A shared spatial topography links the functional connectome correlates of cocaine use disorder and dopamine D

Background: The biological mechanisms that contribute to cocaine and other substance use disorders involve an array of cortical and subcortical systems. Prior work on the development and maintenance of substance use has largely focused on cortico-striatal circuits, with relatively less attention on alterations within and across large-scale functional brain networks, and associated aspects of the dopamine system. The brain-wide pattern of temporal co-activation between distinct brain regions, referred to as the functional connectome, underpins individual differences in behavior. Critically, the functional connectome correlates of substance use and their specificity to dopamine receptor densities relative to other metabotropic receptors classes remains to be established. Methods: We comprehensively characterized brain-wide differences in functional connectivity across multiple scales, including individual connections, regions, and networks in participants with cocaine use disorder (CUD; n=69) and healthy matched controls (n=62), Further, we studied the relationship between the observed functional connectivity signatures of CUD and the spatial distribution of a broad range of normative neurotransmitter receptor and transporter bindings as assessed through 18 different normative positron emission tomography (PET) maps. Results: Our analyses identified a widespread profile of functional connectivity differences between individuals with CUD and matched healthy comparison participants (8.8% of total edges; 8,185 edges; p Conclusions: Our analyses revealed a widespread profile of altered connectivity in individuals with CUD that extends across the functional connectome and implicates multiple circuits. This profile is robustly coupled with normative dopamine D