Disrupted functional connectivity in PD with probable RBD and its cognitive correlates

Abstract

Recent studies associated rapid eye movement sleep behavior disorder (RBD) in Parkinson’s disease (PD) with severe cognitive impairment and brain atrophy. However, whole-brain functional connectivity has never been explored in this group of PD patients. In this study, whole-brain network-based statistics and graph-theoretical approaches were used to characterize resting-state interregional functional connectivity in PD with probable RBD (PD-pRBD) and its relationship with cognition. Our sample consisted of 30 healthy controls, 32 PD without probable RBD (PD-non pRBD), and 27 PD-pRBD. The PD-pRBD group showed reduced functional connectivity compared with controls mainly involving cingulate areas with temporal, frontal, insular, and thalamic regions (p < 0.001). Also, the PD-pRBD group showed reduced functional connectivity between right ventral posterior cingulate and left medial precuneus compared with PD-non pRBD (p < 0.05). We found increased normalized characteristic path length in PD-pRBD compared with PD-non pRBD. In the PD-pRBD group, mean connectivity strength from reduced connections correlated with visuoperceptual task and normalized characteristic path length correlated with processing speed and verbal memory tasks. This work demonstrates the existence of disrupted functional connectivity in PD-pRBD, together with abnormal network integrity, that supports its consideration as a severe PD subtype.

Alterations of Regional Homogeneity in Parkinson’s Disease with Rapid Eye Movement Sleep Behavior Disorder

“…52,53 Previous MRI studies have demonstrated that the functional connectivity between the superior occipital gyrus and the superior parietal gyrus, the precuneus and posterior cingulate gyrus were decreased in patients with PD-RBD, which were related to the poor visuospatial-executive function. 8,54,55 These results concurred with our study, where the decreased brain activity in the posterior regions and significant differences in the score of visuospatial-executive function was exhibited in the PD-RBD group relative to the HCs, suggesting that the PD-RBD group may represent more serious neurodegeneration in terms of cognitive impairment, especially the visuospatial-executive impairment. 3 In addition, Hu et al have demonstrated that visuospatial-executive function impairment might predict the progression of mild cognitive impairment, 6 and a longitudinal follow-up study should be conducted.…”

Neuroimaging of rapid eye movement sleep behavior disorder and its relation to Parkinson's disease

“…The study also used graph theory analysis to find increased normalized characteristic path length, as a global graph measure, in PD patients with probable RBD compared with PD patients. This finding was also present when comparing PD patients with and without probable RBD stratified by the presence of mild cognitive impairment (i.e., increased normalized characteristic path length in PD patients with probable RBD with MCI in comparison to PD patients with MCI and without RBD) (Oltra et al, 2021). Having a longer path length means this network is less efficient overall in integrating information at the whole‐brain level.…”

“…In a study that explored the whole‐brain functional connectivity differences between PD patients with and without probable RBD using a threshold‐free network‐based approach, authors found that medicated PD patients with probable RBD had reduced functional connectivity between the right ventral posterior cingulate and left medial precuneus compared to PD patients without RBD. In addition, PD patients with probable RBD had reduced connectivity between the cingulate cortex and temporal, frontal, insular, and thalamic regions compared to healthy controls (Oltra et al, 2021). These functional connectivity abnormalities were associated with the visuo‐perceptual function in PD patients with probable RBD.…”

“…These findings were consistently similar in PD patients with RBD, with whole‐brain cortico‐cortical and striato‐cortical functional disruptions. Interestingly, along the PD course, global whole‐brain architecture disruptions emerge within the subtype of PD patients with RBD (J. Li et al, 2020; Oltra et al, 2021). Future studies using advanced analytical approaches such as machine learning and graph theory analysis are needed to better understand the underlying neural substrates driving iRBD and the role RBD takes in PD pathology.…”

Imaging the Limbic System in Parkinson’s Disease—A Review of Limbic Pathology and Clinical Symptoms

“…Regarding sleep disorders, PD patients with rapid eye movement sleep behavior disorder (RBD) had reduced functional connectivity to temporal, frontal, insular and thalamic regions when compared to healthy controls. When compared to PD patients without RBD, PD patients with RBD had a reduced connectivity between posterior cingulate and precuneus [ 181 ]. PD patients with pain relieved under deep brain stimulation showed a reduced activity of the anterior cingulate in fMRI as compared to those without relief of pain [ 182 ], with a positive correlation between DAT binding in the posterior cingulate and the pain threshold [ 183 ].…”