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.

Amodal imagery in rostral premotor areas

Abstract: Inspired by Rick Grush's emulation theory, we reinterpreted a series of our neuroimaging experiments which were intended to examine the representations of complex movement, modality-specific imagery, and supramodal imagery The emulation theory can explain motor and cognitive activities observed in cortical motor areas, through the speculation that caudal areas relate to motor-specific imagery and rostral areas embrace an emulator for amodal imagery

Technical advances in deep brain stimulation: How far is enough?

Abstract: The introduction of deep brain stimulation (DBS) represented a major advance in the management of Parkinson’s disease (PD). In this procedure, stimulating electrodes are stereotactically placed in the desired target with the aid of navigation software and neuroimaging. Many teams worldwide also rely on the use of intraoperative microrecording and microstimulation to reduce the risk of suboptimal placement of the electrodes with reduced antiparkinsonian efficacy and/or side effects. However, microrecording requires extensive neurophysiological training and experience. Alternatively, local field potential activity can be used to aid in target localization and stimulation through the implanted lead being used to provide information about the location of neighboring structures. However, none of these approaches guarantees ideal electrode placement with 100% accuracy. In this issue of the journal, Janssen et al describe a new approach to localizing the motor/sensory region of the subthalamic nucleus (STN), with the aim of providing more accurate placement of DBS electrodes. Their work is based on findings in the monkey by Nambu et al, who have shown that microstimulation of the motor cortex induces a triphasic response in the motor regions of the STN. This response comprises an early excitation phase, thought to represent transmission via the hyperdirect cortico-STN pathway, followed by late excitatory and inhibitory responses. A recent study described similar cortical induced responses in the human GPi. In the current report, Janssen et al propose that these responses could be used intraoperatively to more accurately and more simply locate the motor portion of the STN in patients with PD. Although this approach still requires the use of microelectrode recording, the expertise required to identify the motor region of the STN based on increases or decreases in firing rate should be less than that required to identify the different subregions of the nucleus based on identification of specific discharge patterns. However, the procedure requires a second burr hole and placement of subdural electrodes for stimulation of the motor cortex. In this study, 3 of 5 patients experienced seizures. In 1 case this occurred even with prophylactic phenytoin treatment. Thus, although this new procedure has theoretical advantages, it is clearly associated with increased risk, and it remains uncertain if there are any benefits to justify this risk. The article raises another set of important issues— how far is far enough? How much risk are we prepared to accept for small incremental advances? At what point does scientific investigation constitute human experimentation? And, what are the responsibilities of the editors in accepting such articles for publication? In fairness to the authors, they consider that the benefits of achieving correct placement of the DBS lead outweighs the inconvenience of making an additional burr hole and the risk of inducing seizures by cortical stimulation. The intensity used for cortical stimulation was within the usual safety parameters. Their institutional review board approved the protocol. And, the patients were informed about the risks and provided informed consent. After the first 2 patients had seizures, the protocol was revised to include the use of prophylactic anticonvulsants, and the ethics committee was advised and approved continuation of the study. We believe, therefore, that the authors followed established rules in obtaining the appropriate approval of the ethics committee and obtaining proper informed consent from the patients. The risk of seizure with the stimulation parameters employed was considered low and the potential benefits important. In our view, the proper sequence was ------------------------------------------------------------

Diminishing evidence for torsinA-positive neuronal inclusions in DYT1 dystonia.

Abstract: DYT1 dystonia, an early onset generalized dystonia, also known as Oppenheim’s dystonia, is an inherited isolated dystonia characterized by progressive generalized muscle spasms and sustained postures leading to significant disability [1]. The disease is inherited in an autosomal dominant manner with incomplete penetrance (30–40 %) and typically presents in childhood [2]. Patients harbor a 3-bp (GAG) deletion in the coding region of the TOR1A gene on chromosome 9q34 that encodes the protein torsinA [3]. This deletion corresponds to loss of a single glutamate at amino acid residue 302 or 303 (torsinA ΔE) [4]. The function of wildtype torsinA has been speculative, but relatively recent studies have demonstrated its involvement in protein trafficking, quality control, secretion, and degradation (for review, see Dauer 2014 [5]). The pathogenic mechanism leading to disease as a result of this deletion is thought to likely involve disruption of sensorimotor circuit development and function [6]. Recent evidence also suggests striatal cholinergic dysfunction, or dysregulation, as a potential mechanism underlying the pathophysiology of DYT1 dystonia [7].

Ultrasound as Diagnostic Tool for Diaphragmatic Myoclonus

Abstract: Background Diaphragmatic myoclonus is a rare disorder of repetitive diaphragmatic contractions, acknowledged to be a spectrum that includes psychogenic features. Electromyography has been the diagnostic tool most commonly used in the literature. Methods To test whether we could perform a noninvasive technique to delineate the diaphragm as the source of abnormal movements and demonstrate distractibility and entrainability, we used B-mode ultrasound in a patient with diaphragmatic myoclonus. Results Ultrasound imaging clearly delineated the diaphragm as the source of her abdominal movements. We were able to demonstrate entrainability of the diaphragm to hand tapping to a prescribed rhythm set by the examiner. Conclusions We recommend the use of ultrasound as a noninvasive, convenient diagnostic tool for further studies of diaphragmatic myoclonus. We agree with previous findings that diaphragmatic myoclonus may be a functional movement disorder, as evidenced by distractibility and entrainability demonstrated on real-time video with ultrasonography.

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