Brain Wiring Helps Illuminate Range of Uses for Non-Drug Therapies

Imagine if depression or obsessive compulsive disorder (OCD) could be treated with non-drug therapies, such as those currently being used to tackle Parkinson’s disease and other movement disorders. Suzanne Haber, PhD, is working toward that goal in her labs at McLean Hospital and the University of Rochester Medical Center.

For the moment, the research focus is “to understand how the brain is structurally connected,” said Haber, a visiting professor of psychiatry at McLean. Using imaging to identify the movement of blood and water molecules through the brain, she and her team are working to understand the “wiring” that controls our thoughts and movements.

The “wires” are axons, the threadlike part of a nerve cell along which impulses are conducted from the cell body to other cells. By tracking the flow of these molecules, she hopes to clearly identify “who actually talks to who in the brain.”

The work targets the basal ganglia, a group of subcortical nuclei responsible primarily for motor control as well as for other roles, such as motor learning, executive functions and behaviors, and emotions. Disruption of this neural network forms the basis for movement disorders such as Parkinson’s.

Tools such as functional and diffusion magnet resonance imaging allow scientists to “create some of the complex networks and be fairly sure that these are the structural bases for some of these networks,” she explained. When combined with animal studies, imaging results from people with and without disease provide insights about which connectivity profiles are normal and where therapies might be effective.

One of those therapies is deep brain stimulation (DBS), in which neurosurgeons target specific areas of the brain with electrodes with the goal of reducing the symptoms and impact of Parkinson’s and other motor function disorders. Work is also underway with transcranial magnetic stimulation, a non-invasive therapy that is already being used to treat depression—and which is in clinical trials for treating OCD.

The current focus of her work, Haber said, is the subthalamic nucleus, a part of the basal ganglia system that has been identified as an effective area for Parkinson’s treatment.

“We have some ideas from the imaging studies about what brain regions seem to float to the top in terms of depression and OCD,” said Haber. “Our work has been interested in some of those connections and how that network might be put together.”

The ultimate goal is to translate the basic research to create models to determine the best location to place the electrode and the contacts on that electrode to activate a positive response.

How does it work? “Nobody really knows,” she said, adding the basal ganglia is “a very complex set of interactions, and the lack of dopamine causes problems and that stimulation helps.”

One of the key issues that needs to be addressed would be to define ongoing benefits from a treatment like DBS, she said, explaining the relief in Parkinson’s is immediate, and symptoms return once the stimulation is turned off.

“We know a lot about the pharmacology” for treating depression and OCD, but “there isn’t a clear motor system like with Parkinson’s.”

There are clinical trials currently underway in the United States and Europe, but treatments may still be somewhat farther down the road.

For Haber, the near-term future of her work is clear: “The goal is to understand the normal human brain and how things are wired up, and how does that translate into imaging both from a functional standpoint and a structural standpoint.”