title: Reward processing abnormalities in Parkinson's disease.
abstract: The primary motor cortex is important for motor learning and response selection, functions that require information on the expected and actual outcomes of behavior. Therefore, it should receive signals related to reward. Pathways from reward centers to motor cortex exist in primates. Previously, we showed that gamma aminobutyric acid-A-mediated inhibition in the motor cortex, measured by paired transcranial magnetic stimulation, changes with expectation and uncertainty of money rewards generated by a slot machine simulation. We examined the role of dopamine in this phenomenon by testing 13 mildly affected patients with Parkinson's disease, off and on dopaminergic medications, and 13 healthy, age-matched controls. Consistent with a dopaminergic mechanism, reward expectation or predictability modulated the response to paired transcranial magnetic stimulation in controls, but not in unmedicated patients. A single dose of pramipexole restored this effect of reward, mainly by increasing the paired transcranial magnetic stimulation response amplitude during low expectation. Levodopa produced no such effect. Both pramipexole and levodopa increased risk-taking behavior on the Iowa Gambling Task. However, pramipexole increased risk-taking behavior more in patients showing lower paired transcranial magnetic stimulation response amplitude during low expectation. These results provide evidence that modulation of motor cortex inhibition by reward is mediated by dopamine signaling and that the physiological state of the motor cortex changes with risk-taking tendency in patients on pramipexole. The cortical response to reward expectation may represent an endophenotype for risk-taking behavior in patients on agonist treatment.
authors.affiliation: Behavioral Neurology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Kapogiannis
authors.forename: Eric
authors.initials: E
authors.lastname: Mooshagian
authors.forename: Paul
authors.initials: P
authors.lastname: Campion
authors.forename: Jordan
authors.initials: J
authors.lastname: Grafman
authors.forename: Trelawny J
authors.initials: TJ
authors.lastname: Zimmermann
authors.forename: Kelsey C
authors.initials: KC
authors.lastname: Ladt
authors.forename: Eric M
authors.initials: EM
authors.lastname: Wassermann
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000627:therapeutic use; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology*; D004576:Electromyography; D019054:Evoked Potentials, Motor / Q000187:drug effects / Q000502:physiology; D005260:Female; D005717:Games, Experimental; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000150:complications* / Q000188:drug therapy; D012201:Reward; D012309:Risk-Taking; D050781:Transcranial Magnetic Stimulation
chemical_list: D000978:Antiparkinson Agents