summary: Researchers have discovered neural activity patterns that can accurately predict and monitor the clinical status of OCD patients undergoing deep brain stimulation (DBS). This study focuses on how this biomarker can guide DBS therapy to improve outcomes for patients with severe, treatment-resistant OCD.
“Identifying reliable neural signatures is a major advancement in DBS technology, making this treatment more accessible and effective. These findings may also be applicable to other neuropsychiatric disorders, opening new avenues for diagnosis and treatment.”
Key Facts:
- Novel biomarkers were identified: Specific neural activity patterns predict and monitor the clinical status of OCD in patients undergoing DBS.
- Improved DBS Therapy: This biomarker could guide DBS programming and improve treatment outcomes for patients with severe, treatment-resistant OCD.
- Broader impacts: This discovery may extend to other neuropsychiatric disorders and provide new diagnostic and therapeutic opportunities.
sauce: Baylor College of Medicine
A recent study from Baylor College of Medicine and Texas Children’s Hospital has identified specific neural activity patterns as novel biomarkers to accurately predict and monitor the clinical status of obsessive-compulsive disorder (OCD) patients undergoing deep brain stimulation (DBS), a rapidly emerging treatment for serious mental illness.
The study was led by Dr Samir Sheth and Dr Wayne Goodman, with co-first authors Dr Nicole Provenza, Dr Sandy Reddy and Dr Anthony Alam. Nature Medicine.
“Recent advances in surgical neuromodulation have made it possible to continuously monitor brain activity over time in patients with OCD during their daily lives,” said Nicole Provenza, PhD, assistant professor at Baylor College of Medicine and McNair Scholar. “We used this new opportunity to identify key neural characteristics that could serve as predictors of clinical status in 12 patients with treatment-resistant OCD undergoing DBS therapy.”
DBS has emerged as an effective treatment for severe, treatment-resistant OCD.
OCD is a common and debilitating mental illness that affects 2-3% of the population worldwide. Approximately 2 million people in the United States suffer from OCD. In severe cases, patients spend excessive amounts of time repeating seemingly pointless compulsions and fixating on intrusive thoughts.
OCD can take a significant toll on the health and quality of life of patients and their caregivers, interfering with their ability to work and maintain relationships. Psychological and pharmacotherapy are effective for the majority of patients, but approximately 20-40% of people with severe OCD are resistant to these traditional treatments.
Since the early 2000s, DBS therapy has been used to modulate neural activity in specific areas of the brain associated with OCD symptoms. Many patients who are candidates for this therapy have not responded adequately to traditional treatments. In this treatment-resistant patient population, approximately two-thirds of patients show significant improvement in their OCD symptoms after DBS.
Just as a pacemaker device regulates the heart’s electrical activity, a DBS device regulates the brain’s electrical activity.
DBS devices send electrical impulses from a generator implanted, usually in the upper chest, through a pair of thin leads (wires) to specific target areas of the brain. By precisely adjusting the stimulation parameters, the electrical pulses can restore dysfunctional brain circuits to a healthy state.
DBS is an FDA-approved procedure commonly used to treat movement disorders such as essential tremor and Parkinson’s disease, and is increasingly being used to treat severe OCD.
“There have been remarkable advances 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 National Institutes of Health’s Brain Research through Advancing Innovative Neurotechnologies (BRAIN Initiative).
“The advances reported here are just a few examples of how the BRAIN Initiative is contributing to the development of a new generation of DBS technologies, bringing treatments for conditions such as OCD closer to the clinic.”
The need for clinical biomarkers to monitor response to DBS in OCD patients
Defining the appropriate dosage is often more difficult for psychiatric disorders like OCD than it is for movement disorders.
“In patients with movement disorders, correct delivery and coordination of stimuli is even more evident because there is an immediate reduction in abnormal movements such as tremors and rigidity,” said Dr. Sheth, who is also professor and vice chair of research in the Department of Neurosurgery at Baylor College of Medicine, director of the Gordon and Mary Cain Children’s Neurological Research Foundation Institute, and an investigator at the Jean and Dan Duncan Neurological Institute at Texas Children’s Hospital.
“However, with OCD and other psychiatric disorders, this level of precise DBS programming is very difficult to achieve because of the long time between the start of stimulation and symptom improvement, making it difficult to know after several months what adjustments produced specific changes.”
“Therefore, our aim in conducting this study was to find reliable neurobiomarkers to guide us during DBS management and to remotely monitor changes in patients’ symptoms.
“This is especially important because some of our patients travel long distances from across the country and even the world to receive DBS therapy, which is currently only offered at a few specialized centers to treat OCD.”
Targeting the root of your OCD problems
To identify the best targets for biomarker development, the research team focused on one of the most defining behaviors of OCD: pathological avoidance tendencies. OCD patients often suffer from difficult-to-control avoidance of potential harm or pain.
Attempts to avoid these perceived threats in daily life are often accompanied by intrusive inner thoughts and irrational fears (obsessions), which lead to rigid routines and repetitive behaviors (compulsions).
The research team’s goal is to understand how low-frequency brain oscillations in the theta (4-8 Hz) to alpha (8-12 Hz) range, which a growing body of scientific literature has shown to play a key role in cognitive processes, are altered in people with severe, treatment-resistant OCD.
To do so, the researchers took advantage of a new feature of modern DBS devices: their ability to not only deliver stimulation but also record brain activity.
Studies that monitor brain activity patterns are typically designed as brief episodes conducted while participants perform specific cognitive tasks.
However, what makes this study unique is that the researchers were able to use the DBS system to continuously monitor brain activity patterns in the background of everyday activities. What makes this study unique is that it was not confined to an unnatural laboratory environment, but rather brought the research into the natural lives of the study participants.
Recordings began simultaneously with the implantation of the DBS system – stimulation typically begins several days to weeks later – allowing the research team to measure neural activity patterns during severe symptom states.
Interestingly, they found that neural activity in the ventral striatum at 9 Hz (theta-alpha boundary) showed a pronounced circadian rhythm that fluctuated over a 24-h period.
“Prior to DBS, we saw highly predictable, periodic patterns of neural activity in all participants,” said Dr. Goodman, professor, DC, and Eileen Ellwood Chair of Psychiatry in the Menninger Department of Psychiatry and Behavioral Sciences at Baylor College of Medicine.
“However, we found that after DBS activation, this predictable pattern breaks down as patients respond and their symptoms begin to improve. This is a very interesting phenomenon, and we have a theory to explain it: OCD patients have a limited repertoire of responses to certain situations.
“They often perform the same rituals over and over again and rarely change their routines or engage in new activities. As a result, activity in this brain region may be highly predictable.”
“However, after DBS activation, their behavioral repertoire may expand, allowing them to respond more flexibly to situations and not be driven solely by a strong desire to avoid their OCD triggers.
“This expansion of the repertoire may reflect more diverse brain activity patterns. Therefore, this loss of highly predictable neural activity may indicate that participants were engaging in less repetitive and compulsive OCD behaviors.”
“In summary, we have identified neurophysiological biomarkers that can serve as reliable indicators of mood and behavioral improvement in OCD patients following DBS treatment.
“We hope that these findings will change the way patients are monitored throughout DBS therapy,” added Dr. Sheth, who is also a McNair Scholar and Cullen Foundation Endowed Professor at Baylor College of Medicine.
“For example, incorporating this information into a dashboard for clinicians could help guide treatment delivery and demystify the process of DBS programming for OCD, making treatment more accessible to more clinicians and patients.”
“What’s more, we’re excited that these similar signatures of neural activity may underlie other neuropsychiatric disorders and could serve as biomarkers to diagnose, predict and monitor those diseases,” Dr. Provenza concluded.
OCD and DBS research news
author: Graciela Gutierrez
sauce: Baylor College of Medicine
contact: Graciela Gutierrez – Baylor College of Medicine
image: Image courtesy of Neuroscience News
Original Research: Open access.
“Neuroperiodic disturbances predict clinical response after deep brain stimulation for obsessive-compulsive disorderNicole Provenza et al. Nature Medicine
Abstract
Neuroperiodic disturbances predict clinical response after deep brain stimulation for obsessive-compulsive disorder
Recent advances in surgical neuromodulation allow chronic and continuous intracranial monitoring during daily life.
We took advantage of this opportunity to identify neural predictors of clinical status in 12 patients with treatment-resistant obsessive-compulsive disorder (OCD) undergoing deep brain stimulation (DBS) therapy (NCT05915741).
We developed a neurobehavioral model based on continuous neural recordings from the ventral striatal region in an initial cohort of five patients and further tested and validated it in a follow-up cohort of seven patients.
During the most symptomatic state before DBS activation, theta/alpha (9 Hz) power showed a pronounced circadian pattern and a high degree of predictability.
For patients whose symptoms persisted (non-responders), the predictability of the neural data remained consistently high, whereas for patients whose symptoms improved (responders), the predictability of the neural data dropped significantly.
This neurological signature demonstrates generalizability to accurately classify clinical status even in patients with limited recording periods and facilitate therapeutic decision-making.
