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Hesitation, the act of pausing in the face of uncertainty, is a behavior that gives humans and other animals crucial extra time to deliberate on the best option in uncertain situations. Given the ubiquity of hesitation in everyday life, and the devastating toll that impairments in hesitation can play in impulsivity disorders—such as addiction, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder (OCD), and Huntington’s disease—it is critical to better understand the neural circuits mediating hesitation.

Investigators including Matthew Geramita, MD, PhD (Assistant Professor of Psychiatry), Susanne Ahmari, MD, PhD (Associate Professor of Psychiatry), and Eric Yttri, PhD (Carnegie Mellon University), dissected the neural substrates of hesitation by developing one of the first paradigms that reliably evokes hesitation in mice. Then, using a combination of cell-type specific neural recording techniques and optogenetic manipulations, the scientists were able to decipher the distinct roles of the direct and indirect pathway neurons of the dorsomedial striatum during hesitation. 

Results of the study, recently published in Nature Neuroscience, showed that hesitation is mediated by indirect, but not direct, pathway neurons in the dorsomedial striatum.

“As a psychiatrist, I see the devastating impact of impulsivity on a daily basis. For example, when a patient with OCD begins having obsessive thoughts, they often engage in compulsions without hesitating to consider whether this is the best course of action. I’m excited about the possibility of translating these results into therapies aimed at inducing hesitation and preventing maladaptive behaviors,” said Dr. Geramita, lead and co-corresponding author of the study.

The striatal indirect pathway mediates hesitation
Geramita MA, Ahmari SE, Yttri EA.
Nature Neuroscience (2025). https://doi.org/10.1038/s41593-025-02135-6