Convergent pathology, divergent pathways: Structural network dissociation of trait and cognitive disinhibition in...

The transdiagnostic dimensional framework implicates disinhibition as a core dimension associated with cocaine use disorder (CUD) and broader externalizing psychopathology. However, accumulating evidence suggests that disinhibition comprises multiple partially dissociable dimensions. It remains unclear how these dimensions manifest in CUD and whether they are supported by distinct neural architectures. Here, we combined self-report measures, structured clinical assessments, and behavioral tasks to characterize multidimensional disinhibition in individuals with CUD. Connectome-based predictive modeling and graph-theoretical analyses were subsequently employed to identify structural connectome patterns associated with distinct disinhibition dimensions. Exploratory factor analysis revealed two partially dissociable dimensions of disinhibition associated with CUD: trait and cognitive disinhibition. These dimensions showed largely distinct structural connectivity signatures, with only a single overlapping positive predictive connection linking the left amygdala and the right medial prefrontal cortex. Cognitive disinhibition was associated with a distributed positive predictive connectivity pattern spanning multiple large-scale systems, with prominent contributions from visual, somatomotor, default mode, and subcortical networks. In contrast, trait disinhibition was characterized by a negative predictive network involving reduced structural connectivity between somatomotor and control systems, as well as increased nodal clustering coefficients across multiple large-scale networks. Together, these findings demonstrate that distinct dimensions of disinhibition in CUD are associated with partially overlapping but largely separable structural connectome architectures. By moving beyond a unitary conceptualization of disinhibition, this study provides a dimensional framework for understanding the neurobiological organization of behavioral dysregulation in addiction.