Intact inhibitory control processes in abstinent drug abusers (I): a functional neuroimaging study in former cocaine addicts

Abstract

Neuroimaging studies in current cocaine dependent (CD) individuals consistently reveal cortical hypoactivity across regions of the response inhibition circuit (RIC). Dysregulation of this critical executive network is hypothesized to account for the lack of inhibitory control that is a hallmark of the addictive phenotype, and chronic abuse is believed to compound the issue. A crucial question is whether deficits in this circuit persist after drug cessation, and whether recovery of this system will be seen after extended periods of abstinence, a question with implications for treatment course and outcome. Utilizing functional magnetic resonance imaging (fMRI), we examined activation in nodes of the RIC in abstinent CD individuals (n = 27) and non-using controls (n = 45) while they performed a motor response inhibition task. In contrast to current users, these abstinent individuals, despite extended histories of chronic cocaine-abuse (average duration of use = 8.2 years), performed the task just as efficiently as non-users. In line with these behavioral findings, no evidence for between-group differences in activation of the RIC was found and instead, robust activations were apparent in both groups within the well-characterized nodes of the RIC. Similarly, our complementary Electroencephalography (EEG) investigation also showed an absence of behavioral and electrophysiological deficits in abstinent drug abusers. These results are consistent with an amelioration of neurobiological deficits in inhibitory circuitry following drug cessation, and could help explain how long-term abstinence is maintained. Finally, regression analyses revealed a significant association between level of activation in the right insula with inhibition success and increased abstinence duration in the CD cohort suggesting that this region may be integral to successful recovery from cocaine addiction.

Keywords: Abstinence; Cocaine; Insula; Recovery; Response inhibition; fMRI.

Fig. 1

Brain regions that were activated utilizing a t-test contrast of Stops >0 (false discovery rate corrected; q = 0.05) (anatomical resolution) in patients and controls (N = 72). Images are in radiological orientation. Figure only shows positive activations. These activations were utilized to perform a between groups analysis restricted to a mask of task-activated regions. Black boxes show the size of the cubic ROIs within the brain activation map in each respective plane with the white lines intersecting at the peak activation which served as the center of each ROI.

Fig. 2

Scatterplots showing the relationships between right insula activation and duration of abstinence (r² = 0.66; p = 0.01) (1) and the total number of STOPS (r² = 0.66; p = 0.0001) (2) for patients only. Duration of abstinence is in weeks.