Researchers identify a brain circuit that normally supports flexible behavior, but is recruited by cocaine to drive increasingly rigid and repetitive behavior. The findings show that shifting the balance between opposing neural pathways can either promote behavioral rigidity or, conversely, rapidly interrupt cocaine driven repetitive behavior and restore a broader range of actions, offering new insight into the brain mechanisms underlying compulsive and stereotyped behavior.
A new study led by PhD students Ben Jerry Gonzales and Itay Shalom under the supervision of Prof. Ami Citri of ELSC and the Institute of Life Science at Hebrew University reveals how cocaine can restrict a flexible repertoire of natural behaviors into a persistent repetitive pattern. The researchers identified a brain circuit that normally participates in selecting natural mouth and face movements, but which becomes disproportionately engaged as behavior narrows under repeated cocaine exposure.
The striatum is a brain region involved in moment-to-moment action selection. Disruption of the capacity to define actions is associated with the development of repetitive and rigid/maladaptive behaviors seen in a range of neurological and psychiatric conditions, including Tourette syndrome, Parkinson's disease and drug-induced movement disorders.
To examine these processes in detail, the team developed STEREO, a deep-learning system capable of identifying and tracking natural behaviors directly from video. The technology allowed the researchers to follow changes in an entire behavioral repertoire over time, rather than focusing on single actions, annotated manually.
“We wanted to capture behavior as an observer actually sees it: grooming, licking, exploring, but this was impossible to score manually,” said Itay Shalom . “STEREO allowed us to track the entire behavioral repertoire progressively narrowed until one type of action came to dominate.”
Using repeated exposure to cocaine as an experimental model of behavioral rigidity, the researchers observed a striking shift. Diverse and exploratory behavior gradually gave way to persistent repetition. By the fifth day of exposure, licking the floor and walls of the enclosure accounted for more than 60% of the observed time. These behaviors were rarely seen in the absence of cocaine, illustrating how a normally varied set of actions can become restricted to a persistent behavioral pattern.
The researchers mapped this change to the ventrolateral striatum (VLS), an area of the striatum involved particularly in movements of the mouth and tongue. Within this region are two major neural pathways, known as the direct and indirect pathways, which appear to exert opposing influences over which actions are expressed.
When the researchers activated neurons belonging to the indirect pathway, the cocaine-driven repetitive behavior was immediately interrupted, and behavior shifted toward alternative actions. Once the stimulation was terminated, the effect rapidly reversed and repetitive behavior resumed. Suppressing this same pathway produced the opposite result, limiting the ability to switch behavior, driving longer bouts of the repetitive behavior.
The direct pathway showed the opposite pattern. Reducing its activity weakened the drug-induced repetitive behavior, while activating it in the absence of cocaine was itself sufficient to produce rigid patterns of repetitive actions resembling those observed following drug exposure.
“Cocaine does not appear to create an entirely new behavioral program ,” said Ben Jerry Gonzales. “It takes control of a circuit the brain already uses for natural actions and pushes behavior toward persistent repetition.”
Importantly, the same circuit is responsible for the expression of normal, context-appropriate grooming and licking. Cocaine therefore appears to hijack a normal action-selection system rather than recruit a circuit dedicated to abnormal behavior.
The findings may help researchers better understand how repetitive motor behaviors emerge across different neurological and psychiatric conditions. Because different areas of the striatum correspond to different types of movement, the researchers propose that similar imbalances in other striatal circuits could potentially contribute to other forms of behavioral rigidity.
The study also introduces STEREO as a promising tool for behavioral neuroscience. By automatically identifying recognizable actions from raw video, the system could allow researchers to examine complex changes in natural behavior at a scale and level of detail that are difficult to achieve through manual observation alone.
Current Biology
Experimental study
Not applicable
Opponent ventrolateral striatal circuits regulate behavioral flexibility and rigidity
22-Sep-2026