Value-based decision-making and the prefrontal cortex JON WALLIS

1. Value-based decision-making and the prefrontal cortex JON WALLIS

2. Animal models of decision-making

3. Outline • Define the theoretical constructs underpinning our understanding of decision-making • Discuss the anatomical and functional homologies between humans and monkeys • Describe my research into the role of frontal cortex in decision-making • Clinical and pharmacological implications

4. Perceptual decision-making ‘CAT’ ‘DOG’ Decision boundary • subjective • objective reality Types of decision-making Value-based decision-making • no right or wrong

5. Theoretical constructs: perceptual decision-making

6. Theoretical constructs: value-based decision-making

7. Lateral PFC Orbital/medial PFC Neuropsychology and choice behavior Perceptual decision-making Which is more blue? Value-based decision-making Which do you prefer? Fellows and Farah (2007)

8. Outline • Define the theoretical constructs underpinning our understanding of decision-making • Discuss the anatomical and functional homologies between humans and monkeys • Describe my research into the role of frontal cortex in decision-making • Clinical and pharmacological implications

9. PFo homology

10. PFm homology

11. = Role of PFo in valuation 3 1 12 2 1 8 1 1 4 1 2 2 1 4 4 1 12 12 1 16 16 Chosen Value : Padoa-Schioppa and Assad (2006)

12. Neuroimaging and valuation Fast for 4 hours Given 3 dollars Bid on 40 different food items ($1.50) ($2.00) Hare et al (2008)

13. - - - Time Risk Effort PFo and “neuronal currency” + + Payoff

14. (1500 ms) Encoding decision variables across PFC Choice • 9 6 4 2 1 Probability

15. Value All three variables: abstract value Pictures Appear Go Cue Kennerley et al (2009, J Cog Neuro)

16. Value One variable (cost) Kennerley et al (2009, J Cog Neuro)

17. Value Two variables (payoff and cost) Kennerley et al (2009, J Cog Neuro)

18. PFl PFo PFm Recording locations

19. Prevalence of different types of value encoding PFl PFo PFm Cost Cost Cost Kennerley et al (2009, J Cog Neuro)

20. Complex types of value encoding are in PFm PFm % neurons PFo PFl The importance of PFo and PFcs for decision-making, may depend on their ability to multiplex different decision parameters. Kennerley et al (2009, J Cog Neuro)

21. Cost-benefit analysis Effort-based decision-making Delay-based decision-making Reward (mls) Reward (mls) 5 8 11 14 1.8 3 4.2 5.4 Effort (lbs) Delay (s)

22. Probability of selecting picture

23. Value PFm neuron: net value Reward Effort 0.4 g 5 lbs 0.1 g 14 lbs

24. Outline • Define the theoretical constructs underpinning our understanding of decision-making • Discuss the anatomical and functional homologies between humans and monkeys • Overview of our current understanding of the role of frontal cortex in decision-making • Overview of the pharmacological results based on this understanding

25. Clinical implications: depression • Depression is associated with metabolic and neurochemical changes in PFm • also characterized by anhedonia and anergia • does this reflect changes to the effort/reward function? Decreased metabolic activity in depressed patients

26. Clinical implications: delay-based decision-making • Impulsive decisions occur in: • substance abusers (e.g. Monterosso et al 2001) • schizophrenics (e.g. Heerey et al 2007) • alcoholics (Boettiger et al 2007) • individuals with the COMT 158Val/Val genotype (Boettiger et al 2007)

27. dopamine agonists make rats more patient (e.g. Floresco et al 2008) or more impulsive (e.g. Cardinal et al 2001) dose-response curve? OFC 6-OHDA lesions make rats more patient (Kheramin et al 2004) EFFORT-BASED DECISION-MAKING: • nucleus accumbens dopamine depletion makes rats lazy (Salamone et al 1994) • PFm D1 antagonist infusion makes rats lazy (Schweimer & Hauber 2006) Pharmacological considerations: dopamine DELAY-BASED DECISION-MAKING:

28. blockade of serotonin synthesis makes rats more impulsive (Denk et al 2004) in vivo microdialysis reveals changes in serotonin metabolite levels in PFm during delay-based decision-making (Winstanley et al 2006) EFFORT-BASED DECISION-MAKING: • blockade of serotonin synthesis has no effect (Denk et al 2004) Pharmacological considerations: serotonin DELAY-BASED DECISION-MAKING:

29. Conclusions • the orbital and medial prefrontal areas are particularly important for decision-making • there is good anatomical and functional homology between these regions in the human and monkey • disparate clinical symptoms (e.g. anhedonia, impulsivity) might be better understood as disorders of underlying decision-making calculations

30. Conclusion Behavioral and clinical level Single neuron, genetic and pharmacological level

31. Conclusion Behavioral and clinical level Computational level Single neuron, genetic and pharmacological level

32. Acknowledgements Steven Kennerley Asst. Prof. University College London Jen Sloan Graduate student Antonio Lara Graduate student Shima Ovaysikia Research assistant Chung-Hay Luk Graduate student