Dopamine-related dissociation of cortical and subcortical brain activations in cognitively unimpaired Parkinson's disease patients OFF and ON medications

• Main Authors: Cai, W. (Author), Kim, J. (Author), Llanes, S. (Author), Menon, V. (Author), Poston, K.L (Author), Ua Cruadhlaoich, M.A.I (Author), YorkWilliams, S. (Author), Zhang, K. (Author)
• Format: Article
• Language: English
• Published: Elsevier Ltd 2018
• Subjects: adult; aged; amantadine; anterior insula; antiparkinson agent; Antiparkinson Agents; Article; behavior control; brain; Brain; brain mapping; Brain Mapping; carbidopa plus levodopa; Choice Behavior; Choice Reaction Time; clinical article; cognition; Cognition; cohort analysis; Cohort Studies; controlled study; decision making; diagnostic imaging; dopamine; Dopamine; drug effect; electroencephalogram; entacapone; female; Female; fMRI; frontal cortex; functional dissociation; functional magnetic resonance imaging; human; Humans; Magnetic Resonance Imaging; male; Male; measurement accuracy; mental function; metabolism; middle aged; Middle Aged; motor activity; Motor Activity; nuclear magnetic resonance imaging; Parkinson disease; Parkinson Disease; Parkinson's disease; physiology; pramipexole; psychology; putamen; rasagiline; response time; ropinirole; task performance
• Online Access: View Fulltext in Publisher

 Background: Despite dopaminergic depletion that is severe enough to cause the motor symptoms of Parkinson's disease (PD), many patients remain cognitively unimpaired. Little is known about brain mechanisms underlying such preserved cognitive abilities and their alteration by dopaminergic medications. Objectives: We investigated brain activations underlying dopamine-related differences in cognitive function using a unique experimental design with PD patients off and on dopaminergic medications. We tested the dopamine overdose hypothesis, which posits that the excess of exogenous dopamine in the frontal cortical regions can impair cognition. Methods: We used a two-choice forced response Choice Reaction Time (CRT) task to probe cognitive processes underlying response selection and execution. Functional magnetic resonance imaging data were acquired from 16 cognitively unimpaired (Level-II) PD participants and 15 well-matched healthy controls (HC). We compared task performance (i.e. reaction time and accuracy) and brain activation of PD participants off dopaminergic medications (PD_OFF) in comparison with HC, and PD_OFF participants with those on dopaminergic medications (PD_ON). Results: PD_OFF and PD_ON groups did not differ from each other, or from the HC group, in reaction time or accuracy. Compared to HC, PD_OFF activated the bilateral putamen less, and this was compensated by higher activation of the anterior insula. No such differences were observed in the PD_ON group, compared to HC. Compared to both HC and PD_OFF, PD_ON participants showed dopamine-related hyperactivation in the frontal cortical regions and hypoactivation in the amygdala. Conclusion: Our data provide further evidence that PD_OFF and PD_ON participants engage different cortical and subcortical systems to achieve similar levels of cognitive performance as HC. Crucially, our findings demonstrate dopamine-related dissociation in brain activation between cortical and subcortical regions, and provide novel support for the dopamine overdose hypothesis. © 2018 The Authors