A recent study from Baylor College of Medicine and Texas Children’s Hospital has identified a specific neural activity pattern as a novel biomarker to accurately predict and monitor the clinical status of individuals with obsessive-compulsive disorder (OCD) who have undergone deep brain stimulation (DBS), a rapidly emerging therapeutic approach for severe psychiatric disorders. The study, led by Drs. Sameer Sheth and Wayne Goodman along with co-lead authors, Drs. Nicole Provenza, Sandy Reddy, and Anthony Allam, was published in Nature Medicine.
“Recent advances in surgical neuromodulation have enabled long-term continuous monitoring of brain activity in OCD patients during their everyday lives,” said Dr. Nicole Provenza, an assistant professor at Baylor College of Medicine and McNair Scholar. “We used this novel opportunity to identify key neural signatures that can act as predictors of clinical state in twelve individuals with treatment-resistant OCD who were receiving DBS therapy.”
OCD is a common and debilitating mental health condition that affects 2-3% of the population worldwide. About two million people in the US suffer from OCD. In severe cases, patients spend an extraordinary amount of time performing repetitive compulsions and perseverating on intrusive thoughts. While psychotherapy and medications are effective for many affected individuals, approximately 20-40% of those with severe OCD are resistant to these conventional treatments.
Since the early 2000s, DBS therapy has been used to modulate neural activity in specific regions of the brain linked to OCD symptoms. Many patients who qualify for this therapy have not received sufficient benefit from conventional therapies. In this treatment-resistant population, roughly two-thirds show significant improvement after DBS.
Much like pacemaker devices regulate electrical activity in the heart, DBS devices regulate electrical activity in the brain via thin leads implanted into specific target regions. Precise tuning allows electrical pulses to restore dysfunctional brain circuits to healthy states. DBS is an FDA-approved procedure commonly used for movement disorders such as essential tremors and Parkinson’s disease and is increasingly being applied to treat severe OCD.
“We have seen remarkable progress in the field of DBS research,” said Dr. John Ngai, Director of the Brain Research Through Advancing Innovative Neurotechnologies® Initiative (The BRAIN Initiative®) at the National Institutes of Health, which provided partial funding for this study. “The advance reported here represents just one on a growing list where the BRAIN Initiative has helped develop new generation DBS technologies.”
Defining correct dosing is often more challenging for psychiatric disorders like OCD than for movement disorders due to delayed symptom improvement following stimulation initiation.
“In patients with movement disorders, it is more obvious when stimulation delivery is correct because abnormal movements decrease right away,” said Dr. Sheth, professor at Baylor College of Medicine and investigator at Texas Children’s Hospital's Jan and Dan Duncan Neurological Research Institute. “However, it is much more difficult to achieve precise DBS programming for psychiatric disorders because there is a long delay between stimulation initiation and symptom improvement.”
To identify an optimal target for developing a biomarker, researchers focused on pathological avoidance behavior characteristic of OCD—difficult-to-control avoidance leading to rigid routines and repetitive behaviors.
They examined how low-frequency brain oscillations (theta 4-8 Hz; alpha 8-12 Hz) altered in individuals with severe treatment-resistant OCD using modern DBS devices capable not only delivering stimulation but also recording brain activity continuously during everyday activities rather than brief laboratory episodes.
Recordings started upon implantation before initiating stimulation days or weeks later allowing measurement during severely symptomatic states revealing that 9 Hz ventral striatum neural activity demonstrated prominent circadian rhythms fluctuating over 24-hour cycles.
“Before DBS we saw extremely predictable periodic neural patterns,” said Dr.Goodman professor at Baylor College's Menninger Department Psychiatry Behavioral Sciences.“After activation responding improving symptomatically breakdown predictable pattern reflecting expanded behavioral repertoire fewer repetitive compulsive behaviors.”
Dr.Sheth added,“In summary identified neurophysiological biomarker reliable indicator improvements mood behaviors anticipating findings transform patient monitoring throughout therapy.Incorporating clinician-facing dashboard guide delivery demystifying process making accessible greater number clinicians patients.Potential similar signatures underlie other neuropsychiatric conditions serve biomarkers diagnose predict monitor.” concluded Provenza.Other authors involved institutional affiliations found here.Research supported NIH BRAIN Initiative award UH3NS100549 McNair Medical Institute Robert Janice McNair Foundation Gordon Mary Cain Pediatric Neurology Research Foundation Jan Dan Duncan Neurological Research Institute Texas Children’s Hospital.
