Showing papers by "Mark Hallett published in 1994"

Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex.

Abstract: We applied trains of focal, rapid-rate transcranial magnetic stimulation (rTMS) to the motor cortex of 14 healthy volunteers with recording of the EMG from the contralateral abductor pollicis brevis, extensor carpi radialis, biceps brachii and deltoid muscles. Modulation of the amplitude of motor evoked potentials (MEPs) produced in the target muscle during rTMS showed a pattern of inhibitory and excitatory effects which depended on the rTMS frequency and intensity. With the magnetic coil situated over the optimal scalp position for activating the abductor pollicis brevis, rTMS led to spread of excitation, as evident from the induction of progressively larger MEPs in the other muscles. The number of pulses inducing this spread of excitation decreased with increasing rTMS frequency and intensity. Latency of the MEPs produced in the other muscles during the spread of excitation was significantly longer than that produced by single-pulse TMS applied to the optimal scalp positions for their activation. The difference in MEP latency could be explained by a delay in intracortical conduction along myelinated cortico-cortical pathways. Following rTMS, a 3–4 min period of increased excitability was demonstrated by an increase in the amplitude of MEPs produced in the target muscles by single-pulse TMS. Nevertheless, repeated rTMS trains applied I min apart led to similar modulation of the responses and to spread of excitation after approximately the same number of pulses. This suggests that the spread might be due to the breakdown of inhibitory connections or the recruitment of excitatory pathways, whereas the post-stimulation facilitation may be due to a transient increase in the efficacy of excitatory synapses.

Modulation of cortical motor output maps during development of implicit and explicit knowledge

Abstract: The excitability of the human motor cortex during the development of implicit and declarative knowledge of a motor task was examined. During a serial reaction time test, subjects developed implicit knowledge of the test sequence, which was reflected by diminishing response times. Motor cortical mapping with transcranial magnetic stimulation revealed that the cortical output maps to the muscles involved in the task became progressively larger until explicit knowledge was achieved, after which they returned to their baseline topography. These results illustrate the rapid functional plasticity of cortical outputs associated with learning and with the transfer of knowledge from an implicit to explicit state.

Therapy with botulinum toxin

Abstract: Basic Science The Site and Mechanism of Action of Botulinum Neurotoxin, Julie A. Coffield, Robert V. Considine, and Lance L. Simpson Structures of Botulinum Neurotoxin, Its Functional Domains, and Perspectives on the Crystalline Type A Toxin, Bibhuti R. DasGupta Preparation and Characterization of Botulinum Toxin Type A for Human Treatment, Edward J. Schantz and Eric A. Johnson Theoretical Analyses of the Functional Regions of the Heavy Chain of Botulinum Neurotoxin, Frank J. Lebeda, Dallas C. Hack, and Mary K. Gentry Evaluation of Captopril and Other Potential Therapeutic Compounds in Antagonizing Botulinum Toxin-Induced Muscle Paralysis, Michael Adler, Sharad S. Deshpande, Robert E. Sheridan, and Frank J. Lebeda Botulinum Toxin Type B: Experimental and Clinical Experience, Elizabeth Moyer and Paulette E. Setler Production and Properties of Type F Toxin, Tomoko Shimizu and Genji Sakaguchi Immunogenicity of the Neurotoxins of Clostridium botulinum, Charles L. Hatheway and Carol Dang Systemic Effects of Botulinum Toxin, Dale J. Lange Pharmacology and Histology of the Therapeutic Application of Botulinum Toxin, Gary E. Borodic, Robert J. Ferrante, L. Bruce Pearce, and Kathy Alderson Assessment of the Biological Activity of Botulinum Toxin, Christopher M. Shaari and Ira Sanders Dystonia Dystonia, Stanley Fahn Botulinum Toxin for Blepharospasm, John S. Elston Acute and Chronic Effects of Botulinum Toxin in the Management of Blepharospasm, Jonathan J. Dutton Clinical Assessments of Patients with Cervical Dystonia, Earl S. Consky and Anthony E. Lang Anatomy and Neurophysiology of Neck Muscles, Richard M. Dubinsky Clinical Neurophysiology of Cervical Dystonia, Michael J. Aminoff and Richard K. Olney Experience with Botulinum Toxin in Cervical Dystonia, W. Poewe and Jorg Wissel Controlled Trials of Botulinum Toxin for Cervical Dystonia: A Critical Review, Paul Greene Electromyography-Assisted Botulinum Toxin Injections for Cervical Dystonia, Cynthia L. Comella Botulinum Toxin Treatment of Focal Hand Dystonia, Barbara Illowsky Karp and Mark Hallett Limb Dystonia: Treatment with Botulinum Toxin, Seth L. Pullman Clinical Experience with Botulinum Toxin F, Karen Rhew, Christy L. Ludlow, Barbara Illowsky Karp, and Mark Hallett Hemifacial Spasm Hemifacial Spasm: Evaluation and Management, with Emphasis on Botulinum Toxin Therapy, Gary E. Borodic Management on Hemifacial Spasm with Botulinum A Toxin, Albert W. Biglan and Sang-Jin Kim Botulinum Toxin for Facial-Oral-Mandibular Spasms and Bruxism, Alfredo Berardelli, Bruno Mercuri, and Alberto Priori Strabismus Clinical Use of Botulinum Toxin: Clinical Trials for Strabismus, Elbert H. Magoon Strabismus: Other Therapies, Oscar A. Cruz and John T. Flynn Management of Acute and Chronic VI Nerve Palsy, Arthur L. Rosenbaum Speech and Voice Disorders Clinical Aspects of Speech Motor Compromise, David B. Rosenfield Acoustic, Aerodynamic, and Videoendoscopic Assessment of Unilateral Thyroarytenoid Muscle Injection with Botulinum Toxin for Spasmodic Dysphonia, Gayle E. Woodson, Thomas Murry, Petra Zwirner, and Michael R. Swenson Oromandibular Dystonia: Treatment of 96 Patients with Botulinum Toxin Type A, Mitchell F. Brin, Andrew Blitzer, Susan Herman, and Celia Stewart Botulinum Toxin Injection for Adductor Spasmodic Dysphonia, Christy L. Ludlow, Karen Rhew, and Eric Anthony Nash The Evaluation and Management of Abductor Laryngeal Dysphonia, Andrew Blitzer and Mitchell F. Brin Indirect Laryngoscopic Approach for Injection of Botulinum Toxin in Spasmodic Dysphonia, Charles N. Ford Unilateral Injections of Botulinum Toxin in Spasmodic Dysphonia, Donald T. Donovan, Kenneth Schwartz, and Joseph Jankovic Responses of Stutterers and Vocal Tremor Patients to Treatment with Botulinum Toxin, Sheila V. Stager and Christy L. Ludlow Miscellaneous Disorders Treatment of Tremors with Botulinum Toxin, Joseph Jankovic Botulinum Toxin in the Treatment of Tics, Joseph Jankovic Botulinum Toxin: Potential Role in the Management of Cerebral Palsy During Childhood, L. Andrew Koman, James F. Mooney III, and Beth Paterson Smith Clinical Trials for Spasticity, Joseph King, Ching Tsui, and Christopher F. O'Brien Effects of Botulinum Toxin Type A on Detrusor-Sphincter Dyssynergia in Spinal Cord Injury Patients, Dennis D. Dykstra Botulinum Toxin in the Treatment of Gastrointestinal Disorders, Pankaj Jay Pasricha and Anthony N. Kalloo Botulinum Toxin for Spasms and Spasticity in the Lower Extremities, Reiner Benecke Botulinum Toxin Treatment of Palatal Tremor (Myoclonus), Gunther Deuschl, E. Lohle, Camilo Toro, Mark Hallett, and Robert S. Lebovics Botulinum Toxin in the Treatment of Glabellar Frown Lines and Other Facial Wrinkles, Alastair Carruthers and Jean D. A. Carruthers

Akinesia in Parkinson's disease. II. Effects of subthreshold repetitive transcranial motor cortex stimulation

Abstract: We studied the effects of repetitive transcranial stimulation of the motor cortex (rTMS) on choice reaction time (cRT), movement time (MT), and error rate (ER) in a serial reaction-time task in six medicated patients with Parkinson's disease (PD) and 10 age-matched normal controls. In normal subjects, subthreshold 5-Hz rTMS did not significantly change cRT, slightly shortened MT, but increased ER. In the patients, rTMS significantly shortened cRT and MT without affecting ER. These effects did not impair procedural learning. Performance on a grooved peg-board test was improved by rTMS in the same PD patients, especially when they were off medications, but worsened in the normal subjects. Repetitive, subthreshold motor cortex stimulation can improve performance in patients with PD and could be useful therapeutically.

Abnormal facilitation of the response to transcranial magnetic stimulation in patients with Parkinson's disease

Abstract: We studied the facilitation of the motor evoked potential (MEP) elicited with transcranial magnetic stimulation by increasing the stimulus intensity and the degree of voluntary activation of the target muscle in patients with Parkinson's disease (PD) and in normal volunteers. The threshold intensity for eliciting MEPs with the muscle at rest did not differ in PD patients and normal subjects. At rest, stimuli of similar intensity, related to the individual's threshold, elicited MEPs with amplitudes consistently larger in patients than in normal subjects, although when we compared the averaged MEP amplitude across all stimulus intensities, the differences reached only borderline statistical significance. Voluntary muscle activation elicited a smaller increase in the MEP area in PD patients than in normal subjects. Increasing the degree of voluntary muscle activation at fixed stimulus intensities elicited a smaller increase of MEP amplitude, duration, and area in PD patients than in normal subjects. These results suggest that control of the excitability of the motor system is abnormal in PD patients, with enhancement of excitability at rest and weak energization during voluntary muscle activation.

Induction of visual extinction by rapid‐rate transcranial magnetic stimulation of parietal lobe

Abstract: We used repetitive, rapid-rate transcranial magnetic stimulation (rTMS) for the noninvasive study of visual attention in humans. Six right-handed volunteers completed eight blocks of 20 single- and 10 double-visual-stimulus trials. The visual stimulus was a single asterisk on the right or left side of a computer screen or two asterisks presented simultaneously. The subject had to respond to the stimulus by pressing the right or left response key or both keys simultaneously. During six of the blocks, we applied focal rTMS in trains of five pulses at 25 Hz and 115% of the subject9s motor threshold intensity to scalp positions O1, O2, P3, P4, T5, or T6. Occipital rTMS led to a large number of misses of the contralateral asterisk regardless of whether a single or double stimulus was presented. Parietal rTMS did not induce misses of single stimuli but led to a large number of misses of the contralateral asterisk in the double-stimulus condition. The effects of temporal rTMS were inconsistent. We conclude that rTMS to the occipital lobe causes a sensory detection block, whereas rTMS to the parietal lobe can induce selective extinction of contralateral visual stimuli during a simultaneous double stimulus.

Cortical motor representation of the ipsilateral hand and arm

Abstract: We sought to determine whether motor evoked potentials (MEPs) as well as silent periods could be produced in hand and shoulder muscles by transcranial magnetic stimulation (TMS) of the ipsilateral cerebral hemisphere and, if so, whether their cortical representations could be mapped with respect to those of contralateral muscles. In six normal subjects, we delivered ten stimuli each to a grid of sites 1 cm apart on the scalp. The EMG was recorded and averaged from the contralateral first dorsal interosseous (FDI) and risorius (facial) muscles at rest and the ipsilateral FDI muscle, which was voluntarily contracted. In four of these subjects and an additional subject, we used the same mapping technique and recorded from the deltoid muscle on the right and left sides and the contralateral FDI during activation of the ipsilateral deltoid. In all subjects, the cortical representation of the contralateral risorius was anterolateral to that of the FDI. The contralateral deltoid could be activated in only three subjects. In them, its representation was slightly medial to that of the FDI. All subjects had at least one scalp site where TMS produced MEPs in the ipsilateral FDI. Two subjects had rich ipsilateral hand representations with multiple ipsilateral MEP sites. Both had ipsilateral MEP sites near the representation of the contralateral FDI, but the largest ipsilateral MEPs occurred with TMS at more lateral sites, which were near the representation of the contralateral risorius. In these subjects, the ipsilateral deltoid was preferentially activated at sites medial and posterior to those activating the contralateral muscle. Ipsilateral TMS also produced silent periods in the FDI in all subjects. These silent periods were much more frequent than the ipsilateral MEPs and tended to occur with TMS near the representation of the contralateral FDI. The excitatory cortical representation of the ipsilateral arm muscles is accessible to TMS in normal subjects and is different from that of the homologous contralateral muscles. The hand may have two ipsilateral representations, one of which produces silent periods and the other MEPs at the same stimulus intensity.

Akinesia in Parkinson's disease. I. Shortening of simple reaction time with focal, single‐pulse transcranial magnetic stimulation

Abstract: We studied the effects of transcranial magnetic stimulation (TMS) of the motor cortex on simple reaction time (RT) in 10 patients with Parkinson's disease compared with 10 age-matched normal controls. The subjects flexed their right elbow rapidly in response to a visual go-signal. In random trials, TMS was applied to the left motor cortex at varying delays after the go-signal. In trials without TMS, RT was longer in the patients. However, in the trials with subthreshold TMS, RT in the patients became as fast as RT in trials without TMS in the controls. This shortening was associated with normalization of the voluntary triphasic EMG pattern and the pre-movement cortical excitability increase.

Central fatigue as revealed by postexercise decrement of motor evoked potentials.

Abstract: We have previously shown that the amplitudes of motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) were transiently decreased after exercise, indicating fatigue of motor pathways in the central nervous system. The responsible mechanism is apparently decreased efficiency in the generation of the descending volleys in the motor cortex. We also noted a progressive decrement in amplitude from the first to the fourth MEP. To further clarify the mechanism of this phenomenon, 5 subjects were studied with TMS delivered at the rates of 0.1, 0.15, 0.3, 1, 3, and 6 Hz. The effect was best demonstrated at 0.3 Hz, and occurred after both isometric and isotonic exercise. Three of the subjects also had 0.3-Hz percutaneous electrical stimulation of the brainstem, and a decrement in MEP amplitude did not occur. Further, the delivery of TMS during muscle contraction after muscle fatigue failed to produce a decrement. The results are similar to those found at the neuromuscular junction in myasthenia gravis and are consistent with a reduced safety factor of cortical synaptic transmission in central nervous system fatigue.

Induction of errors in a delayed response task by repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex.

Abstract: WE used repetitive transcranial magnetic stimulation to study the function of the dorsolateral frontal cortex in a delayed response task in 10 normal volunteers. Unilateral stimulation of right or left prefrontal cortex during the delay period between instruction and execution cues led to a signific

Movement-related cortical potentials.

Abstract: Movement-related cortical potentials represent averaged electroencephalographic activity before and after a voluntary movement. They begin with a slowly rising negativity, called the Bereitschaftspotential (BP), and progress to a steeper, later negativity starting about 400 msec before the onset of movement, called the negativity slope (NS'). They are followed by the motor potential, which is seen partly before and partly after the movement. The initial slope of motor potential (isMP) occurs just before the onset of electromyographic (EMG) activity, is focal topographically over the primary motor cortex, and probably represents activation of the primary motor cortex. This contralateral focal negativity persists for 30 to 50 msec after the onset of EMG activity, when it then drops off in the central and parietal regions, an event called the parietal peak of motor potential (ppMP). Subsequently, the peak negativity shifts toward the anterior contralateral area, where it reaches the highest negativity of the recording, called the frontal peak of motor potential (fpMP). The fpMP appears to represent feedback from the movement and may originate, in part, from the supplementary motor area. In patients with congenital mirror movements, the isMP occurs bilaterally. In patients with Parkinson's disease and cerebellar disease, the isMP is more diffuse and the fpMP is more posterior than normal. Movement-related cortical potentials are useful research tools, but are not yet appropriate for clinical applications.

Induction of a recall deficit by rapid-rate transcranial magnetic stimulation

Abstract: WE used rapid-rate, repetitive transcranial magnetic stimulation (rTMS) for the noninvasive study of verbal recall. Five right-handed normal subjects were studied. Recall followed immediately after presentation of a 12-word list. Focal rTMS was applied with a figure eight coil in trains of 500 ms duration to F7, F8, T5, T6, P3, P4, or 01, 02 at latencies of 0, 250, 500, or 1000 ms during word list presentation. Recall was consistently significantly diminished only after left mid-temporal and bilateral dorsofrontal rTMS at both 0 and 250 ms latencies. We conclude that rTMS may be useful as a non-invasive tool for the study of verbal memory processes.

Long-term botulinum toxin treatment of focal hand dystonia.

Abstract: We treated focal hand dystonia in 53 patients with botulinum toxin injections for up to 6 years. Eighty-one percent of the patients improved with at least one injection session. Sixty-five percent of the injections produced transient weakness. We followed 37 of the patients for at least 2 years from the start of treatment, 24 of whom discontinued treatment because of inadequate response, loss of response, inaccessibility of a treatment provider, or the expense of the toxin. Women, who had a greater extent and longer duration of benefit than men, were more likely to continue treatment. The mean interval between injection sessions was 6 months. In most patients, we injected the toxin into the same combination of muscles at each session. The dose of toxin generally fluctuated within a range of 20 units. Side effects were mild and transient and unrelated to the long-term use of botulinum toxin. Botulinum toxin injection is safe and effective for the long-term management of focal hand dystonia.

Disturbances of kinaesthesia in patients with cerebellar disorders

Abstract: We studied the ability of patients with cerebellar degeneration to perceive differences in kinaesthetic stimuli and compared it with that of normal subjects. All participants were tested for duration, amplitude and velocity sensation. In separate experiments, the responses of muscle spindle afferents and slowly adapting cutaneous mechanoreceptors to the kinaesthetic stimuli were recorded. The performance of patients with cerebellar degeneration was significantly worse than that of normal subjects on the tasks testing for duration and velocity perception. Although both spindle afferents and slowly adapting cutaneous mechanoreceptors were able to provide relevant sensory information during the kinaesthetic tasks, spindle afferents were superior in detecting velocity changes. These results suggest that the cerebellum may be involved in processing sensory signals that are involved in motor control as well as in conscious perception.

Resetting of essential tremor and postural tremor in Parkinson's disease with transcranial magnetic stimulation.

Abstract: We studied the effects of transcranial motor cortex stimulation on the electromyographic characteristics of tremor in 9 patients with familial essential tremor and in 12 patients with postural tremor associated with Parkinson's disease. Transcranial magnetic stimulation reset both types of tremor equally. The resetting depended on the stimulus intensity, but was most closely correlated with the duration of the electromyographic silent period that followed the stimulus-induced motor evoked potential. Tremor resetting was present bilaterally even after focal, unilateral stimulation. Transcranial electrical stimulation failed to reset the tremor in either patient group. These results emphasize the role of central, intracortical structures in the generation of essential tremor and postural tremor in Parkinson's disease. © 1994 John Wiley & Sons, Inc.

Cortical magnetic and electric fields associated with voluntary finger movements.

Abstract: Multichannel recordings of both movement-related magnetic fields (MRMFs) and movement-related cortical potentials (MRCPs) were simultaneously recorded in association with voluntary unilateral self-paced index finger abduction movement in two normal volunteers. 1) Slow magnetic field (readiness field; RF) can be detected several hundred msec before the movement onset, and its field distribution indicates the existence of the largest generator source over the contralateral primary motor area. Taken together with the vertex-maximal Bereitschaftspotential which corresponds to the earlier part of the RF, the complexity of this magnetic field suggested by relatively low correlation value in single dipole model indicates the co-activation of other underlying generators besides this largest dipole. 2) The utilization of MRMF with MRCP facilitates the separation of two distinct electrophysiological events in proximity to the movement onset, which are difficult to be determined by the technique of MRCP only. Those are the motor field (MF) and the movement evoked field I (MEFI) in MRMF, and the parietal peak motor potential (ppMP) and the frontal peak motor potential (fpMP) in MRCP, which occur approximately 20 and 100 msec after EMG onset, respectively. These two subcomponents may imply the culmination of motor cortex and sensory feedback activation, respectively. Combined study of MRMF and MRCP will provide better definition of cortical events related to voluntary movement than the study of either modality alone.

Implicit and explicit memory in patients with Parkinson's disease with and without dementia.

Abstract: Objective: To study explicit and implicit memory processes in patients with Parkinson's disease. Design: Case-control design. All subjects were given a neuropsychological test battery, and the test scores were compared among the groups. Setting: Government-funded research facility. All subjects were examined as outpatients. Patients: We tested nondemented (n=13) and demented (n=5) patients with Parkinson's disease and normal controls (n=12) matched for age, gender, and educational level. Main Outcome Measures: Memory for verbal and pictorial stimuli under both explicit and implicit retrieval conditions. Results: Both nondemented and demented patients with Parkinson's disease exhibited impairment on tests of explicit memory. Their impairment could be graded based on the level of effort required by the task: impaired free recall in nondemented patients and impaired free recall, cued recall, and recognition in demented patients. By contrast, neither group showed evidence of impairment on automatic (modality monitoring and word frequency estimation) or implicit (word and picture fragment identification) memory tasks. Correlation analyses did not support any association between the effortful memory deficits and neurologic variables, mood, or performance on executive function tests. Conclusions: Memory deficits in patients with Parkinson's disease primarily involve the conscious, effortful strategic aspects of searching long-term memory.

Limitations of electromyography and magnetic stimulation for assessing laryngeal muscle control.

Abstract: The development of new phonosurgical techniques has increased the level of interest in the field of neurolaryngology. This field requires valid techniques for determining if muscle activation is normal. Laryngeal electromyography is being used more frequently to assess muscle innervation and synkinesis. Further, magnetic stimulation has been introduced as a noninvasive technique for nerve stimulation. Technical limitations that affect the clinical utility of both these techniques are reviewed: 1) difficulties obtaining selective and accurate electromyographic laryngeal muscle recordings, 2) normal variation in movement and muscle activation patterns within and between normal individuals when producing the same speech syllables, and 3) variation in laryngeal muscle response latencies between and within normal subjects during peripheral magnetic stimulation. Given the normal variation in laryngeal electromyography and magnetic stimulation response latencies, these techniques may not yet be reliable or accurate for assessing reinnervation or synkinesis following recurrent laryngeal nerve injury.