Legacy

Spring 2022
Issues/Contents
Feature

Circuit override

U of M researchers combine engineering and brain science expertise to give people better control over severe mental illness

SYLVER ARTS/ISTOCK IMAGES

In the video, the woman sitting on the hospital bed describes what it’s like when her anxiety takes over.

“I’m notorious for being my own worst critic and overthinking to the point that it’s counterproductive for me,” she says. “If I’m nervous about anything, it gets a hold of me instead of me controlling it.”

From off camera, Alik Widge, M.D., Ph.D., an M Health Fairview psychiatrist and assistant professor at the University of Minnesota Medical School, asks her a follow-up question.

“And for a few minutes, it sounds like that was a little bit different?” he inquires. “It [the anxiety] was there, but not as much?”

“Yeah,” the woman says, her voice turning hopeful. “But it just couldn’t get to me.”

The woman in the video was recounting her experience as a participant in Widge’s clinical study that uses brain stimulation technology to treat severe mental illness. The video clip lasts less than 30 seconds, but it provides a tantalizing glimpse of what Widge hopes is possible in the future of mental health care.

“For that moment, this patient had control over her own brain,” he says. “What if we could give people that control not just for a moment, but all the time?”

Computational psychiatry

To understand Widge’s vision, you have to think about the brain the way he does—as the world’s most complex computer.

Nowadays, Widge calls himself a clinical brain engineer, but as a kid, he might have gone by something different: a computer nerd. He loved tinkering with electronics of all kinds, figuring out how they’re wired and how circuits communicate. His childhood wonder evolved into a fascination with the human brain, which led him down a path to become one of only a few people in the world trained as both a biomedical engineer and a clinical psychiatrist.

It’s a combination of expertise that allows him to view the brain less as a monolithic lump of gray matter and more as a computational device made up of circuits that communicate with each other through electrical rhythms.

“For our minds to function, that communication has to happen,” Widge says. “And mental illnesses are when that communication breaks down.”

Of course, the brain is far more complicated than your average computer, so figuring out when and where communication is breaking down is no easy task. Widge turned to his training as a psychiatrist for more clues.

He realized that mental illnesses thought to be very different—like anxiety, addiction, and obsessive-compulsive disorder, for example—might actually have a common culprit: the inability to think flexibly.

For most people, when harmful thoughts go through their heads, they’re quickly over ridden by healthy, more normal ones. But for some people with mental illness, that flexibility doesn’t exist. No matter how much they want to move past their anxiety, craving, or obsession, Widge says, part of their brains won’t let them.

He put on his engineering cap and wondered: what if we could find and correct the out-of-sync electrical rhythms in the brain that are responsible for inflexible thinking, and by extension, a whole host of mental illnesses?

Alik Widge, M.D., Ph.D., talks about how to heal mental illness through brain network stimulation in this TEDxMinneapolis talk.

Search and stimulate

Widge joined forces with researchers at Massachusetts General Hospital to test the theory.

They identified 12 patients who were undergoing brain surgery for epilepsy. Part of these patients’ procedures required the placement of hundreds of electrodes throughout the brain to monitor activity and find the source of their seizures.

“These people agreed to participate in our study,” Widge explains, “which meant we could use the electrodes that were already inside their brains to monitor and stimulate their brain activity as they completed a lab task we designed.”

The task tested the patients’ ability to think flexibly. As the participants performed the task, Widge and his team mapped the regions and rhythms in the brain responsible for flexible thinking.

They identified a specific rhythm, known as the theta band, that appeared to be particularly conducive to flexible thinking. And as luck would have it, previous research told them that a certain region in the brain could boost theta band activity throughout the rest of the brain, if stimulated with a small amount of electrical current. When a patient began to perform poorly on the lab task, Widge and company stimulated that region of their brain. Sure enough, their mental function improved.

MODEL BEHAVIOR

Sarah Heilbronner, Ph.D., is bridging the gap between brains—human and animal brains to be specific.

A McKnight Land-Grant Professor in the Department of Neuroscience, Heilbronner builds diagrams that show how different parts of animals’ brains connect and communicate. (A wiring diagram of part of the human brain is shown above.) And because mammals share some brain anatomy, those diagrams can be valuable to studies of human brain function.

“Ideally, what we wind up with are maps of connectivity that then give us information about similarities across species,” she says.

In a recent study, Heilbronner confirmed that the brain circuits Widge believes are responsible for some mental illnesses in people also exist in rodents. It’s a breakthrough connection that will allow researchers to better understand mental illness and accelerate their pursuit of new therapies.
IMAGE COURTESY DANIEL BULLOCK

Several of the patients in the study—including the woman in the video—also suffered from severe anxiety. After receiving the targeted stimulation, they reported a reduction in their symptoms and a renewed ability to focus on thoughts of their choice.

Widge cautions that inflexible thinking is only one aspect of mental illness, and deep brain stimulation isn’t a viable treatment for every person who suffers from disorders like anxiety and depression. But for some people with severe illness, more control over their thinking might be just what they need to move forward.

“For these people, [inflexible thinking] is a single stone that’s holding up the whole archway of their mental illness,” he says. “I think if we can knock out this one problem and just give them a little bit of mental wiggle room, they’ll be able to do the rest on their own, and the whole illness will just come cascading down.”

Looking forward

Widge and his team are now preparing to test their findings in a larger M Health Fairview clinical trial, which he hopes will launch next year.

They’re also on a mission to engineer a noninvasive medical device that could be used in a doctor’s office to monitor a person’s specific brain rhythms and provide timely stimulation to boost their mental function. It’s a precise, personalized approach that could not only help millions of people manage severe mental illness, but also save lives, Widge says.

“These tools could give people back control of their brains,” he says. “They could maybe even stop a suicide attempt before it starts.”

Widge believes the world of psychiatry is on the cusp of an explosion of new approaches to treat mental illness that are reinforced by a computational understanding of the brain.

Unfortunately, he says, mental health care today can rely too much on a psychiatrist observing patients’ behavior and not enough on what’s going on inside their brains. But Widge envisions something different.

“In the future, you’ll still talk to a psychiatrist, but you’ll also go through tests and brain scans to see what’s happening inside your head,” he says. “With that information, your psychiatrist can sit down with you and say, ‘Here is how your specific brain circuits are causing you to feel bad. And here’s what we’re going to do about that.’”

To find out how your gift can make a difference in mental health research, contact Kristen Rasmussen at kristenr@umn.edu or 612-625-5192.

Next