A recent study from Baylor College of Medicine and Texas Children’s Hospital has identified a specific pattern of neural activity as a new biomarker to accurately predict and monitor the clinical status of individuals with obsessive-compulsive disorder (OCD) who have undergone deep brain stimulation (DBS), a rapid-onset therapeutic approach for severe psychiatric disorders. The study, led by Drs. Sameer Sheth and Wayne Goodman along with co-senior authors Drs. Nicole Provenza, Sandy Reddy, and Anthony Allam, was published in Natural medicine.
“Recent advances in surgical neuromodulation have enabled long-term, continuous monitoring of brain activity in OCD patients throughout their daily lives,” said Nicole Provenza, MD, an assistant professor at Baylor College of Medicine and a McNair Fellow. “We took advantage of this novel opportunity to identify key neural signatures that may act as predictors of clinical status in twelve individuals with treatment-resistant OCD who were receiving DBS therapy.”
Deep brain stimulation is emerging as an effective treatment for severe and treatment-resistant OCD.
OCD is a common and debilitating mental illness that affects 2-3% of the world’s population. Approximately two million people in the U.S. have OCD. In severe cases, patients spend an extraordinary amount of time performing repetitive, seemingly meaningless compulsions and perseverating intrusive thoughts. OCD has a major impact 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 for most affected individuals, approximately 20-40% of people 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 linked to OCD symptoms. Many patients who qualify for this therapy have not gained sufficient benefit from conventional therapies. In this treatment-resistant population, approximately two-thirds of patients show significant improvement in OCD symptoms after DBS therapy.
Much like pacemakers regulate the electrical activity of the heart, deep brain stimulation devices regulate the electrical activity of the brain. Deep brain stimulation devices transmit electrical impulses from the generator, which is typically implanted in the upper chest, through a pair of thin wires to specific regions of the brain. Precise adjustment of the stimulation parameters allows the electrical pulses to restore a dysfunctional brain circuit to a healthy state.
Deep brain stimulation is an FDA-approved procedure commonly used to treat movement disorders such as essential tremor and Parkinson’s disease, and is increasingly used to treat severe OCD.
“We have seen remarkable progress in the field of deep brain stimulation research, a technology that has been used for decades to treat movement disorders,” said Dr. John Ngai, director of the Brain research through the advancement of innovative neurotechnologies® Initiative (The BRAIN Initiative®) of the National Institutes of Health, which provided partial funding for this study. “The breakthrough reported here represents just one in a growing list of success stories in which the BRAIN Initiative has helped develop a new generation of deep brain stimulation technologies, bringing treatments for conditions like OCD closer to the clinic.”
Need for a clinical biomarker to monitor the response of OCD patients to deep brain stimulation
Defining the correct dose is often more difficult for psychiatric disorders such as OCD than for movement disorders. “In patients with movement disorders, it’s more obvious that the stimulation has been delivered and titrated correctly because abnormal movements, such as tremors or rigidity, immediately subside,” 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 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 the start of stimulation and the improvement of symptoms. It is difficult to know which particular adjustment led to a particular change months later. Our goal in conducting 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 a number of our patients travel long distances from across the country or the world to receive 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 of OCD: the tendency toward pathological avoidance. People with OCD often suffer from difficult-to-control avoidance of potential harm or distress. In attempting to avoid these 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 a large body of scientific literature has shown to play a prominent role in cognitive processes, were altered in people with severe, treatment-resistant OCD. To do so, they took advantage of a novel feature of modern deep brain stimulation devices: the ability to not only deliver stimulation but also record brain activity.
Typically, studies that monitor brain activity patterns are designed to be brief episodes that take place while participants perform a specific cognitive task. However, this study is unique in that the researchers were able to use the DBS system to continuously monitor brain activity patterns in the context 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 began after DBS implantation. Because stimulation typically begins days or weeks later, the team was able to measure patterns of neural activity in the severe symptomatic state. Interestingly, they found that 9 Hz ventral striatum neural activity (theta-alpha border) showed a prominent circadian rhythm that fluctuated over the 24-hour cycle.
“Prior to deep brain stimulation, we observed an extremely predictable and periodic pattern of neural activity across all participants,” said Dr. Goodman, professor and DC and Irene Ellwood Chair of Psychiatry in the Menninger Department of Psychiatry and Behavioral Sciences at Baylor College of Medicine. “However, after DBS activation, as individuals began to respond and improve symptomatically, we observed a break 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 rarely 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 expands; they are able to respond more flexibly to situations and not be driven only by a strong desire to avoid OCD triggers. This expanded repertoire may be a reflection of the more diverse pattern of brain activity. Therefore, we believe that this loss of highly predictable neural activity indicates that 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 following DBS treatment. We anticipate that these findings will transform the way patients are monitored during DBS therapy,” added Dr. Sheth, who is also a McNair Scholar and Cullen Foundation Chair at Baylor College of Medicine.
“Incorporating this information into a clinician-friendly dashboard, for example, could help guide therapy delivery, thereby demystifying the DBS programming process for OCD and making the therapy more accessible to a wider range of clinicians and patients. Furthermore, we are excited by the potential possibility that these similar neural activity signatures may underlie other neuropsychiatric disorders and could serve as biomarkers to diagnose, predict, and monitor those conditions,” concluded Dr. Provenza.