Summary: Researchers have identified a specific pattern of high-frequency brain activity in the anteromedial orbitofrontal cortex (amOFC) that is consistently linked to compulsive behaviors in people with obsessive-compulsive disorder (OCD). In three patients with severe, treatment-resistant OCD, briefly disrupting this signal through targeted deep-brain stimulation (DBS) rapidly reduced symptoms.
The findings suggest that OCD symptoms may be driven by abnormal frontal brain circuitry and open the door to more precise, responsive DBS systems that activate only when pathological signals appear.
Key Facts
- Frontal Cortex Signal: Abnormally strong high-frequency activity in the right anteromedial orbitofrontal cortex correlates with OCD symptoms.
- Rapid Symptom Relief: Targeted stimulation reduced pathological brain activity and quickly eased compulsive behaviors in three treatment-resistant patients.
- Toward Responsive DBS: Findings may support next-generation DBS systems that activate only when OCD-related signals are detected.
Source: University of Pennsylvania
A specific pattern of brain activity in a frontal brain region is linked to compulsive behaviors like excessive hand washing, chronic hair-pulling, and skin-picking in people with obsessive compulsive disorder, according to new research.
But briefly disrupting that signal can rapidly ease symptoms three people with severe, treatment resistant OCD, according to a study published this month in Cell by scientists at.
“Compulsive thoughts and behaviors can vary widely across people with OCD,” said senior author, Casey Halpern, MD, a professor of Neurosurgery and division head of Functional and Stereotactic Neurosurgery.
“Identifying brain activity that is consistent despite individuals having different symptoms is a huge step forward in developing new therapies to manage OCD symptoms.”
What’s happening in the brain
Abnormally powerful high-frequency brain-circuit activity occurs in an area of the frontal cortex called the anteromedial orbitofrontal cortex (amOFC) during symptoms of OCD. The amOFC is thought to be involved in risk-versus-reward decision making, which can be disrupted in people with OCD.
In three OCD patients who had not found relief with medication or psychotherapy, researchers implanted electrodes to stimulate a small brain region deep in the right side of the brain—called the nucleus accumbens–ventral pallidum.
After placing the probes, a team of neuroscientists and psychiatrists gave the patients verbal and visual prompts that were designed to elicit OCD symptoms. For example, one participant who is often triggered by contamination was encouraged to touch various dirty objects, like the bottom of a shoe.
During that exercise, the team monitored her brain activity as she became distressed. They found a signal correlating strongly with OCD symptoms in all three patients in the right amOFC. They also found that when the amOFC was stimulated, the activity lessened and symptoms disappeared.
New strategies for managing OCD
OCD currently affects about two percent of people in the United States, and involves intrusive, obsessive thoughts that can lead to repetitive, compulsive behaviors, like cleaning, checking on things, and mental acts like counting that are disruptive to daily life.
The disorder can cause significant emotional distress or interfere with social interactions. While OCD often responds to antidepressant drugs and/or psychotherapy, at least 30 percent of patients are not helped by either strategy.
Since 2009, deep brain stimulation (DBS) has been approved by the Food and Drug Administration, under a Humanitarian Device Exemption, to treat severe, treatment-resistant OCD in adults.
This type of DBS delivers continuous stimulation to a set of brain structures deep within the brain but interconnected with the frontal cortex. It is effective for about sixty percent of patients who receive it, and is thought to work by disrupting abnormal, OCD-related patterns of activity in the brain circuits that run between the basal ganglia and frontal cortex, the areas responsible for motivation, learning, and habit formation.
“Our focus in this study is zeroing in on the exact brain structures and circuits involved in OCD symptoms, so that we can optimize electrode placement for future patients,” said the study’s first author, Younghoon Nho, PhD, a research associate in the department of Neurosurgery.
“Our overall goal is to use this signaling to develop a responsive DBS system that monitors brain activity but only delivers stimulation when OCD symptoms are triggered, which our previous research has suggested is an effective strategy for treating OCD.”
Researchers hope that responsive DBS will lead to more precise treatments that are tailored to each individual patient’s symptoms, according to co-author Katherine Scangos, MD, PhD, an associate professor of Psychiatry.
Funding: The study was supported by the National Institutes of Health (NCT05623306), the Foundation for OCD Research (FFOR) and AE Foundation.
Key Questions Answered:
A: Researchers identified abnormal high-frequency activity in the right anteromedial orbitofrontal cortex (amOFC) during compulsive symptoms.
A: Targeted stimulation reduced the abnormal signal and rapidly eased symptoms in three treatment-resistant patients.
A: A next-generation system that monitors brain activity and delivers stimulation only when pathological OCD-related signals are detected.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this OCD and neuroscience research news
Author: Kelsey Geesler
Source: University of Pennsylvania
Contact: Kelsey Geesler – University of Pennsylvania
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Human orbitofrontal neural activity is linked to obsessive-compulsive behavioral dynamics” by Young-Hoon Nho, Liming Qiu, Robert L. Seilheimer, Gustavo Campos, Andrew Chang, Zhengjia Wang, John F. Magnotti, Michael S. Beauchamp, Daniel A.N. Barbosa, Andreas Horn, Nolan R. Williams, Lily A. Brown, Taneeta M. Ganguly, Mario Cristancho, Bijan Pesaran, Desmond J. Oathes, Kai J. Miller, Katherine W. Scangos, Casey H. Halpern. Cell
DOI:10.1016/j.cell.2025.12.037
Abstract
Human orbitofrontal neural activity is linked to obsessive-compulsive behavioral dynamics
Biomarkers of obsessive-compulsive disorder (OCD) symptom dynamics and related behavior could advance personalized interventions. Aberrant activity in the orbitofrontal cortex (OFC) has been implicated in symptom exacerbation in OCD.
We conducted an intracranial monitoring assay to identify high-resolution neurophysiologic correlates of OCD symptoms in the human OFC. We found that low-gamma power in the anteromedial OFC was consistently elevated during high symptom states in a symptom provocation task.
Furthermore, electrical stimulation of the ventral basal ganglia that reduced OCD symptoms also reduced anteromedial OFC gamma power.
These results link OFC gamma activity to moment-to-moment expression of OCD symptoms, providing mechanistic insights to guide therapeutic strategies such as deep brain stimulation.
