While there are as of yet no FDA-approved medications for cocaine dependence, behavioral therapies such as cognitive-behavioral therapy (CBT) have strong empirical support as well as durability of effects. Evaluation of neurobiological factors is a promising strategy for evaluating mechanisms of empirically supported therapies, as well as for identifying potentially novel targets for treatment development. We propose to add three imaging sessions (pre-treatment, post-treatment, and 6-month follow-up) to a recently initiated randomized clinical trial evaluating two forms of CBT (therapist- and computer-delivered) versus manual-guided standard counseling for 96 cocaine-dependent individuals drawn from the parent trial. Using hypotheses derived from preliminary data using the proposed tasks (Stroop Color-Word Interference and Monetary Incentive Delay Tasks) and measures (white matter integrity, regional brain volumes and resting state brain function), we will: 1) investigate the extent to which the baseline measures of the imaging tasks predict treatment outcomes;2) evaluate changes in fMRI measures from pre- to post-treatment (baseline to 12 weeks) and by treatment condition (CBT versus standard counseling);3) examine the relationship of within- treatment change in brain activation to 6-month follow-up outcomes (with an emphasis on understanding CBT's durability and "sleeper" effect);and 4) investigate the relationships between brain activations and CBT "dosing" (CBT sessions and homework completed). This project leverages a rare opportunity to evaluate neural mechanisms of action associated with addiction treatment in general and CBT in particular, as well as a unique opportunity to examining neural factors related to the durability of effects ("sleeper" effects) in CBT. Demonstration of durable changes in brain activation paralleling CBT-related improvements in cognitive control would represent an important step in elucidating and strengthening treatment effects, as well as understanding CBT's mechanisms of action, enabling clinicians to target specific skills and strategies to the individuals most likely to beneit from them.

Public Health Relevance

This project proposes to leverage yield from an existing clinical trial comparing efficacy of a novel computer- delivered cognitive-behavioral therapy with demonstrated efficacy to clinician-delivered CBT and a manualized drug treatment control by adding multiple neuroimaging assessments at pre-treatment, post-treatment and follow-up. The goal of this project is to identify neurobiological correlates of treatment outcome and response, and to extend our understanding of CBT's mechanism of action and durability, with the long-range aim of maximizing the effectiveness of this form of treatment.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Study Section
Risk, Prevention and Intervention for Addictions Study Section (RPIA)
Program Officer
Grossman, Debra
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Yale University
Schools of Medicine
New Haven
United States
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Balodis, Iris M; Potenza, Marc N (2015) Anticipatory reward processing in addicted populations: a focus on the monetary incentive delay task. Biol Psychiatry 77:434-44
Fineberg, Naomi A; Chamberlain, Samuel R; Goudriaan, Anna E et al. (2014) New developments in human neurocognition: clinical, genetic, and brain imaging correlates of impulsivity and compulsivity. CNS Spectr 19:69-89
Potenza, Marc N (2014) The neural bases of cognitive processes in gambling disorder. Trends Cogn Sci 18:429-38
Kober, Hedy; DeVito, Elise E; DeLeone, Cameron M et al. (2014) Cannabis abstinence during treatment and one-year follow-up: relationship to neural activity in men. Neuropsychopharmacology 39:2288-98
Yip, Sarah W; DeVito, Elise E; Kober, Hedy et al. (2014) Pretreatment measures of brain structure and reward-processing brain function in cannabis dependence: an exploratory study of relationships with abstinence during behavioral treatment. Drug Alcohol Depend 140:33-41
Xu, Jiansong; Kober, Hedy; Wang, Xin et al. (2014) Hippocampal volume mediates the relationship between measures of pre-treatment cocaine use and within-treatment cocaine abstinence. Drug Alcohol Depend 143:74-80
Potenza, Marc N (2014) Biased behaviors: towards understanding vulnerability and resilience factors in addictions. Biol Psychiatry 75:94-5
Garrison, Kathleen A; Potenza, Marc N (2014) Neuroimaging and biomarkers in addiction treatment. Curr Psychiatry Rep 16:513
Mitchell, Marci R; Potenza, Marc N (2014) Recent Insights into the Neurobiology of Impulsivity. Curr Addict Rep 1:309-319
Mitchell, Marci R; Potenza, Marc N (2014) Addictions and Personality Traits: Impulsivity and Related Constructs. Curr Behav Neurosci Rep 1:1-12

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