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.

The cerebellum in dual-task performance in Parkinson’s disease

Abstract: Parkinson's disease (PD) patients have difficulty in performing a dual-task. It has been suggested that the cerebellum is important in dual-tasking. We used functional MRI to investigate the role of the cerebellum in performing a dual motor and cognitive task in PD patients. We have examined whether there are any areas additionally activated for dual-task performance, and compared the neural activity and functional connectivity pattern in the cerebellum between PD patients and healthy controls. We found that the right cerebellar vermis and left lobule V of cerebellar anterior lobe were additionally activated for dual-task performance in healthy controls and for motor task in PD patients. We didn't find any cerebellar regions additionally activated while performing dual-task in PD patients. In addition, the right cerebellar vermis had enhanced connectivity with motor and cognitive associated networks in PD patients. PD patients have limited cerebellar resources that are already utilized for single tasks and, for dual tasks, cannot augment as necessary in order to integrate motor and cognitive networks.

Movement-related cortical potentials in primary lateral sclerosis.

Abstract: Objective Some patients with primary lateral sclerosis (PLS) have a clinical course suggestive of a length-dependent dying-back of corticospinal axons. We measured movement-related cortical potentials (MRCPs) in these patients to determine whether cortical functions that are generated through short, intracortical connections were preserved when functions conducted by longer corticospinal projections were impaired. Methods An electroencephalogram was recorded from scalp electrodes of 10 PLS patients and 7 age-matched healthy control subjects as they made individual finger-tap movements on a keypad. MRCPs were derived from back-averaging the electroencephalogram to the movement. Results MRCPs produced by finger taps were markedly reduced in PLS patients, including components generated by premotor areas of the cortex as well as the primary motor cortex. In contrast, the β-band event-related desynchronization from the motor cortex was preserved. Interpretation These findings suggest that impairment in PLS is not limited to the distal axons of corticospinal neurons, but also affects neurons within the primary motor cortex and premotor cortical areas. The loss of the MRCP may serve as a useful marker of upper motor neuron dysfunction. Preservation of event-related desynchronization suggests that the cells of origin differ from the large pyramidal cells that generate the MRCP. Ann Neurol 2006;59:682–690

Paired associative stimulation induces change in presynaptic inhibition of Ia terminals in wrist flexors in humans

Abstract: Enhancements in the strength of corticospinal projections to muscles are induced in conscious humans by paired associative stimulation (PAS) to the motor cortex. Although most of the previous studies support the hypothesis that the increase of the amplitude of motor evoked potentials (MEPs) by PAS involves long-term potentiation (LTP)-like mechanism in cortical synapses, changes in spinal excitability after PAS have been reported, suggestive of parallel modifications in both cortical and spinal excitability. In a first series of experiments (experiment 1), we confirmed that both flexor carpi radialis (FCR) MEPs and FCR H reflex recruitment curves are enhanced by PAS. To elucidate the mechanism responsible for this change in the H reflex amplitude, we tested, using the same subjects, the hypothesis that enhanced H reflexes are caused by a down-regulation of the efficacy of mechanisms controlling Ia afferent discharge, including presynaptic Ia inhibition and postactivation depression. To address this question, amounts of both presynaptic Ia inhibition of FCR Ia terminals (D1and D2 inhibitions methods; experiment 2) and postactivation depression (experiment 3) were determined before and after PAS. Results showed that PAS induces a significant decrease of presynaptic Ia inhibition of FCR terminals, which was concomitant with the facilitation of the H reflex. Postactivation depression was unaffected by PAS. It is argued that enhancement of segmental excitation by PAS relies on a selective effect of PAS on the interneurons controlling presynaptic inhibition of Ia terminals.

Assessment of patients with functional neurologic disorders.

Abstract: We describe an overall approach and structure to the clinical assessment of the patient with a functional neurologic disorder. Whilst the primary purpose of the assessment is to make a diagnosis and develop a treatment plan, we believe the assessment also plays a key role in treatment in its own right, as it sets a tone and context for future clinical interactions. We aim to set up an atmosphere of collaboration based on taking the patient's problems seriously, and emphasizing that all facets of the patient's presentation – physical, psychologic, and social – are of importance. Patients with functional disorders can be perceived as difficult to help and yet with the correct approaches we believe the consultation can be much more satisfying for both patient and doctor. Finally, we discuss and list some of the common diagnostic pitfalls in the assessment of functional neurologic disorders, looking at features that lead to erroneous diagnosis of neurologic disease (such as old age, la belle indifference, and lack of psychiatric comorbidity) and an erroneous diagnosis of a functional disorder (such as “bizarre” gait in stiff-person syndrome).

The Pathophysiology of Dystonic Tremors and Comparison With Essential Tremor.

Abstract: There are two types of dystonic tremor syndromes (DTS), dystonic tremor (DT) and tremor associated with dystonia (TAWD), and neither is understood. DTS likely share some mechanisms with nontremulous dystonia, and there may also be overlaps with essential tremor (ET). We studied 21 ET (8 females, 13 males) and 22 DTS human patients (10 females, 12 males), including 13 human patients with DT (writer's cramp with writing tremor) and 9 human patients with tremor associated with dystonia (TAWD; cervical dystonia with hand tremor). Tremors were analyzed using accelerometry and surface EMG of the antagonist pairs of arm muscles during posture, simple kinetic movement, and writing. Cerebellar inhibition was performed to assess cerebello-thalamo-cortical involvement. DT exhibited higher variability of peak frequency and greater instability of tremor burst intervals over time (higher tremor stability index) than ET or TAWD regardless of tasks. Intermuscular coherence magnitude between the antagonist pairs increased during the writing task in DT, but not ET or TAWD. ET and TAWD exhibited different phase relationships of the temporal fluctuations of voluntary movement and tremor in the kinetic condition. A linear discriminant classifier based on these tremor parameters was able to distinguish the three groups with a classification accuracy of 95.1%. Cerebellar inhibition was significantly reduced in DT, but not in TAWD, compared with ET and healthy controls. Our study shows that the two DTS are distinct entities with DT closer to nontremorous dystonia and TAWD closer to ET.SIGNIFICANCE STATEMENT This study provides novel findings about characteristics and pathophysiology of the two different types of dystonic tremor syndromes compared with essential tremor. Patients with DTS are classified into DT who have dystonia and tremor in the same area, and tremor associated with dystonia (TAWD) who have dystonia and tremor elsewhere. Our results showed that DT exhibits increased tremor variability, instability, and intermuscular coherence, and decreased cerebello-thalamo-cortical inhibition compared with TAWD. Our study shows that DT and TAWD are distinct phenotypes, and that the physiological characteristics of DT are more similar to nontremorous dystonia, and TAWD is closer to ET.

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