Gina Arata was in her final semester of college, preparing to apply to law school, when she was involved in an automobile accident in 2001. Her ability to focus was so impaired by the injuries that she struggled at her work sorting mail.
“I couldn’t remember anything. My left foot dropped, so I’d trip over things all the time. I was always in car accidents. And I had no filter—I’d get pissed off really easily,”
said Arata, who lives in Modesto with her parents.
Her parents learnt about brain injury research being undertaken at Stanford Medicine and contacted the researchers; Arata was accepted as a participant. In 2018, doctors surgically placed a device deep inside her brain, then carefully regulated the it’s electrical activity to stimulate the networks that had been suppressed by the lesion. The clinical trial’s findings were published in Nature Medicine on December 4th.
Cognition Restoration
Gina noticed the difference immediately. She could rattle off fruits and vegetables when asked to list products in a grocery store’s produce aisle. Then a researcher turned off the device, and she couldn’t think of any.
“Since the implant I haven’t had any speeding tickets,” Arata said. “I don’t trip anymore. I can 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 Crawdads Sing,’ and loved it and remembered it. And I don’t have that quick temper.”
For Arata and four others, the experimental deep-brain-stimulation device restored, to different degrees, the cognitive abilities they had lost to brain injuries years before. The new method, which Stanford Medicine researchers and collaborators from other institutions developed, is the first to show promise against the long-lasting impairments from moderate to severe traumatic brain injuries.
Long-term Brain Injury Effects
The long-term effects of mild to severe traumatic brain injury, such as difficulties focusing, remembering, and making decisions, affect more than 5 million Americans. Though many people recover sufficiently to live independently, their disabilities prevent them from returning to school or job or resuming their social life.
“In general, there’s very little in the way of treatment for these patients,”
said co-senior author Jaimie Henderson, MD, professor of neurosurgery.
However, the fact that these patients had awoken from comas and recovered a fair 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 focus on a task — were relatively preserved.
Central Lateral Nucleus Stimulation
These systems connect the thalamus, a relay station deep within the brain, to points throughout the cortex, the brain’s outer layer, which control higher cognitive functions.
“In these patients, those pathways are largely intact, but everything has been down-regulated. It’s as if the lights had been dimmed and there just wasn’t enough electricity to turn them back up,”
said Henderson.
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 nucleus is optimized to drive things broadly, but its vulnerability is that if you have a multifocal injury, it tends to take a greater hit because a hit can come from almost anywhere in the brain,”
said Nicholas Schiff, MD, a 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 would reactivate these pathways, turning the lights back on.
Precise Positioning
The trial included five patients who had persistent cognitive impairments more than two years after a moderate to severe traumatic brain injury. They ranged in age from 22 to 60, and had suffered injuries three to 18 years prior.
The difficulty was in precisely positioning the stimulation device, which differed from person to person. Each brain is naturally structured differently, and the damage had resulted in additional changes.
So the researchers created a virtual model of each brain that allowed them to pinpoint the location and level of stimulation that would activate the central lateral nucleus. Henderson surgically implanted the devices in the five participants using these models as a guide.
“It’s important to target the area precisely. If you’re even a few millimeters off target, you’re outside the effective zone,”
he said.
Focus, Concentration and Planning Improvement
The subjects spent 90 days with the gadget turned on for 12 hours a day after a two-week titration phase to optimize the stimulation. Their development was tested using the trail-making test, a typical test of mental processing speed that includes drawing lines linking a jumble of letters and numbers.
“It’s a very sensitive test of exactly the things that we’re looking at: the ability to focus, concentrate and plan, and to do this in a way that is sensitive to time,”
Henderson said.
At the end of the 90-day treatment period, participants had improved their test speeds by 32% on average, far exceeding the 10% target set by the researchers.The benefits were visible in the participants’ and their families’ daily lives.
They resumed previously impossible activities such as reading books, watching TV shows, playing video games, or completing a homework assignment. They felt less tired and were able to go through the day without taking a nap.
A Pioneering Moment
The therapy was so effective that the researchers had difficulty finishing the final phase of their trial. They had planned a blinded withdrawal phase in which half of the participants’ devices would be turned off at random. Two patients declined, hesitant to accept that risk.
Of the three who participated in the withdrawal phase, one was randomized to have their device turned off. After three weeks without stimulation, that 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 traumatic brain injury, and it offers hope to many who have reached a stalemate in their recovery.
“This is a pioneering moment. Our goal now is to try to take the systematic steps to make this a therapy. This is enough of a signal for us to make every effort,”
Schiff said.
Reference:
- Schiff, N.D., Giacino, J.T., Butson, C.R. et al. Thalamic deep brain stimulation in traumatic brain injury: a phase 1, randomized feasibility study. Nat Med (2023). Doi: 10.1038/s41591-023-02638-4