How a Deep Brain Stimulation Implant Helped Treat Woman's Severe Depression

Physicians have successfully treated a patient with severe depression by resetting the brain circuit involved with depressive brain patterns using a device that is the equivalent of a pacemaker for the brain.

The University of California (UCSF) researchers discovered a neural biomarker, a specific pattern of brain activity that indicates the onset of depression in a patient and customized a commercially available device to recognize that pattern and electrically stimulate another specific area of the brain.

By surgically implanting the device, the team, led by assistant professor of psychiatry at UCSF's Weill Institute for Neurosciences, Katherine Scangos, created an immediate "on-demand" therapy that was unique to the patient and to the neural circuit that triggers her treatment-resistant depression.

"This study points the way to a new paradigm that is desperately needed in psychiatry," professor of psychiatry and member of the UCSF Weill Institute for Neurosciences Andrew Krystal said in a press release from the university. "We've developed a precision-medicine approach that has successfully managed our patient's treatment-resistant depression by identifying and modulating the circuit in her brain that's uniquely associated with her symptoms."

The team's proof of concept research is published in the journal Nature Medicine.

The method employed by the team is a form of deep brain stimulation (DBS), which has shown promise in treating depression during clinical trials but has delivered little success. This could be because the markers in the brain that indicate the onset of depression vary from person to person.

Whereas previous methods of DBS deliver constant stimulation to one area of the brain, the approach developed by the UCSF team takes into account the fact that in different people depression may involve different areas of the brain and identifies individual biomarkers.

Krystal points out that taking this customized approach relieved the symptoms of depression in the patient, a 36-year-old-woman who goes by the name Sarah, almost immediately. This relief has lasted for the full 15 months in which she has had the implant.

The team mapped Sarah's stimulus-response over a period of 10 days using electrodes implanted in her frontal cortex aligning responses to stimulation to a symptom rating scale she filled in.

They found that when certain changes in the amygdala region of the brain occurred Sarah's symptoms lessened. When these changes did not happen her depression did not alleviate.

They then implanted a NeuroPace RNS (Responsive NeuroStimulation) System into the right hemisphere of Sarah's brain which constantly sensed neurological activity in response to the patterns the team had prespecified. The UCSF researchers also wirelessly gathered 10-minute streams of data from Sarah's brain as she went about her normal day-to-day activities.

One electrode lead from the device was placed in the brain area where the biomarker had been found and the other was connected to another region of Sarah's brain where the team had found stimulation led to relief.

When the closed-loop the team had created sensed the biomarker in the first area it applied a tiny 1 milliampere (1/1000 of an ampere) of electricity to the second region for six seconds.

This caused Sarah's neural activity to change and validated to the researchers that the changes in Sarah's amygdala were indeed connected to her depression. Applying their closed-loop method of stimulation to this marker improved Sarah's condition significantly.

"I was at the end of the line. I was severely depressed," Sarah said in the UCSF press release. "Now, those thoughts still come up, but it's just...poof...the cycle stops."

What the team can't do from this trial is tell if this individualized treatment could work for all patients. The team points out the limitations of this proof-of-concept study in the Nature Medicine paper. In addition to pointing out that this trial has a sample size of one, the team also point out that while Sarah was unaware when treatment was applied, they themselves were aware of treatment. This could have potentially skewered results.

The team hopes that following this successful proof-of-concept study that their closed-loop neuromodulation method can be tested in much larger trials and eventually could bring relief to many sufferers of long-term, treatment-resistant depression, and other neuropsychiatric conditions as it has helped Sarah.

"There's still a lot of work to do," Scangos said in the press release. "We need to look at how these circuits vary across patients and repeat this work multiple times. And we need to see whether an individual's biomarker or brain circuit changes over time as the treatment continues."

Depression
A stock image of a woman suffering from depression. Researchers from UCSF have relieved the symptoms of depression in a woman by targeting biomarkers and applying a tiny jolt of electricity to a specific area. chameleonseye/Getty