Brain-Computer Interface Research

The largely basic science issues which we focus on in much of our work culminates in a practical launching point with our work on brain-computer interfaces. The focus of these projects is on mechanisms through which recording and therapeutic systems can be interfaced with the nervous system – a form of brain-machine interface research.

This work has included collaborations with the BrainGate team as well as the development of novel closed loop approaches such as CLoSES, with the eventual goal of neurotherapeutic tools for interfacing with the nervous system.


Hosman T, Hynes JB, Saab J, Wilcoxen KG, Buchbinder BR, Schmansky N, Cash SS, Eskandar EN, Simeral JD, Franco B, Kelemen J, Vargas-Irwin CE, Hochberg LR. Auditory cues reveal intended movement information in middle frontal gyrus neuronal ensemble activity of a person with tetraplegia. Sci Rep. 2021 Jan 11;11(1):98. DOI: 10.1038/s41598-020-77616-8.

Milekovic T, Bacher D, Sarma AA, Simeral JD, Saab J, Pandarinath C, Yvert B, Sorice BL, Blabe C, Oakley EM, Tringale KR, Eskandar E, Cash SS, Shenoy KV, Henderson JM, Hochberg LR, Donoghue JP. “Volitional control of single-electrode high gamma local field potentials by people with paralysis.” J Neurophysiol. (2019); PMC30785814.

Vargas-Irwin CE, Feldman JM, King B, Simeral JD, Sorice BL, Oakley EM, Cash SS, Eskandar EN, Friehs GM, Hochberg LR, Donoghue JP. “Watch, Imagine, Attempt: Motor Cortex Single-Unit Activity Reveals Context-Dependent Movement Encoding in Humans With Tetraplegia.” Front Hum Neurosci. (2018); PMC30524258.

Closed-Loop Direct Electrical Intracranial Stimulation in Humans

Closed-loop brain stimulation is a promising area of treatment for neurological and neuropsychiatric diseases and an interesting research tool. Using closed-loop stimulation as a probe we can study neural dynamics and interaction between brain states and stimulation responses. This could provide novel insights into the mechanism of normal and pathological brain activity, advance the discovery and evaluation of potential electrographic biomarkers of neurological and psychiatric disorders, and the development and testing of patient-specific stimulation targets and control signals before implanting a therapeutic device.

This work has led to the development of Closed-Loop System for Electrical Stimulation (CLoSES) for use with Real-Time Simulink and MATLAB. As a research tool, CLoSES allows for the direct application and interface with ongoing neural activity through efficient, and informed, neuromodulation through direct electrical stimulation.

Github code for CLoSES



Zelmann R, Paulk AC, Basu I, Sarma A, Yousefi A, Crocker B, Eskandar E, Williams Z, Cosgrove GR, Weisholtz DS, Dougherty DD, Truccolo W, Widge AS, Cash SS. CLoSES: A platform for closed-loop intracranial stimulation in humans. Neuroimage. 2020 Dec;223:117314. DOI: 10.1016/j.neuroimage.2020.117314.

Krempp C, Paulk AC, Truccolo W, Cash SS, Zelmann R. Effect of Closed-Loop Direct Electrical Stimulation during Sleep Spindles in Humans. Annu Int Conf IEEE Eng Med Biol Soc. 2020 Jul;2020:3586-3589. DOI: 10.1109/EMBC44109.2020.9175404.