title: Prefrontal and striatal dopaminergic genes predict individual differences in exploration and exploitation.
abstract: The basal ganglia support learning to exploit decisions that have yielded positive outcomes in the past. In contrast, limited evidence implicates the prefrontal cortex in the process of making strategic exploratory decisions when the magnitude of potential outcomes is unknown. Here we examine neurogenetic contributions to individual differences in these distinct aspects of motivated human behavior, using a temporal decision-making task and computational analysis. We show that two genes controlling striatal dopamine function, DARPP-32 (also called PPP1R1B) and DRD2, are associated with exploitative learning to adjust response times incrementally as a function of positive and negative decision outcomes. In contrast, a gene primarily controlling prefrontal dopamine function (COMT) is associated with a particular type of 'directed exploration', in which exploratory decisions are made in proportion to Bayesian uncertainty about whether other choices might produce outcomes that are better than the status quo. Quantitative model fits reveal that genetic factors modulate independent parameters of a reinforcement learning system.
authors.affiliation: Departments of Cognitive & Linguistic Sciences, Brown Institute for Brain Science, Brown University, Providence, Rhode Island, USA. michael_frank@brown.edu <michael_frank@brown.edu>
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Frank
authors.forename: Bradley B
authors.initials: BB
authors.lastname: Doll
authors.forename: Jen
authors.initials: J
authors.lastname: Oas-Terpstra
authors.forename: Francisco
authors.initials: F
authors.lastname: Moreno
mesh_terms: D000293:Adolescent; D000465:Algorithms; D001499:Bayes Theorem; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003198:Computer Simulation; D003342:Corpus Striatum / Q000378:metabolism*; D003657:Decision Making / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000235:genetics; D005106:Exploratory Behavior / Q000502:physiology*; D005260:Female; D006801:Humans; D007858:Learning / Q000502:physiology; D008297:Male; D009042:Motivation; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000378:metabolism*; D012054:Reinforcement, Psychology; D013998:Time Perception; D055815:Young Adult
chemical_list: D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; C497928:PPP1R1B protein, human; D002394:Catechol O-Methyltransferase; D004298:Dopamine