title: Cognitive states influence dopamine-driven aberrant learning in Parkinson's disease.
abstract: Individual differences in dopaminergic tone underlie tendencies to learn from reward versus punishment. These effects are well documented in Parkinson's patients, who vacillate between low and high tonic dopaminergic states as a function of medication. Yet very few studies have investigated the influence of higher-level cognitive states known to affect downstream dopaminergic learning in Parkinson's patients. A dopamine-dependent cognitive influence over learning would provide a candidate mechanism for declining cognitive integrity and motivation in Parkinson's patients. In this report we tested the influence of two high-level cognitive states (cost of conflict and value of volition) that have recently been shown to cause predictable learning biases in healthy young adults as a function of dopamine receptor subtype and dopaminergic challenge. It was hypothesized that Parkinson's patients OFF medication would have an enhanced cost of conflict and a decreased value of volition, and that these effects would be remediated or reversed ON medication. Participants included N = 28 Parkinson's disease patients who were each tested ON and OFF dopaminergic medication and 28 age- and sex-matched controls. The expected cost of conflict effect was observed in Parkinson's patients OFF versus ON medication, but only in those that were more recently diagnosed (<5 years). We found an unexpected effect in the value of volition task: medication compromised the ability to learn from difficult a-volitional (instructed) choices. This novel finding was also enhanced in recently diagnosed patients. The difference in learning biases ON versus OFF medication between these two tasks was strongly correlated, bolstering the idea that they tapped into a common underlying imbalance in dopaminergic tone that is particularly variable in earlier stage Parkinsonism. The finding that these decision biases are specific to earlier but not later stage disease may offer a chance for future studies to quantify phenotypic expressions of idiosyncratic disease progression.
authors.affiliation: Department of Psychology, University of New Mexico, USA. Electronic address: jcavanagh@unm.edu.
authors.forename: James F
authors.initials: JF
authors.lastname: Cavanagh
authors.affiliation: Department of Psychology, University of New Mexico, USA.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Mueller
authors.affiliation: Department of Psychology, University of New Mexico, USA.
authors.forename: Darin R
authors.initials: DR
authors.lastname: Brown
authors.affiliation: Department of Psychology, University of New Mexico, USA.
authors.forename: Jacqueline R
authors.initials: JR
authors.lastname: Janowich
authors.affiliation: Department of Psychology, University of New Mexico, USA.
authors.forename: Jacqueline H
authors.initials: JH
authors.lastname: Story-Remer
authors.affiliation: Department of Neurology, University of New Mexico, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Wegele
authors.affiliation: Department of Neurology, University of New Mexico, USA.
authors.forename: Sarah Pirio
authors.initials: SP
authors.lastname: Richardson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003071:Cognition / Q000502:physiology*; D060825:Cognitive Dysfunction / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006801:Humans; D007858:Learning / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009042:Motivation / Q000502:physiology; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000378:metabolism* / Q000503:physiopathology; D011597:Psychomotor Performance / Q000502:physiology*
chemical_list: D004298:Dopamine
keywords: Conflict; Dopamine; Parkinson's disease; Reinforcement learning; Volition