(msTBI) and chronic sequelae.
Participants in this first-in-humans trial experienced brain injuries between 3-18 years before the study that left them with persistent neuropsychological impairment and a range of functional disabilities.
This is the first time a DBS device has been implanted in the central thalamus in humans, an area of the brain measuring only a few millimeters wide that helps regulate consciousness.
Placing the electrodes required a novel surgical technique developed by the investigators that included virtual models of each participant’s brain, microelectrode recording, and neuroimaging to identify neuronal circuits affected by the TBI.
After 3 months of 12-hour daily DBS treatments, participants’ performance on cognitive tests improved by an average of 32% from baseline. Participants were able to read books, watch TV shows, play video games, complete schoolwork, and felt significantly less fatigued during the day.
Although the small trial only included five patients, the work is already being hailed by other experts as significant.“We were looking for partial restoration of executive attention and expected [the treatment] would have an effect, but I wouldn’t have anticipated the effect size we saw,” co-lead investigator Nicholas Schiff, MD, professor of neuroscience at Weill Cornell Medical College, New York City, said in an interview.
The findings were published online Dec. 4 in Nature Medicine.
“No Trivial Feat”
An estimated 5.3 million children and adults are living with a permanent TBI-related disability in the US today. There currently is no effective therapy for impaired attention, executive function, working memory or information-processing speed caused by the initial injury.
Previous research suggests that a loss of activity in key brain circuits in the thalamus may be associated with a loss of cognitive function.
The investigators recruited six adults (four men and two women) between the ages of 22 and 60 years with a history of msTBI and chronic neuropsychological impairment and functional disability. One participant was later withdrawn from the trial for protocol noncompliance.
Participants completed a range of questionnaires and tests to establish baseline cognitive, psychological, and quality-of-life status.
To restore lost executive functioning in the brain, investigators had to target not only the central lateral nucleus, but also the neuronal network connected to the region that reaches other parts of the brain.
“To do both of those things we had to develop a whole toolset in order to model both the target and trajectory, which had to be right to make it work properly,” co-lead investigator Jaimie Henderson, MD, professor of neurosurgery at Stanford University College of Medicine, Stanford, California, said in an interview. “That gave us a pretty narrow window in which to work and getting an electrode accurately to this target is not a trivial feat.”
“A Moving Target”
Each participant’s brain physiology was slightly different, meaning the path that worked for one individual might not work for another. The surgery was further complicated by shifting in the brain that occurred as individual electrodes were placed.