Clinical trial results indicate low rate of adverse events associated with implanted brain computer interface

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,." said 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," said Lee 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.

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

Key Takeaways

• Brain-computer interfaces, which provide a direct communication link between the brain and a computer or other external device, may help people with difficulty communicating due to paralysis caused by ALS, brainstem stroke, spinal cord injury, and other neurologic conditions
• The most sophisticated of these devices use sensors that are surgically placed into parts of the brain that control movement; however, the safety of these chronic brain implants is unknown
• Results from the largest and longest-running clinical trial of an implanted brain computer interface suggests that the investigational BrainGate Neural Interface system safety is comparable to other chronically implanted devices used to manage neurologic disease