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.

Mechanisms of Deafferentation-Induced Plasticity in Human Motor Cortex

Abstract: Deafferentation induces rapid plastic changes in the cerebral cortex, probably via unmasking of pre-existent connections. Several mechanisms may contribute, such as changes in neuronal membrane excitability, removal of local inhibition, or various forms of short- or long-term synaptic plasticity. To understand further the mechanisms involved in cortical plasticity, we tested the effects of CNS-active drugs in a plasticity model, in which forearm ischemic nerve block (INB) was combined with low-frequency repetitive transcranial magnetic stimulation (rTMS) of the deafferented human motor cortex. rTMS was used to upregulate the plastic changes caused by INB. We studied six healthy subjects. In two control sessions without drug application, INB plus rTMS increased the motor-evoked potential (MEP) size and decreased intracortical inhibition (ICI) measured with single- and paired-pulse TMS in the biceps brachii muscle proximal to INB. A single oral dose of the benzodiazepine lorazepam (2 mg) or the voltage-gated Na+ and Ca2+ channel blocker lamotrigine (300 mg) abolished these changes. The NMDA receptor blocker dextromethorphan (150 mg) suppressed the reduction in ICI but not the increase in MEP size. With sleep deprivation, used to eliminate sedation as a major factor of these drug effects, INB plus rTMS induced changes similar to that seen in the control sessions. The findings suggest that (1) the INB plus rTMS-induced increase in MEP size involves rapid removal of GABA-related cortical inhibition and short-term changes in synaptic efficacy dependent on Na+ or Ca2+ channels and that (2) the long-lasting (>60 min) reduction in ICI is related to long-term potentiation-like mechanisms given its duration and the involvement of NMDA receptor activation.

Human corticospinal excitability evaluated with transcranial magnetic stimulation during different reaction time paradigms.

Abstract: The aim of this study was to evaluate corticospinal excitability of both hemispheres during the reaction time (RT) using transcranial magnetic stimulation (TMS). Nine right-handed subjects performed right and left thumb extensions in simple (SRT), choice (CRT) and go/no-go auditory RT paradigms. TMS, inducing motor-evoked potentials (MEPs) simultaneously in the extensor pollicis brevis muscles bilaterally, was applied at different latencies from the tone. For all paradigms, MEP amplitudes on the side of movement increased progressively in the 80-120 ms before EMG onset, while the resting side showed inhibition. The inhibition was significantly more pronounced for right than for left thumb movements. For the left SRT, significant facilitation occurred on the right after EMG onset. Initial bilateral facilitation occurred in SRT trials with slow RT. After no-go tones, bilateral inhibition occurred at a time corresponding to the mean RT to go tones. The timing of the corticospinal rise in excitability on the side of movement was independent of task difficulty and RT. This suggests that corticospinal activation is, to some extent, in series and not in parallel with stimulus processing and response selection. Corticospinal inhibition on the side not to be moved implies that suppression of movement is an active process. This inhibition is more efficient for right- than for left-side movements in right-handed subjects, possibly because of left hemispheric dominance for movement.

Time course of corticospinal excitability in reaction time and self‐paced movements

Abstract: We used transcranial magnetic stimulation (TMS) to study the time course of corticospinal excitability before and after brisk thumb abduction movements, either in a simple reaction time (RT) paradigm or self-paced. Premovement increase in corticospinal excitability began about 20 msec earlier for self-paced compared with simple RT movements. For both simple RT and self-paced movements after electromyographic (EMG) offset, there was a first period of increased excitability from 0 to 100 msec, followed by a second period from 100 to 160 msec. Corticospinal excitability was decreased from about 500 to 1,000 msec after EMG offset for both types of movements. Our results show that motor preparation that begins 1.5 to 2 seconds before self-paced movement is not associated with increased corticospinal excitability. The first phase of increased corticospinal excitability after EMG offset may be due to activity of motor cortex neuron subthreshold for activating spinal motor neurons, and the second phase may reflect a subthreshold second agonist burst. The period of decreased corticospinal excitability after movement corresponds to the onset of event-related synchronization (ERS) of electroencephalographic signals in the 20-Hz band, and supports the hypothesis that ERS may be related to an inactive, idling state of the motor cortex.

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