In an effort to improve treatment for obsessive compulsive disorder (OCD), researchers headed by teams at Brown University, and Baylor College of Medicine, have for the first time recorded electrical signals in the human brain that are associated with ebbs and flows in OCD symptoms, over an extended period, while individuals went about daily living in their homes. The research could be an important step in making an emerging therapy called deep brain stimulation (DBS) responsive to everyday changes in OCD symptoms.
“In addition to advancing DBS therapy for cases of severe and treatment resistant OCD, this study has the potential for improving our understanding of the underlying neurocircuitry of the disorder,” said Wayne Goodman, PhD, at Baylor College of Medicine. “This deepened understanding may allow us to identify new anatomic targets for treatment that may be amenable to novel interventions that are less invasive than DBS.” Goodman is co-author of the researchers’ published paper in Nature Medicine, which is titled, “Long-term ecological assessment of intracranial electrophysiology synchronized to behavioural markers in obsessive-compulsive disorder.”
OCD causes recurring unwanted thoughts and repetitive behaviors, and is a leading cause of disability. The condition, which is often debilitating, may affect perhaps 2-3% of the world’s population, the authors noted. Up to 20-40% of cases don’t respond to traditional drug or behavioral treatments. “Approximately 10% of individuals fail to achieve benefit from any intervention.”
Deep brain stimulation, a technique that involves delivering mild electrical pulses via small electrodes precisely placed in the brain, can be effective in treating more than 50% of patients for whom other therapies failed. “Over half of patients with treatment-resistant OCD are responders to DBS targeted to the ventral capsule/ventral striatum (VC/VS) region,” the researchers further noted. To date, however, the number of patients who have received DBS for OCD is still in the hundreds.
One limitation of DBS is that it is unable to adjust to moment-to-moment changes in OCD symptoms, which are impacted by the physical and social environment. But adaptive DBS —which can adjust the intensity of stimulation in response to real-time signals recorded in the brain—could be more effective than traditional DBS and reduce unwanted side effects.
“OCD is a disorder in which symptom severity is highly variable over time and can be elicited by triggers in the environment,” said David Borton, PhD, an associate professor of biomedical engineering at Brown University, a biomedical engineer at the US Department of Veterans Affairs Center for Neurorestoration and Neurotechnology and a senior author of the new research. “A DBS system that can adjust stimulation intensity in response to symptoms may provide more relief and fewer side effects for patients. But in order to enable that technology, we must first identify the biomarkers in the brain associated with OCD symptoms, and that is what we are working to do in this study.” As the authors noted, “An electrophysiological biomarker of symptom state would enable aDBS for OCD and other psychiatric disorders, which may provide a better approach for treating fluctuations in symptom intensity.”
The research, led by Nicole Provenza, a recent Brown biomedical engineering PhD graduate from Borton’s laboratory, was a collaboration between Borton’s research group, affiliated with Brown’s Carney Institute for Brain Science and School of Engineering; the research groups of Wayne Goodman PhD, and Sameer Sheth MD, PhD, at Baylor College of Medicine; and Jeff Cohn, PhD, from the University of Pittsburgh’s Department of Psychology and Intelligent Systems Program and Carnegie Mellon University.
For their study, Goodman’s team recruited five participants with severe OCD who were eligible for DBS treatment. Sheth, lead neurosurgeon, implanted in each participant an investigational DBS device from Medtronic, which is capable of both delivering stimulation and recording native electrical brain signals. Using the sensing capabilities of the hardware, the team gathered brain-signal data from participants in both clinical settings and at home as they went about daily activities. “The DBS implants used in our study allow for real-time frequency-domain analysis of electrophysiological activity recorded simultaneously during stimulation delivery from the implanted electrodes,” they wrote.
Along with the brain signal data, the team also collected a suite of behavioral biomarkers. In the clinical setting, these included facial expression (automatic facial affect recognition; AFAR) and body movement. Using computer vision and machine learning, they discovered that the behavioral features were associated with changes in internal brain states. At the participants’ homes, the team measured self-reports of OCD symptom intensity as well as biometric data—heart rate and general activity levels—recorded by a smart watch and paired smartphone application, provided by Rune Labs. All of those behavioral measures were then time-synched to the brain-sensing data, enabling the researchers to look for correlations between the two.
“Here, we acquired electrophysiological data with behavioral readouts over both short and long timescales,” the team commented. “In the clinic, we examined changes in affect (AFAR) during DBS parameter changes over short timescales (seconds to minutes). At home during participant-controlled recordings, we captured behavioral changes (self-reported OCD symptoms) over longer timescales (days to weeks to months) in natural settings, collected continuous data during natural and planned exposures, and developed methods to synchronize behavioral metrics to intracranial electrophysiology.”
“This is the first time brain signals from participants with neuropsychiatric illness have been recorded chronically at home alongside relevant behavioral measures,” Provenza said. “Using these brain signals, we may be able to differentiate between when someone is experiencing OCD symptoms, and when they are not, and this technique made it possible to record this diversity of behavior and brain activity.”
Provenza’s analysis of the data showed that the strategy did pick out brain-signal patterns potentially linked to OCD symptom fluctuation. While more work needs to be done across a larger cohort, this initial study shows that this technique is a promising way forward in confirming candidate biomarkers of OCD. “… we demonstrated the utility of at-home data collection for biomarker identification by observing correlations between spectral power and self-reported OCD symptom intensity.”
“We were able to collect a far richer dataset than has been collected before, and we found some tantalizing trends that we’d like to explore in a larger cohort of patients,” Borton said. “Now we know that we have the toolset to nail down control signals that could be used to adjust stimulation level according to people’s symptoms.”
Once those biomarkers are positively identified, they could then be used in an adaptive DBS system. Currently, DBS systems employ a constant level of stimulation, which can be adjusted by a clinician at clinical visits. Adaptive DBS systems, in contrast, would stimulate and record brain activity and behavior continuously without the need to attend clinic. When the system detects signals associated with an increase in symptom severity, it could ramp up stimulation to potentially provide additional relief. Likewise, stimulation could be toned down when symptoms abate. Such a system could potentially improve DBS therapy while reducing side effects.
Work on this line of research is ongoing. Because OCD is a complex disorder than manifests itself in highly variable ways across patients, the team hopes to expand the number of participants to capture more of that variability. They seek to identify a fuller set of OCD biomarkers that could be used to guide adaptive DBS systems. Once those biomarkers are in place, the team hopes to work with device makers to implement their DBS devices.
“Our goal is to understand what those brain recordings are telling us and to train the device to recognize certain patterns associated with specific symptoms,” Sheth said. “The better we understand the neural signatures of health and disease, the greater our chances of using DBS to successfully treat challenging brain disorders like OCD.” As the authors concluded, “This work demonstrates the feasibility and utility of capturing chronic intracranial electrophysiology during daily symptom fluctuations to enable neural biomarker identification, a prerequisite for future development of adaptive DBS for OCD and other psychiatric disorders,” the author concluded. “The platform presented here lays the groundwork for future transformational studies reliant on ecological neural and behavioral monitoring and assessment of neuropsychiatric illness.”
