Furman, D. J. | Search bioRxiv

bioRxiv2025

Temporal fMRI Dynamics Map Dopamine Physiology

Spatial variations in dopamine function are linked to cognition and substance use disorders but are challenging to characterize with current methods. Because dopamine influences blood vessel dilation, we hypothesized that hemodynamic latency, which reflects BOLD signal timing, could serve as an indirect marker of dopamine physiology. Across four datasets, we found a topography of hemodynamic latencies that precisely distinguished the nucleus accumbens, a dopaminergic region implicated in motivation and substance abuse, from other striatal regions. Using PET, genetics, and pharmacology, we found that hemodynamic latencies are robustly related to dopamine function and dopamine-linked behavior. In individuals with cocaine use disorder, we observed a spatial gradient of altered hemodynamic latencies in the striatum. This pattern independently predicted nicotine use, revealing a conserved physiological profile associated with addictive substance use. Hemodynamic latencies map regional, individual, and pathological differences linked to dopamine, opening new avenues for indirectly assessing the role of dopamine in healthy cognition and disease.

neuroscience↗

bioRxiv2024

A dopaminergic basis of behavioral control

Both goal-directed and automatic processes shape human behavior, but these processes often conflict. Behavioral control is the decision about which process guides behavior. Despite the importance of behavioral control for adaptive decision-making, its neural mechanisms remain unclear. Critically, it is unknown if there are mechanisms for behavioral control that are distinct from those supporting the formation of goal-relevant knowledge. We performed deep phenotyping of individual dopamine system function by combining multiple PET scans, fMRI, and dopaminergic drug administration in a within-subject, double-blind, placebo-controlled design. Subjects performed a rule-based response time task, with goal-directed and automatic decision-making operationalized as model-based and model-free influences on behavior. We found a double dissociation between two aspects of ventral striatal dopamine physiology: D2/3 receptor availability and dopamine synthesis capacity. Convergent and causal evidence indicated that D2/3 receptors regulate behavioral control by enhancing model-based and blunting model-free influences on behavior but do not affect model-based knowledge formation. In contrast, dopamine synthesis capacity was linked to the formation of model-based knowledge but not behavioral control. D2/3 receptors also modulated frontostriatal functional connectivity, suggesting they regulate behavioral control by gating prefrontal inputs to the striatum. These results identify central mechanisms underlying individual and state differences in behavioral control and point to striatal D2/3 receptors as targets for interventions for improving goal-directed behavior.

neuroscience↗