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The Journal of Neuroscience, July 16, 2003, 23(15):6351-6356
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Cognitive Impairments in Early Parkinson's Disease Are Accompanied by Reductions in Activity in Frontostriatal Neural Circuitry
Simon J. G. Lewis,1,2 Anja Dove,4 Trevor W. Robbins,3 Roger A. Barker,1,2 * andAdrian M. Owen4 * 1Cambridge Centre for Brain Repair and Departments of 2Neurology and 3Experimental Psychology, University of Cambridge, and 4Medical Research Council Cognition and Brain Sciences Unit, Cambridge, United Kingdom CB2 2EF
Studies in patients with Parkinson's disease (PD) suggest that the characteristic motor symptoms of the disorder are frequently accompanied by impairments in cognition that are most profound in tasks of executive function. Neuropsychological deficits are not an inevitable consequence of the disease, yet the reasons underlying cognitive heterogeneity in PD are not well understood. To determine the underlying neural correlate of these cognitive deficits, we used event-related functional magnetic resonance imaging (fMRI) to compare groups of cognitively impaired and unimpaired patients, matched on all other clinical measures. fMRI revealed significant signal intensity reductions during a working-memory paradigm in specific striatal and frontal lobe sites in patients with cognitive impairment compared with those patients who were not cognitively unimpaired. These results demonstrate that cognitive deficits in PD are accompanied by neural changes that are related to, but distinct from, those changes that underlie motoric deficits in these patients. Furthermore, they suggest that fMRI may provide a valuable tool for identifying patients who may benefit from targeted therapeutic strategies.
Key words: Parkinson's disease; working memory; functional MRI; heterogeneity; frontal lobes; basal ganglia
Received Jan. 21, 2003; revised Apr. 29, 2003; accepted May. 16, 2003.
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