Brain implants revive cognitive abilities long after head trauma in clinical trial

In 2001, Gina Arata was in her final 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 difficulty sorting mail.

“I didn’t remember anything,” said Arata, who lives in Modesto with his parents. “My left foot was falling off, so I was tripping all the time. I was always in car accidents. And I didn’t have a filter, I got upset very easily.”

His parents learned about research being done at Stanford Medicine and contacted him; Arata was accepted as a participant. In 2018, doctors surgically implanted a device deep into his brain, then carefully calibrated the device’s electrical activity to stimulate networks that the injury had overpowered. The results of the clinical trial were published on December 4 in Natural medicine.

She noticed the difference immediately. When asked to list items in the produce aisle of a grocery store, she was able to name fruits and vegetables. Then a researcher turned off the device and she couldn’t name any of them.

“Since the implementation, I have not received a single speeding ticket,” Arata said. “I don’t stumble anymore. I remember how much money is in my bank account. I wasn’t able to read, but after the implant I bought a book, ‘Where the Crayfish Sing,’ I loved it and I remembered it. . And I don’t have that angry character.”

For Arata and four others, the experimental deep brain stimulation device restored, to varying degrees, the cognitive abilities they had lost due to brain damage years earlier. The new technique, developed by researchers at Stanford Medicine and collaborators at other institutions, is the first to show promise against long-term impairments linked to moderate to severe head trauma.

Dim lights

More than 5 million Americans live with the lasting effects of moderate to severe traumatic brain injury: difficulty concentrating, remembering, and making decisions. Although many recover sufficiently to live independently, their disabilities prevent them from returning to school or work and resuming their social lives.

“In general, there are very few treatments for these patients,” said Jaimie Henderson, MD, professor of neurosurgery and co-senior author of the study.

But the fact that these patients emerged from the coma and recovered much of their cognitive function suggests that the brain systems that support attention and arousal – the ability to stay awake, to pay attention to a conversation, to concentrate on a task – were relatively preserved.

These systems connect the thalamus, a relay station deep in the brain, to points in the cortex, the outer layer of the brain, that control higher cognitive functions.

“In these patients, these 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 been dimmed 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 hub that regulates many aspects of consciousness.

“The central lateral core is optimized to run things holistically, but its vulnerability is that if you have a multifocal injury, it tends to take a greater shock, because a shock can come from almost anywhere in 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 and turn the lights back on.

Precise placement

In the trial, researchers recruited five participants who suffered from lasting cognitive impairments more than two years after moderate to severe head trauma. They ranged in age from 22 to 60 and had suffered injuries three to 18 years earlier.

The challenge was placing the stimulation device in exactly the right place, which varied from person to person. Each brain initially has a different shape, and injuries have led to other changes.

“So we developed a number of tools to better define what that field 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 all five participants.

“It’s important to target the area precisely,” he said. “If you are a few millimeters from the target, you are outside the effective zone.”

A pioneering moment

After a two-week titration phase to optimize stimulation, participants spent 90 days with the device on 12 hours a day.

Their progress was measured by a standard test of mental processing speed, called the trail-making test, which involves drawing lines connecting a jumble of letters and numbers.

“It’s a very sensitive test of exactly what we’re looking at: the ability to focus and concentrate and plan, and to do it in a way that is time sensitive,” Henderson said.

At the end of the 90-day treatment period, participants had improved their test speed by an average of 32%, far exceeding the 10% targeted by the researchers.

“The only surprising thing is that it worked as we predicted, which is not always a given,” Henderson said.

For participants and their families, the improvements were visible in their daily lives. They resumed activities that seemed impossible: reading books, watching TV shows, playing video games or completing an assignment. They felt less tired and could get through the day without taking a nap.

The therapy proved so effective that the researchers struggled to complete the latter part of their study. They planned a blind withdrawal phase, during which half of the participants would be randomly selected to turn off their devices. Two of the patients refused, not wanting to take the risk.

Of the three participants in the withdrawal phase, one was randomized to have their device turned off. After three weeks without stimulation, this participant performed 34% slower on the trail-making test.

The clinical trial is the first to target this region of the brain in patients with moderate to severe head trauma, and it offers hope to 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 it a therapy. That’s enough of a signal for us to make every effort.”

Researchers from Weill Cornell Medicine, Spaulding Rehabilitation Hospital in Boston, Harvard Medical School, University of Utah, University of Florida, Vanderbilt University, University of Washington, the University of Bordeaux and the Cleveland Clinic also contributed to the study.