Research Reveals a Specific Brain Circuit Implicated in OCD

Joshua L. Plotkin, PhD Credit: Jeanne Neville, Stony Brook Medicine

The findings, published in Neuron, could lead to better targeted treatments for the mental health condition

STONY BROOK, NY, September 28, 2026 - Treating obsessive-compulsive disorder (OCD), a mental health condition characterized by distressing and uncontrollable thoughts accompanied by repetitive behaviors, has centered on psychotherapy and medicines to curb symptoms. New research that identifies a previously unknown brain circuit involved in the OCD process could be a key step to developing treatments that directly target certain brain regions to better control the condition.

Published early online in the journal Neuron and led by Joshua L. Plotkin, PhD, Associate Professor in the Department of Neurobiology and Behavior in the Renaissance School of Medicine (RSOM) at Stony Brook University, the research is based on a murine model. While the full capacity of a human brain is quite different from that of a mouse, their brains share strikingly similar structures and regional organizational principles.

This work involved using sensory stimuli to cause a mouse to make a behavioral action. During experimentation, Dr. Plotkin and his colleagues focused on two areas of the brain - the amygdala, a brain region that processes emotionally important experiences such as fear and anxiety, and the dorsolateral striatum (DLS), a region important for habitual and automatic behaviors.

The research team discovered that the amygdala directly connects to and influences the DLS, a connection not identified in previous research.

This created brain image illustrates the circuit connection between regions of the amygdala (in red) and the dorsolateral striatum (DLS) in a model of obsessive-compulsive disorder (OCD).
Credit: Zachary Hobel using Brainrender

This is because the connection originates from only a small number of amygdala neurons, a scenario easy to overlook.

By using new imaging tools to functionally map brain circuits at the single synapse level, Zachary Hobel, the study's first author and postdoctoral fellow in the Department of Neurobiology and Behavior, found that although it's small, the amygdala-DLS connection can have an outsized influence over the DLS. Experimental measures and neuronal models confirmed that this connection both amplifies and promotes synaptic plasticity of other inputs to the DLS - inputs that are likely to encode sensory-evoked behaviors.

The team found in this study that repeatedly stimulating inputs from the amygdala to the DLS amplifies sensory-evoked behaviors. And this effect persisted long after the stimulation ended. More specifically, placing a droplet of water on a mouse's nose prompted the mouse to groom its face. When they stimulated the amygdala-to-DLS circuit while the mouse experienced the water droplet, that same water droplet subsequently caused the mouse to groom for much longer, even after the sensation and brain stimulation had stopped. Remarkably, the mouse continued to respond more strongly to the water, even after the experimental pairing ended.

The researchers further demonstrated that this circuit is stronger, more active and abnormally regulated in a mouse model of OCD. Therefore, by chronically inhibiting the amygdala in these mice, the researchers prevented OCD-like behavior - a key finding.

"Our study reveals a clear mechanism through which emotionally important experiences may strengthen the connection between sensory cues and actions, and this potentially helps to explain how otherwise normal behaviors can be transformed into compulsive behaviors," summarizes Dr. Plotkin, corresponding author and a researcher affiliated with Stony Brook's Center for Nervous System Disorders.

Dr. Plotkin pointed out that the mice are a strong model of OCD in that they are responsive to the same common medicines used to treat people with OCD.

He cautioned that the exact neuronal connections and dysfunctions being altered and/or corrected with OCD treatments are not fully known, and the specific brain connections and processes underlying OCD are complex. However, the authors conclude that the findings from this study provide important insights into the underpinnings of OCD-like behaviors and identify specific brain circuit dysfunctions - advances that give researchers a new place to look for more precise OCD treatment targets.

The research team included investigators from the RSOM's Department of Neurobiology and Behavior, the National Institutes of Health's Center on Compulsive Behavior, Laboratory on Neuronal Circuits and Behavior, and National Institute of Mental Health; and the Department of Biomedical Engineering at the University of Iowa.

Funding for this work included support from several federal agencies: The National Institutes of Health's (NIH) National Institute of Neurological Disorders and Stroke, National Institute on Alcohol Abuse and Alcoholism, and the National Institute of Mental Health.