Deep brain stimulation for Parkinson’s disease and epilepsy has already proven effective for many patients. But where and how to manipulate the brain’s electrical activity to treat mental disorders such as addiction, obsessive-compulsive disorder, post-traumatic stress disorder, and depression has remained elusive.
Tomorrow, scientists at the University of Minnesota will propose a new idea: that all of those illnesses stem from a set of brain circuits called cortico-striatal loops that can be manipulated with a specific type of electrical stimulation to bring relief to patients.
“Whether it’s for depression, obsessive-compulsive disorder (OCD), or addiction, nobody right now can actually give you the statement: Here is a specific physiologic signature in the brain, and when I change it people get better,” says Widge. “But we have that partially worked out for Parkinson's, and it certainly exists for epilepsy. So it should be possible for things like addiction.”
Widge, who is both a psychiatrist and a biomedical engineer, views many psychiatric illnesses as having a common thread: Patients with symptoms of these diseases all feel “stuck,” he says.
People with depression, for example, get stuck in a negative-thinking loop. People with OCD know that the stove is almost certainly off or the door is surely locked, but they’re stuck with the thought that they have to keep checking it. People with PTSD get stuck thinking about the same traumatic experience over and over. People with addiction go back to the same harmful substance, even when their physical dependence upon it has been broken.
Widge believes that the feeling of being stuck in a habitual loop, whether it’s taking cocaine or checking the stove, comes from the cortico-striatal loop circuits in the brain, he says. This spiral-shaped set of structures connects the cortex on the surface of the brain to an evolutionarily old, deep interior region called the striatum. Some of these circuits are involved in our most basic, habitual drives.
“We think this older system goes into overdrive” in people with psychiatric disorders that involve inflexibility and stuck thinking, Widge says. “The brain doesn’t know how to make it take a step back and let other decisional systems have a turn at controlling behavior.”
He was encouraged by previous clinical evidence that deep brain stimulation had positive effects on both OCD and depression. These disorders “are two different chapters in the Diagnostic and Statistical Manual, and are traditionally treated differently, but there must be something in common if you can treat them with the same intervention,” he says. Also encouraging were the results of study Widge and colleagues published this month, which demonstrated some of the neuronal underpinnings of flexible decision making.
To test the hypothesis, Widge and his colleagues have surgically implanted electrodes in this deep area of the brain in rodents and in one man with severe OCD. The electrodes in the man’s brain have been continuously recording activity and delivering stimulation to the habit-driving parts of the cortico-striatal loops for over a year, Widge says.
“What we see [in this man] is that during the brief periods when he’s dramatically better, that loop is shut down,” says Widge. That suggests that when connections between the deep brain and surface brain calm down, goal-directed thinking can take over.
Widge and his colleagues also noticed that when the circuit is overactive it tends to synchronize with other areas of the brain, such as the prefrontal cortex. This is the area of the brain that controls goal-directed, non-habitual decision making. When the cortico-striatal loop gets going, it syncs with the prefrontal cortex, producing a rhythmic firing of neurons—almost like the habit-controlling part of the brain is hypnotizing the decision-making part of the brain.
This overactive circuit in the brain needs to be jammed, Widge says. To do that, Widge and his team implant two stimulators, wiring one to the cortex and the other to the deep brain target. The devices deliver stimulation at different frequencies, creating a mismatch that blocks the cortex and the striatum from syncing up.
Widge aims to implant the system in another OCD patient within the next few months, he says. The goal is to gather enough evidence to demonstrate that a cortico-striatal loop is indeed the culprit of stuck thinking, and that jamming its synchronizing activity tamps down its effects.
Then—because it’s hard to justify invasive brain surgery—Widge says he hopes to find a noninvasive, or at least less-invasive, way to get the same result. Perhaps that can be achieved using ultrasound or temporally interfering electric fields, he says. Or perhaps there’s a way to inject a sensitizing material deep into the brain to make it more sensitive to transcranial magnetic stimulation, he says.
Ultimately, Widge wants to see the therapy work in an assistive manner—not as a way to control the brain, but more of a nudge that enables more volitional, rational control over decision making. “We want our patients to feel a little less stuck,” says Widge. “The addiction patient says: ‘Just this once, I’ll go to an AA meeting.’ Or the depression patient says: ‘Just this once I’ll get out of bed and call a therapist.’ If you add up enough of those ‘just this once’ decisions, that’s the road to recovery.”