Mass General Neurosurgeons and Psychiatrists Team Up To Treat Mental Illness

New treatments are desperately needed for severe, intractable psychiatric diseases. When patients do not respond to medication or other conventional therapies, their options are limited. That’s where the Massachusetts General Hospital Psychiatric  Neurosurgery Committee can help, offering surgical approaches to obsessive compulsive disorder (OCD) and major depression, and the newest treatment, neurostimulation for OCD.  For other conditions, Mass General psychiatrists and neurosurgeons are collaborating on a major effort to develop a second-generation neurostimulator to treat a wide range of disorders, from post-traumatic stress to depression to addiction.

Surgical treatments for psychiatric disease have come a long way since the 1960’s, when the overuse of crude techniques resulted in tragic results for many mentally ill people. Today, psychiatric neurosurgeries are precise, sterotactically-guided, minimally invasive, and reserved for the most severe and medically intractable cases of OCD and depression. The surgeries—anterior cingulotomy and limbic leucotomy—remain a good option for a small group of carefully selected, severely affected patients, says Emad N. Eskandar, MD, director of Stereotactic and Functional Neurosurgery at Mass General.

“The idea is to target very small areas that are critical in these disorders without disrupting the rest of the brain function. For the most part, these patients don't have any cognitive, memory or personality side effects. The lesion is imperceptible except for the changes it causes in the severity of their illness,” Eskandar says. Mass General neurosurgeons perform more of these surgeries than any other center in the US, and find they produce symptoms relief in 50-70% of patients who have tried and failed all conventional treatments.

In 2009, OCD patients gained a new option for treatment, deep brain stimulation (DBS). In DBS, implantable electrodes are used to electrically stimulate targeted brain areas, which modulates abnormal neural activity and relieves neurological and neuropsychiatric symptoms. Mass General was one of the first hospitals to use DBS, initially approved to treat movement disorders, including Parkinson’s disease.

To treat OCD, a neurosurgeon places the electrodes in the ventral striatum, a brain region involved in compulsive behavior. A pulse generator, which sits under the skin near the collarbone, delivers a steady electric current to the tissue. The current does not kill the neurons, but changes their firing, leading to relief of obsessive thoughts and behavior. “It’s not a lesion, and the chronically implanted electrode has two advantages. It’s adjustable—you can titrate the current and frequency—and it’s reversible,” explains Eskandar.
 
The DBS device was also tested for treating major depression, but failed a pivotal clinical trial performed partly at Mass General. That was a disappointment, says Eskandar. Despite some significant recoveries and several case examples of patients whose lives were “completely and miraculously turned around,” the device did not show significant efficacy in the randomized, controlled clinical trial, Eskandar says.

Mass General psychiatrist Darin D. Dougherty, MD, MSc, chief of the Division of Neurotherapeutics, was the lead investigator on the depression trial. The group is pursuing ways to personalize the use of DBS, including adjusting the electrode placement, hoping to make it work for more people, he says.

At the same time, Dougherty and Eskandar are leading a massive effort to create a powerful second-generation DBS device, one that can actually detect troublesome brain states, and respond with appropriate stimulation to nudge brain activity back towards normal.

Backed by a $30 million dollar, 5 year grant from the Defense Advanced Research Projects Agency (DARPA), a multidisciplinary “dream team” team of physicians, neuroscientists, engineers, and computer scientists from Mass General and surrounding institutions is developing a fully implantable, responsive neurostimulator to treat psychiatric disorders prevalent among veterans, including post-traumatic stress disorder (PTSD), major depression, traumatic brain injury (TBI), substance abuse/addiction, and fibromyalgia/chronic pain. Other indications include general anxiety disorder and borderline personality disorder.

Two years into the project, the team has made considerable progress. Draper Lab engineers have produced a miniaturized processor designed to be implanted into the top of the skull, with 5 flexible tethers bearing recording or stimulating electrodes. Dougherty, Eskandar and their colleagues have been working to map the brain circuits they’ll need to monitor and modulate to impact symptoms. Using a combination of neuropsychological testing, noninvasive neuroimaging and even direct recording of brain activity in some patients, the researchers are decoding the neurosignatures associated with a variety of mood, behavior and cognitive tasks, moods and behaviors, and investigating how to suppress those signatures with appropriate stimulation.

The goal is to have the device tested in actual patients by then end of the five-year project. It’s an ambitious goal, says Eskandar, but one he thinks the team will accomplish. His hope is that, much in the same way that DBS has changed the approach to severe Parkinson’s disease, this project will dramatically change the way psychiatrists and neurosurgeons approach the treatment of neuropsychiatric diseases.

For more information, please contact Valerie Giorgione, coordinator of the MGH Psychiatric Neurosurgery Committee, 617-726-3407 and vgiorgione@partners.org.