1. An fMRI Study of the Interaction of Stress and Cocaine Cues on Cocaine Craving in Cocaine-Dependent Men

2.  Cocaine addiction tough to treat because many patients show chronic relapse  Relapse is often preceded by 1) Negative emotions 2) Stressful life events

3.  Limbic areas - Motivation and emotion  Areas linked to dopamine system - reward  Anterior cingulate cortex  Amygdala  Nucleus accumbens  Insula  Amygdala  Bed nucleus of stria terminalis

4.  Script-guided imagery of stressful situations  Found that female cocaine users had increased frontal and cingulate activation  How stress influences cocaine craving to better understand relapse process  About relationship between stress and craving in the brain

5. Stressful stimuli would enhance the activation of craving related neural pathways. IVs: Stressor and Script-Type DV: subjective measure of emotion OR fMRI activation

6. 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

7. 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

9.  fMRI scanning  BOLD fMRI  Data analysis done with statistical parametric mapping software  Based on probability of areas being activated due solely to chance

10. MeasureMean (SD)Range CCS—cocaine craving 4.85 (2.4)1–10 QMI59.4 (31)35–116 CAARS-SL12.11 (8.4)2–24 BPRS26.2 (6.6)19–38 Baseline assessments

11. 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

12. Cocaine Scripts to Neutral Scripts 1) Early: Early Significant activation of:  Anterior cingulate cortex  Insula  Posterior cingulate cortex 2) Late: Late Significant activation of:  Anterior cingulate cortex  Insula 3) Entire cocaine script minus entire neutral Activation of:  Anterior cingulate cortex  Insula  Posterior cingulate cortex

14. 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

15.  Effects seen in parietal lobes  For “Early” these effects were significant in the posterior cingulate cortex and right parietal (For Cocaine*Stress)

16. 1 st 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

17. 2 nd Main Finding Stressor in cocaine condition resulted in activation of:  Left insula  Anterior cingulate cortex  Evaluation of incentive cues and decision-making regarding reward

18. 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

19. 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

20.  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

22. 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.