Mapping Brain Circuitry in Bipolar Disorder

Novel imaging techniques help identify surgical targets for deep brain stimulation

Innovations in Neurology & Neurosurgery | Winer 2021

 Jennifer Sweet, MD

For decades, doctors have explored surgical options to treat patients with psychiatric disorders. But the practice has been fraught with controversy and ethical questions about its effectiveness.

New research of the brain could change that by improving visualization in psychiatric neurosurgery.

“As our technology for brain imaging has become more sophisticated, we can look at different regions of the brain in unique ways,” says Jennifer Sweet, MD, FAANS, FACS, a neurosurgeon at University Hospitals Cleveland Medical Center specializing in sterotactic and functional neurosurgery, and Associate Professor at Case Western Reserve University School of Medicine. “That opens up new possibilities for advanced surgical techniques.”

 Keming Gao, MD, PhD

Dr. Sweet is currently leading a University Hospitals study to investigate areas of the brain that may be unique to patients with bipolar disorder who do not respond to currently available treatments — and may represent  effective surgical targets for deep brain stimulation (DBS). With DBS, neurosurgeons place an electrode inside the patient’s brain to regulate brain activity using electrical impulses.

“We know that DBS can be more effective when you target specific neural pathways of the brain,” explains Keming Gao, MD, PhD, Director of the Mood Disorder Program at UH, and Professor of Psychiatry at the School of Medicine. “Before we put in electrodes, we want to understand where to target in the brain of a bipolar patient who fails conventional treatments.”

VISUALIZING BRAIN CIRCUITRY

Bipolar disorder can be extremely debilitating in patients with a severe form of the disease. They may suffer from extreme episodes of mania and depression and other physical symptoms that impact daily life.

“Most people with bipolar disorder reach remission with medications and/or electroconvulsive therapy,” Dr. Gao says, “but the small number who don’t respond to conventional treatments could benefit from DBS.”

The current UH study, funded by the National Institutes of Health (NIH) is using an MR-based imaging technique, called tractography, to assess the brain circuitry of bipolar patients compared to healthy controls.

With standard MRI imaging, doctors can only see holistic white matter and not the individual white matter tracts, or circuitry, of a patient’s brain. Tractography allows them to take that raw data and manipulate it through different software programs and algorithms to visualize that circuitry – and study it.

“This is one of the areas in neuroimaging that has grown substantially,” Dr. Sweet says. “It's an exciting process because we're trying to discover something new, and everyone is contributing to that.”

UH neurosurgeon Jonathan Miller, MD, FAANS, FACS, and psychiatrist Joseph R. Calabrese, MD, former Director of the Mood Disorders Program, initiated the collaboration between neurosurgery and psychiatry in 2012. The focus then was to use DBS for bipolar depression. Dr. Miller was later joined by Dr. Sweet, who is now the principal investigator.

“When I got involved, I incorporated some different imaging technologies, including tractography, and we added more members to our team,” she says.

That included adding the medical expertise of Dr. Gao as well as Cameron McIntyre, PhD, from the Case Western Reserve School of Medicine Department of Biomedical Engineering. McIntyre specializes in computer modeling and creating mathematical algorithms for DBS.

“We're utilizing all these fantastic tools and sub-specialized expertise that are unique to our institution,” Dr. Sweet says. “We are fortunate to have so many people with such amazing skill sets to contribute. It’s a true collaboration.”

STUDY DETAILS

To participate in the study, patients complete multiple clinical evaluations and neurological testing over three visits. On their third visit, they also receive the MR imaging. Drs. Sweet and McIntyre take that data and creates maps of the white matter fibers in the brain to compare differences across patient groups. They can then use computer modeling to explores how DBS impacts the brain’s white matter pathways using computational modeling to visualize the effects.

So far, the findings from a small pilot study are promising.

“We’ve been placing these electrodes in the brain for decades, and we know that they help to reduce tremor and other symptoms in patients with movement disorders, but these models help us to visualize the effects of stimulation in a new way,” Dr. Sweet says.

“We’ve found that there are differences in the brain circuitry of bipolar patients compared to healthy controls. Globally, we know that regions of the brain can differ in bipolar patients. But we’re specifically focusing on differences in an area of brain that can be easily targeted with surgery.”

She and her team recently secured a new, one-year grant from NIH to expand their research, recruit more patients and continue investigating their hypothesis before moving to clinical trials.

“Surgery isn’t a difficult decision for patients who are truly suffering and don’t have alternatives,” she says. “Many subjects have told us they would love to have surgery right now if they could, but we need to be thoughtful and make sure that we're doing what's best for patients. We first need to figure out what's happening in the brain and model that.”

To learn more about the University Hospitals study, call 216-844-2863..