Cognitive impairment and resting-state network connectivity in Parkinson's disease

Abstract

The purpose of this work was to evaluate changes in the connectivity patterns of a set of cognitively relevant, dynamically interrelated brain networks in association with cognitive deficits in Parkinson's disease (PD) using resting-state functional MRI. Sixty-five nondemented PD patients and 36 matched healthy controls were included. Thirty-four percent of PD patients were classified as having mild cognitive impairment (MCI) based on performance in attention/executive, visuospatial/visuoperceptual (VS/VP) and memory functions. A data-driven approach using independent component analysis (ICA) was used to identify the default-mode network (DMN), the dorsal attention network (DAN) and the bilateral frontoparietal networks (FPN), which were compared between groups using a dual-regression approach controlling for gray matter atrophy. Additional seed-based analyses using a priori defined regions of interest were used to characterize local changes in intranetwork and internetwork connectivity. Structural group comparisons through voxel-based morphometry and cortical thickness were additionally performed to assess associated gray matter atrophy. ICA results revealed reduced connectivity between the DAN and right frontoinsular regions in MCI patients, associated with worse performance in attention/executive functions. The DMN displayed increased connectivity with medial and lateral occipito-parietal regions in MCI patients, associated with worse VS/VP performance, and with occipital reductions in cortical thickness. In line with data-driven results, seed-based analyses mainly revealed reduced within-DAN, within-DMN and DAN-FPN connectivity, as well as loss of normal DAN-DMN anticorrelation in MCI patients. Our findings demonstrate differential connectivity changes affecting the networks evaluated, which we hypothesize to be related to the pathophysiological bases of different types of cognitive impairment in PD.

Keywords: Parkinson's disease; fMRI; mild cognitive impairment; resting-state connectivity.

Figure 1

Resting‐state networks of interest. Left‐sided images: maps obtained from independent component analyses (ICA) of the whole sample. Right‐sided images: group‐level maps obtained from dual‐regression analyses (P < 0.05, FDR corrected). DAN: dorsal attention network; DMN: default‐mode network; FPN: frontoparietal network. The right hemisphere is displayed on the left side of axial and coronal views.

Figure 2

Data‐driven analysis intergroup connectivity comparisons. Left side: clusters of significant (P < 0.05, FDR‐corrected; 100‐voxel threshold) connectivity group differences for PD patients with mild cognitive impairment (PD‐MCI) versus HC or patients without mild cognitive impairment (PD‐NMCI) for the dorsal attention network (DAN) and the default‐mode network (DMN). FDR‐corrected P values are color‐coded according to the bar at the top. MNI Y and Z coordinates of the slices shown are indicated. Right side: scatterplots showing the correlation between connectivity values (*regression coefficients obtained from the clusters of significant PD‐MCI versus PD‐NMCI differences) and age‐, sex‐, and education‐corrected z‐scores in attention/executive (A/E) and visuospatial/visuoperceptual (VS/VP) functions in the PD patient group. r: partial‐correlation coefficient. The right hemisphere is displayed on the left side.

Figure 3

Seed‐based connectivity analysis results. Left side: schematic representation of the interregional connections where significant (P < 0.05) ordered connectivity changes were observed. Network affiliation of the nodes shown as well as of the internodal connections is indicated in the legend above. Abbreviations refer to those described in Table 1. Right side: plots showing r coefficient levels according to group for the connections where significant effects were found, according to the network affiliation of the involved nodes. Only intranetwork or internetwork changes comprising more than three connections are plotted. DAN: dorsal attention network; DMN: default‐mode network; FPN: frontoparietal network; HC: healthy controls; PD‐NMCI: Parkinson's disease patients without mild cognitive impairment; PD‐MCI: Parkinson's disease patients with mild cognitive impairment.

Figure 4

Vertexwise comparison of cortical thickness between HC, Parkinson's disease patients without mild cognitive impairment (PD‐NMCI), and Parkinson's disease patient with mild cognitive impairment (PD‐MCI). Red clusters indicate areas of significantly reduced cortical thickness in PD‐NMCI compared with HC (left) and in PD‐MCI compared with HC (right; P < 0.05). [Color figure can be viewed in the online issue, which is available at http://wileyonlinelibrary.com.]