An fMRI Study of the An fMRI Study of the Interaction of Stress and Interaction of Stress and Cocaine Cues on Cocaine Cocaine Cues on Cocaine

Craving in Cocaine-Craving in Cocaine-Dependent MenDependent Men

Cocaine addiction tough to treat because many patients show chronic relapse

Relapse is often preceded by1) Negative emotions2) Stressful life events

Limbic areas - Motivation and emotion Areas linked to dopamine system - reward

Anterior cingulate cortex Amygdala Nucleus accumbens Insula

Amygdala Bed nucleus of stria terminalis

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

Stressful stimuli would enhance the activation of craving related neural pathways.

IVs: Stressor and Script-TypeDV: subjective measure of emotion OR fMRI activation

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

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

fMRI scanning BOLD fMRI

Data analysis done with statistical parametric mapping software Based on probability of areas being activated

due solely to chance

Measure Mean (SD) RangeCCS—cocaine craving

4.85 (2.4) 1–10

QMI 59.4 (31) 35–116CAARS-SL 12.11 (8.4) 2–24BPRS 26.2 (6.6) 19–38

Baseline assessments

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

Cocaine Scripts to Neutral Scripts1) Early: Early

Significant activation of: Anterior cingulate cortex Insula Posterior cingulate cortex

2) Late: LateSignificant activation of: Anterior cingulate cortex Insula

3) Entire cocaine script minus entire neutralActivation of: Anterior cingulate cortex Insula Posterior cingulate cortex

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

Effects seen in parietal lobes For “Early” these effects were significant in

the posterior cingulate cortex and right parietal

(For Cocaine*Stress)

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

2nd Main FindingStressor in cocaine condition resulted in

activation of: Left insula Anterior cingulate cortex

Evaluation of incentive cues and decision-making regarding reward

Results seen for stress situation not surprising as they are areas previously associated with conditioned cocaine craving.→ Responses not as strong as in prior studiesResults for reward make sense but areas missingNucleus accumbensPrefrontal cortexOrbitofrontal cortex

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

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

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.