A new technique that uses deep brain stimulation tailored to each patient has exceeded researchers’ expectations in the treatment of cognitive impairments caused by moderate to severe traumatic brain injury.
In 2001, Gina Arata was in her last semester of college and planning to apply to law school, when she suffered a traumatic brain injury in a car accident. The injury compromised her ability to concentrate so much that she had trouble at a job sorting mail.
“I couldn’t remember anything,” said Arata, who lives in Modesto with his parents. “My left foot fell off, so he was tripping over things all the time. I was always in car accidents. And I had no filter: I got angry very easily.”
His parents heard about the research being done at Stanford Medicine and reached out; Arata was accepted as a participant. In 2018, doctors surgically implanted a device deep in his brain and then carefully calibrated the device’s electrical activity to stimulate networks that the injury had attenuated.
She noticed the difference right away: When asked to list items in the produce aisle of a grocery store, she could recite fruits and vegetables. A researcher then turned off the device and could not name any.
“Since the implant, I have not received fines for speeding,” Arata said. “I don’t stumble anymore. I can remember how much money is in my bank account. I didn’t know how to read, but after the implant I bought a book, Where the crabs sing, and I loved it and remembered it. And I don’t have that quick temper.”
Advances in the treatment of brain injuries
For Arata and four others, the experimental deep brain stimulation device restored, to varying degrees, the cognitive abilities they had lost to brain injuries years earlier. The new technique, developed by researchers at Stanford Medicine and collaborators at other institutions, is the first to show promise against lasting impairments resulting from moderate to severe traumatic brain injuries.
The results of the clinical trial were published on December 4 in the journal Nature medicine.
Living with a traumatic brain injury
More than 5 million Americans live with the lasting effects of a moderate to severe traumatic brain injury: difficulty concentrating, remembering, and making decisions. Although many recover enough to live independently, their impairments prevent them from returning to school or work and resuming their social lives.
“In general, there is very little treatment for these patients,” said Jaimie Henderson, MD, professor of neurosurgery and co-senior author of the study.
However, the fact that these patients had emerged from comas and regained a good amount of cognitive function suggested that the brain systems that support attention and arousal (the ability to stay awake, pay attention to a conversation, and concentrate on a task) ) were relatively preserved.
Understanding and targeting the brain
These systems connect the thalamus, a relay station deep in the brain, with points along the cortex, the outer layer of the brain, which controls higher cognitive functions.
“In these patients, those pathways are largely intact, but everything has been downregulated,” said Henderson, the John and Jene Blume-Robert and Ruth Halperin Professor. “It’s like the lights have gone dim and there just isn’t enough electricity to turn them back on.”
In particular, an area of the thalamus called the central lateral nucleus acts as a center that regulates many aspects of consciousness.
“The central lateral nucleus is optimized to drive things broadly, but its vulnerability is that if you have a multifocal injury, it tends to take a bigger hit because a hit can come from almost any part of the brain,” said Nicholas Schiff, MD, professor at Weill Cornell Medicine and co-senior author of the study.
The researchers hoped that precise electrical stimulation of the central lateral nucleus and its connections could reactivate these pathways, turning the lights back on.
Clinical trial success
In the trial, researchers recruited five participants who had lasting cognitive impairments more than two years after a moderate to severe traumatic brain injury. They were between 22 and 60 years old and had suffered injuries between three and 18 years earlier.
The challenge was to place the stimulation device in exactly the right place, which varied from person to person. For starters, each brain is shaped differently, and the lesions caused additional changes.
“That’s why we developed a series of tools to better define what that area was,” Henderson said. The researchers created a virtual model of each brain that allowed them to identify the location and level of stimulation that would activate the central lateral nucleus.
Guided by these models, Henderson surgically implanted the devices in the five participants.
“It’s important to target the area precisely,” he said. “If you deviate even a few millimeters from the target, you are outside the effective zone.”
A pioneering moment
Following a two-week titration phase to optimize stimulation, participants spent 90 days with the device on for 12 hours a day.
Their progress was measured using a standard mental processing speed test, called a trace test, which involves drawing lines connecting a mix of letters and numbers.
“It’s a very sensitive test of exactly the things we’re looking at: the ability to focus, concentrate and plan, and do it in a way that’s time-sensitive,” Henderson said.
At the end of the 90-day treatment period, participants had improved their speed on the test, on average, by 32%, far exceeding the 10% the researchers had targeted.
“The only surprising thing is that it worked as we predicted, which is not always a fact,” Henderson said.
Impact on the lives of participants
For participants and their families, improvements were evident in their daily lives. They resumed activities that seemed impossible: reading books, watching TV shows, playing video games, or completing a task. They felt less fatigued and could get through the day without taking naps.
The therapy was so effective that the researchers had trouble completing the last part of their study. They had planned a blind withdrawal phase, in which half of the participants would be randomly selected to turn off their devices. Two of the patients refused, not wanting to take that risk. Of the three who participated in the withdrawal phase, one was randomly assigned to have his device turned off. After three weeks without stimulation, that participant performed 34% slower on the trail-making test.
Advances in the treatment of brain injuries
The clinical trial is the first to focus on this region of the brain in patients with moderate to severe traumatic brain injury, and offers hope for many who have stalled in their recovery.
“This is a pioneering moment,” Schiff said. “Our goal now is to try to take systematic steps to make this a therapy. This is enough of a signal for us to do everything we can.”
Reference: “Thalamic Deep Brain Stimulation in Traumatic Brain Injury: A Phase 1 Randomized Feasibility Study” by Nicholas D. Schiff, Joseph T. Giacino, Christopher R. Butson, Eun Young Choi, Jonathan L. Baker, Kyle P. O ‘ Sullivan, Andrew P. Janson, Michael Bergin, Helen M. Brontë-Stewart, Jason Chua, Laurel DeGeorge, Sureyya Dikmen, Adam Fogarty, Linda M. Gerber, Mark Krel, Jose Maldonado, Matthew Radovan, Sudhin A. Shah, Jason Su, Nancy Temkin, Thomas Tourdias, Jonathan D. Victor, Abigail Waters, Stephanie A. Kolakowsky-Hayner, Joseph J. Fins, Andre G. Machado, Brian K. Rutt, and Jaimie M. Henderson, December 4, 2023, Nature medicine.
Researchers from Weill Cornell Medicine, Spaulding Rehabilitation Hospital in Boston, Harvard Medical School, the University of Utah, the University of FloridaVanderbilt University, the University of Washingtonthe University of Bordeaux and the Cleveland Clinic also contributed to the study.
The study was supported by funding from the National Institutes of Health’s BRAIN Initiative and a grant from the Center for Translational Sciences at Weill Cornell Medical College. Medtronic provided the surgical implants.