Functional correlates of cognitive slowing in Parkinson's disease

Although attentional impairments (particularly cognitive slowing) are frequent in Parkinson's disease (PD), the mechanisms underlying these phenomena have not been fully characterized. The MRI-compatible version of the Symbol Digit Modalities Test (SDMT) has been applied to healthy individuals but not previously to patients with PD. We sought to assess functional changes in brain activation patterns associated with cognitive slowing in PD. Eighteen patients with PD and 11 matched healthy controls (HCs) were enrolled. High-resolution three-dimensional T1-weighted images and blood-oxygen-level-dependent images were acquired during the SDMT. SDMT-related brain networks for the HC and PD groups were extracted from one-sample T-test maps. In each hemisphere, correlated regions were identified by selecting 120 voxels around the peak of each significant cluster (p_uncorrected<0.001). Regions of interest were then analyzed. When performing the SDMT, both groups displayed activation in the frontal, parietal and occipital regions known to be involved in attention. In the PD group, activation was lower in several parts of the cerebellum, left and right occipital cortices, and right supramarginal gyrus. In eight of these regions, fMRI activation was positively correlated with performance in the SDMT task. Our results suggest that the right supramarginal gyrus (an important interface for information integration), the cerebellum, and the left and right occipital cortices are involved in cognitive slowing in PD. A lower level of brain activation was associated with greater cognitive impairment.