Clinical Trial Results Indicate Low Rate of Adverse Events Associated With Implanted Brain Computer Interface

BOSTON – For people with paralysis caused by neurologic injury or disease—such as ALS (also known as Lou Gehrig’s disease), stroke, or spinal cord injury—brain-computer interfaces (BCIs) have the potential to restore communication, mobility, and independence by transmitting information directly from the brain to a computer or other assistive technology.

Although implanted brain sensors, the core component of many brain-computer interfaces, have been used in neuroscientific studies with animals for decades and have been approved for short term use (<30 days) in humans, the long-term safety of this technology in humans is unknown.

New results from the prospective, open-label, non-randomized BrainGate feasibility study, the largest and longest-running clinical trial of an implanted BCI, suggests that these sensors’ safety is similar to other chronically implanted neurologic devices.

The BrainGate clinical trial is run by a collaborative consortium of investigators at multiple institutions, including Massachusetts General Hospital (MGH), who are working to develop BCIs for people affected by paralysis caused by neurologic disease or injury.

This new report, which is published in Neurology by an MGH-led team, examined data from 14 adults with quadriparesis (weakness in all four limbs) from spinal cord injury, brainstem stroke, or ALS who were enrolled in the BrainGate trial from 2004 to 2021 through seven clinical sites in the United States.

Participants underwent surgical implantation of one or two microelectrode arrays in a part of the brain responsible for generating the electrical signals that control limb movement.

With these “Utah” microelectrode arrays, the brain signals associated with the intent to move a limb can then be sent to a nearby computer that decodes the signal in real-time and allows the user to control an external device simply by thinking about moving a part of their body.

The authors of the study report that across the 14 enrolled research participants, the average duration of device implantation was 872 days, yielding a total of 12,203 days for safety analyses. There were 68 device-related adverse events, including 6 device-related serious adverse events.

The most common device-related adverse event was skin irritation around the portion of the device that connects the implanted sensor to the external computer system.

Importantly, they report that there were no safety events that required removal of the device, no infections of the brain or nervous system, and no adverse events resulting in permanently increased disability related to the investigational device.

“This interim report demonstrates that the investigational BrainGate Neural Interface system, which is still in ongoing clinical trials, thus far has a safety profile comparable to that of many approved implanted neurologic devices, such as deep brain stimulators and responsive neurostimulators,” says lead author Daniel Rubin, MD, PhD, a physician investigator in the Center for Neurotechnology and Neurorecovery (CTNR) in the Department of Neurology at MGH and an instructor in Neurology at Harvard Medical School.

“Given the 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.”

Daniel Rubin, MD, PhD

Leigh Hochberg, MD, PhD, director of the BrainGate consortium and clinical trials and the article’s senior author emphasized the importance of ongoing safety analyses as surgically placed brain-computer interfaces advance through clinical studies. 

“While our consortium has published more than 60 articles detailing the ever-advancing ability to harness neural signals for the intuitive control of devices for communication and mobility, safety is the sine qua non of any potentially useful medical technology,” says Hochberg, who also co-directs CNTR, and is the L. Herbert Ballou University Professor of Engineering at Brown University, director of the VA RR&D Center for Neurorestoration and Neurotechnology at VA Providence Healthcare System, and senior lecturer on Neurology at Harvard Medical School.

"The extraordinary people who enroll in our ongoing BrainGate clinical trials, and in early trials of any neurotechnology, deserve tremendous credit. They are enrolling not to gain personal benefit, but because they want to help"

Leigh Hochberg, MD, PhD

Merit Cudkowicz, MD, MSc, chief of MGH’s Department of Neurology, director of the Sean M. Healey & AMD Center for ALS, and Julianne Dorn Professor of Neurology at Harvard Medical School applauded the BrainGate study.

“Clinical trials of innovative neurotechnologies and BCIs are incredibly exciting, especially with respect to diseases like ALS or spinal cord injury, where there is still no cure,” she says.

“Alongside platform trials of novel medications, our Center for Neurotechnology and Neurorecovery continues to lead in directing, performing, and growing the clinical trials that are providing promising new methods to improve the quality of life for people with neurologic disease.”

Additional MGH co-authors include Laurie Barefoot, APRN, Sydney S. Cash, MD, PhD, Carol Grant, BSN, RN, CCRN, CCRP, Rose Marujo, RN, Maryam Masood, MS, and Ziv M. Williams, MD. Drs. Hochberg and Cash co-direct the CNTR at Mass General.

Contributing authors are from institutions including Brown University, VA Providence Healthcare system, Stanford University, Case Western Reserve University, the University of Chicago, Barrow Neurological Institute, Rush University Medical Center, Cleveland Clinic, Sargent Rehabilitation Center, and Northwestern University.

Additional information is available in the Brown University press release and at www.braingate.org.

This work was supported by the Department of Veterans Affairs; the National Institutes of Health, National Institute on Deafness and Other Communication Disorders (NIDCD); the National Institutes of Health, National Center for Medical Rehabilitation Research (NCMRR); the National Institutes of Health, National Institute of Neurological Disorders and Stroke (NINDS); the Office of Naval Research; Simons Foundation; Howard Hughes Medical Institute; Doris Duke Charitable Foundation; Conquer Paralysis Now; American Heart Association; ALS Association; Movement Disorder Foundation (Australia); The American Academy of Neurology; L. and P. Garlick, S. and B. Reeves; the Massachusetts General Hospital (MGH) Deane Institute, The MGH Executive Committee on Research; Stanford University Wu Tsai Neurosciences Institute, Bio-X Institute at Stanford; Robert J. & Nancy D. Carney Institute for Brain Science at Brown University, Brown University School of Engineering, Brown University Office of the Vice President for Research; and Harvard Catalyst. The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the Department of Veterans Affairs, or the United States Government.

CAUTION: Investigational Device. Limited by Federal (or U.S.) law to investigational use.

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments. In July 2022, Mass General was named #8 in the U.S. News & World Report list of "America’s Best Hospitals." MGH is a founding member of the Mass General Brigham healthcare system.