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U. researchers identify OCD biomarkers

New intracranial recording technology paves way for adaptive deep brain stimulation treatment

<p>Deep Brain Stimulation, a procedure in which surgically implanted electrodes deliver electric pulses into the patient’s brain, is used for severe cases of OCD that have been resistant to other forms of treatment.</p>

Deep Brain Stimulation, a procedure in which surgically implanted electrodes deliver electric pulses into the patient’s brain, is used for severe cases of OCD that have been resistant to other forms of treatment.

For the first time, researchers have recorded electrical signals from the brains of patients undergoing deep brain stimulation for obsessive compulsive disorder over a prolonged period of time, allowing them to capture the brain activity of patients with daily OCD symptom fluctuations. In a study recently published in Nature medicine, researchers used this data to identify potential neurological markers for OCD symptoms — a breakthrough in the development of more effective OCD treatments.

The study, led by Associate Professor of Engineering David Borton PhD ’12 and Professor

of the Menninger Department of Psychiatry and Behavioral Sciences at Baylor College of Medicine Wayne Goodman, was a result of a collaboration between researchers at Brown University’s Carney Institute of Brain Science, Baylor College of Medicine, University of Pittsburgh’s Department of Psychology and Intelligent Systems Program and Carnegie Mellon University.

OCD is a psychological disorder characterized by uncontrollable recurring thoughts and/or behaviors, as defined by the National Institute of Mental Health. Deep brain stimulation — a procedure in which electrodes that deliver electric pulses are surgically implanted into the patient’s brain — is used for severe cases of OCD that have been resistant to other forms of treatment, said lead author of the study Nicole Provenza ’15 MA ’17 PhD ’21, a postdoctoral fellow at Baylor College of Medicine.

A traditional form of treatment to relieve OCD symptoms involves DBS stimulation to the ventral capsule/ventral striatum, a region of the brain that is involved in decision making and rewards; but this treatment is only effective for approximately 50 to 70% of patients, Provenza added.

Current DBS devices provide constant stimulation and do not adapt to fluctuations in OCD symptom severity. This is problematic because while too little stimulation might not be effective in combating OCD symptoms, too much can lead to side effects such as hypomania, Provenza said.

“We want to be able to deliver a more stable therapy with fewer side effects,” Borton said. Ultimately, the researchers aim to build a “closed-loop” DBS device that is “​​responsive to minute to minute, day to day changes in a person's mental state,” and automatically changes stimulation levels based on stimulation needs, Borton added.

But in order to develop a device that adapts to symptom fluctuations, scientists must first identify a biomarker, or a biological indicator, of OCD symptoms in the brain that the device can respond to.

A reliable biomarker has yet to be identified, largely due to “limited opportunities for intracranial recordings in humans with severe psychiatric disorders outside a research setting,” Provenza said. Because of their limited ability to observe subjects over a longer period, researchers “aren't capturing the natural fluctuations in symptom intensity that might evolve over days or weeks. (They’re) capturing what's happening in the lab in that hour, which is just a snapshot of… the relationship between brain and behavior.”

“The mission of this (study was) to find a biological marker, or a neurological signature, of these brain states for when someone is feeling OCD-related anxieties or compulsions,” Borton said.

The researchers used new Medtronic recording technology to measure the brain activity of five OCD patients over a prolonged period of time as they went about their daily lives. Over 1,000 hours of brain recordings of patients during daily behavioral tasks and teletherapy sessions were collected. By comparing these recordings with self-reported OCD symptom intensity, researchers were able to identify brain signaling patterns that correlated to high symptom intensity. They also recorded participant facial expressions, and used computer-vision machine learning techniques to compare changes in emotional states to brain recordings.

“We demonstrated for the first time that we can record brain signals from patients with severe psychiatric illness over long periods of time,” Borton said. This opens the door to more accurate data collection on OCD and other psychiatric symptoms by allowing scientists to record the brain “in the wild.” 

“This study is a remarkable achievement, primarily as a proof-of-concept demonstration of the feasibility of the (recording) approaches,” Professor of Psychiatry and Human Behavior Lawrence Price wrote in an email to The Herald. “This study amply demonstrates (DBS’s) potential utility in helping us better understand the pathophysiology of major psychiatric illness. That in itself could help us design more effective treatments that are less invasive and more broadly applicable,” he added.

After comparing patient behavioral reports to recorded brain activity, the researchers found that less brain activity at a specific delta frequency of electrical impulse emitted from the DBS corresponded to higher levels of OCD symptoms, said co-author and lead neurosurgeon Sameer Sheth, an associate professor and vice-chair of clinical research in the Department of Neurosurgery at Baylor College of Medicine. They identified this specific delta frequency as a potential biomarker for OCD symptoms.

Although further testing must be done to validate this biomarker, “the first step in identifying a potential candidate control signal (for DBS) has been accomplished,” Sheth said.

“This is groundbreaking work … (which is) important in that it could help us understand how patterns of brain activity relate to symptoms,” said Benjamin Greenberg, professor of psychiatry and human behavior, director of the COBRE Center for Neuromodulation at Butler Hospital and co-director of the Center for Neurorestoration and Neurotechnology.

He added that this information could be used to improve not only DBS but other brain circuit-based surgical treatments like capsulotomy as well as non-invasive treatments like transcranial magnetic stimulation. These treatments could be applicable to a wide variety of psychiatric disorders.

In a follow up study, researchers will measure signals from two areas of the brain: the ventral striatum where the electrodes are implanted, and the orbitofrontal cortex, which the researchers hypothesize also plays a strong role in OCD, Sheth said. Of the five patients enrolled in this follow-up study, two have already undergone surgery and the next three will have electrodes implanted by the end of 2022.

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