Altered Resting State Brain Networks in Parkinson’s Disease

Abstract

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.

Age-Related Reorganizational Changes in Modularity and Functional Connectivity of Human Brain Networks

“…Several studies have reported that the modular organization could be affected under neuropsychological conditions and disorders, including depression (Peng et al, 2014), Schizophrenia (Alexander-Bloch et al, 2014), epilepsy (Xu et al, 2013), and age-related neurodegenerative diseases such as Parkinson's disease (Gottlich et al, 2013) and AD (Kikuchi et al, 2013). One study also observed age-related alterations in the modular organization using cortical thickness analysis (Chen et al, 2011).…”

“…Modules consist of densely intraconnected brain regions that are sparsely inter-connected with regions in other modules (Newman and Girvan, 2004). Modular organization may represent stable subcomponents of the brain that facilitate the construction of a complex system from simple building blocks, and can be theoretically linked to network development (Alexander-Bloch et al, 2010), which has provided insights into abnormal brain development, neuropsychological conditions (Alexander-Bloch et al, 2014;Peng et al, 2014;Xu et al, 2013), and age-related neurodegenerative diseases (Gottlich et al, 2013;Kikuchi et al, 2013). Therefore, in this study, we hypothesize that the brain functional modular structure can be affected by aging and that age-related changes in modularity can be revealed by graph theory analysis.…”

Exercise Therapy for Parkinson's Disease: Pedaling Rate Is Related to Changes in Motor Connectivity

“…This is of particular importance in movement disorders such as Parkinson's disease (PD), as patients with these disorders tend to move more than controls, as seen in previous studies (Göttlich et al, 2013;Helmich et al, 2010). Retrospective motion correction is imperfect, because current methods use a volumetric approach (Beall and Lowe, 2014).…”

“…The study of functional connectivity (FC) in PD is relatively young (Baudrexel et al, 2011;Göttlich et al, 2013;Hacker et al, 2012;Helmich et al, 2010;Luo et al, 2014;Poston and Eidelberg, 2012;Sharman et al, 2013;Wu et al, 2009Wu et al, , 2011aWu et al, , 2012Yu et al, 2013). An early study evaluating resting-state FC (rsFC) in PD showed that rsFC between the pre-supplementary motor area (pre-SMA) and putamen was decreased, whereas that between the pre-SMA and primary motor cortex (M1) was increased (Wu et al, 2011a).…”

The evaluation of the changes in enzymatic antioxidant reserves and lipid peroxidation in chosen parts of the brain in an animal model of Parkinson disease

“…This damage may cause the appearance of symptoms other than characteristic motor symptoms, which include, inter alia, cognitive impairments, affective changes, depression, psychosis, memory deficits and other non-motor symptoms. 22 The chronic exposure to ROS can cause atrophy and abnormal functioning in many key areas of the brain structures, including the hippocampus and frontal cortex. 23 It has been proved that atrophy of the hippocampus may be a biomarker of the early stages of cognitive disorders and memory disorders in patients with PD.…”