About

Professor Sydney Cash, M.D., Ph.D., is the Division Chief of the Division of Epilepsy in the Mass General Brigham (MGB) Department of Neurology at Massachusetts General Hospital. His role involves leading research and clinical efforts related to epilepsy, contributing to the understanding and treatment of this neurological condition. As a senior member of the department, he is involved in advancing epilepsy research and patient care within the institution.

Research topics

• Computer Science
• Neuroscience
• Psychology
• Medicine
• Physical medicine and rehabilitation
• Internal medicine
• Data science
• Biology
• Sociology
• Algorithm
• Psychiatry
• Optoelectronics
• Telecommunications
• Physics
• Surgery
• Physical therapy
• Engineering
• Materials science
• Nanotechnology
• Computational biology
• Business
• Internet privacy
• Anesthesia
• Electrical engineering

Selected publications

• Interim Safety Profile From the Feasibility Study of the BrainGate Neural Interface System

  Neurology · 2023 · 71 citations

  • Medicine
  • Physical medicine and rehabilitation
  • Surgery

  BACKGROUND AND OBJECTIVES: Brain-computer interfaces (BCIs) are being developed to restore mobility, communication, and functional independence to people with paralysis. Though supported by decades of preclinical data, the safety of chronically implanted microelectrode array BCIs in humans is unknown. We report safety results from the prospective, open-label, nonrandomized BrainGate feasibility study (NCT00912041), the largest and longest-running clinical trial of an implanted BCI. METHODS: Adults aged 18-75 years with quadriparesis from spinal cord injury, brainstem stroke, or motor neuron disease were enrolled through 7 clinical sites in the United States. Participants underwent surgical implantation of 1 or 2 microelectrode arrays in the motor cortex of the dominant cerebral hemisphere. The primary safety outcome was device-related serious adverse events (SAEs) requiring device explantation or resulting in death or permanently increased disability during the 1-year postimplant evaluation period. The secondary outcomes included the type and frequency of other adverse events and the feasibility of the BrainGate system for controlling a computer or other assistive technologies. RESULTS: From 2004 to 2021, 14 adults enrolled in the BrainGate trial had devices surgically implanted. The average duration of device implantation was 872 days, yielding 12,203 days of safety experience. There were 68 device-related adverse events, including 6 device-related SAEs. The most common device-related adverse event was skin irritation around the percutaneous pedestal. There were no safety events that required device explantation, no unanticipated adverse device events, no intracranial infections, and no participant deaths or adverse events resulting in permanently increased disability related to the investigational device. DISCUSSION: The BrainGate Neural Interface system has a safety record comparable with other chronically implanted medical devices. Given rapid recent advances in this technology and continued performance gains, these data suggest a favorable risk/benefit ratio in appropriately selected individuals to support ongoing research and development. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT00912041. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that the neurosurgically placed BrainGate Neural Interface system is associated with a low rate of SAEs defined as those requiring device explantation, resulting in death, or resulting in permanently increased disability during the 1-year postimplant period.

  PublisherDOI

• Propofol disrupts alpha dynamics in functionally distinct thalamocortical networks during loss of consciousness

  Proceedings of the National Academy of Sciences · 2023 · 52 citations

  • Neuroscience
  • Psychology
  • Biology

  During propofol-induced general anesthesia, alpha rhythms measured using electroencephalography undergo a striking shift from posterior to anterior, termed anteriorization, where the ubiquitous waking alpha is lost and a frontal alpha emerges. The functional significance of alpha anteriorization and the precise brain regions contributing to the phenomenon are a mystery. While posterior alpha is thought to be generated by thalamocortical circuits connecting nuclei of the sensory thalamus with their cortical partners, the thalamic origins of the propofol-induced alpha remain poorly understood. Here, we used human intracranial recordings to identify regions in sensory cortices where propofol attenuates a coherent alpha network, distinct from those in the frontal cortex where it amplifies coherent alpha and beta activities. We then performed diffusion tractography between these identified regions and individual thalamic nuclei to show that the opposing dynamics of anteriorization occur within two distinct thalamocortical networks. We found that propofol disrupted a posterior alpha network structurally connected with nuclei in the sensory and sensory associational regions of the thalamus. At the same time, propofol induced a coherent alpha oscillation within prefrontal cortical areas that were connected with thalamic nuclei involved in cognition, such as the mediodorsal nucleus. The cortical and thalamic anatomy involved, as well as their known functional roles, suggests multiple means by which propofol dismantles sensory and cognitive processes to achieve loss of consciousness.

  DOI

• Benefits of sharing neurophysiology data from the BRAIN Initiative Research Opportunities in Humans Consortium

  Neuron · 2023 · 14 citations

  • Computer Science
  • Sociology
  • Neuroscience
  PublisherOA PDFDOI

• Ultra-compact dual-band smart NEMS magnetoelectric antennas for simultaneous wireless energy harvesting and magnetic field sensing

  Nature Communications · 2021 · 186 citations

  • Computer Science
  • Electrical engineering
  • Computer Science

  that can efficiently perform wireless energy harvesting and sense ultra-small magnetic fields. The proposed ME antenna has a wireless PTE 1-2 orders of magnitude higher than any other reported miniaturized micro-coil, allowing the wireless IMDs to be compliant with the SAR limit. Furthermore, the antenna's magnetic field detectivity of 300-500 pT allows the IMDs to record neural magnetic fields.

  DOI

• Closed-loop enhancement and neural decoding of cognitive control in humans

  Nature Biomedical Engineering · 2021 · 102 citations

  • Computer Science
  • Neuroscience
  • Computer Science
  DOI

• Auditory cues reveal intended movement information in middle frontal gyrus neuronal ensemble activity of a person with tetraplegia

  Scientific Reports · 2021 · 25 citations

  • Computer Science
  • Neuroscience
  • Computer Science

  Intracortical brain-computer interfaces (iBCIs) allow people with paralysis to directly control assistive devices using neural activity associated with the intent to move. Realizing the full potential of iBCIs critically depends on continued progress in understanding how different cortical areas contribute to movement control. Here we present the first comparison between neuronal ensemble recordings from the left middle frontal gyrus (MFG) and precentral gyrus (PCG) of a person with tetraplegia using an iBCI. As expected, PCG was more engaged in selecting and generating intended movements than in earlier perceptual stages of action planning. By contrast, MFG displayed movement-related information during the sensorimotor processing steps preceding the appearance of the action plan in PCG, but only when the actions were instructed using auditory cues. These results describe a previously unreported function for neurons in the human left MFG in auditory processing contributing to motor control.

  PublisherOA PDFDOI

• Robust dynamic community detection with applications to human brain functional networks

  Nature Communications · 2020 · 61 citations

  • Computer Science
  • Computer Science
  • Computational biology

  While current technology permits inference of dynamic brain networks over long time periods at high temporal resolution, the detailed structure of dynamic network communities during human seizures remains poorly understood. We introduce a new methodology that addresses critical aspects unique to the analysis of dynamic functional networks inferred from noisy data. We propose a dynamic plex percolation method (DPPM) that is robust to edge noise, and yields well-defined spatiotemporal communities that span forward and backwards in time. We show in simulation that DPPM outperforms existing methods in accurately capturing certain stereotypical dynamic community behaviors in noisy situations. We then illustrate the ability of this method to track dynamic community organization during human seizures, using invasive brain voltage recordings at seizure onset. We conjecture that application of this method will yield new targets for surgical treatment of epilepsy, and more generally could provide new insights in other network neuroscience applications.

  DOI

• Neural Representation of Observed, Imagined, and Attempted Grasping Force in Motor Cortex of Individuals with Chronic Tetraplegia

  Scientific Reports · 2020 · 30 citations

  • Computer Science
  • Physical medicine and rehabilitation
  • Neuroscience

  Hybrid kinetic and kinematic intracortical brain-computer interfaces (iBCIs) have the potential to restore functional grasping and object interaction capabilities in individuals with tetraplegia. This requires an understanding of how kinetic information is represented in neural activity, and how this representation is affected by non-motor parameters such as volitional state (VoS), namely, whether one observes, imagines, or attempts an action. To this end, this work investigates how motor cortical neural activity changes when three human participants with tetraplegia observe, imagine, and attempt to produce three discrete hand grasping forces with the dominant hand. We show that force representation follows the same VoS-related trends as previously shown for directional arm movements; namely, that attempted force production recruits more neural activity compared to observed or imagined force production. Additionally, VoS-modulated neural activity to a greater extent than grasping force. Neural representation of forces was lower than expected, possibly due to compromised somatosensory pathways in individuals with tetraplegia, which have been shown to influence motor cortical activity. Nevertheless, attempted forces (but not always observed or imagined forces) could be decoded significantly above chance, thereby potentially providing relevant information towards the development of a hybrid kinetic and kinematic iBCI.

  PublisherOA PDFDOI

• Nine-year prospective efficacy and safety of brain-responsive neurostimulation for focal epilepsy

  Neurology · 2020 · 481 citations

  • Medicine
  • Anesthesia
  • Internal medicine

  OBJECTIVE: To prospectively evaluate safety and efficacy of brain-responsive neurostimulation in adults with medically intractable focal onset seizures (FOS) over 9 years. METHODS: Adults treated with brain-responsive neurostimulation in 2-year feasibility or randomized controlled trials were enrolled in a long-term prospective open label trial (LTT) to assess safety, efficacy, and quality of life (QOL) over an additional 7 years. Safety was assessed as adverse events (AEs), efficacy as median percent change in seizure frequency and responder rate, and QOL with the Quality of Life in Epilepsy (QOLIE-89) inventory. RESULTS: ). CONCLUSIONS: Adjunctive brain-responsive neurostimulation provides significant and sustained reductions in the frequency of FOS with improved QOL. Stimulation was well tolerated; implantation-related AEs were typical of other neurostimulation devices; and SUDEP rates were low. CLINICALTRIALSGOV IDENTIFIER: NCT00572195. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that brain-responsive neurostimulation significantly reduces focal seizures with acceptable safety over 9 years.

  PublisherOA PDFDOI

Recent grants

• From ion channel dynamics to human EEG and MEG: multiscale neuronal models validated by human data

  NIH · $3.7M · 2018–2023

• Novel Implantable Smart Magnetoelectric NanoRFIDs for Large-Scale Neural Magnetic Recording and Modulation

  NIH · $1.8M · 2018–2022

• Understanding the Neural Basis of Volitional State through Continuous Recordings in Humans

  NIH · $4.7M · 2016–2020

• Neurophysiology of Human Cortical Epilepsy

  NIH · $3.4M · 2010–2023

• NIH Grant R56NS062092

  NIH · $608k · 2018

Frequent coauthors

• Leigh R. Hochberg

  Harvard University

  478 shared

• Angelique C. Paulk

  Massachusetts General Hospital

  258 shared

• M. Brandon Westover

  Harvard University

  234 shared

• Emad N. Eskandar

  208 shared

• Ziv M. Williams

  Harvard University

  182 shared

• Eric Halgren

  University of California, San Diego

  165 shared

• Emad N. Eskandar

  135 shared

• Andrew J. Cole

  132 shared

Labs

• CashLabPI

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