neural underpinnings of substance use disorders

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. Here, we characterize patterns of functional connectivity in cocaine use disorder and their spatial association with neurotransmitter receptor densities and transporter bindings assessed through PET. Profiles of functional connectivity in cocaine use disorder reliably linked with spatial densities of dopamine D2/3 receptors across independent datasets. These findings demonstrate that the topography of dopamine receptor densities may underlie patterns of functional connectivity in cocaine use disorder, as assessed through fMRI.

Individual differences in neural circuits underlying emotional regulation, motivation, and decision-making are implicated in many psychiatric illnesses. Interindividual variability in these circuits may manifest, at least in part, as individual differences in impulsivity. Impulsivity reflects a tendency towards rapid, unplanned reactions to internal or external stimuli without considering potential negative consequences, coupled with difficulty inhibiting responses. Here, we use multivariate machine learning approaches (brain-based predictive models) to explore the neural bases of impulsivity. Using brain-based predictive models, we demonstrate that regional variations in cortical thickness, surface area, and gray matter volume significantly predict self-reported impulsivity measures, with associations varying across impulsivity dimensions and developmental timepoints. Impulsivity broadly maps onto default mode, limbic, ventral attention, and visual networks, as well as cerebellar and brain stem structures. While many relationships are stable across sexes and developmental time points, others exhibit sex effects and dynamic changes. These results suggest that neuroanatomy is linked to self-reported impulsivity in youth and highlight the complexity of these relationships across measures, features, sexes, and time points.