Researchers discover a new neural biomarker for obsessive-compulsive disorder

A recent study from Baylor College of Medicine and Texas Children’s Hospital has found that a specific neural activity pattern is a novel biomarker that can accurately predict and monitor the clinical status of individuals with obsessive-compulsive disorder (OCD) who have undergone deep brain stimulation (DBS). DBS is a rapidly emerging therapeutic approach for serious 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 Naturopathy.

“Recent advances in surgical neuromodulation have enabled long-term continuous monitoring of brain activity in OCD patients as they go about their daily lives,” said Dr. Nicole Provenza, assistant professor at Baylor College of Medicine and a McNair Scholar. “We used this new opportunity to identify key neural signatures that may serve as predictors of clinical outcome in twelve individuals with treatment-resistant OCD who received DBS therapy.”

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

OCD is a common and debilitating mental disorder that affects 2-3% of the population worldwide. Approximately two million people in the United States suffer from OCD. In severe cases, patients spend excessive amounts of time performing repetitive, seemingly meaningless compulsions and persisting in intrusive thoughts.

OCD takes a huge toll on the well-being and quality of life of sufferers and their caregivers, and can interfere with the ability to maintain work and relationships. Although psychotherapy and medication are effective in the majority of 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 brain regions associated with OCD symptoms. Many patients who are candidates for this therapy have not responded adequately to conventional therapies. In this treatment-resistant population, approximately two-thirds of patients show significant improvement in OCD symptoms after DBS.

Just as pacemaker devices regulate electrical activity in the heart, DBS devices regulate electrical activity in the brain. DBS devices deliver electrical impulses from the generator, which is usually implanted in the upper chest, through a pair of thin wires to specific target areas in the brain. Precise tuning of the stimulation parameters allows the electrical impulses to restore dysfunctional brain circuits to a healthy state.

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

“We have seen remarkable progress in 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 (BRAIN Initiative) at the National Institutes of Health.

“The progress reported here is just one of many success stories in which the BRAIN Initiative has helped develop a new generation of DBS technologies, bringing treatments for conditions such as OCD closer to the clinic.”

Need for a clinical biomarker to monitor OCD patients’ response to DBS

Determining the correct dosage is often more difficult for psychiatric disorders such as OCD than for movement disorders.

“In patients with movement disorders, it is more apparent when the stimulation and tuning are correct because abnormal movements such as tremor or stiffness are immediately reduced,” said Dr. Sheth, professor and vice chair of the Department of Neurosurgery at Baylor College of Medicine, director of the Gordon and Mary Cain Pediatric Neurology Research Foundation Laboratories and an 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 starting stimulation and improving symptoms. It is difficult to know which specific adjustment led to a specific change months later.

“Our goal in conducting this study was therefore to find a reliable neural biomarker that would guide us during DBS management, and to remotely monitor changes in our patients’ symptoms. This is particularly important because several of our patients travel great distances from across the country or world to receive DBS treatment, which for OCD is currently only offered in a few specialized centers.”

Addressing the core of the OCD problem

To identify an optimal target for biomarker development, the team focused on one of the most characteristic behaviors in OCD: the tendency toward pathological avoidance. People with OCD often suffer from a difficult-to-control avoidance of potential harm or distress. In their attempts to avoid such perceived threats in everyday 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 established in much of the scientific literature to play a prominent role in cognitive processes, were altered in individuals with severe, treatment-resistant OCD. To do this, they took advantage of a novel property of modern DBS devices: the ability to not only deliver stimulation, but also record brain activity.

Typically, studies that monitor brain activity patterns are designed as brief episodes that are performed while participants are performing 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 daily activities. This feature of the study brought the study into the natural lives of the participants rather than limiting it to unnatural laboratory settings.

Recordings began 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 threshold) ventral striatum neural activity exhibited a prominent circadian rhythm that fluctuated across the 24-hour cycle.

“Before we used DBS, we saw a highly predictable and periodic pattern of neural activity in all participants,” said Dr. Goodman, professor and DC and Irene Ellwood Chair in Psychiatry in the Menninger Department of Psychiatry and Behavioral Sciences at Baylor College of Medicine.

“However, after DBS activation, we saw a breakdown of this predictable pattern, as individuals began to respond and improve symptomatically. This is a very interesting phenomenon and we have a theory to explain it. Individuals with OCD have a limited repertoire of responses to a given situation. They often perform the same rituals repeatedly and rarely vary their routines or undertake new activities, which may result in a high predictability of activity in this brain region.

“However, after DBS activation, their behavioral repertoire is expanded; they may respond more flexibly to situations and not be driven solely by a strong desire to avoid OCD triggers. This expanded repertoire may reflect the more diverse pattern of brain activity. Therefore, we think that this loss of highly predictable neural activity indicates that the participants exhibited 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 behavior in OCD patients following DBS treatment. We expect that these findings will change the way patients are monitored during 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 dashboard targeted at clinicians, for example, could help guide therapy delivery, demystifying the process of DBS programming for OCD and making the therapy more accessible to a greater number of clinicians and patients. Additionally, we are excited about the potential possibility that such similar neural activity signatures could underlie other neuropsychiatric disorders and serve as biomarkers to diagnose, predict, and monitor those disorders,” Dr. Provenza concluded.