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.

Clinical physiology of dopa dyskinesia.

Abstract: Levodopa-induced dyskinesias are clinically heterogeneous, both in appearance and timing with respect to dose. Electromyogram observations indicate that levodopa-induced dyskinesias are comprised of irregular bursts of either synchronous or asynchronous neuronal firing in antagonist muscles. Studies of the blink reflex and spontaneous blinking have provided useful neurophysiologic information on brainstem function that is sensitive to changes in brain dopamine concentrations. The blink rate is reduced in Parkinson's disease (PD) and increased with dopamine treatment. The blink rate in patients with levodopa-induced dyskinesias, however, has been shown to be faster than that in optimally treated PD patients and normal individuals. These results suggest that dyskinesias are associated with a relative hyperdopaminergic state. However, there appears to be no correlation of dopaminergic benefit to the parkinsonian symptoms, indicating perhaps that there are several dopaminergic systems, including one responsible for motor function and one for dyskinesia. Alternatively, it may be that the pattern of neural firing influences dyskinesias, while the average firing rate may be responsible for motor benefits.

Endophenotyping: a window to the pathophysiology of dystonia.

Abstract: Neuroimaging-based endophenotyping is becoming popular. The aim is to discover markers for altered CNS gene expression in nonmanifesting gene carriers for illnesses with reduced penetrance, preclinical gene carriers for illnesses with a late onset, and even healthy subjects with allelic variants possibly related to an increased susceptibility for development of given personality traits or psychiatric disorders. As examples, using PET and fMRI, imaging biomarkers have been described for the gene responsible for primary torsion dystonia (DYT1),1 for the Parkin gene mutation responsible for early-onset parkinsonism,2 and for allelic variants in the promoter region of the serotonin transporter implicated in abnormal level of anxiety.3 Neuroimaging endophenotyping is made possible by using highly specialized expensive equipment with well-trained experimenters. These studies cannot determine, however, whether the abnormal activity network associated with the gene is directly gene-related or part of a compensatory mechanism. In this issue of Neurology , O’Dwyer et al.4 show that even relatively simple clinical testing is able to detect subclinical abnormal spatial discrimination capability (SDT) in unaffected relatives of patients with a genetic …

Sports-related concussion: ongoing debate

Abstract: Research in mild traumatic brain injury (mTBI), also known as concussion, has increased significantly within the past decade parallel to the increased attention being given from injured athletes on high school, collegiate and professional sports teams. These patients have focused the research community's efforts into further understanding the pathophysiological underpinnings of the injury as well as its both short-term and long-term effects.1 Widespread media coverage and several high-profile cases have raised the issue of possible severe and devastating long-term consequences of repetitive sports-related brain trauma that may involve the acquisition of a proteinopathy2 as well as an increased risk for developing neurodegenerative diseases associated with repetitive concussive and subconcussive blows.3 Following a concussive episode there is a destructive pathophysiological and biochemical response that initiates a chain of neurometabolic and neurochemical reactions that include activation of inflammatory response, imbalances of ion concentrations, increase in the presence of excitatory amino acids, dysregulation of neurotransmitter synthesis and release, imbalance in mitochondrial functions and energy metabolism, and production of free radicals.4 Most of these molecular changes resolve spontaneously but, since cells are highly vulnerable, a second concussive event during this period of altered cell functions may have catastrophic …

The "Whack-a-Mole" Sign in Functional Movement Disorders.

Abstract: Making the diagnosis of functional movement disorders can be challenging. Identifying positive physical signs and diagnostic maneuvers is critical to this process. Distractibility, entrainability, and variability are examples of classic physical findings in these patients. In this case series, we identify and characterize another phenomenon observed in some of these patients. In this phenomenon, movement suppression of one body part is followed by immediate reemergence of movement in another. We propose that this phenomenon be referred to as the "whack-a-mole" sign. This name is derived from the arcade game whack-a-mole, in which a mole, when hit into its original hole, re-emerges elsewhere. We present a case series of 4 patients with functional movement disorders who exhibit this sign.

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