Research published in the journal Neuron has identified a previously unknown brain circuit implicated in obsessive-compulsive disorder (OCD), which may pave the way for more targeted treatments. OCD is characterized by distressing thoughts and repetitive behaviors, and current treatment methods primarily involve psychotherapy and medication.
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Led by Joshua L. Plotkin, an associate professor at Stony Brook University's Renaissance School of Medicine, the study utilized a murine model to explore brain connectivity. Despite the differences between human and mouse brains, they share similar structures and functions.
The research focused on two key brain regions: the amygdala, which processes emotional experiences like fear and anxiety, and the dorsolateral striatum (DLS), essential for habitual behaviors. The study revealed a direct connection from the amygdala to the DLS, a link that had not been recognized in prior studies, largely due to the small number of neurons involved.
Using advanced imaging techniques, first author Zachary Hobel found that this small connection can significantly amplify DLS activity. Specifically, the study demonstrated that stimulating the amygdala-DLS circuit heightened sensory-evoked behaviors in mice, resulting in prolonged grooming responses even after stimulation ceased. For instance, when water was applied to a mouse’s nose, those previously groomed behaviors were greatly enhanced following amygdala stimulation.
The researchers noted that in a model of OCD, this circuit exhibited heightened activity and abnormal regulation. Chronic inhibition of the amygdala in these mice effectively prevented OCD-like behaviors, providing key insights into the disorder's mechanisms.
Plotkin emphasized that the findings elucidate how emotionally significant experiences can convert normal behaviors into compulsive ones. The study suggests that while mice are a valid model for OCD, the exact neuronal changes from human treatments remain unclear. Nevertheless, the research identifies specific circuit dysfunctions in OCD, offering potential new targets for treatment development.
The study involved collaboration with investigators from various institutions, including the National Institutes of Health and the University of Iowa. Funding came from multiple federal agencies, including the NIH’s National Institute of Neurological Disorders and Stroke and the National Institute of Mental Health.