Error Processing and Gender-Shared and -Specific Neural Predictors of Relapse in Cocaine Dependence

Deficits in cognitive control are implicated in cocaine dependence. Previously, combining functional magnetic resonance imaging and a stop signal task, we demonstrated altered cognitive control in cocaine-dependent individuals. However, the clinical implications of these cross-sectional findings and, in particular, whether the changes were associated with relapse to drug use, were not clear. In a prospective study, we recruited 97 treatment-seeking individuals with cocaine dependence to perform the stop signal task during functional magnetic resonance imaging and participate in follow-up assessments for 3 months, during which time cocaine use was evaluated with timeline follow back and ascertained by urine toxicology tests. Functional magnetic resonance imaging data were analysed using general linear models as implemented in Statistical Parametric Mapping 8, with the contrast "stop error greater than stop success trials" to index error processing. Using voxelwise analysis with logistic and Cox regressions, we identified brain activations of error processing that predict relapse and time to relapse. In females, decreased error-related activations of the thalamus and dorsal anterior cingulate cortex predicted relapse and an earlier time to relapse. In males, decreased error-related activations of the dorsal anterior cingulate cortex and left insula predicted relapse and an earlier time to relapse. These regional activations were validated with data resampling and predicted relapse with an average area under the curve of 0.849 in receiver operating characteristic analyses. These findings provide direct evidence linking deficits in cognitive control to clinical outcome in a moderate-sized cohort of cocaine-dependent individuals. These results may provide a useful basis for future studies to examine how psychosocial factors interact with cognitive control to determine drug use and to evaluate the efficacy of pharmacological or behavioural treatment in remediating deficits of cognitive control in cocaine addicts.