No abstract

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.

Although the role of the frontal cortex in executive performance has been widely accepted, issues regarding the contribution of subcortical structures to these functions remain unresolved. In this study, the neural circuitry underlying selective subcomponents of working memory was investigated using event-related functional magnetic resonance imaging (fMRI). Ten healthy volunteers performed a verbal memory task, which allowed different aspects of working memory function such as maintenance, retrieval and manipulation to be tested within the same general paradigm. During performance of this task as a whole, fMRI revealed increases in signal intensity throughout the frontostriatal network. However, when signal intensity during the manipulation of information within working memory was compared to that during periods requiring only simple maintenance and retrieval, significant changes were observed only in the caudate nuclei, bilaterally. These results suggest an essential and specific role for the caudate nucleus in executive function, which may underlie the cognitive disturbances observed in frontostriatal neurodegenerative disorders such as Parkinson's disease.