of patients with FA, we developed a multigradient echo magnetic resonance sequence for the three-dimensional imaging of brain iron-induced contrast. Relaxation rate (R2*) values in the unaffected globus pallidus were equal in FA patients and controls, although R2* values in the dentate nucleus of patients were significantly higher, which is most likely due to increased iron. Ann Neurol 1999;46:123–125

A PET study of sequential finger movements of varying length in patients with Parkinson's disease.

Abstract: Summary To study the difficulty that patients with Parkinson’s disease have in performing long sequential movements, we used H2 15 O PET to assess the regional cerebral blood flow (rCBF) associated with the performance of simple repetitive movements, well-learned sequential finger movements of varying length and self-selected movements. Sequential finger movements in the Parkinson’s disease patients were associated with an activation pattern similar to that found in normal subjects, but Parkinson’s disease patients showed relative overactivity in the precuneus, premotor and parietal cortices. Increasing the complexity of movements resulted in increased rCBF in the premotor

Deficient activation of the motor cortical network in patients with writer’s cramp

Abstract: Objective: To study regional cerebral blood flow (rCBF) in patients with simple writer’s cramp using PET to identify regions that malfunction. Background: Several lines of evidence indicate impaired cortical function in patients with focal dystonia, but the precise pathophysiology is still unknown. Methods: Seven patients with writer’s cramp were compared with seven age- and sex-matched control subjects. Control subjects and patients were scanned during sustained contraction, tapping, and writing with the right hand. After realignment and stereotactic normalization of the scans, all tasks were compared with a rest condition. For each task, an intra- and intergroup comparison was performed using statistical parametric mapping. For each condition and within groups, rCBF correlation analysis was performed between some selected regions that were activated during movement. Results: In control subjects and patients, significant increases of rCBF were observed for each task in areas already known to be activated in motor paradigms. The intergroup comparison disclosed less activation in writer’s cramp patients for several areas for all three tasks. This decrease reached significance for the sensorimotor cortex during the sustained contraction task and for the premotor cortex during writing. rCBF correlation analysis showed different patterns between control subjects and patients. At rest and during writing, the correlations between the putamen and premotor cortical regions and between the premotor cortical regions themselves were stronger in control subjects. Conclusions: Deficient activation of premotor cortex and decreased correlation between premotor cortical regions and putamen suggest a dysfunction of the premotor cortical network in patients with writer’s cramp possibly arising in the basal ganglia. The dysfunction is compatible with a loss of inhibition during the generation of motor commands, which in turn could be responsible for the dystonic movements.

Timing of activity in early visual cortex as revealed by transcranial magnetic stimulation.

Abstract: To determine the timing of visual processing in the early visual cortex, we applied single pulse transcranial magnetic stimulation to the occipital pole of healthy subjects while they were engaged in a forced-choice visual letter-identification task. We found two separate periods of activity, the first ranging from 20 to 60 ms after the onset of the visual stimulus, and the second ranging from 100 to 140 ms after the onset of the visual stimulus. We suggest that these two periods reflect necessary activity in V1, before and after re-entry.

Applications of magnetic cortical stimulation.

Abstract: At the beginning of the 1980s, in Cambridge, UK, a special stimulator able to elicit contralateral muscle twitches by discharging electric pulses to the scalp overlying the motor cortex was developed (Merton and Morton 1980a,b). Such responses ± thereafter named motor evoked potentials (MEPs) ± were elicited after a brief latency (,20 ms to the hand muscles, and ,30±40 ms to the leg and foot muscles), utilising the paucisynaptic, fast-propagating corticospinal tract. The required intensity was painful and not well tolerated. However, it was shown very soon that this technique could open new frontiers in research and clinical contexts concerning motor behaviour (Rossini et al. 1985). A further re®nement employing a pericranial cathode and a stimulating anode was developed in the following years. This allowed obtaining MEPs with signi®cantly lower amounts of current. However, the real impetus to transcranial stimulation came from the introduction of the magnetic stimulator (Barker et al. 1985). Since then, brain stimulation has become a frequent procedure in clinical neurophysiology. Details concerning physiological and technical aspects are given in another section of this Book (Rothwell et al.). By employing commonly used circular coils (for example with an inner diameter of about 10 cm) absolute latencies of MEPs, excitability threshold for a given muscle as well as silent period duration and central conduction time can be measured. However, studies concerning interhemispheric differences of the examined parameters and mapping of the motor output from each hemisphere cannot be reliably done due to the possibility of contralateral stimulation and non-focal brain activation. To avoid this problem, in recent years, ®gure-of-eight coils that allow more focal stimulation were introduced. Moreover, double stimulators able to discharge paired stimuli or triplets within 171 Recommendations for the Practice of Clinical Neurophysiology: Guidelines of the International Federation of Clinical Physiology (EEG Suppl. 52) Editors: G. Deuschl and A. Eisen q 1999 International Federation of Clinical Neurophysiology. All rights reserved. Published by Elsevier Science B.V.

The time course of changes in motor cortex excitability associated with voluntary movement.

Abstract: The excitability of the motor cortex is modulated before and after voluntary movements. Transcranial magnetic stimulation studies showed increased corticospinal excitability from about 80 and 100 ms before EMG onset for simple reaction time and self-paced movements, respectively. Following voluntary movements, there are two phases of increased corticospinal excitability from 0 to approximately 100 ms and from approximately 100 to 160 ms after EMG offset. The first phase may correspond to the frontal peak of motor potential in movement-related cortical potentials studies and the movement-evoked magnetic field I (MEFI) in magnetoencephalographic (MEG) studies, and likely represents a time when decreasing output from the motor cortex falls below that required for activation of spinal motoneurons, but is still above resting levels. The second phase of increased corticospinal excitability may be due to peripheral proprioceptive inputs or may be centrally programmed representing a subthreshold, second agonist burst. This may correspond to the MEFII in MEG studies. Corticospinal excitability was reduced below baseline levels from about 500 to 1,000 ms after EMG offset, similar to the timing of increase in the power (event-related synchronization, ERS) of motor cortical rhythm. Similarly, motor cortex excitability is reduced at the time of ERS of motor cortical rhythm following median nerve stimulation. These findings support the hypothesis that ERS represents an inactive, idling state of the cortex. The time course of cortical activation is abnormal in movement disorders such as Parkinson's disease and dystonia, reflecting abnormalities in both movement preparation and in cortical excitability following movement.

One man's poison--clinical applications of botulinum toxin.

Abstract: Botulinum toxin is one of the deadliest poisons known, causing death by muscle paralysis. As a poison, it is most commonly encountered as a source of food poisoning, and there are shivers around the world when it surfaces as a possible biologic weapon. Botulinum toxin is produced by the bacterium Clostridium botulinum. It is a polypeptide consisting of a light chain and a heavy chain bridged by a single disulfide bond. There are seven serologically distinct but structurally similar types of botulinum toxin: A, B, C, D, E, F, and G. Alan Scott first had the idea that small doses . . .

Simultaneous repetitive transcranial magnetic stimulation does not speed fine movement in PD

Abstract: To the Editor: I read with interest the paper of Ghabra et al.1 Using the Grooved Pegboard Test, the authors reevaluated the effect of simultaneous subthreshold 5-Hz repetitive transcranial magnetic stimulation (rTMS) over the primary motor hand area (M1) on fine hand movement in PD. In contrast to a previous study,2 Ghabra et al.1 found no improvement of motor performance during simultaneous 5-Hz rTMS over the contralateral M1 applied at an intensity just below active motor threshold. The data of Ghabra et al.1 confirm our previous study, which demonstrated no beneficial effects of simultaneous subthreshold 5-Hz rTMS on handwriting in unmedicated PD patients.3 Ghabra et al.1 investigated the immediate effects of subthreshold rTMS on concurrent fine manual movements to define the potential therapeutic role of rTMS in PD. However, the authors provide …

Learning in Parkinson's disease: eyeblink conditioning, declarative learning, and procedural learning.

Abstract: OBJECTIVE—To assess the degree of learning ability in Parkinson's disease. METHODS—Three different learning tasks: eyeblink classical conditioning with delay and trace paradigms, the California verbal learning test (CVLT), and a serial reaction time task (SRTT) were studied in patients with Parkinson's disease and normal (control) subjects. RESULTS—In the eyeblink conditioning tasks, both patients and normal subjects showed significant learning effects without between group differences. In the CVLT, patients remembered significantly fewer words than normal subjects in both short term and long term cued recall tasks. In the SRTT, normal subjects had significantly reduced response time and error rates across blocks of repeated sequence trials, whereas patients had significantly reduced error, but not response time rates. CONCLUSION—Impairment of nigrostriatal pathways selectively affects performance in complex learning tasks that are competitive and require alertness such as the SRTT, but not in simple learning procedures such as eyeblink conditioning.

Effect of muscle activity immediately after botulinum toxin injection for writer's cramp.

Abstract: Animal and human studies have shown that nerve stimulation enhances some effects of botulinum toxin (btx A) injection. Voluntary muscle activity might work similarly and would focus the effect of an injection into the active muscles. We studied the effects of exercise immediately after btx A injection in eight patients with writer's cramp with established response to btx A over two injection cycles with a single-blinded, randomized, crossover design. Immediately after the first study injection, they were randomly assigned to write continuously for 30 min or have their hand and forearm immobilized for 30 min. Following the second injection, they were assigned the alternate condition. Patients were assessed just before each injection, and at 2 weeks, 6 weeks, and 3 months post-injection. Assessment included objective strength testing, self-reported rating of benefit and weakness, and blinded evaluation of videotapes and writing samples of the patients writing a standard passage. Strength testing showed that the maximum weakness occurred at 2 weeks post-injection, but the benefit was maximum at 6 weeks post-injection. The "write" condition resulted in greater reduction in strength than the "rest" condition. Btx A treatment led to improvement in self-reported ratings, writer's cramp rating scale scores by blinded raters, and reduction in writing time, but the differences between the "write" and "rest" conditions were not significant. We conclude that voluntary muscle activity immediately after btx A injection leads to greater reduction in muscle strength. Our findings raise the possibility that voluntary muscle activation may allow reduction of btx A doses and favorably alter the balance of benefit and side effects of btx A injections.

The effect of movement amplitude on activation in functional magnetic resonance imaging studies.

Abstract: To evaluate the effect of movement amplitude on the "blood oxygen level-dependent effect," the authors studied six normal subjects while they extended their index finger with two different amplitudes. Images were analyzed using SPM96. In five subjects, the signal intensity increase in the primary sensorimotor area was significantly greater with the larger amplitude movement. In other areas of interest (supplementary motor area, premotor cortex, insula, postcentral area, cerebellum), the large-amplitude movement often showed significant activation when the small-amplitude movement did not. The authors conclude that, in studies of the motor system, movement amplitude needs to be controlled.

Blink reflex recovery in facial weakness: An electrophysiologic study of adaptive changes

Abstract: Objective: To study the electrophysiologic effects of unilateral facial weakness on the excitability of the neuronal circuitry underlying blink reflex, and to localize the site of changes in blink reflex excitability that occur after facial weakness. Background: Eyelid kinematic studies suggest that adaptive modification of the blink reflex occurs after facial weakness. Such adaptations generally optimize eye closure. A report of blepharospasm following Bell’s palsy suggests that dysfunctional adaptive changes can also occur. Methods: Blink reflex recovery was evaluated with paired stimulation of the supraorbital nerve at different interstimulus intervals. Comparisons were made between normal control subjects and patients with Bell’s palsy who either recovered facial strength or who had persistent weakness. Results: Blink reflex recovery was enhanced in patients with residual weakness but not in patients who recovered facial strength. Facial muscles on weak and unaffected sides showed enhancement. In patients with residual weakness, earlier blink reflex recovery occurred when stimulating the supraorbital nerve on the weak side. Sensory thresholds were symmetric. Conclusion: Enhancement of blink reflex recovery is dependent on ongoing facial weakness. Faster recovery when stimulating the supraorbital nerve on the paretic side suggests that sensitization may be lateralized, and suggests a role for abnormal afferent input in maintaining sensitization. Interneurons in the blink reflex pathway are the best candidates for the locus of this plasticity.

An open trial of clozapine for dystonia.

Abstract: Pharmacologic treatment of severe dystonia is often unsatisfactory. The atypical antipsychotic medication clozapine appears to improve tardive dystonia associated with conventional neuroleptic use. We studied the efficacy of clozapine for severe dystonia in five patients in an open trial. The patient cohort included four with generalized dystonia and one with Meige syndrome. All patients were evaluated at baseline and at least weekly while on medication with subjective assessment of response by the patient and physician rating using the Burke-Fahn-Marsden Evaluation Scale for Dystonia. All five subjects had significant improvement detected by the Burke-Fahn-Marsden Evaluation Scale as well as subjective improvement while on clozapine. Side effects, such as sedation and orthostatic hypotension, developed in all patients but was only treatment-limiting in one subject who developed persistent symptomatic orthostatic hypotension and tachycardia. Two of the four remaining patients continued clozapine after completion of the study; an additional patient was uncertain if the benefit outweighed the side effects. One patient discontinued treatment because of difficulty obtaining the FDA-required weekly white blood cell counts for patients on clozapine. We conclude that clozapine appears to be effective for generalized and refractory focal dystonia although its use may be limited by the side effects and need for hematologic monitoring.

Novel PRNP sequence variant associated with familial encephalopathy.

Abstract: Human transmissible spongiform encephalopathies (TSEs) are a group of chronic progressive neurodegenerative disorders that may be hereditary, infectious, or sporadic. Hereditary TSEs are associated with mutations in the PRNP gene on chromosome 20p12-pter. We report on a family in which seven patients developed limb and truncal ataxia, dysarthria, myoclonic jerks, and cognitive decline. The age of onset in the 30s, 40s, or 50s, prolonged disease duration, cerebellar atrophy on imaging, and the presence of synchronic periodic discharges on electroencephalogram suggested a familial encephalopathy resembling Gerstmann-Straussler-Scheinker disease. A novel H187R mutation has been identified in affected, but not in unaffected, family members or unrelated controls suggesting a pathogenic role for this mutation. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:653-656, 1999. Published 1999 Wiley-Liss, Inc.

Parkinsonism after a wasp sting

Abstract: A 49-year-old man had mild parkinsonism after being stung by a wasp, a member of the Hymenoptera order. His clinical course was stable for 6 months after which his condition rapidly progressed to a severe akinetic-rigid syndrome with evidence, on a magnetic resonance imaging brain scan, of marked destruction of the basal ganglia. The symptoms did not respond to standard antiparkinsonian medications. Repeated courses of plasmapheresis followed by monthly intravenous infusions of immunoglobulin and long-term administration of azathioprine halted and appeared to partially reverse his deterioration. The literature on the neurologic, particularly the extrapyramidal, manifestations of stings by insects of the Hymenoptera order is reviewed and the possible pathophysiological mechanisms of injury are discussed. Hymenoptera stings should be included in the differential diagnosis of acute and chronic extrapyramidal syndromes.