Response inhibition and fronto-striatal-thalamic circuit dysfunction in cocaine addiction

Abstract

BackgroundMany studies have investigated how cognitive control may be compromised in cocaine addiction. Here, we extend this literature by employing spatial Independent Component Analysis (ICA) to describe circuit dysfunction in relation to impairment in response inhibition in cocaine addiction. MethodsFifty-five cocaine-dependent (CD) and 55 age- and sex-matched non-drug-using healthy control individuals (HC) participated in the study. Task-relatedness of 40 independent components (ICs) was assessed using multiple regression analyses of component time courses with the modeled time courses of hemodynamic activity convolved with go success (GS), stop success (SS) and stop error (SE). This procedure produced beta-weights that represented the degree to which each IC was temporally associated with, or ‘engaged’, by each task event. ResultsBehaviorally, CD participants showed prolonged stop signal reaction times (SSRTs) as compared to HC participants (p < 0.01). ICA identified two networks that showed differences in engagement related to SS between CD and HC (p < 0.05, FDR-corrected). The activity of the fronto-striatal-thalamic network was negatively correlated with SSRTs in HC but not in CD, suggesting a specific role of this network in mediating deficits of response inhibition in CD individuals. In contrast, the engagement of the fronto-parietal-temporal network did not relate to SSRTs, was similarly less engaged for both SS and SE trials, and may reflect attentional dysfunction in cocaine addiction. ConclusionsThis study highlights the utility of ICA in identifying neural circuitry engagement related to SST performance and suggests that specific networks may represent important targets in remedying executive-control impairment in cocaine addiction.