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An fMRI Study of the Interaction of Stress and Cocaine Cues on Cocaine Craving in Cocaine-Dependent Men. Introduction. Cocaine addiction tough to treat because many patients show chronic relapse Relapse is often preceded by Negative emotions Stressful life events.
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An fMRI Study of the Interaction of Stress and Cocaine Cues on Cocaine Craving in Cocaine-Dependent Men
Introduction • Cocaine addiction tough to treat because many patients show chronic relapse • Relapse is often preceded by • Negative emotions • Stressful life events
Areas Activated During Craving • Limbic areas - Motivation and emotion • Areas linked to dopamine system - reward • Anterior cingulate cortex • Amygdala • Nucleus accumbens • Insula Areas Activated During Stress • Amygdala • Bed nucleus of striaterminalis
Basis of Study • Script-guided imagery of stressful situations • Found that female cocaine users had increased frontal and cingulate activation So they wanted to know... • How stress influences cocaine craving to better understand relapse process • About relationship between stress and craving in the brain
Hypothesis Stressful stimuli would enhance the activation of craving related neural pathways. IVs: Stressor and Script-Type DV: subjective measure of emotion OR fMRI activation
Method Participants • Ten right-handed African American males • Age range: 37-49 • Administration method: smoking crack • In early stage of drug abstinence (on avg 8) • Met DSM-IV criteria for cocaine dependence but no other disorders • Unless substance-induced mood disorder
Method Procedure • Baseline assessments of: • cocaine craving the week before testing • ADHD • Psychopathology • Mental imagery ability • Script-guided mental imagery • Listened to and mentally re-enacted scripts • One drug-related • One drug-neutral • Stressor: threat of mild electric shock to wrist • Told which part of testing would occur
Method (cont’d) • fMRI scanning • BOLD fMRI • Data analysis done with statistical parametric mapping software • Based on probability of areas being activated due solely to chance
Results Baseline assessments
Results – Subjective Measures Within-Subjects ANOVA for: • Shock condition – not significant • Timepoint – Cocaine script resulted in significantly higher craving than neutral script and baseline • Shock*Timepoint interaction – not significant • No significant changes at any timepoint during the session in subjective ratings of sadness, anxiety, or anger
Results – fMRIScripts Cocaine Scripts to Neutral Scripts • Early: Early Significant activation of: • Anterior cingulate cortex • Insula • Posterior cingulate cortex • Late: Late Significant activation of: • Anterior cingulate cortex • Insula • Entire cocaine script minus entire neutral Activation of: • Anterior cingulate cortex • Insula • Posterior cingulate cortex
Results – fMRIStress Conditions Cocaine (no stress): Cocaine (stress) • Right thalamus • Precuneus/posterior cingulate cortex → Not significant Cocaine (stress, late): Neutral (stress, late) • Left insula → Not significant No activation differences when no stress: no stress
Results – fMRIInteraction (Stress*Script) • Effects seen in parietal lobes • For “Early” these effects were significant in the posterior cingulate cortex and right parietal (For Cocaine*Stress)
Discussion 1st Main Finding: Cocaine compared to neutral showed activation of: • Posterior cingulate cortex • Linked to anterior cingulate and amygdala; reward • Left insula • Integration of internal body state associated with emotions • Right thalamus • Information relaying
Discussion 2nd Main Finding Stressor in cocaine condition resulted in activation of: • Left insula • Anterior cingulate cortex • Evaluation of incentive cues and decision-making regarding reward
Discussion (cont’d) Results seen for stress situation not surprising as they are areas previously associated with conditioned cocaine craving. → Responses not as strong as in prior studies Results for reward make sense but areas missing • Nucleus accumbens • Prefrontal cortex • Orbitofrontal cortex
Why the Discrepancy? Limitations • fMRI loud – harder to fully immerse self in script • Used PET in past • Imagery skills were not the same across all participants • Desired responding • Not stressful enough
Overall Conclusion • Cocaine scripts elicited responses in areas associated with rewards • Presence of cocaine script and stressor enhanced cocaine-induced reward activation • Also attentional areas Implications? Relaxation training for recovering addicts Future studies: • More participants
References Duncan, E., Boshoven, W., Harenski, K., Fiallos, A., Tracy, H., Jovanovic, T., Hu, X., Drexler, K. & Kilts, C. (2007). An fMRI study of the interaction of stress and cocaine cues on cocaine craving in cocaine-dependent men. The American Journal on Addictions, 16, 174-182.