scispace - formally typeset
Search or ask a question

Showing papers by "Mark Hallett published in 2002"


Journal ArticleDOI
07 Feb 2002-Nature
TL;DR: Low-frequency, repetitive transcranial magnetic stimulation of M1 but not other brain areas specifically disrupted the retention of the behavioural improvement, but did not affect basal motor behaviour, task performance, motor learning by subsequent practice, or recall of the newly acquired motor skill.
Abstract: Behavioural studies indicate that a newly acquired motor skill is rapidly consolidated from an initially unstable state to a more stable state, whereas neuroimaging studies demonstrate that the brain engages new regions for performance of the task as a result of this consolidation. However, it is not known where a new skill is retained and processed before it is firmly consolidated. Some early aspects of motor skill acquisition involve the primary motor cortex (M1), but the nature of that involvement is unclear. We tested the possibility that the human M1 is essential to early motor consolidation. We monitored changes in elementary motor behaviour while subjects practised fast finger movements that rapidly improved in movement acceleration and muscle force generation. Here we show that low-frequency, repetitive transcranial magnetic stimulation of M1 but not other brain areas specifically disrupted the retention of the behavioural improvement, but did not affect basal motor behaviour, task performance, motor learning by subsequent practice, or recall of the newly acquired motor skill. These findings indicate that the human M1 is specifically engaged during the early stage of motor consolidation.

754 citations


Journal ArticleDOI
TL;DR: 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.

704 citations


Journal ArticleDOI
TL;DR: The suggested coil is likely to have the ability of deep brain stimulation without the need to increase the intensity to levels that stimulate cortical regions to a much higher extent and possibly cause undesirable side effects.
Abstract: Noninvasive magnetic stimulation of the human central nervous system has been used in research and the clinic for several years. However, the coils used previously stimulated mainly the cortical brain regions but could not stimulate deeper brain regions directly. The purpose of the current study was to develop a coil to stimulate deep brain regions. Stimulation of the nucleus accumbens and the nerve fibers connecting the prefrontal cortex with the nucleus accumbens was one major target of the authors' coil design. Numeric simulations of the electrical field induced by several types of coils were performed and accordingly an optimized coil for deep brain stimulation was designed. The electrical field induced by the new coil design was measured in a phantom brain and compared with the double-cone coil. The numeric simulations show that the electrical fields induced by various types of coils are always greater in cortical regions (closer to the coil placement); however, the decrease in electrical field within the brain (as a function of the distance from the coil) is markedly slower for the new coil design. The phantom brain measurements basically confirmed the numeric simulations. The suggested coil is likely to have the ability of deep brain stimulation without the need to increase the intensity to levels that stimulate cortical regions to a much higher extent and possibly cause undesirable side effects.

305 citations


Journal ArticleDOI
TL;DR: Deafferentation, produced by a new technique of regional anesthesia of the upper arm during hand motor practice, dramatically improved hand motor function including some activities of daily living.
Abstract: Background Recovery of function following stroke plateaus in about 1 year, typically leaving upper arm function better than that in the hand. Since there is competition among body parts for territory in the sensorimotor cortex, even limited activity of the upper arm might prevent the hand from gaining more control, particularly when the territory is reduced in size because of the stroke. Deafferentation of a body part in a healthy brain enhances cortical representations of adjacent body parts, and this effect is markedly increased by voluntary activity of the adjacent part. Objective To explore whether deafferentation of the upper arm, produced by a new technique of regional anesthesia during hand motor practice, helps recovery of hand function in patients with long-term stable weakness of their hand following stroke. Methods and Results Deafferentation, produced by a new technique of regional anesthesia of the upper arm during hand motor practice, dramatically improved hand motor function including some activities of daily living. The improvement was associated with an increase in transcranial magnetic stimulation–evoked motor output to the practice hand muscles. Conclusion This is a novel therapeutic strategy that may help improve hand function in patients with long-term weakness after stroke.

230 citations


Journal ArticleDOI
TL;DR: A novel method using two‐dimensional J‐resolved magnetic resonance spectroscopy revealed that brain GABA levels are decreased in specific brain regions of the focal dystonia patients compared to normal controls.
Abstract: Patients with task-specific dystonia (writer's cramp) have impaired cortical inhibition likely arising from striatal dysfunction. However, the levels of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the brains of these patients are not known. In this study, we evaluated 7 patients with right-sided focal, task-specific dystonia and 17 normal control subjects. A novel method using two-dimensional J-resolved magnetic resonance spectroscopy revealed that brain GABA levels are decreased in specific brain regions of the focal dystonia patients compared to normal controls. A significant decrease in GABA level was observed in the sensorimotor cortex and lentiform nuclei contralateral to the affected hand, while there was only a small nonsignificant decrease in the ipsilateral sensorimotor cortex and lentiform nuclei. GABA changes in the posterior occipital region of patients were not significant. The impaired cortical GABA level correlates with prior physiologic studies showing reduced intracortical inhibition. Reduced GABA in the striatum is consistent with striatal dysfunction since GABA is a principal neurotransmitter in that region. The reduction of brain GABA in dystonia patients may explain the clinical symptomatology of focal dystonia. Magnetic resonance spectroscopy may be a useful noninvasive tool in the evaluation of regional brain GABA changes and in monitoring the effects of various therapies.

196 citations


Journal ArticleDOI
TL;DR: TMS applications have an important place among the investigative tools to study patients with motor disorders and give information on the pathophysiology of the processes underlying the various clinical conditions.
Abstract: 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.

178 citations


Journal ArticleDOI
TL;DR: 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.
Abstract: 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

173 citations


Journal ArticleDOI
TL;DR: It is concluded that training in braille reading improves deficits in spatial discrimination and decreases disability in patients with focal hand dystonia.
Abstract: Some patients with focal hand dystonia have impaired sensory perception. Abnormal sensory processing may lead to problems with fine motor control. For patients with focal hand dystonia who demonstrate sensory dysfunction, sensory training may reverse sensory impairment and dystonic symptoms. We studied the efficacy of learning to read braille as a method of sensory training for patients with focal hand dystonia. Sensory spatial discrimination was evaluated in 10 patients who had focal hand dystonia and 10 age- and gender-matched controls with a spatial acuity test (JVP domes were used in this test). Clinical dystonia evaluation included the Fahn dystonia scale and time needed to write a standard paragraph. Each individual was trained in braille reading at the grade 1 level for 8 weeks, between 30 and 60 minutes daily, and was monitored closely to ensure that reading was done regularly. Both controls and patients demonstrated improvement on the spatial acuity test. Patients showed a significant mean difference from baseline to 8 weeks on the Fahn dystonia scale. Sixty percent of the patients shortened the time they needed to write a standard paragraph. Improved sensory perception correlated positively with improvement on the Fahn dystonia scale. We conclude that training in braille reading improves deficits in spatial discrimination and decreases disability in patients with focal hand dystonia.

153 citations



Journal ArticleDOI
TL;DR: It is demonstrated that volitional inhibition enhances SICI but reduces LICI nonselectively, suggesting that these two inhibitory mechanisms act differently during execution and suppression of voluntary movements.
Abstract: To investigate the effect of volitional inhibition on cortical inhibitory mechanisms, we performed transcranial magnetic stimulation (TMS) studies with a Go/NoGo reaction task in seven healthy subjects. Subjects were asked to extend their right index finger only after Go, but to remain relaxed after NoGo. Single- and paired-pulse TMS were triggered at the average reaction time for the Go response in each subject after Go or NoGo cues. Motor evoked potentials were recorded in the extensor indicis proprius (EIP) and abductor digiti minimi (ADM) muscles of right hand. Paired-pulse TMS with subthreshold conditioning stimuli at interstimulus intervals (ISIs) of 2 ms [short intracortical inhibition (SICI)] and 15 ms [intracortical facilitation (ICF)] and that with suprathreshold conditioning stimuli at ISI of 80 ms [long intracortical inhibition (LICI)] were performed in both Go/NoGo and control conditions. Inhibition of SICI was enhanced in both EIP and ADM after NoGo and was reduced only in EIP after Go. Inhibition of LICI was reduced in both muscles during both conditions, while ICF was not altered. The present results demonstrate that volitional inhibition enhances SICI but reduces LICI nonselectively. These results suggest that these two inhibitory mechanisms act differently during execution and suppression of voluntary movements.

138 citations


Journal ArticleDOI
TL;DR: Benign essential blepharospasm is a common focal dystonia characterized by involuntary eyelid closure that appears to be multifactorial, representing the influence of a genetic background and an environmental trigger.
Abstract: Benign essential blepharospasm is a common focal dystonia characterized by involuntary eyelid closure. Its etiology, supported by animal models, appears to be multifactorial, representing the influence of a genetic background and an environmental trigger. The genetic background could be responsible for the reduced brain inhibition, identified with physiologic studies that would set up a permissive condition for increased brain plasticity. Reduced D2 receptors identified with PET might be an indicator of this reduced inhibition. The trigger could be repetitive use or local ocular disease. Although symptomatic therapy is available, better approaches are needed and will likely become available as the genetics and pathophysiology become well understood.

Journal ArticleDOI
TL;DR: The results suggested that for slow repetitive movements, each individual movement is separately controlled, and EEG activation and coupling of the motor cortical areas were immediately followed by transient deactivation and decoupling, having clear temporal modulation locked to each movement.
Abstract: We investigated changes in the activation and functional coupling of bilateral primary sensorimotor (SM1) and supplementary motor (SMA) areas with different movement rates in eight normal volunteer...

Journal ArticleDOI
TL;DR: To clarify the precise location and timing of the cortical activation in voluntary movement, dipole source analysis integrating multiple constraints wa conducted for the movement-related cortical potentia (MRCP) and deduced patterns of activation similar to that of the bilateral precentral gyri.

Journal ArticleDOI
TL;DR: After hemiparetic stroke, although there is typically some recovery of motor function in the weakened limb, it is often not adequate, and it has not been clear whether this improvement could be facilitated by any intervention.
Abstract: Following hemiparetic stroke, recovery of motor function is often not adequate. There are now multiple approaches that seem promising for promoting recovery of the weakened limb, and they are often guided by new understandings of biological principles, many relating to brain plasticity, including: (a) Use of a body part enhances its function. Intensive, focused physical therapy does help, as has been demonstrated, for example, by constraint-induced movement therapy. Other techniques use the same principle. (b) The ipsilateral hemisphere can contribute to motor control, and bilateral, symmetrical arm movement training may help on this basis. (c) Sensory stimulation enhances plasticity. (d) Reduction of inhibition enhances plasticity. This has been demonstrated to be useful for rehabilitation utilizing transient deafferentation. (e) Pharmacological agents such as amphetamines can enhance plasticity. (f) Transcranial magnetic stimulation can enhance plasticity. (g) Spasticity can be reduced with oral, intrathecal, or intramuscular agents. (h) Cortical activity can be interpreted for the intended movement and a signal derived to control a prosthesis. (i) Lost tissue might be replaced with either regrowth of tissue or implantation. Following hemiparetic stroke, although there is typically some recovery of motor function in the weakened limb, it is often not adequate. Until recently, it has not been clear whether this improvement could be facilitated by any intervention. Clearly, physical and occupational therapy directed to activities of daily living are commonly successful, but this may be due to substitutions by the unaffected body parts. There are now multiple approaches that seem promising for promoting recovery of the weakened limb, and they are often guided by new understandings of biological principles, many relating to brain plasticity. Brain plasticity is the concept that the brain is able to change (Hallett 1999, 2000, 2001a, 2001b). Neurons and neural networks can change their function by several mechanisms. Alterations in the balance of excitation and inhibition may occur, including reduction in inhibition called “unmasking.” Synaptic strength can increase or decrease by mechanisms such as long-term potentiation or depression. The excitability of neuronal membrane can change, and new synapses can form. Not only can these processes occur, they are constantly occurring. To harness these for recovery is now a major task for rehabilitation.

Journal ArticleDOI
TL;DR: 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, which suggests that output to the hand evoked from the cortex by TMS was not decreased by ischaemic block.
Abstract: 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.

Journal ArticleDOI
TL;DR: Levetiracetam interferes with rapid motor learning; this is consistent with a negative influence on long-term potentiation.
Abstract: Background The human motor cortex (M1) has a role in motor learning. Antiepileptic drugs that suppress M1 excitability may affect learning, presumably by inhibiting long-term potentiation. Levetiracetam, a new antiepileptic drug with a unique preclinical profile, also suppresses M1 excitability, but in a way that is different from other antiepileptic drugs. The effect of levetiracetam on motor learning has yet to be addressed. Objective To investigate whether levetiracetam alters rapid motor learning in humans. Methods We measured pinch force and acceleration and motor excitability before and after 30 minutes of pinch practice at 0.5 Hz in 10 healthy volunteers. Either 3000 mg of levetiracetam or placebo was administered 1 hour before the experiment. Results After practice, pinch acceleration was significantly increased with placebo, but not with levetiracetam. All other measures showed no significant change. Conclusion Levetiracetam interferes with rapid motor learning; this is consistent with a negative influence on long-term potentiation.

Journal ArticleDOI
TL;DR: Single-pulse transcranial magnetic stimulation was applied to the occipital pole of healthy subjects while they performed a forced-choice visual letter-identification task, consistent with the possibility that also the earlier delay interval reflects visual cortical processing.
Abstract: Single-pulse transcranial magnetic stimulation (TMS) was applied to the occipital pole of healthy subjects while they performed a forced-choice visual letter-identification task Pulses were applied on the midline but with a left-right asymmetric polarity; pulse application occurred at a variable delay after letter presentation onset; letters were presented in left or right hemifield Averaging data over subjects and hemifields showed that performance attained local minima at 20 ms and 100 ms; averaging data over subjects and delays showed that performance was biased towards the same hemifield during both delay intervals; averaging data over subjects showed that the hemifield bias progressively decreased from 20 ms to 50 ms The data are consistent with the possibility that also the earlier delay interval reflects visual cortical processing

Journal ArticleDOI
TL;DR: Transcranial magnetic stimulation may also improve symptoms in patients with motor system disorders such as Parkinson’s disease or dystonia and be an excellent tool to study brain plasticity in situations such as stroke and recovery of function.
Abstract: Transcranial magnetic stimulation (TMS) is an exciting new tool for clinical neurophysiology (Hallett, 2000). Although it followed quickly on the heels of transcranial electrical stimulation, TMS has only been around for approximately 15 years. In this time, its use has expanded rapidly. At first, it was applied simply to the motor cortex to produce motor evoked potentials. This allowed measurement of central motor conduction times in the corticospinal tract. This capability is clearly valuable and has been applicable immediately in the clinic to the assessment of situations such as multiple sclerosis, cervical spondylosis, and primary lateral sclerosis. It became rapidly clear, however, that its value far exceeded the ability to measure central motor conduction. It was able to localize muscle representations and allowed mapping of the motor strip. Using a variety of clever procedures, it became possible to assess excitability in various ways, including the ability to determine intracortical networks of excitation and inhibition. The physiologic insights are increasingly exposing the great complexity of cortical processing. The value of TMS is not limited to its study of the motor cortex. Studies have shown that it can be used to study many regions including visual cortex, somatosensory cortex, and areas of parietal and frontal cortex with functions including language and memory. Transcranial magnetic stimulation can be used to excite or to inhibit different regions transiently. Its ability to inhibit regions of cortex transiently is particularly valuable because this allows a temporary, reversible “lesion” of the normal human brain. This capability has permitted conclusions relating to the functional relevance of different brain regions for specific functions (Cohen et al., 1997). Note that this conclusion cannot necessarily be made with neuroimaging, such as the popular functional MRI. Imaging studies say that a region is involved in a particular task, but not that it is critical for that task. Using all these methods, it has been possible to gather important insights into the pathophysiology of neurologic disorders. Disorders of the motor system have been most investigated, but other conditions such as epilepsy and migraine have also been studied. TMS has also been an excellent tool to study brain plasticity in situations such as stroke and recovery of function (Hallett, 2001). The next step was made when it was recognized that TMS may well influence the function of the brain even after the stimulation was finished (Wassermann and Lisanby, 2001). In general, slow rates of repetitive TMS tend to suppress function, whereas a rapid rate enhances it. Psychiatrists have jumped quickly onto this possibility and see in TMS a new tool that may replace electroconvulsive therapy. Transcranial magnetic stimulation may also improve symptoms in patients with motor system disorders such as Parkinson’s disease or dystonia. Transcranial magnetic stimulation is a safe technique. With single pulses and paired (double) pulses, there has not been any problem with TMS at all. In rare individuals with brain lesions and a tendency to epilepsy, single pulses have apparently triggered a seizure, but even trying to trigger seizures in epileptic patients has been difficult. Repetitive stimulation at high rates, if given for long periods or with intense stimulation, can produce seizures even in normal individuals. Thus, repetitive stimulation needs to be given with care. There are guidelines published for safe stimulation parameters, and when these are followed, repetitive stimulation can be used safely with confidence (Wassermann, 1998). Although TMS is making great strides in research achievements, its application to the clinic so far, although distinct, has been limited. It is partly for this reason that in the United States, TMS remains a research procedure. It is necessary for clinical neurophysiologists to get approval of their institutional review board (ethics committee). When doing procedures of greater than usual risk, the Food and Drug Administration may also require an investigational device exemption. It will require a notable effort on the part of a manufacturer to demonstrate the utility (and corresponding safety) of the method. Meanwhile, in many other countries, TMS is readily available in the clinic. In this special issue of the Journal of Clinical Neurophysiology experts have summarized current knowledge Journal of Clinical Neurophysiology 19(4):253–254, Lippincott Williams & Wilkins, Inc., Philadelphia © 2002 American Clinical Neurophysiology Society


Journal ArticleDOI
01 Mar 2002-Brain
TL;DR: Full disclosure of financial interests by authors is essential to retain public trust in biomedical research, the peer‐review process and the integrity of the authors and of the universities.
Abstract: Biomedical research is becoming more complex as a result of involvement by individual investigators, universities, commercial research units and industry. Financial conflicts of interest have been the subject of many editorials, and most peer‐reviewed journals now require any conflicts to be identified and explained when authors submit manuscripts for publication. Clear statements of industry sponsored research and author participation in corporate activities are required for evaluation of a manuscript. Full disclosure of financial interests by authors is essential to retain public trust in biomedical research, the peer‐review process and the integrity of the authors and of the universities (DeAngelis et al ., 2001). We already require that each author sign a statement of his or her financial arrangements with public, private and industry sources of support. These declarations alert the editor, reviewer and physician‐reader to any potential bias …

01 Jan 2002
TL;DR: In this article, the authors defined epileptic myoclonus as an elementary electroclinical manifestation of epilepsy involving descending neurons, whose spatial (spread) or temporal (self-sustained repetition) amplification can trigger overt epileptic activity and can be classified as cortical, secondarily generalized, thalamo-cortical, and reticular.
Abstract: Epileptic myoclonus can be defined as an elementary electroclinical manifestation of epilepsy involving descending neurons, whose spatial (spread) or temporal (self-sustained repetition) amplification can trigger overt epileptic activity and can be classified as cortical (positive and negative), secondarily generalized, thalamo-cortical, and reticular. Cortical epileptic myoclonus represents a fragment of partial or symptomatic generalized epilepsy; thalamo-cortical epileptic myoclonus is a fragment of idiopathic generalized epilepsy. Reflex reticular myoclonus represents the clinical counterpart of fragments of hypersynchronous epileptic activity of neurons in the brainstem reticular formation. Epileptic myoclonus, in the setting of an epilepsy syndrome, can be only one component of a seizure, the only seizure manifestations, one of the multiple seizure types or a more stable condition that is manifested in a nonparoxysmal fashion and mimics a movement disorder. This complex correlation is more obvious in patients with epilepsia partialis continua in which cortical myoclonus and overt focal motor seizures usually start in the same somatic (and cortical) region. In patients with cortical tremor this correlation is less obvious and requires neurophysiological studies to be demonstrated.

Journal ArticleDOI
TL;DR: Recovery from stroke in any location is explained by at least a minimal projection from all cortical face areas to all parts of the face, and that one component of the corticofacial projection arises from the limbic proisocortices (M3 and M4) suggests an anatomical substrate which may contribute to the clinical dissociation of emotional and volitional facial movement.
Abstract: Cranial Nerve Motor Nuclei The general principle for cortical control of cranial nerve motor nuclei 5, 7, 9, 10, 11, and 12 is that there is predominant contralateral influence and variable, but important, ipsilateral influence as well. The importance of the bilaterality of innervation is clearly different than for limb motor control and is helpful in understanding clinical phenomena such as recovery from stroke. The best understood situation is the 7th nerve, thanks in part to a new anatomical study in the rhesus monkey by Morecraft and colleagues. The corticobulbar projection was defined by injecting anterograde tracers into the face representation of each motor cortex, and in the same animals, the musculotopic organization of the facial nucleus was defined by injecting fluorescent retrograde tracers into individual muscles of the upper and lower face. Perioral muscles, prototypical for the lower face, are innervated largely contralaterally from the primary motor cortex (M1); lateral premotor cortex, ventral and dorsal (LPMCv, LPMCd); and caudal cingulate (M4). For upper face muscles, orbicularis oculi are innervated mostly by rostral cingulate (M3) and auricular muscles by the supplementary motor area (M2), both bilaterally. Such a pattern explains the upper face sparing in typical middle cerebral artery stroke. Recovery from stroke in any location is explained by at least a minimal projection from all cortical face areas to all parts of the face. In addition, that one component of the corticofacial projection arises from the limbic proisocortices (M3 and M4) and another component arises from frontal isocortices (M1, M2, LPMCv, and LPMCd) suggests an anatomical substrate which may contribute to the clinical dissociation of emotional and volitional facial movement. Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation studies have explored cortical connections to muscles of both the lower and upper face. Only a few studies have reported data for orbicularis oculi in the upper face. Latencies are reported to be about 10 msec and bilateral in nature, but given that the R1 component of the blink reflex has about the same latency, this response may well be contaminated by the blink reflex. Additionally, stimulation was done over M1 regions for the face, and, as noted in the study by Morecraft and associates, there is only very sparse projection to the eyelid muscles from M1. TMS studies of the orbicularis oris in the lower face are much better documented. The effects here are primarily contralateral with latencies of 9 to 10 msec. Studies of single motor unit latency histograms show that the earliest responses, which ranged from 9.2 to 16.5 msec, are very likely to be monosynaptic. The relative slowness of this projection is due to slow central conduction and a relatively longer length of the 7th nerve than other cranial motor nerves. It is also possible to find inhibitory responses in orbicular oris, and these can be seen even without a preceding motor evoked potential. Because the facial muscles remain responsive to trigeminal stimulation during this silent period, the origin of the inhibition must be intracortical. Muscles of the 5th cranial nerve have also been studied with TMS. Responses in the masseter muscle are heavily contralateral, but with some ipsilateral influence. The latency for the contracting masseter muscle is approximately 6 msec. The ipsilateral response can be inhibitory as well as excitatory. Poststimulus time histograms of single motor unit responses show the earliest


Book ChapterDOI
TL;DR: It is reasoned that anesthesia of the proximal muscles and exercise of the hand might increase cortical representation of theHand and concomitantly improve hand function.
Abstract: Publisher Summary Most transcranial magnetic stimulation (TMS) studies have shown that the presence of contralateral motor evoked potentials (MEPs), early after the stroke, is a marker for good recovery. MEPs can indicate this good prognosis even in the face of complete hemiplegia. Conversely, the absence of MEPs gives a bad prognosis. Preservation of the corticospinal tract, with magnetic resonance imaging (MRI), is also found to correlate with good recovery confirming the TMS studies. One situation, where the undamaged hemisphere is likely important, is in recovery from dysphagia. Currently, investigation on a new method that takes advantage of several features of plasticity is going on. After hemiplegic stroke, there is often significant loss of hand function, with relatively retained strength, in the proximal arm muscles. As there is a “competition” between the body parts for territory in the motor cortex, it is possible that the use of the proximal muscles makes it difficult for hand muscles to increase their representation. It is known that peripheral deafferentation, with a tourniquet, increases the MEP of the proximal muscles, and recently it has been established that this increase is magnified by exercise of the proximal muscles during the peripheral block. It is reasoned that anesthesia of the proximal muscles and exercise of the hand might increase cortical representation of the hand and concomitantly improve hand function.

Journal ArticleDOI
TL;DR: Authors will be required to sign a statement indicating that they accept full responsibility for the conduct of the study, had access to all the data and had the authority to publish it, and this new policy will ensure not only greater academic freedom, but also increased credibility for data in journals that have been the product of academic and corporate alliances.
Abstract: Biomedical research is becoming more complex as a result of involvement by individual investigators, universities, commercial research units and industry. Financial con ̄icts of interest have been the subject of many editorials, and most peer-reviewed journals now require any con ̄icts to be identi®ed and explained when authors submit manuscripts for publication. Clear statements of industry sponsored research and author participation in corporate activities are required for evaluation of a manuscript. Full disclosure of ®nancial interests by authors is essential to retain public trust in biomedical research, the peer-review process and the integrity of the authors and of the universities (DeAngelis et al., 2001). We already require that each author sign a statement of his or her ®nancial arrangements with public, private and industry sources of support. These declarations alert the editor, reviewer and physician-reader to any potential bias in the interpretation and presentation of the data. Patients' lives may depend on an accurate and complete understanding of how and why authors obtained facts relating to therapies. Non-®nancial con ̄icts of interest between authors and corporate sponsors are of equal concern and require our attention. These include the need for an open and candid relationship between authors and the policies of the sponsoring companies with regard to academic freedom. Issues of control and complete access to all data, conduct of statistical studies and analyses, manuscript preparation and decisions to publish are of increasing importance and concern. Corporate sponsors must not be allowed to in ̄uence publication, or indeed to prevent it, especially when the data are not supportive of their product. Authors, editors and industry sponsors are aware of these matters and it is now time to address them (DeAngelis et al., 2001). These issues have been addressed in recent editorials in JAMA and The New England Journal of Medicine. The editors of JAMA, The New England Journal of Medicine, Canadian Medical Association Journal, Journal of the Danish Medical Association, The Lancet, MEDLINE/Index Medicus, New Zealand Medical Journal, Journal of the Norwegian Medical Association, Dutch Journal of Medicine, Annals of Internal Medicine, Medical Journal of Australia and the Western Journal of Medicine have all agreed to require authors to disclose details of their own and the sponsor's role in the study (Davido€ et al., 2001). Authors will be required to sign a statement indicating that they accept full responsibility for the conduct of the study, had access to all the data and had the authority to publish it. An amendment was made allowing the sponsor up to 60 days to review a manuscript before publication to allow for the ®ling of additional patent protection, if necessary. These policies will also be incorporated into the next revision of `Uniform Requirements for Manuscripts Submitted to Biomedical Journals' (Davidson et al., 1997). We believe that neurology journals should invoke the same philosophy and implement the same procedures. We ®rmly believe that manuscripts submitted to our journals are the intellectual property of the authors, not the study sponsor. Academic freedom includes the right of authors to have access to all of the data obtained in their study, to review it, obtain statistical analyses independently and to publish their data based on their own decisions and not those of the ®nancial sponsor (Davidson et al., 1997; Davido€ et al., 2001; DeAngelis et al., 2001). We will now require the principal author to declare in writing that he or she will take full responsibility for the data, the analyses and interpretation, and the conduct of the research; that he or she had full access to all of the data; and that he or she had the right to publish any and all data, separate and apart from the attitudes of the sponsor. Without these written assurances, we will not consider the paper for review. We believe this new policy will ensure not only greater academic freedom, but also increased credibility for data in our journals that have been the product of academic and corporate alliances.

Journal ArticleDOI
01 Apr 2002
TL;DR: It is proposed that the visual maintenance of stability in association with saccades and blinks relies on dynamic modulation within the striate cortex, a non-visual stimulus dependent saccadic role of the striates.
Abstract: While much has been learned about the role of frontal and parietal cortices in saccades and in visuospatial attention, the role of the visual cortex remains an enigma. Traditionally, the striate cortex was considered a way station to transmit static information about the features and retinotopical loci of elementary visual stimuli. Recent multielectrode studies in the monkey, however, established visual context dependent dynamic properties of the striate cortex, beyond retinotopy. Our studies evaluate eye movement related modulation of the visual cortex. We have studied the frontal, parietal and occipital cortex using functional MRI (fMRI) in normal observers. Our results show that in addition to the frontal cortex, the striate cortex and the precuneus are active in association with quick, darting eye movements called saccades (S) even in the dark without visual input . Single pulse Transcranial Magnetic Stimulation (sTMS) reveals that the conscious perception of a visual cue is a prerequisite to execute a cued saccade, or antisaccade. Wavelet analysis of the perisaccadic EEG reveals a burst of high frequency components of the occipital cortex, both in light and in dark. Apparently, there is a non-visual stimulus dependent saccadic role of the striate cortex. Even though saccades are executed constantly by awake humans, we are not aware of a shifting visual scene by saccades. We propose that the visual maintenance of stability in association with saccades and blinks relies on dynamic modulation within the striate cortex.

Journal ArticleDOI
TL;DR: Full disclosure of financial interests by authors is essential to retain public trust in biomedical research, the peer-review process, and the integrity of the authors and universities.
Abstract: Biomedical research is becoming more complex as a result of involvement by individual investigators, universities, commercial research units, and industry. Financial conflicts of interest have been the subject of many editorials, and most peer-reviewed journals now require authors to identify and explain any conflicts when submitting manuscripts for publication. Clear statements of industry-sponsored research and author participation in corporate activities are required for evaluation of a manuscript. Full disclosure of financial interests by authors is essential to retain public trust in biomedical research, the peer-review process, and the integrity of the authors and universities.1 We already require that each author sign a statement of his or her financial arrangements with public, private, and industry sources of support. These declarations alert the editor, reviewer, and physician-reader to …


Book ChapterDOI
TL;DR: ERPs and MRPs reveal decreased excitation or disfacilitation of neural networks at the “closure” of the task-specific cortical processes, and the chapter discusses the Mu ERD/ERS opening/closing of modality-specific thalamocortical channels.
Abstract: Publisher Summary Electroencephalography (EEG) is a neuroimaging technique. Movement-related potentials (MRPs) reflect EEG components time- and phase-locked to the movement, nonphase-locked EEG components being attenuated by the averaging. Prestimulus EEG amplitude affects event related potentials (ERPs) and the ERPs might result from a nonlinear transformation of the concomitant phase-locked EEG oscillations. MRPs depend on the cerebellar inputs. MRPs are absent with dyssynergia cerebellaris myoclonica and lesions of dentate nucleus or superior cerebellar peduncle. MRPs are normal with cerebellar cortical degeneration. Sensorimotor events also result in desynchronization/synchronization (ERD/ERS) of nonphase-locked central EEG oscillations. The ERD/ERS of alpha- and beta-bands (mu rhythm) starts in frontomesial and contralateral central areas and in ipsilateral central area close to the movement onset. Mu ERD arises from MI-S1 and supplementary motor area (SMA), as indicated by magnetoencephalography (MEG) and high-resolution EEG studies. Following the movement offset, alpha and beta ERS has been the maximum in contralateral central-parietal areas overlying contralateral M1-S1. Scalp mu ERD begins more focally and ends more widespread than MRPs. Cortical sites responsive to electrical stimulation fit those generating MRPs, but not always those generating mu ERD. In the EEG study mentioned in this chapter, the stress is on the different topography of human mu MRPs and ERD related to unilateral right finger movements in a self-paced movement paradigm and in visuomotor tasks. During unilateral sensorimotor tasks, mu ERD reflects changes in the background oscillatory areas over primary and nonprimary cortical sensorimotor areas, including the posterior parietal activity, whereas MRPs represent increased, task-specific responses of SMA and contralateral M1-S1. MRPs are sensitive to spatio-temporal features of the cortical information processes. The chapter discusses the Mu ERD/ERS opening/closing of modality-specific thalamocortical channels. ERPs and MRPs reveal decreased excitation or disfacilitation of neural networks at the “closure” of the task-specific cortical processes.

Book
01 Jan 2002
TL;DR: The role of the basal ganglia in the control of tremor and epilepsy, and some neurophysiological aspects in Chagas' disease, are discussed.
Abstract: Preface. List of Contributors. Section I. Special Lectures. The Berger Lecture. 1. Cognition, gamma oscillations and neuronal synchrony (W. Singer). The Kugelberg Lecture. 2. The role of the basal ganglia in the control of tremor and epilepsy (C.H. Lucking, B. Hellwig, C. Deransart). Section II. Ion Channel Disorders. 3. Basic mechanisms of ion channel function (B.A. Kotsias). 4. Ion channel disorders in neuropathy (K. Arimura, Y. Sonoda, O. Watanabe et al.). 5. Calcium channelopathies in neuromuscular transmission (O.D. Uchitel). 6. Disorders of membrane channels or channelopathies (G.G. Celesia). 7. Ion channels, epilepsy and anticonvulsants (G.G. Celesia). 8. Sodium channelopathies in skeletal muscle and brain (H. Lerche, N. Mitrovic, K. Jurkat-Rott et al.). Section III. Neuromuscular and Autonomic Disorders. 9. Basic mechanisms of muscle fatigue in humans (V. Galea, A. Hicks, A.J. McComas). 10. Motor unit estimates in amyotrophic lateral sclerosis (V. Galea, M. Dantes, H. DeBruin et al.). 11. Pathogenesis of amyotrophic lateral sclerosis (R.E.P. Sica). 12. Leprosy neuropathy (W. Marques Jr.). 13. An appraisal of the role of clinical neurophysiology in toxic neuropathy (G. Singh, J.S. Chopra). 14. Immune mediated peripheral neuropathies (A.M. Villa). 15. HIV-related peripheral neuropathies (R.K. Olney). 16. Some neurophysiological aspects in Chagas' disease (J.H. Xavier de Castro). 17. Neurophysiological features in HAM/TSP (HTLV-I associated myelopathy/tropical spastic paraparesis) (J.L. Castillo). 18. The autonomic neuropathies (P.A. Low). 19. Microneurography may differentiate between neural and effector organ dysfunctions in autonomic disorders (M. Elam). 20. Breathing control in neurological diseases (M.A. Nogues). Section IV. Pain and Paresthesias. 21. Methods of study of neuropathic pain (R.J. Verdugo). 22. Neurophysiologic assessment of pain (R. Kakigi, S. Watanabe,