Center for Neurorestoration and Neurotechnology

Providence, RI, United States

Center for Neurorestoration and Neurotechnology

Providence, RI, United States
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Milekovic T.,Albert Ludwigs University of Freiburg | Milekovic T.,Imperial College London | Truccolo W.,Brown University | Truccolo W.,Center for Neurorestoration and Neurotechnology | And 7 more authors.
NeuroImage | Year: 2015

Reach and grasp kinematics are known to be encoded in the spiking activity of neuronal ensembles and in local field potentials (LFPs) recorded from primate motor cortex during movement planning and execution. However, little is known, especially in LFPs, about the encoding of kinetic parameters, such as forces exerted on the object during the same actions. We implanted two monkeys with microelectrode arrays in the motor cortical areas MI and PMd to investigate encoding of grasp-related parameters in motor cortical LFPs during planning and execution of reach-and-grasp movements. We identified three components of the LFP that modulated during grasps corresponding to low (0.3-7. Hz), intermediate (~. 10-~. 40. Hz) and high (~. 80-250. Hz) frequency bands. We show that all three components can be used to classify not only grip types but also object loads during planning and execution of a grasping movement. In addition, we demonstrate that all three components recorded during planning or execution can be used to continuously decode finger pressure forces and hand position related to the grasping movement. Low and high frequency components provide similar classification and decoding accuracies, which were substantially higher than those obtained from the intermediate frequency component. Our results demonstrate that intended reach and grasp kinetic parameters are encoded in multiple LFP bands during both movement planning and execution. These findings also suggest that the LFP is a reliable signal for the control of parameters related to object load and applied pressure forces in brain-machine interfaces. © 2015 Elsevier Inc.


Truccolo W.,Brown University | Truccolo W.,Center for Neurorestoration and Neurotechnology | Ahmed O.J.,Harvard University | Harrison M.T.,Brown University | And 9 more authors.
Journal of Neuroscience | Year: 2014

Seizures are classically characterized as the expression of hypersynchronous neural activity, yet the true degree of synchrony in neuronal spiking (action potentials) during human seizures remains a fundamental question. We quantified the temporal precision of spike synchrony in ensembles of neocortical neurons during seizures in people with pharmacologically intractable epilepsy. Two seizure types were analyzed: those characterized by sustained gamma (~40-60 Hz) local field potential (LFP) oscillations or by spike-wave complexes (SWCs; ~3 Hz). Fine (<10 ms) temporal synchrony was rarely present during gamma-band seizures, where neuronal spiking remained highly irregular and asynchronous. In SWC seizures, phase locking of neuronal spiking to the SWC spike phase induced synchrony at a coarse 50-100 ms level. In addition, transient fine synchrony occurred primarily during the initial ~20 ms period of the SWC spike phase and varied across subjects and seizures. Sporadic coherence events between neuronal population spike counts and LFPs were observed during SWC seizures in high (~80 Hz) gamma-band and during high-frequency oscillations (~130 Hz). Maximum entropy models of the joint neuronal spiking probability, constrained only on single neurons' nonstationary coarse spiking rates and local network activation, explained most of the fine synchrony in both seizure types. Our findings indicate that fine neuronal ensemble synchrony occurs mostly during SWC, not gamma-band, seizures, and primarily during the initial phase of SWC spikes. Furthermore, these fine synchrony events result mostly from transient increases in overall neuronal network spiking rates, rather than changes in precise spiking correlations between specific pairs of neurons. © 2014 the authors.


Y. Ho E.C.,Brown University | Y. Ho E.C.,Center for Neurorestoration and Neurotechnology | Truccolo W.,Brown University | Truccolo W.,Center for Neurorestoration and Neurotechnology
Journal of Computational Neuroscience | Year: 2016

How focal seizures initiate and evolve in human neocortex remains a fundamental problem in neuroscience. Here, we use biophysical neuronal network models of neocortical patches to study how the interaction between inhibition and extracellular potassium ([K+]o) dynamics may contribute to different types of focal seizures. Three main types of propagated focal seizures observed in recent intracortical microelectrode recordings in humans were modelled: seizures characterized by sustained (∼30−60 Hz) gamma local field potential (LFP) oscillations; seizures where the onset in the propagated site consisted of LFP spikes that later evolved into rhythmic (∼2−3 Hz) spike-wave complexes (SWCs); and seizures where a brief stage of low-amplitude fast-oscillation (∼10−20 Hz) LFPs preceded the SWC activity. Our findings are fourfold: (1) The interaction between elevated [K+]o (due to abnormal potassium buffering by glial cells) and the strength of synaptic inhibition plays a predominant role in shaping these three types of seizures. (2) Strengthening of inhibition leads to the onset of sustained narrowband gamma seizures. (3) Transition into SWC seizures is obtained either by the weakening of inhibitory synapses, or by a transient strengthening followed by an inhibitory breakdown (e.g. GABA depletion). This reduction or breakdown of inhibition among fast-spiking (FS) inhibitory interneurons increases their spiking activity and leads them eventually into depolarization block. Ictal spike-wave discharges in the model are then sustained solely by pyramidal neurons. (4) FS cell dynamics are also critical for seizures where the evolution into SWC activity is preceded by low-amplitude fast oscillations. Different levels of elevated [K+]o were important for transitions into and maintenance of sustained gamma oscillations and SWC discharges. Overall, our modelling study predicts that the interaction between inhibitory interneurons and [K+]o glial buffering under abnormal conditions may explain different types of ictal transitions and dynamics during propagated seizures in human focal epilepsy. © 2016, The Author(s).


Shaikhouni A.,Brown University | Donoghue J.P.,Brown University | Donoghue J.P.,Center for Neurorestoration and Neurotechnology | Hochberg L.R.,Brown University | And 2 more authors.
Journal of Neurophysiology | Year: 2013

Somatic sensory signals provide a major source of feedback to motor cortex. Changes in somatosensory systems after stroke or injury could profoundly influence brain computer interfaces (BCI) being developed to create new output signals from motor cortex activity patterns. We had the unique opportunity to study the responses of hand/arm area neurons in primary motor cortex to passive joint manipulation in a person with a long-standing brain stem stroke but intact sensory pathways. Neurons responded to passive manipulation of the contralateral shoulder, elbow, or wrist as predicted from prior studies of intact primates. Thus fundamental properties and organization were preserved despite arm/hand paralysis and damage to cortical outputs. The same neurons were engaged by attempted arm actions. These results indicate that intact sensory pathways retain the potential to influence primary motor cortex firing rates years after cortical outputs are interrupted and may contribute to online decoding of motor intentions for BCI applications. © 2013 the American Physiological Society.


Homer M.L.,Brown University | Nurmikko A.V.,Brown University | Donoghue J.P.,Brown University | Donoghue J.P.,Center for Neurorestoration and Neurotechnology | And 3 more authors.
Annual Review of Biomedical Engineering | Year: 2013

Intracortical brain computer interfaces (iBCIs) are being developed to enable people to drive an output device, such as a computer cursor, directly from their neural activity. One goal of the technology is to help people with severe paralysis or limb loss. Key elements of an iBCI are the implanted sensor that records the neural signals and the software that decodes the user's intended movement from those signals. Here, we focus on recent advances in these two areas, placing special attention on contributions that are or may soon be adopted by the iBCI research community. We discuss how these innovations increase the technology's capability, accuracy, and longevity, all important steps that are expanding the range of possible future clinical applications. Copyright © 2013 by Annual Reviews.


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 | Ridout S.J.,Brown University | Albright S.E.,Center for Neurorestoration and Neurotechnology | Sanchez G.,Center for Neurorestoration and Neurotechnology | Carpenter L.L.,Brown University
Journal of Traumatic Stress | Year: 2016

Current treatment options for posttraumatic stress disorder (PTSD) offer modest benefits, underscoring the need for new treatments. Repetitive transcranial magnetic stimulation (rTMS) depolarizes neurons in a targeted brain region with magnetic fields typically pulsed at low (1 Hz) or high (10 Hz) frequency to relieve major depressive disorder (MDD). Prior work suggests an intermediate pulse frequency, 5 Hz, is also efficacious for treating comorbid depressive and anxiety symptoms. In this chart review study, we systematically examined the clinical and safety outcomes in 10 patients with comorbid MDD and PTSD syndromes who received 5-Hz rTMS therapy at the Providence VA Medical Center Neuromodulation Clinic. Self-report scales measured illness severity prior to treatment, after every 5 treatments, and upon completion of treatment. Results showed significant reduction in symptoms of PTSD (p = .003, effect size = 1.12, 8/10 with reliable change) and MDD (p = .005, effect size = 1.09, 6/10 with reliable change). Stimulation was well tolerated and there were no serious adverse events. These data indicate 5-Hz rTMS may be a useful option to treat these comorbid disorders. Larger, controlled trials are needed to confirm the benefits of 5-Hz protocols observed in this pilot study. © 2016 International Society for Traumatic Stress Studies.


Bedard P.,Brown University | Sanes J.N.,Brown University | Sanes J.N.,Center for Neurorestoration and Neurotechnology
NeuroImage | Year: 2014

Humans readily learn and remember new motor skills, a process that likely underlies adaptation to changing environments. During adaptation, the brain develops new sensory-motor relationships, and if consolidation occurs, a memory of the adaptation can be retained for extended periods. Considerable evidence exists that multiple brain circuits participate in acquiring new sensory-motor memories, though the networks engaged in recalling these and whether the same brain circuits participate in their formation and recall have less clarity. To address these issues, we assessed brain activation with functional MRI while young healthy adults learned and recalled new sensory-motor skills by adapting to world-view rotations of visual feedback that guided hand movements. We found cerebellar activation related to adaptation rate, likely reflecting changes related to overall adjustments to the visual rotation. A set of parietal and frontal regions, including inferior and superior parietal lobules, premotor area, supplementary motor area and primary somatosensory cortex, exhibited non-linear learning-related activation that peaked in the middle of the adaptation phase. Activation in some of these areas, including the inferior parietal lobule, intra-parietal sulcus and somatosensory cortex, likely reflected actual learning, since the activation correlated with learning after-effects. Lastly, we identified several structures having recall-related activation, including the anterior cingulate and the posterior putamen, since the activation correlated with recall efficacy. These findings demonstrate dynamic aspects of brain activation patterns related to formation and recall of a sensory-motor skill, such that non-overlapping brain regions participate in distinctive behavioral events. © 2014.


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.


Barrese J.C.,UMDNJ New Jersey Medical School | Barrese J.C.,Brown University | Barrese J.C.,Center for Neurorestoration and Neurotechnology | Rao N.,Brown University | And 6 more authors.
Journal of Neural Engineering | Year: 2013

Objective. Brain-computer interfaces (BCIs) using chronically implanted intracortical microelectrode arrays (MEAs) have the potential to restore lost function to people with disabilities if they work reliably for years. Current sensors fail to provide reliably useful signals over extended periods of time for reasons that are not clear. This study reports a comprehensive retrospective analysis from a large set of implants of a single type of intracortical MEA in a single species, with a common set of measures in order to evaluate failure modes. Approach. Since 1996, 78 silicon MEAs were implanted in 27 monkeys (Macaca mulatta). We used two approaches to find reasons for sensor failure. First, we classified the time course leading up to complete recording failure as acute (abrupt) or chronic (progressive). Second, we evaluated the quality of electrode recordings over time based on signal features and electrode impedance. Failure modes were divided into four categories: biological, material, mechanical, and unknown. Main results. Recording duration ranged from 0 to 2104 days (5.75 years), with a mean of 387 days and a median of 182 days (n = 78). Sixty-two arrays failed completely with a mean time to failure of 332 days (median = 133 days) while nine array experiments were electively terminated for experimental reasons (mean = 486 days). Seven remained active at the close of this study (mean = 753 days). Most failures (56%) occurred within a year of implantation, with acute mechanical failures the most common class (48%), largely because of connector issues (83%). Among grossly observable biological failures (24%), a progressive meningeal reaction that separated the array from the parenchyma was most prevalent (14.5%). In the absence of acute interruptions, electrode recordings showed a slow progressive decline in spike amplitude, noise amplitude, and number of viable channels that predicts complete signal loss by about eight years. Impedance measurements showed systematic early increases, which did not appear to affect recording quality, followed by a slow decline over years. The combination of slowly falling impedance and signal quality in these arrays indicates that insulating material failure is the most significant factor. Significance. This is the first long-term failure mode analysis of an emerging BCI technology in a large series of non-human primates. The classification system introduced here may be used to standardize how neuroprosthetic failure modes are evaluated. The results demonstrate the potential for these arrays to record for many years, but achieving reliable sensors will require replacing connectors with implantable wireless systems, controlling the meningeal reaction, and improving insulation materials. These results will focus future research in order to create clinical neuroprosthetic sensors, as well as valuable research tools, that are able to safely provide reliable neural signals for over a decade. © 2013 IOP Publishing Ltd.

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