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Providence, RI, United States

Cash S.S.,Harvard University | Hochberg L.R.,Harvard University | Hochberg L.R.,Brown University | Hochberg L.R.,Center for Neurorestoration and Neurotechnology
Neuron | Year: 2015

Single neuron actions and interactions are the sine qua non of brain function, and nearly all diseases and injuries of the CNS trace their clinical sequelae to neuronal dysfunction or failure. Remarkably, discussion of neuronal activity is largely absent in clinical neuroscience. Advances in neurotechnology and computational capabilities, accompanied by shifts in theoretical frameworks, have led to renewed interest in the information represented by single neurons. Using direct interfaces with the nervous system, millisecond-scale information will soon be extracted from single neurons in clinical environments, supporting personalized treatment of neurologic and psychiatric disease. In this Perspective, we focus on single-neuronal activity in restoring communication and motor control in patients suffering from devastating neurological injuries. We also explore the single neuron's role in epilepsy and movement disorders, surgical anesthesia, and in cognitive processes disrupted in neurodegenerative and neuropsychiatric disease. Finally, we speculate on how technological advances will revolutionize neurotherapeutics. © 2015 Elsevier Inc.

Philip N.S.,Center for Neurorestoration and Neurotechnology | Dunner D.L.,Center for Anxiety and Depression | Dowd S.M.,Rush University Medical Center | Aaronson S.T.,Sheppard Pratt Health System | And 7 more authors.
Brain Stimulation | Year: 2016

Background Repetitive transcranial magnetic stimulation (TMS) is efficacious for acute treatment of resistant major depressive disorder (MDD), but there is little information on maintenance TMS after acute response. Objective/hypothesis This pilot feasibility study investigated 12-month outcomes comparing two maintenance TMS approaches - a scheduled, single TMS session delivered monthly (SCH) vs. observation only (OBS). Methods Antidepressant-free patients with unipolar, non-psychotic, treatment-resistant MDD participated in a randomized, open-label, multisite trial. Patients meeting protocol-defined criteria for improvement after six weeks of acute TMS were randomized to SCH or OBS regimens. TMS reintroduction was available for symptomatic worsening; all patients remained antidepressant-free during the trial. Results Sixty-seven patients enrolled in the acute phase, and 49 (73%) met randomization criteria. Groups were matched, although more patients in the SCH group had failed ≥2 antidepressants (p =.035). There were no significant group differences on any outcome measure. SCH patients had nonsignificantly longer time to first TMS reintroduction, 91 ± 66 days, vs. OBS, 77 ± 52 days; OBS patients were nonsignificantly more likely to need reintroduction (odds ratio = 1.21, 95% CI.38-3.89). Reintroduction lasted 14.3 ± 17.8 days (SCH) and 16.9 ± 18.9 days (OBS); 14/18 (78%) SCH and 17/27 (63%) OBS responded to reintroduction. Sixteen patients (32.7%) completed all 53 weeks of the study. Conclusions Maintaining treatment-resistant depressed patients off medications with periodic TMS appears feasible in some cases. There was no statistical advantage of SCH vs. OBS, although SCH was associated with a nonsignificantly longer time to relapse. Those who initially respond to TMS have a strong chance of re-responding if relapse occurs. © 2016 Elsevier Inc. All rights reserved.

Fasoli S.E.,Center for Neurorestoration and Neurotechnology | Fasoli S.E.,Brown University | Chen C.C.,Columbia University
Archives of Physical Medicine and Rehabilitation | Year: 2014

Clinician feedback and thought processes about treatment classification and description will aid development of the rehabilitation treatment taxonomy (RTT) presented in this supplement. Here, we discuss comparisons between the proposed RTT and an inductive practice-based evidence (PBE) model used to describe rehabilitation treatments. Interviews with clinicians well versed with PBE highlight the complexity of rehabilitation treatments, and bring to light potential advantages and challenges of a deductive, theory-driven classification to uncover the black box of rehabilitation. © 2014 by the American Congress of Rehabilitation Medicine.

Yin M.,Brown University | Borton D.A.,Brown University | Borton D.A.,Ecole Polytechnique Federale de Lausanne | Komar J.,Brown University | And 15 more authors.
Neuron | Year: 2014

Brain recordings in large animal models and humans typically rely on a tethered connection, which has restricted the spectrum of accessible experimental and clinical applications. To overcome this limitation, we have engineered a compact, lightweight, high data rate wireless neurosensor capable of recording the full spectrum of electrophysiological signals fromthe cortex of mobile subjects. The wireless communication system exploits a spatially distributed network of synchronized receivers that is scalable to hundreds of channels and vast environments. To demonstrate the versatility of our wireless neurosensor, we monitored cortical neuron populations in freely behaving nonhuman primates during natural locomotion and sleep-wake transitions in ecologically equivalent settings. The interface is electrically safe and compatible with the majority of existing neural probes, which may support previously inaccessible experimental and clinical research. © 2014 Elsevier Inc.

Aghagolzadeh M.,Brown University | Truccolo W.,Brown University | Truccolo W.,Center for Neurorestoration and Neurotechnology
IEEE Transactions on Neural Systems and Rehabilitation Engineering | Year: 2016

Motor cortex neuronal ensemble spiking activity exhibits strong low-dimensional collective dynamics (i.e., coordinated modes of activity) during behavior. Here, we demonstrate that these low-dimensional dynamics, revealed by unsupervised latent state-space models, can provide as accurate or better reconstruction of movement kinematics as direct decoding from the entire recorded ensemble. Ensembles of single neurons were recorded with triple microelectrode arrays (MEAs) implanted in ventral and dorsal premotor (PMv, PMd) and primary motor (M1) cortices while nonhuman primates performed 3-D reach-to-grasp actions. Low-dimensional dynamics were estimated via various types of latent state-space models including, for example, Poisson linear dynamic system (PLDS) models. Decoding from low-dimensional dynamics was implemented via point process and Kalman filters coupled in series. We also examined decoding based on a predictive subsampling of the recorded population. In this case, a supervised greedy procedure selected neuronal subsets that optimized decoding performance. When comparing decoding based on predictive subsampling and latent state-space models, the size of the neuronal subset was set to the same number of latent state dimensions. Overall, our findings suggest that information about naturalistic reach kinematics present in the recorded population is preserved in the inferred low-dimensional motor cortex dynamics. Furthermore, decoding based on unsupervised PLDS models may also outperform previous approaches based on direct decoding from the recorded population or on predictive subsampling. © 2001-2011 IEEE.

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