1. 1 Impaired Decision Making In Substance Use Disorders Claire Wilcox MD UNM Dept of Psychiatry Alcohol Medical Scholars Program © AMSP

2. 2 Case  55 y.o. male  Physician  High intelligence  Methamphetamine dependent  Multiple prior treatments  Negative consequences: unemployed  Repeated relapses  Wants to quit © AMSP

3. 3 Decision Making Impairment  Not question of self-control/intelligence  Initial use of substances  Escalation of problems  Repeated relapses  Decision making impairment → relapse © AMSP

4. 4 This Lecture Will Cover  Neurocognitive aspects  Neuroanatomical/neurochemical systems  Malfunction in substance use disorder (SUD)  Treatment implications © AMSP

5. 5 How Are Decisions Made?  Mental process  Neurocognitive  Involves 3 stages Interconnected Experience-driven © AMSP

6. 6 Stage 1: Stimulus Assessment  Preference  Valence  Salience  Context © AMSP

7. 7 Stage 1: Assessment Stage 2: Execution  Action selection  Action performance © AMSP

8. 8 Stage 3: EFFECT!!  Evaluation/feedback: pros and cons of choice © AMSP

9. 9 Stage 1: Assessment Stage 2: Execution Stage 3: Effect Stage 3: Learning © AMSP

10. 10 Stage 1 Modifiers  State (hunger, mood, intox, withdrawal)  Psychological processes/traits “Impulsivity” Emotion regulation Attention (stimulus) Craving Cost-benefit analysis Assessment © AMSP

11. 11 Stage 2 Modifiers  Preference from stage 1  Moderating psychological processes/traits Flexibility Inhibitory control o Selective attention o Sustained attention © AMSP Execution

12. 12 Stage 3 Modifiers  Action from Stage 2  Experience of outcome  Timing of effect  Moderating psychological processes/traits Value/reward encoding Ability to process pros/cons Error calculation Learning © AMSP Learning Effect

13. 13 Stages In Case  Stage 2 Became obsessed Unable to fight impulse  Stage 3 Use  pleasure, relief  drug use reinforced  Stage 1 Saw friend use Frustrated/stressed © AMSP

14. 14 Lecture  Neurocognitive aspects  Neuroanatomical/neurochemical systems  Malfunction in substance use disorder (SUD)  Treatment implications © AMSP

15. 15 Dopamine  Salience  Cost benefit analysis  Action  Inhibitory control  ‘High’  Learning © AMSP Stage 1: Assessment Stage 2: Execution Stage 3: Effect & Learning 

16. 16 Glutamate  Learning  Stimulus  Preference © AMSP Stage 1: Assessment Stage 2: Execution Stage 3: Learning

17. 17 Noradrenaline  Stress response Sympathetic NS CRF release  Focus on task  Exploration © AMSP Stage 1:Assessment Stage 2: Execution Stage 3: Learning

18. Prefrontal Cortex (PFC) Anterior Cingulate (ACC) Dorsal Striatum (DS) Ventral Striatum (VS) © AMSP 18 Stage1: Assessment DS VS PFC/ACC Stage2: Execution DS PFC/ACC Stage3: Effect VS PFC/ACC Learning VS PFC/ACC

19.  Brain areas activated by: Alcohol cues Cocaine cues © AMSP 20

20. © AMSP Dopamine: From Ventral Tegmental Area (VTA) & Substantia Nigra (SN) PFC/ACC Striatum VTA/SN

21. 21 Noradrenaline From Locus Coeruleus (LC) © AMSP LC PFC/ACC Amygdala

22. 22 Glutamate © AMSP PFC/ACC Striatum Amygdala From PFC/ACC

23. 23 Lecture  Neurocognitive aspects  Neuroanatomical/neurochemical systems  Malfunction in substance use disorder (SUD)  Treatment implications © AMSP

24. 24 Decision Making In SUDs  Failure at any of 3 stages  Biological root  Possible pre-morbid deficits  Worsened by drug use  DA release to reward  DA receptor density  NA and CRF to stress © AMSP

25. 25 Assessment Deficits  Response to cue  Preference,short-term reward/”high”  Stress,  cue salience © AMSP

26. 26 Execution Deficits Habitual actions favored Can’t see other options  Inhibitory control Can’t hold back © AMSP

27. 27 Effect/Learning Deficits  Imbalanced reward encoding First drug use,  reward Once dependent o  Drug reward o Further drug consumption   Learning from negative © AMSP

28. 28 Case  Assessment:  preference for drug  Execution:  inhibitory control  Effect:  /  response to drug  Learning:  response neg consequence © AMSP

29. 29 Lecture  Neurocognitive aspects  Neuroanatomical/neurochemical systems  Malfunction in substance use disorder (SUD)  Treatment implications © AMSP

30. 30 Prevention  Exposure  Target high-risk Adolescents Genetically vulnerable Cognitive probs (schizophrenia, brain injury)  Stress reactive (depressed/anxious) © AMSP

31. 31 Treatment of SUD  Medications (target any of 3 stages)  Psychotherapy Improve choices Avoid triggers  Adaptive decision making   relapse © AMSP

32. 32 Medications  Drug cue effect  Naltrexone (AUDs), opioid blocker  DA release  craving  relapse © AMSP

33. 33 Medications  Negative emotional states  drug craving  Methadone (opioid use disorder)  Withdrawal/craving  brain stress response/  anxiety  Treat co-occurring disorders © AMSP

34. 34 Medications  Cognitive function  inhibitory control  Experimental Varenicline (Nicotine Use Disorders) Memantine (Alzheimer’s Disease) © AMSP

35. 35 Medications  Drug reward  Under development  Cocaine & nicotine vaccines  Abs block drug entry into brain © AMSP

36. 36 Psychotherapies  Contingency Management Therapy Reward changes behaviors Learn abstinence  earn $$$  Relapse Prevention Therapy Identify triggers Learn avoidance © AMSP

37. 37 This lecture covered  Neurocognitive aspects of decision making  Neuroanatomical/neurochemical systems  How systems can malfunction in SUD  Treatment implications © AMSP

38. 38 Thanks to:  Dr. Ann Manzardo (a power point genius)  Dr. Marc Schuckit (for an excellent learning experience, and all of his help and time)  Alcohol Medical Scholars Program (for the yummy food and spectacular hotels) © AMSP