Brain Advance Access published online on June 24, 2008
Brain, doi:10.1093/brain/awn112
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Parkinson's disease and dopaminergic therapy—differential effects on movement, reward and cognition
1University of Cambridge Department of Clinical Neurosciences, CB2 2QQ, 2Medical Research Council Cognition and Brain Sciences Unit, Cambridge, CB2 7EF, 3University of Cambridge Behavioural and Clinical Neurosciences Institute, CB2 3EB and 4Cambridge Centre for Brain Repair, CB2 OPY, UK
Correspondence to:
Dr J. B. Rowe, MRC-CBU, 15 Chaucer Road, Cambridge, CB2 7EF, UK E-mail: james.rowe{at}mrc-cbu.cam.ac.uk
Cognitive deficits are very common in Parkinson's disease particularly for ‘executive functions’ associated with frontal cortico-striatal networks. Previous work has identified deficits in tasks that require attentional control like task-switching, and reward-based tasks like gambling or reversal learning. However, there is a complex relationship between the specific cognitive problems faced by an individual patient, their stage of disease and dopaminergic treatment. We used a bimodality continuous performance task during fMRI to examine how patients with Parkinson's disease represent the prospect of reward and switch between competing task rules accordingly. The task-switch was not separately cued but was based on the implicit reward relevance of spatial and verbal dimensions of successive compound stimuli. Nineteen patients were studied in relative ‘on’ and ‘off’ states, induced by dopaminergic medication withdrawal (Hoehn and Yahr stages 1–4). Patients were able to successfully complete the task and establish a bias to one or other dimension in order to gain reward. However the lateral prefrontal cortex and caudate nucleus showed a non-linear U-shape relationship between motor disease severity and regional brain activation. Dopaminergic treatment led to a shift in this U-shape function, supporting the hypothesis of differential neurodegeneration in separate motor and cognitive cortico–striato–thalamo–cortical circuits. In addition, anterior cingulate activation associated with reward expectation declined with more severe disease, whereas activation following actual rewards increased with more severe disease. This may facilitate a change in goal-directed behaviours from deferred predicted rewards to immediate actual rewards, particularly when on dopaminergic treatment. We discuss the implications for investigation and optimal treatment of this common condition at different stages of disease.
Key Words: Parkinson's disease; reward; task-shift; fMRI; dopamine
Received January 27, 2008. Revised May 11, 2008. Accepted May 12, 2008.
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