Short CommunicationfMRI Stroop and behavioral treatment for cocaine-dependence: Preliminary findings in methadone-maintained individuals
Introduction
Despite almost universal use of behavioral treatments for cocaine-use disorders and research spanning decades on their mechanisms of action, application of cognitive neuroscience methods to address these mechanisms remains limited (Kazdin, 2007; Morgenstern, Naqvi, Debellis, & Breiter, 2013). One approach to this question uses functional magnetic resonance imaging (fMRI) tasks measuring cognitive constructs with hypothesized relevance to addiction or treatment response. This enables assessment of how task-related functional activity changes with treatment or relates to abstinence outcomes. Cognitive control may be central to cocaine-use disorders (Garavan & Hester, 2007) and achievement of abstinence (Garavan, Brennan, Hester, & Whelan, 2013). The Color-Word Stroop (MacLeod, 1991) is one cognitive control task that taps response inhibition and selective attention processes- constructs implicated in addiction vulnerability, development, and maintenance (Bechara, 2005; Everitt & Robbins, 2005; Field & Cox, 2008; Jentsch & Taylor, 1999; Kober, DeVito, DeLeone, Carroll, & Potenza, 2014; Moeller et al., 2001; Torregrossa, Corlett, & Taylor, 2011; Volkow, Fowler, Wang, & Goldstein, 2002). Poor Color-Word Stroop behavioral performance has been associated with worse treatment adherence (Fagan et al., 2015) and cocaine use, and performance has improved across treatment (Nuijten, Blanken, Van den Brink, Goudriaan, & Hendriks, 2016). In cocaine users, fMRI Stroop measures differ from healthy controls (Mayer, Wilcox, Teshiba, Ling, & Yang, 2013; Mitchell et al., 2013; Moeller et al., 2014), are associated with within-treatment cocaine abstinence (Brewer, Worhunsky, Carroll, Rounsaville, & Potenza, 2008; Mitchell et al., 2013), and change across treatment (DeVito et al., 2012, 2017). Cognitive-control may be particularly relevant to cognitive-behavioral therapy (CBT), which targets cognitive-control-related processes with skills training (Carroll, 1998).
Prior studies used fMRI and Color-Word Stroop to measure cognitive-control-related activity in the context of behavioral treatment for substance-use disorders. Studies in different substance-dependent populations (cocaine, cannabis, tobacco) employing different treatments generally found higher pre-treatment Stroop-related activity associated with better abstinence outcomes (Brewer et al., 2008; Kober et al., 2014; Krishnan-Sarin et al., 2013). In two prior studies, we assessed pre- to post-treatment changes in fMRI color-word Stroop-related activity in substance users. In a mixed substance-dependent sample (N = 12) randomized to computer-based training for CBT (CBT4CBT) or treatment as usual (TAU), Stroop-related activity was reduced at post-treatment versus pre-treatment in regions implicated in cognitive-control, including the thalamus/subthalamic nucleus/midbrain, middle/superior temporal gyrus, IFG/caudate, cuneus, anterior cingulate gyrus, middle frontal gyrus and superior frontal gyrus (DeVito et al., 2012). These changes were interpreted as consistent with improved cognitive-control-related neural efficiency following treatment. Similarly, we found, in cocaine-dependent individuals (N = 35) randomized to TAU with or without CBT, contingency management and/or disulfiram, Stroop-related activity was reduced at post- versus beginning-of-treatment in the hippocampus, thalamus, cingulate, postcentral and precentral gyri, precuneus and culmen. Furthermore, greater reductions in Stroop-related activity were associated with more CBT engagement and contingency-management prizes, but not with disulfiram-related measures (DeVito et al., 2017). However, changes in neural activity from pre- to post-treatment have not yet been associated with drug use outcomes.
The current study extends prior research, in an independent randomized controlled trial (RCT) sample. Individuals seeking treatment for current primary cocaine dependence, who were already stabilized on methadone (for opioid dependence), were randomized to CBT4CBT or TAU within an outpatient methadone-maintenance-treatment setting. We assessed associations between beginning-of-treatment fMRI Stroop-related activity (N = 19) with substance-use history, methadone dose, and within-treatment cocaine-abstinence. Within participants who also completed the fMRI Stroop task at the end of the 8-week treatment (N = 10), we assessed changes in Stroop-related activity at post-treatment versus beginning-of-treatment, and correlations between within-treatment cocaine abstinence or methadone dose with ‘changes in Stroop-related activity’. We hypothesized that greater Stroop-related activity at beginning-of-treatment would be associated with better abstinence outcomes, and participants would show reduced Stroop-related activity at post-treatment versus pre-treatment in regions involved in cognitive-control and that reductions in Stroop-related activity would be associated with better cocaine-use outcomes.
Section snippets
Participants
Treatment-seeking participants were recruited to the fMRI study prior to randomization to treatment for cocaine dependence (Carroll et al., 2014). Participants met DSM-IV criteria for current cocaine dependence (past 30 days, per SCID interviews), were on a stable dose of methadone for at least 2 months (to manage opioid use disorder), aged ≥18 years, spoke English, read at ≥6th grade level, and had no current unstabilized psychotic disorder, suicidal or homicidal ideation, claustrophobia,
Results
The sample (N = 19) was predominantly Caucasian (63%), female (74%), and (average (SD)) 41.7 (9.6) years old, having 11.8 (7.7) years of lifetime cocaine use, 13.2 (10.0) days of cocaine use in month prior to treatment, and methadone dosed 80.0 (31.8) mg/day. For more details on demographics, clinical characteristics, treatment engagement and drug use outcomes see Supplemental Table 1. Out of scanner Stroop data indicated the expected ‘Stroop effect’ (i.e., slower response time to incongruent
Main findings
Within methadone-maintained cocaine-dependent participants, methadone dose correlated positively with Stroop-effect-related neural activity at beginning-of-treatment. Stroop-related activity was reduced at post- versus beginning-of-treatment. Greater reduction in Stroop-related activity was associated with more within-treatment abstinence.
Consistency with prior research
Prior studies in marijuana users, a mixed substance-use-disorder sample, and adolescent cigarette smokers, generally found that greater Stroop-related
Role of funding source
Support for the study was provided by National Institute on Drug Abuse grants R37-DA 015969 and P50-DA09241. The funding agencies did not provide input or comment on the content of the manuscript. The manuscript reflects the contributions and thoughts of the authors and not necessarily the views of the funding agencies. Clinicaltrials.gov ID number NCT00350610.
Contributors
Drs. Potenza and Carroll designed the study (neuroimaging component: Dr. Potenza; RCT: Dr. Carroll). Dr. DeVito planned and performed the analyses and wrote the manuscript. Dr. Kober consulted on the fMRI analyses. All authors contributed to the interpretation of results, provided edits to the manuscript and approved the final version of the manuscript.
Conflict of Interest
Drs. DeVito and Kober report no competing interests. Dr. Potenza has consulted for Lundbeck, Ironwood, Shire, and INSYS pharmaceuticals and RiverMend Health and has received research support from Pfizer Pharmaceuticals. Dr. Carroll is a member of CBT4CBT LLC, which makes CBT4CBT, a computer-based version of cognitive behavioral therapy, available to qualified clinical providers and organizations on a commercial basis. Dr. Carroll works with Yale University to manage any potential conflicts of
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