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

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.

Baggio HC ，Segura B ，Sala-Llonch R ，Marti MJ ，Valldeoriola F ，Compta Y ，Tolosa E ，Junqué C ... -  《-》

Altered functional connectivity in the default mode network is associated with cognitive impairment and brain anatomical changes in Parkinson's disease.

To assess whether functional neural connectivity is disrupted between the regions of the default mode network (DMN) in Parkinson's disease (PD) and how this connectivity is related to cognition, brain gray matter structure and white matter integrity and diffusivity. Thirty-seven PD patients and 16 healthy controls were evaluated, using resting-state functional magnetic resonance imaging (MRI), T1-weighted MRI, diffusion-weighted imaging and a battery of cognitive tests. Functional connectivity between the regions of the DMN, specifically in the precuneus, anterior and posterior cingulate, medial prefrontal and temporal and inferior parietal cortices was assessed with seed-to-voxel connectivity; gray matter volume and white matter values were determined using voxel-based morphometry and tract-based spatial statistics. Reduced functional connectivity was observed between the posterior cingulate and medial temporal lobe in PD. Lower cognitive performance, gray matter loss in posterior, medial temporal and parietal areas, and fractional anisotropy reduction in the white matter adjacent to DMN regions were also observed in PD patients compared with healthy controls. Lower DMN functional connectivity correlated with lower verbal and visual memory and visual abilities performance in PD. In addition, lower DMN functional connectivity correlated with lower gray matter volume in the posterior cingulate and precuneus, and with lower white matter fractional anisotropy of the inferior longitudinal and posterior cingulate fasciculi in PD. By combining different neuroimaging techniques and cognitive data, results showed that functional connectivity alteration between the regions of the DMN is associated with lower cognitive performance and gray and white matter abnormalities in PD.

Lucas-Jiménez O ，Ojeda N ，Peña J ，Díez-Cirarda M ，Cabrera-Zubizarreta A ，Gómez-Esteban JC ，Gómez-Beldarrain MÁ ，Ibarretxe-Bilbao N ... -  《-》

Resting-state network connectivity in cognitively unimpaired drug-naïve patients with rigidity-dominant Parkinson's disease.

Parkinson's disease (PD) could be classified into akinetic-rigidity (PDAR), tremor-dominant (PDTD) and mixed subtypes. PDAR patients are more prone to develop cognitive deficits. The default mode network (DMN), fronto-parietal network (FPN) and dorsal attention network (DAN) play important roles in cognitive processing. Our aim was to evaluate changes in connectivity patterns of the DMN, and its interrelation with the FPN and DAN in cognitively unimpaired drug-naïve PDAR patients. Resting-state functional MRI (rs-fMRI) data was collected in 20 cognitively unimpaired early-stage drug-naïve PDAR patients and 20 age-, gender- and cognition- matched healthy controls (HCs). Group-level independent component analysis (ICA) was used to investigate changes in functional connectivity (FC) within the DMN between PDAR and HCs groups, and relationships between the DMN and FPN/DAN were evaluated by seed-based approach. In PDAR patients, a significantly decreased FC, as compared with HCs, was observed in the left inferior parietal lobule (IPL) within the DMN. And the left IPL had a reduced FC with the left anterior cingulate cortex (ACC), left superior frontal gyrus (SFG), and left precuneus. However, no differences were detected in the FC between the left IPL and FPN/DAN. In addition, cognitive scores on the brief visuospatial memory test revised (BVMT-R), representing for cognitive memory domain, were positively correlated with the FC of the left IPL with bilateral SFG. Our study mainly revealed altered within-DMN connectivity in cognitively unimpaired PDAR patients, which could provide further insights into the mechanism underlying cognitive decline evolution in the PD subtype.

Hou Y ，Yang J ，Luo C ，Ou R ，Zou Y ，Song W ，Gong Q ，Shang H ... -  《-》

Default mode network connectivity patterns associated with visual processing at different stages of Parkinson's disease.

Rektorova I ，Krajcovicova L ，Marecek R ，Novakova M ，Mikl M ... -  《-》

Group comparison of spatiotemporal dynamics of intrinsic networks in Parkinson's disease.

Recent advances with functional connectivity magnetic resonance imaging have demonstrated that at rest the brain exhibits coherent activity within a number of spatially independent maps, normally called 'intrinsic' or 'resting state' networks. These networks support cognition and behaviour, and are altered in neurodegenerative disease. However, there is a longstanding perspective, and ample functional magnetic resonance imaging evidence, demonstrating that intrinsic networks may be fractionated and that cortical elements may participate in multiple intrinsic networks at different times, dynamically changing alliances to adapt to cognitive demands. A method to probe the fine-grained spatiotemporal structure of networks may be more sensitive to subtle network changes that accompany heterogeneous cognitive deficits caused by a neurodegenerative disease such as Parkinson's disease. Here we tested the hypothesis that alterations to the latent (hidden) structure of intrinsic networks may reveal the impact of underlying pathophysiologic processes as assessed with cerebrospinal fluid biomarkers. Using a novel modelling approach that we call 'network kernel analysis', we compared fine-grained network ensembles (network kernels) that include overlapping cortical elements in 24 patients with Parkinson's disease (ages 45-86, 17 male) and normal cognition or mild cognitive impairment (n = 13), and 21 cognitively normal control subjects (ages 41-76, nine male). An omnibus measure of network disruption, calculated from correlations among network kernels, was correlated with cerebrospinal fluid biomarkers of pathophysiological processes in Parkinson's disease: concentrations of α-synuclein and amyloid-β42. Correlations among network kernels more accurately classified Parkinson's disease from controls than other functional neuroimaging measures. Inspection of the spatial maps related to the default mode network and a frontoparietal task control network kernel showed that the right insula, an area implicated in network shifting and associated with cognitive impairment in Parkinson's disease, was more highly correlated with both these networks in Parkinson's disease than in controls. In Parkinson's disease, increased correlation of the insula with the default mode network was related to lower attentional accuracy. We demonstrated that in an omnibus sense, correlations among network kernels describe biological impact of pathophysiological processes (through correlation with cerebrospinal fluid biomarkers) and clinical status (by classification of patient group). At a greater level of detail, we demonstrate aberrant involvement of the insula in the default mode network and the frontal frontoparietal task control network kernel. Network kernel analysis holds promise as a sensitive method for detecting biologically and clinical relevant changes to specific networks that support cognition and are impaired in Parkinson's disease.

Madhyastha TM ，Askren MK ，Zhang J ，Leverenz JB ，Montine TJ ，Grabowski TJ ... -  《-》