Functional Magnetic Resonance Imaging Clinical Trial of a Dual-Processing Treatment Protocol for Substance-Dependent Adults

Background and Purpose: Prefrontal impairment and cognitive control deficits are associated with alcohol use disorders (Li, et al., 2009), with heightened amygdala reactivity to drug stimuli (Hester & Garavan, 2009), and lack of cognitive control contributing to sustained drug abuse (Goldstein & Volkow, 2002). Impairments in decision making are theorized to result from a dominant ‘‘amygdala-driven impulsive system’’ and weakened prefrontal ‘‘reflective system’’ (Bechara, 2004).

Our dual-processing (DP) treatment model is designed to improve behavioral decision making by engaging both implicit and explicit areas of the brain using an integrated visual processing-CBT model. In a randomized controlled trial (RCT), this study examined the efficacy of this 10-week DP protocol on neurobiological functioning, as compared to a standard care didactic relapse prevention (RP) model.  It was hypothesized that DP participants would show greater blood-oxygenation-level-dependent (BOLD) signal decrease in the amygdaloid region and greater BOLD signal increase in the prefrontal cortex at end of treatment, as compared to RP.

Methods: Our study sample (N=29; n=10 pre-post fMRI) consisted of adult outpatients seeking treatment at a large hospital-based facility.  fMRI data were obtained before and after participation in the 10-week treatment conditions. MRI data were acquired and analyzed at the Center for Functional and Molecular Imaging at Georgetown University on a Siemens Tim Trio 3.0 Tesla scanner. E-Prime software was used to present 48 drug stressor and 24 neutral images; a task similar to Goldin, et al., (2008). The functional data were preprocessed and statistically analyzed using SPM5.  Analysis consisted of two stages to control for within-subject repeated measures and between-subject variance.  First-level analysis used a fixed-effects single subject analysis from which contrast images for each trial type were computed for each subject; followed by a second-level analysis that used a random effects group analysis on the contrast images from the first-level analysis. The analysis of the difference between DP and RP at post-treatment was assessed using a flexible factorial design.  Analysis of pre- versus post-treatment in DP used a two-sample t-test.

Results: Eighteen participants completed pretreatment fMRI and 10 of these participants also completed posttreatment fMRI.  In the passive watch condition (drug cue exposure), RP showed greater amygdala and reward center activation than DP at posttreatment scan, along with greater left anterior cingulate and right superior frontal gyrus activation.  In the passive watch condition, DP showed no reward center or amygdala activation at posttest as compared to pretest, and did show greater activation in the left and right anterior cingulate as well as in the left and right medial frontal gyrus.

Conclusions and Implications: Results suggest that in the passive watch condition, heightened emotional reactivity, signaled by reward center and amygdala activation, was present for RP but not DP.  DP, therefore, showed enhanced regulatory capacity in the face of drug stressor images at posttest, as compared to RP.  Findings suggest the importance of recognizing and engaging implicit areas of the brain in relapse prevention protocols, which can be done by incorporating creative arts based techniques within a standard explicit/verbal CBT approach.