Researchers Discover New Neural Biomarker for Obsessive-Compulsive Disorder

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 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.”

DBS is emerging as an effective treatment for severe, treatment-resistant OCD 

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, seemingly senseless compulsions and perseverating on intrusive thoughts. OCD has a huge toll on the well-being and quality of life of patients and their caregivers and can interfere with the ability to maintain employment and relationships. While psychotherapy and medications are effective in a majority of the affected individuals, approximately 20-40% of individuals 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 of patients show significant improvement in OCD symptoms after DBS.

Much like how pacemaker devices regulate electrical activity in the heart, DBS devices regulate electrical activity in the brain. DBS devices carry electrical impulses from the generator, typically implanted in the upper chest, via a pair of thin leads (wires) to specific target regions in the brain. Precise tuning of the stimulation parameters allows the electrical pulses to restore a dysfunctional brain circuit to a healthy state. 

DBS is an FDA-approved procedure commonly used to treat movement disorders such as essential tremors and Parkinson’s disease and is increasingly being used to treat severe OCD.

“We have seen remarkable progress in the field of DBS research, a technology that has been used for decades to treat movement disorders,” 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 of success stories where the BRAIN Initiative has helped develop a new generation of DBS technologies, bringing treatments for conditions like OCD closer to the clinic.”

Need for a clinical biomarker to monitor OCD patient’s response to DBS 

Defining the correct dose is oftentimes more difficult for psychiatric disorders like OCD than for movement disorders. “In patients with movement disorders, it is more obvious when stimulation delivery and tuning is correct because abnormal movements such as tremors or stiffness decrease right away,” said Dr. Sheth, professor and Vice Chair of Research in the Department of Neurosurgery at Baylor College of Medicine, director of the Gordon and Mary Cain Pediatric Neurology Research Foundation Laboratories, and investigator at the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital.

“However, it is much more difficult to achieve this level of precise DBS programming for OCD and other psychiatric disorders because there is a long delay between stimulation initiation and symptom improvement. It is difficult to know what particular adjustment led to a particular change months later. Our goal in undertaking this study was therefore to find a reliable neural biomarker to guide us during DBS management, and to remotely monitor changes in our patients’ symptoms. This is particularly important because several of our patients travel long distances from around the country or world to get DBS treatment, which for OCD is currently offered only in very few specialized centers.”

Targeting the root of the OCD problem

To identify an optimal target for developing a biomarker, the team focused on one of the most characteristic behaviors in OCD – the tendency for pathological avoidance. Individuals with OCD often suffer from difficult-to-control avoidance of potential harm or distress. In trying to avoid such perceived threats in daily life, they are often plagued by intrusive internal thoughts and irrational fears (obsessions), which lead to rigid routines and repetitive behaviors (compulsions).

The team’s goal was to understand how low-frequency brain oscillations in the theta (4-8 Hz) to alpha (8-12 Hz) range, which have been found by a large body of scientific literature to play a prominent role in cognitive processes, were altered in individuals with severe, treatment-resistant OCD. To do so, they took advantage of a novel feature of modern DBS devices – the ability to not only deliver stimulation but also record brain activity.

Usually, studies that monitor brain activity patterns are designed to be brief episodes that are conducted as participants perform a specific cognitive task. However, this study is unique because the researchers were able to use the DBS system to continuously monitor brain activity patterns in the background of everyday activities. This feature of the study brought the research into the natural lives of the study participants rather than confining it to unnatural laboratory settings.

Recordings started upon implantation of the DBS system. Because stimulation is typically initiated days to weeks later, the team was able to measure neural activity patterns in the severely symptomatic state. Interestingly, they found that 9 Hz (theta-alpha border) ventral striatum neural activity demonstrated a prominent circadian rhythm that fluctuated over the 24-hour cycle.

“Before DBS, we saw an extremely predictable and periodic neural activity pattern in all participants,” said Dr. Goodman, professor and D. C. and Irene Ellwood Chair in Psychiatry in the Menninger Department of Psychiatry and Behavioral Sciences at Baylor College of Medicine. “However, after DBS activation, as individuals began responding and improving symptomatically, we saw a breakdown in this predictable pattern. This is a very interesting phenomenon and we have a theory to explain it. Individuals with OCD have a limited repertoire of responses to any given situation. They often perform the same rituals repeatedly and seldom vary their routines or engage in new activities, which may result in high predictability of activity in this brain region. However, after DBS activation, their behavioral repertoire is expanded; they might respond more flexibly to situations and not be just driven by a strong desire to avoid OCD triggers. This expanded repertoire may be a reflection of the more diverse brain activity pattern. Thus, we think this loss of a highly predictable neural activity indicates that the participants engaged in fewer repetitive and compulsive OCD behaviors.”

“In summary, we have identified a neurophysiological biomarker that can serve as a reliable indicator of improvements in mood and behaviors in OCD patients after DBS treatment. We anticipate these findings to transform how patients are monitored throughout DBS therapy,” added Dr. Sheth, who is also a McNair Scholar and Cullen Foundation Endowed Chair at Baylor College of Medicine.

“Incorporating this information into a clinician-facing dashboard, for example, could help guide therapy delivery, thus demystifying the process of DBS programming for OCD and making the therapy more accessible to a greater number of clinicians and patients. Moreover, we are excited by the potential possibility that such similar neural activity signatures may underlie other neuropsychiatric disorders and could serve as biomarkers to diagnose, predict, and monitor those conditions,” Dr. Provenza concluded.

Reference: Provenza NR, Reddy S, Allam AK, et al. Disruption of neural periodicity predicts clinical response after deep brain stimulation for obsessive-compulsive disorder. Nat Med. 2024. doi: 10.1038/s41591-024-03125-0

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