1. Acute Effects of Cocaine on Human Brain Activity & Emotion John W. Candler Biology Department Eastern Connecticut State University

2. Acute Effects of Cocaine on Human Brain Activity & Emotion Breiter, H.C., R.L. Gollub, R.M. Weisskoff, et al. 1997. Acute effects of cocaine on human brain activity and emotion. Neuron. 19: 591-613.

3. Cocaine Causes: Profound state of addictionProfound state of addiction Inability to control use, despite adverse consequencesInability to control use, despite adverse consequences Reinforcing types of behavior changesReinforcing types of behavior changes

4. Previous Studies: ExaminedExamined neural pathways of addiction ConfinedConfined to invasive animal studies LimitedLimited detail due to available imaging technology

5. Purpose: Map dynamic patterns of brain activity in humansMap dynamic patterns of brain activity in humans Following cocaine infusionFollowing cocaine infusion Utilizing non-invasive technologyUtilizing non-invasive technology High resolution imaging, previously unavailableHigh resolution imaging, previously unavailable Provide evidence of dynamic neurological networks associated with drug induced euphoria and cravingProvide evidence of dynamic neurological networks associated with drug induced euphoria and craving

6. Methods: 17 subjects (13 men, 4 women)17 subjects (13 men, 4 women) Mean age 34.5 years (± 4.6 yrs)Mean age 34.5 years (± 4.6 yrs) Addicted to cocaine, otherwise healthy by physical examinationAddicted to cocaine, otherwise healthy by physical examination No history of head traumaNo history of head trauma

7. Methods: Double-blind with saline controlsDouble-blind with saline controls Cocaine infusion administered (0.6mg/kg over 30sec.)Cocaine infusion administered (0.6mg/kg over 30sec.) Monitored 5 min. pre-infusion, 15 min. post-infusionMonitored 5 min. pre-infusion, 15 min. post-infusion Subjects rate the high, rush, craving, & low associated with infusionSubjects rate the high, rush, craving, & low associated with infusion Evaluate brain region activity with fMRIEvaluate brain region activity with fMRI

8. Results: Behavioral Ratings (High vs. Rush) Infusion

9. Results: Behavioral Ratings (High vs. Craving) Infusion

10. Results: Behavioral Ratings (High vs. Low) Infusion

11. Results: Brain Region Activity Measured activity using fMRIMeasured activity using fMRI Increased / decreased blood flow and oxygenationIncreased / decreased blood flow and oxygenation Compared fMRI data to behavioral ratingsCompared fMRI data to behavioral ratings

12. Results: Brain Activity During High Short Duration ChangesShort Duration Changes Limbic & Paralimbic RegionsLimbic & Paralimbic Regions Ventral TegmentumVentral Tegmentum Basal ForebrainBasal Forebrain Pontine BrainstemPontine Brainstem CaudateCaudate InsulaInsula Cingulate GyrusCingulate Gyrus Prefrontal CortexPrefrontal Cortex

13. Results: Brain Activity During Rush Short Duration ChangesShort Duration Changes Limbic & Paralimbic RegionsLimbic & Paralimbic Regions Ventral TegmentumVentral Tegmentum Left Basal ForebrainLeft Basal Forebrain CaudateCaudate Rt. InsulaRt. Insula Rt. Anterior CingulateRt. Anterior Cingulate Rt. Posterior CingulateRt. Posterior Cingulate Posterior ThalmusPosterior Thalmus Rt. PutamenRt. Putamen Lt. Posterior HippocampusLt. Posterior Hippocampus

14. Results: Brain Activity During low & craving Sustained Duration ChangesSustained Duration Changes Nucleus AccumbensNucleus Accumbens Left AmygdalaLeft Amygdala Rt. Parahippocampal GyrusRt. Parahippocampal Gyrus

15. Summary: Euphoria Activity in Ventral Tegmentum, Basal Forebrain, and other regions:Activity in Ventral Tegmentum, Basal Forebrain, and other regions: –Correlated well with euphoria ratings –VT is a major source of dopamine for NAC region –Euphoria may be associated with Dopamine transmission As suggested by previous animal research evidenceAs suggested by previous animal research evidence

16. Summary: Craving Activation in Nucleus Accumbens, Amygdala, and Hippocampus:Activation in Nucleus Accumbens, Amygdala, and Hippocampus: –Correlated with craving responses Not a strong correlation as compared to euphoria resultsNot a strong correlation as compared to euphoria results –Craving may not be mediated by these 2 – 3 areas alone… –Craving may reflect the numbers of activated regions –Suggests a distributed network of regions involved with craving –Further research necessary

17. Conclusions: In Humans, functional integration of circuits involved in:In Humans, functional integration of circuits involved in: –Euphoria –Reinforcement –Craving Future research:Future research: –Do these regions function the same way in humans as in animals? –How do these functions produce incentive and reward?