Mark Hallett

Bio: Mark Hallett is an academic researcher from National Institutes of Health. The author has contributed to research in topics: Transcranial magnetic stimulation & Motor cortex. The author has an hindex of 186, co-authored 1170 publications receiving 123741 citations. Previous affiliations of Mark Hallett include Government of the United States of America & Armed Forces Institute of Pathology.

Past, present, and future of Parkinson's disease: A special essay on the 200th Anniversary of the Shaking Palsy

Abstract: This article reviews and summarizes 200 years of Parkinson's disease. It comprises a relevant history of Dr. James Parkinson's himself and what he described accurately and what he missed from today's perspective. Parkinson's disease today is understood as a multietiological condition with uncertain etiopathogenesis. Many advances have occurred regarding pathophysiology and symptomatic treatments, but critically important issues are still pending resolution. Among the latter, the need to modify disease progression is undoubtedly a priority. In sum, this multiple-author article, prepared to commemorate the bicentenary of the shaking palsy, provides a historical state-of-the-art account of what has been achieved, the current situation, and how to progress toward resolving Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society.

Practice Parameter: Treatment of Parkinson Disease With Motor Fluctuations and Dyskinesia (An Evidence-Based Review): Report of the Quality Standards Subcommittee of the American Academy of Neurology

Abstract: Objective: To make evidence-based treatment recommendations for the medical and surgical treatment of patients with Parkinson disease (PD) with levodopa-induced motor fluctuations and dyskinesia. To that end, five questions were addressed. 1. Which medications reduce off time? 2. What is the relative efficacy of medications in reducing off time? 3. Which medications reduce dyskinesia? 4. Does deep brain stimulation (DBS) of the subthalamic nucleus (STN), globus pallidus interna (GPi), or ventral intermediate (VIM) nucleus of the thalamus reduce off time, dyskinesia, and antiparkinsonian medication usage and improve motor function? 5. Which factors predict improvement after DBS? Methods: A 10-member committee including movement disorder specialists and general neurologists evaluated the available evidence based on a structured literature review including MEDLINE, EMBASE, and Ovid databases from 1965 through June 2004. Results, Conclusions, and Recommendations: 1. Entacapone and rasagiline should be offered to reduce off time (Level A). Pergolide, pramipexole, ropinirole, and tolcapone should be considered to reduce off time (Level B). Apomorphine, cabergoline, and selegiline may be considered to reduce off time (Level C). 2. The available evidence does not establish superiority of one medicine over another in reducing off time (Level B). Sustained release carbidopa/levodopa and bromocriptine may be disregarded to reduce off time (Level C). 3. Amantadine may be considered to reduce dyskinesia (Level C). 4. Deep brain stimulation of the STN may be considered to improve motor function and reduce off time, dyskinesia, and medication usage (Level C). There is insufficient evidence to support or refute the efficacy of DBS of the GPi or VIM nucleus of the thalamus in reducing off time, dyskinesia, or medication usage, or to improve motor function. 5. Preoperative response to levodopa predicts better outcome after DBS of the STN (Level B).

Cerebral structures participating in motor preparation in humans: a positron emission tomography study.

Abstract: 1. Using positron emission tomography and measurement of regional cerebral blood flow (rCBF) as an index of cerebral activity we investigated the central processing of motor preparation in 13 healthy volunteers. 2. We used a motor reaction time paradigm with visual cues as preparatory and response signals. A preparatory stimulus (PS) provided either full, partial, or no information regarding two variables of a forthcoming right finger movement: finger type (index or little finger) and movement direction (abduction or elevation). After a variable delay period, a response stimulus (RS) prompted the movement. A condition was also tested in which the subject could freely select any of the four possible movements during the preparation period ("free" condition). The timing of events was designed to emphasize the motor preparation phase over the motor execution component during the scanning time of 1 min. 3. Distinct preparatory processes, which depended on the information contained in the PS, were demonstrated by significant differences in reaction time between conditions. The reaction time was shorter in the "full" and free conditions, intermediate in the two partial information conditions ("finger" and "direction"), and longer when no preparatory information was available ("none" condition). Conversely, movement time and movement amplitude were similar between conditions, establishing the constancy of the motor executive output. 4. In comparison with a "rest" condition, which had matched visual inputs, the different conditions of motor preparation were associated with increased rCBF in a common set of cerebral regions: the contralateral frontal cortex (sensorimotor, premotor, cingulate, and supplementary motor cortex), the contralateral parietal association cortex (anterior and posterior regions), the ipsilateral cerebellum, the contralateral basal ganglia, and the thalamus. This observation substantiates the participation of those cerebral structures in the preparation for movement. Furthermore, the similarity of the activated areas among the different conditions compared with the rest condition suggests a single anatomic substrate for motor preparation, independent of the movement information context. 5. Differing amounts of movement information contained in the PS affected rCBF changes in some cerebral regions. In particular, the rCBF in the anterior parietal cortex (Brodmann's area 40) was significantly larger in each of the full, finger, and direction conditions, individually, compared with the none condition. This observation supports the hypothesis that the anterior parietal association cortex plays a major role in the use of visual instructions contained in the PS for partial or complete preparation to perform a motor act. On the other hand, the posterior parietal association cortex (Brodmann's area 7) was more activated in the finger, direction, and none conditions than in the full condition. This increased activity with restricted advance information suggests that the posterior region of the parietal cortex is concerned with correct movement selection on the basis of enhanced spatial attention to the RS. 6. In contrast with the parietal cortex, the secondary motor areas (i.e, premotor cortex, cingulate cortex, and supplementary motor area) showed similar activity regardless of the degree of preparation allowed by the advance visual information. Thus the parietal cortex may play a more crucial role than the secondary motor areas in integrating visual information in preparation for movement. 7. The effect on brain activity of the internal (self-generated) versus the external (cued) mode of movement selection was assessed by comparing the free and full conditions, the preparatory component being matched in the two conditions. The anterior part of the supplementary motor area was the main area preferentially involved in the internal selection of movement, independently of motor preparation processes.

Modulation of practice-dependent plasticity in human motor cortex

Abstract: Motor practice may lead to expansion of trained representations in the motor cortex, but it is unknown whether this practice-dependent plasticity can be purposefully enhanced or depressed. Evidence, mainly based on animal experiments, indicates that the activity of GABA-related cortical inhibition is important in controlling the extent to which plasticity may occur. We tested the role of GABA in modulating practice-dependent plasticity in the human motor cortex. A decrease in GABA-related cortical inhibition was achieved by ischaemic nerve block (INB) in the hand by deafferentation/deefferentation and an increase was achieved by administration of the GABA(A) receptor agonist lorazepam. In Experiment 1, healthy subjects performed motor practice (MP), consisting of repeated ballistic contractions of the biceps muscle in the absence (MP alone) or presence of INB (MP+INB). Changes in the biceps motor cortex representation were assessed by transcranial magnetic stimulation (TMS). MP+INB resulted in a dramatic increase in the size of the motor evoked potential (MEP) and in paired-pulse excitability compared with mild or no changes in the MP-alone and INB-alone conditions. In Experiment 2, this dramatic increase in biceps representation induced by MP+INB was replicated when subjects were pretreated with placebo, but this increase was prevented or even switched to a decrease when subjects were pretreated with lorazepam. These findings indicate that a decrease in GABA-related inhibition facilitates practice-dependent plasticity in the human motor cortex, whereas an increase depresses it. In Experiment 3, practice-dependent plasticity (assessed by TMS, as in the first two experiments) was also tested at the behavioural level. The dramatic increase in biceps MEP size induced by MP+INB was paralleled by an increase in peak acceleration of the fastest elbow flexion movements. Similarly, the lack of change in MEP size in the MP-alone condition was paralleled by a lack of change in peak acceleration. We propose that changes in GABA activity may be instrumented to modulate plasticity purposefully; for instance, to enhance plastic change and recovery of function after a lesion in neurological patients.

Adaptation to lateral displacement of vision in patients with lesions of the central nervous system

Abstract: The visual-motor adaptation to lateral displacement of vision by prism glasses was studied in normal individuals and patients with cerebellar dysfunction, Parkinson's disease, right or left cerebral hemisphere lesions, Alzheimer's disease, or Korsakoff's syndrome. Adaptation was analyzed in two phases, the return to normal pointing with prism glasses in place (the "error reduction portion") and the mispointing in the opposite direction after the glasses were removed (the "negative aftereffect portion"). Negative aftereffect, which seems to be the best measure of true adaptation, was significantly reduced only for the cerebellar patients. This poor performance supports the involvement of the cerebellum in motor learning.

The Brain's Default Network Anatomy, Function, and Relevance to Disease

Abstract: Thirty years of brain imaging research has converged to define the brain’s default network—a novel and only recently appreciated brain system that participates in internal modes of cognition Here we synthesize past observations to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment Analysis of connectional anatomy in the monkey supports the presence of an interconnected brain system Providing insight into function, the default network is active when individuals are engaged in internally focused tasks including autobiographical memory retrieval, envisioning the future, and conceiving the perspectives of others Probing the functional anatomy of the network in detail reveals that it is best understood as multiple interacting subsystems The medial temporal lobe subsystem provides information from prior experiences in the form of memories and associations that are the building blocks of mental simulation The medial prefrontal subsystem facilitates the flexible use of this information during the construction of self-relevant mental simulations These two subsystems converge on important nodes of integration including the posterior cingulate cortex The implications of these functional and anatomical observations are discussed in relation to possible adaptive roles of the default network for using past experiences to plan for the future, navigate social interactions, and maximize the utility of moments when we are not otherwise engaged by the external world We conclude by discussing the relevance of the default network for understanding mental disorders including autism, schizophrenia, and Alzheimer’s disease

Parallel Organization of Functionally Segregated Circuits Linking Basal Ganglia and Cortex

Abstract: Information about the basal ganglia has accumulated at a prodigious pace over the past decade, necessitating major revisions in our concepts of the structural and functional organization of these nuclei. From earlier data it had appeared that the basal ganglia served primarily to integrate diverse inputs from the entire cerebral cortex and to "funnel" these influences, via the ventrolateral thalamus, to the motor cortex (Allen & Tsukahara 1974, Evarts & Thach 1969, Kemp & Powell 1971). In particular, the basal

FieldTrip: open source software for advanced analysis of MEG, EEG, and invasive electrophysiological data

Abstract: This paper describes FieldTrip, an open source software package that we developed for the analysis of MEG, EEG, and other electrophysiological data. The software is implemented as a MATLAB toolbox and includes a complete set of consistent and user-friendly high-level functions that allow experimental neuroscientists to analyze experimental data. It includes algorithms for simple and advanced analysis, such as time-frequency analysis using multitapers, source reconstruction using dipoles, distributed sources and beamformers, connectivity analysis, and nonparametric statistical permutation tests at the channel and source level. The implementation as toolbox allows the user to perform elaborate and structured analyses of large data sets using the MATLAB command line and batch scripting. Furthermore, users and developers can easily extend the functionality and implement new algorithms. The modular design facilitates the reuse in other software packages.

Principles of Neural Science

Abstract: I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or