Dataset Information

Alteration of Brain Functional Networks in Early-Stage Parkinson's Disease: A Resting-State fMRI Study.

ABSTRACT: Although alterations of topological organization have previously been reported in the brain functional network of Parkinson's disease (PD) patients, the topological properties of the brain network in early-stage PD patients who received antiparkinson treatment are largely unknown. This study sought to determine the topological characteristics of the large-scale functional network in early-stage PD patients. First, 26early-stage PD patients (Hoehn and Yahr stage:1-2) and 30 age-matched normal controls were scanned using resting-state functional MRI. Subsequently, graph theoretical analysis was employed to investigate the abnormal topological configuration of the brain network in early-stage PD patients. We found that both the PD patient and control groups showed small-world properties in their functional brain networks. However, compared with the controls, the early-stage PD patients exhibited abnormal global properties, characterized by lower global efficiency. Moreover, the modular structure and the hub distribution were markedly altered in early-stage PD patients. Furthermore, PD patients exhibited increased nodal centrality, primarily in the bilateral pallidum, the inferior parietal lobule, and the medial superior frontal gyrus, and decreased nodal centrality in the caudate nucleus, the supplementary motor areas, the precentral gyrus, and the middle frontal gyrus. There were significant negative correlations between the Unified Parkinson Disease Rating Scale motor scores and nodal centralities of superior parietal gyrus. These results suggest that the topological organization of the brain functional network was altered in early-stage PD patients who received antiparkinson treatment, and we speculated that the antiparkinson treatment may affect the efficiency of the brain network to effectively relieve clinical symptoms of PD.

SUBMITTER: Sang L

PROVIDER: S-EPMC4627652 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Alteration of Brain Functional Networks in Early-Stage Parkinson's Disease: A Resting-State fMRI Study.

Sang Linqiong L Zhang Jiuquan J Wang Li L Zhang Jingna J Zhang Ye Y Li Pengyue P Wang Jian J Qiu Mingguo M

PloS one 20151030 10

Although alterations of topological organization have previously been reported in the brain functional network of Parkinson's disease (PD) patients, the topological properties of the brain network in early-stage PD patients who received antiparkinson treatment are largely unknown. This study sought to determine the topological characteristics of the large-scale functional network in early-stage PD patients. First, 26early-stage PD patients (Hoehn and Yahr stage:1-2) and 30 age-matched normal con ...[more]

PMID: 26517128

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Project description:Parkinson's disease (PD) is a neurodegenerative disorder affecting dopaminergic neurons in the substantia nigra leading to dysfunctional cortico-striato-thalamic-cortical loops. In addition to the characteristic motor symptoms, PD patients often show cognitive impairments, affective changes and other non-motor symptoms, suggesting system-wide effects on brain function. Here, we used functional magnetic resonance imaging and graph-theory based analysis methods to investigate altered whole-brain intrinsic functional connectivity in PD patients (n = 37) compared to healthy controls (n = 20). Global network properties indicated less efficient processing in PD. Analysis of brain network modules pointed to increased connectivity within the sensorimotor network, but decreased interaction of the visual network with other brain modules. We found lower connectivity mainly between the cuneus and the ventral caudate, medial orbitofrontal cortex and the temporal lobe. To identify regions of altered connectivity, we mapped the degree of intrinsic functional connectivity both on ROI- and on voxel-level across the brain. Compared to healthy controls, PD patients showed lower connectedness in the medial and middle orbitofrontal cortex. The degree of connectivity was also decreased in the occipital lobe (cuneus and calcarine), but increased in the superior parietal cortex, posterior cingulate gyrus, supramarginal gyrus and supplementary motor area. Our results on global network and module properties indicated that PD manifests as a disconnection syndrome. This was most apparent in the visual network module. The higher connectedness within the sensorimotor module in PD patients may be related to compensation mechanism in order to overcome the functional deficit of the striato-cortical motor loops or to loss of mutual inhibition between brain networks. Abnormal connectivity in the visual network may be related to adaptation and compensation processes as a consequence of altered motor function. Our analysis approach proved sensitive for detecting disease-related localized effects as well as changes in network functions on intermediate and global scale.

Project description:fMRI studies in mice typically require the use of anesthetics. Yet, it is known that anesthesia alters responses to stimuli or functional networks at rest. In this work, we have used Dual Regression analysis Network Modeling to investigate the effects of two commonly used anesthetics, isoflurane and medetomidine, on rs-fMRI derived functional networks, and in particular to what extent anesthesia affected the interaction within and between these networks. Experimental data have been used from a previous study (Grandjean et al., 2014). We applied multivariate ICA analysis and Dual Regression to infer the differences in functional connectivity between isoflurane- and medetomidine-anesthetized mice. Further network analysis was performed to investigate within- and between-network connectivity differences between these anesthetic regimens. The results revealed five major networks in the mouse brain: lateral cortical, associative cortical, default mode, subcortical, and thalamic network. The anesthesia regime had a profound effect both on within- and between-network interactions. Under isoflurane anesthesia predominantly intra- and inter-cortical interactions have been observed, with only minor interactions involving subcortical structures and in particular attenuated cortico-thalamic connectivity. In contrast, medetomidine-anesthetized mice displayed subcortical functional connectivity including interactions between cortical and thalamic ICA components. Combining the two anesthetics at low dose resulted in network interaction that constituted the superposition of the interaction observed for each anesthetic alone. The study demonstrated that network modeling is a promising tool for analyzing the brain functional architecture in mice and comparing alterations therein caused by different physiological or pathological states. Understanding the differential effects of anesthetics on brain networks and their interaction is essential when interpreting fMRI data recorded under specific physiological and pathological conditions.

Project description:Deficits in cognitive functioning are a common yet poorly understood symptom in Parkinson's disease (PD). Recent studies have highlighted the importance of (dynamic) interactions between resting-state networks for cognition, which remains understudied in PD. We investigated how altered (dynamic) functional interactions between brain networks relate to cognitive dysfunction in PD patients. In this fMRI study, 50 PD patients (mean age 65.5 years ± 6.27) on dopaminergic medication were studied cross-sectionally, and of this cohort 31 PD patients were studied longitudinally. MRI imaging and neuropsychological testing was performed at two time points, with a follow-up duration of approximately three years. Functional connectivity within and between seven resting-state networks was calculated (both statically and dynamically) and correlated with four neuropsychological test scores; a combined score of (four) executive tasks, a motor perseveration, memory, and category fluency task. Cognitive dysfunction was determined based on a longitudinal sample of age-matched healthy controls (n = 13). PD patients showed dysfunction on six out of seven cognitive tasks when compared to healthy controls. Severity of executive dysfunction was correlated with higher static and lower dynamic functional connectivity between deep gray matter regions and the frontoparietal network (DGM-FPN). Over time, declining executive function was related to increasing static DGM-FPN connectivity, together with changes of connectivity involving the dorsal attention network (amongst others with the ventral attention network). Static functional connectivity between the ventral and dorsal attention network correlated with motor perseveration. Our findings demonstrate that in PD patients, dysfunctional communication between (i) subcortical, fronto-parietal and attention networks mostly underlies worsening of executive functioning, (ii) attention networks are involved in motor perseveration.

Dataset Information

Alteration of Brain Functional Networks in Early-Stage Parkinson's Disease: A Resting-State fMRI Study.

Publications

Alteration of Brain Functional Networks in Early-Stage Parkinson's Disease: A Resting-State fMRI Study.

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