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Biomedical subjects

M Hallett

Publications and source records attributed to M Hallett.

At least 37 records · Page 2Linked to original sources
PubMed2004

Small de novo duplication in the repeat region of the TATA-box-binding protein gene manifest with a phenotype similar to variant Creutzfeldt-Jakob disease.

A 20-year-old North American patient developed rapidly progressive cognitive decline and pronounced ataxia, a phenotype compatible with prion disease. No structural changes were found in the PRNP gene, which excludes genetic prion disease, but the patient's PRNP codon 129 Met/Met genotype is known to predispose to variant Creutzfeldt-Jakob disease (vCJD). Further studies identified an expanded allele with 55 CAG/CAA repeats in the TBP gene. The increase of trinucleotide repeat number in the coding region of the TBP gene has previously been associated with spinocerebellar ataxia type 17 (SCA17). The patient's unaffected parents and siblings show normal-size TBP alleles with 37-38 repeats. Haplotype and nucleotide sequence analyses clearly indicate that the mutation has occurred de novo on a paternal chromosome by insertion/duplication of a (CAA)(CAG)(CAA)(CAG)(15) sequence. This report presents a second fully investigated sporadic case of SCA17 occurring as a result of a DNA rearrangement within the polymorphic TBP trinucleotide repeat region. Our findings suggest that patients suspected of vCJD should undergo testing for SCA17, Huntington's disease and other neurodegenerative disorders having phenotypic similarities with vCJD.

Adult↗
PubMed2003

Accelerometry to distinguish psychogenic from essential or parkinsonian tremor.

The authors measured postural wrist tremor with accelerometry in patients with psychogenic (n = 6), essential (n = 11), and parkinsonian (n = 12) tremor. Tremor was measured in one hand, while the other hand either rested or tapped to an auditory stimulus at 3 and 4 or 5 Hz. Psychogenic tremors showed larger tremor frequency changes and higher intraindividual variability while tapping. Accelerometry may differentiate psychogenic from essential and parkinsonian tremor.

Acceleration↗
PubMed2003

Abnormalities of spatial discrimination in focal and generalized dystonia.

Sensory processing is impaired in focal hand dystonia (FHD), with most previous studies having evaluated only the symptomatic limb. The purpose of this study was to establish whether the sensory system is affected in other types of dystonias and whether the contralateral hand is also involved in FHD. We used a spatial acuity measure (Johnson-Van Boven-Phillips domes) to evaluate sensory spatial discrimination in both hands of patients with different forms of dystonias including primary generalized DYT1 dystonia (associated with a unique deletion in the DYT1 gene) (n = 13), FHD (n = 15), benign essential blepharospasm (n = 9), cervical dystonia (n = 10) and in age-matched controls. Clinical evaluation included the Fahn dystonia scale for the focal dystonia groups and the Marsden-Burke-Fahn scale for the generalized dystonia group. Spatial discrimination was normal in patients with DYT1 dystonia, despite all of these patients having hand dystonia. However, spatial discrimination thresholds were significantly increased in both hands in the focal dystonia groups (thresholds were similar for each group) and did not correlate significantly with either severity or duration of dystonic symptoms. Thresholds were significantly increased in the dominant hand compared with the non-dominant hand only within the FHD group. Our observations demonstrate involvement of both the dominant and non-dominant somatosensory cortices, and suggest that abnormal sensory processing is a fundamental disturbance in patients with focal dystonia. These findings of altered sensory processing in idiopathic focal but not generalized DYT1 dystonia suggest both a primary pathophysiological role for the phenomenon in focal dystonia and divergent pathophysiological processes in the two conditions.

Adult↗
PubMed2003

The effect of transcranial magnetic stimulation on movement selection.

OBJECTIVE: To attempt to replicate previous findings that showed an influence of transcranial magnetic stimulation of the cortical motor areas on the selection of motor programmes on the contralateral side. METHODS: Healthy volunteers were asked to choose to make a right or left index finger extension movement freely after hearing the click produced by transcranial magnetic stimulation. The stimulation was applied to the motor areas (test), including the motor cortex, vertex, and prefrontal cortex, and in the air (control). RESULTS: There was no preference for choosing the hand contralateral to the stimulation site, in either test or control trials. CONCLUSIONS: Previous results could not be reproduced. Simple magnetic stimulation of the motor areas is insufficient to affect voluntary selection of movement.

Adult↗
PubMed2003

Towards identifying lateral gene transfer events.

This paper is concerned with evaluating the performance of the model and algorithm in 5 for detecting lateral gene transfers events. Using a Poisson process to describe arrival times of transfer events, a simulation is used to generate "synthetic" gene and species trees. An implementation of an efficient algorithm in 5 is used to estimate the minimum number of transfers necessary to explain disagreements between the generated gene and species trees. Our first result suggests that the algorithm can solve realistic size instances of the problem. Our second result suggests that the mean error and variance are low when saturation does not occur. Additionally, certain plausible evolutionary events allowed by our model of evolution used to generate gene and species trees but not detectable by the algorithm occur rarely implying the framework should work well in practice. Our third, surprising result suggests that the number of optimal scenarios is on average low for realistic input sizes.

Algorithms↗
PubMed2002

Transcranial magnetic stimulation techniques in clinical investigation.

Transcranial magnetic stimulation (TMS) is a technique that can activate cortical motor areas and the corticospinal tract without causing the subject discomfort. Since TMS was introduced, numerous applications of the technique have been developed for the evaluation of neurologic diseases. Standard TMS applications (central motor conduction time, threshold and amplitude of motor evoked potentials) allow the evaluation of motor conduction in the CNS. Conduction studies provide specific information in neurologic conditions characterized by clinical and subclinical upper motor neuron involvement. In addition, they have proved useful in monitoring motor abnormalities and the recovery of motor function. TMS also gives information on the pathophysiology of the processes underlying the various clinical conditions. More complex TMS applications (paired-pulse stimulation, silent period, ipsilateral silent period, input-output curve, and evaluation of central fatigue) allow investigation into the mechanisms of diseases causing changes in the excitability of cortical motor areas. These techniques are also useful in monitoring the effects of neurotrophic drugs on cortical activity. TMS applications have an important place among the investigative tools to study patients with motor disorders.

Brain↗
PubMed2002

Cortically evoked neural volleys to the human hand are increased during ischaemic block of the forearm.

Reorganisation of the motor cortex may occur after limb amputation or spinal cord injury. In humans, transcranial magnetic stimulation (TMS) shows expansion of motor cortical representations of muscles proximal to the injury. Similarly, ischaemic block of the hand can increase acutely the representation of the biceps muscle, measured by increased biceps motor potentials evoked by TMS. It is thought that this increase occurs at the expense of the cortical representation of the paralysed and deafferented hand muscles but this has never been investigated. To study what changes occur in the cortical representation of the hand muscles during ischaemic block, a tungsten microelectrode was inserted into the ulnar or median nerve above the elbow and the size of the neural potential elicited by TMS in fascicles supplying the hand was measured in seven subjects. Prior to ischaemia, TMS evoked EMG responses in the intrinsic hand muscles. In the nerve, a brief motor potential preceded the response in the muscle and was followed by a contraction-induced sensory potential. During 40 min of ischaemia produced by a blood pressure cuff inflated around the forearm to 210 mmHg, the EMG response to TMS and the sensory potential from the hand were progressively blocked. However, the motor neural evoked potential showed a significant increase in amplitude during the ischaemic period (30.5 %, P = 0.005). The increase in the neural potential suggests that output to the hand evoked from the cortex by TMS was not decreased by ischaemic block. Thus, we conclude that the increased response of biceps to TMS during distal ischaemia is not accompanied by a corresponding decrease in the motor cortical representation of the hand.

Adult↗
PubMed2002

Nervous system reorganization following injury.

Contrary to the classical view of a pre-determined wiring pattern, there is considerable evidence that cortical representation of body parts is continuously modulated in response to activity, behavior and skill acquisition. Both animal and human studies showed that following injury of the peripheral nervous system such as nerve injury or amputation, the somatosensory cortex that responded to the deafferented body parts become responsive to neighboring body parts. Similarly, there is expansion of the motor representation of the stump area following amputation. Reorganization of the sensory and motor systems following peripheral injury occurs in multiple levels including the spinal cord, brainstem, thalamus and cortex. In early-blind subjects, the occipital cortex plays an important role in Braille reading, suggesting that there is cross-modal plasticity. Functional recovery frequently occurs following a CNS injury such as stroke. Motor recovery from stroke may be associated with the adjacent cortical areas taking over the function of the damaged areas or utilization of alternative motor pathways. The ipsilateral motor pathway may mediate motor recovery in patients who undergo hemispherectomy early in life and in children with hemiplegic cerebral palsy, but it remains to be determined if it plays a significant role in the recovery of adult stroke. One of the challenges in stroke recovery is to identify which of the many neuroimaging and neurophysiological changes demonstrated are important in mediating recovery. The mechanism of plasticity probably differs depending on the time frame. Rapid changes in motor representations within minutes are likely due to unmasking of latent synapses involving modulation of GABAergic inhibition. Changes over a longer time likely involve other additional mechanisms such as long-term potentiation, axonal regeneration and sprouting. While cross-modal plasticity appears to be useful in enhancing the perceptions of compensatory sensory modalities, the functional significance of motor reorganization following peripheral injury remains unclear and some forms of sensory reorganization may even be associated with deleterious consequences like phantom pain. An understanding of the mechanism of plasticity will help to develop treatment programs to improve functional outcome.

Aging↗
PubMed2002

Focal enhancement of motor cortex excitability during motor imagery: a transcranial magnetic stimulation study.

OBJECTIVES: In order to learn more about the physiology of the motor cortex during motor imagery, we evaluated the changes in excitability of two different hand muscle representations in the primary motor cortex (M1) of both hemispheres during two imagery conditions. MATERIALS AND METHODS: We applied focal transcranial magnetic stimulation (TMS) over each M1, recording motor evoked potentials (MEPs) from the contralateral abductor pollicis brevis (APB) and first dorsal interosseus (FDI) muscles during rest, imagery of contralateral thumb abduction (C-APB), and imagery of ipsilateral thumb abduction (I-APB). We obtained measures of motor threshold (MT), MEP recruitment curve (MEP-rc) and F waves. RESULTS: Motor imagery compared with rest significantly decreased the MT and increased MEPs amplitude at stimulation intensities clearly above MT in condition C-APB, but not in condition I-APB. These effects were not significantly different between right and left hemisphere. MEPs simultaneously recorded from the FDI, which was not involved in the task, did not show facilitatory effects. There were no significant changes in F wave amplitude during motor imagery compared with rest. CONCLUSIONS: Imagery of unilateral simple movements is associated with increased excitability only of a highly specific representation in the contralateral M1 and does not differ between hemispheres.

Adult↗
PubMed2001

Effect of levetiracetam on human corticospinal excitability.

OBJECTIVE: To investigate whether levetiracetam (LTC) alters corticospinal excitability in humans. BACKGROUND: Although the antiepileptic activity of LTC is well recognized, its mechanism of action has yet to be determined. Transcranial magnetic stimulation (TMS) has been used to investigate the pharmacologic effects of various antiepileptic drugs on human corticospinal excitability. METHODS: The authors performed TMS before and after double-blind administration of 3000 mg LTC or placebo in six healthy volunteers. TMS measurements included resting and active motor threshold (MT), recruitment curve of motor-evoked potential amplitudes, intracortical inhibition, and facilitation using the paired-pulse technique and silent period. F-wave and compound muscle action potential (CMAP) were also measured. RESULTS: In recruitment curve measurements, motor-evoked potential amplitude was reduced for LTC with high stimulation intensity (130% and 140% of resting MT) compared with placebo (p < 0.05 and p < 0.01), but not with relatively low stimulation intensity (110% and 120%). The changes in other TMS measurements as well as F-wave and CMAP after LTC did not differ significantly from those observed after placebo administration. CONCLUSION: These results suggest that LTC reduces the corticospinal neuronal response to magnetic stimulation, preferentially affecting less excitable neurons. The lack of change in F-wave and CMAP suggests that this effect is mainly derived from the motor cortex.

Adult↗
PubMed2001

Randomized placebo-controlled trial of donepezil in patients with progressive supranuclear palsy.

OBJECTIVE: There is no effective treatment for progressive supranuclear palsy (PSP). Because results of immunochemical and pharmacologic studies suggest that the cholinergic system may play a role in the cognitive and motor features of PSP, the authors investigated the effects of donepezil (10 mg/day), an acetylcholinesterase inhibitor, in 21 patients with PSP (mean age +/- SD; 65.7 +/- 4.7 years) by a randomized, double-blind, placebo-controlled crossover trial. METHODS: Donepezil and placebo were administered for 6 weeks each with a 1-month washout period. Patients were evaluated before and at the end of each treatment phase. Outcome measures evaluated neuropsychiatric, global cognitive, frontal, memory, motor, and activities of daily living (ADL) status. RESULTS: Two patients withdrew during the washout phase because of unrelated medical problems. Donepezil-induced systemic side effects were transient and generally mild. Because of worsening of motor function, three patients received 5 mg/day of donepezil. All patients achieved blood and CSF therapeutic levels of donepezil. While the patients were taking donepezil, their Double Memory Test scores improved, whereas their ADL/mobility scores significantly worsened. CONCLUSION: The findings suggest that acetylcholinesterase inhibitors such as donepezil have at best selective, modest effects on cognition in patients with PSP. In light of its deleterious effects on ADL/mobility, donepezil is not recommended for this patient population.

Aged↗
PubMed2001

Transient interhemispheric neuronal synchrony correlates with object recognition.

Object recognition might be achieved by the recreation of a meaningful internal image from visual fragments. This recreation might be achieved by neuronal synchronization that has been proposed as a solution for the perceptual binding problem. In this study, we evaluated synchronization between the occipitotemporal regions bilaterally using electroencephalograms during several visual recognition tasks. Conscious recognition of familiar objects spanning the visual midline induced transient interhemispheric electroencephalographic coherence in the alpha band, which did not occur with meaningless objects or with passive viewing. Moreover, there was no interhemispheric coherence when midline objects were not recognized as meaningful or when familiar objects were presented in one visual hemifield. These data suggest a close link between site-specific interregional synchronization and object recognition.

Adult↗
PubMed2001

Somatosensory evoked potentials as a marker of disease burden in type 3 Gaucher disease.

The authors compared stretch-evoked somatosensory evoked potentials (SEP) of 18 type 3 Gaucher disease (GD3) patients (two with progressive myoclonus epilepsy [PME]) with 22 age-matched normal controls and six patients with type 1 (nonneuronopathic) Gaucher disease (GD1). The mean P1-N2 SEP amplitude in GD3 patients was significantly larger than the SEP in controls and in GD1 patients, and there was a significant negative correlation between SEP amplitude and the IQ of GD3 patients. The authors conclude that abnormal cortical inhibition is a unifying feature of GD3 patients and correlates with the degree of cognitive deficit.

Adolescent↗
PubMed2001

Neural correlates of auditory-visual stimulus onset asynchrony detection.

Intersensory temporal synchrony is an ubiquitous sensory attribute that has proven to be critical for binding multisensory inputs, sometimes erroneously leading to dramatic perceptual illusions. However, little is known about how the brain detects temporal synchrony between multimodal sensory inputs. We used positron emission tomography to demonstrate that detecting auditory-visual stimulus onset asynchrony activates a large-scale neural network of insular, posterior parietal, prefrontal, and cerebellar areas with the highest and task-specific activity localized to the right insula. Interregional covariance analysis further showed significant task-related functional interactions between the insula, the posterior thalamus, and superior colliculus. Based on these results and the available electrophysiological and anatomical connectivity data in animals, we propose that the insula, via its known short-latency connections with the tectal system, mediates temporally defined auditory-visual interaction at an early stage of cortical processing permitting phenomena such as the ventriloquist and the McGurk illusions.

Acoustic Stimulation↗