The functional brain connectome in isolated rapid eye movement sleep behavior disorder and Parkinson ' s disease

Background: Isolated rapid-eye-movement behavior disorder (iRBD) often precedes the development of alphasynucleinopathies such as Parkinson 's disease (PD). Magnetic resonance imaging (MRI) studies have revealed structural brain alterations in iRBD partially resembling those observed in PD. However, relatively little is known about whole-brain functional brain alterations in iRBD. Here, we characterize the functional brain connectome of iRBD compared with PD patients and healthy controls (HC) using resting-state functional MRI (rs-fMRI). Methods: Eighteen iRBD subjects (67.3 +/- 6.6 years), 18 subjects with PD (65.4 +/- 5.8 years), and 39 age- and sexmatched HC (64.4 +/- 9.2 years) underwent rs-fMRI at 3 T. We applied a graph theoretical approach to analyze the brain functional connectome at the global and regional levels. Data were analyzed using both frequentist and Bayesian statistics. Results: Global connectivity was largely preserved in iRBD and PD individuals. In contrast, both disease groups displayed altered local connectivity mainly in the motor network, temporal cortical regions including the limbic system, and the visual system. There were some group specific alterations, and connectivity changes were pronounced in PD individuals. Overall, however, there was a good agreement of the connectome changes observed in both disease groups. Conclusions: This study provides evidence for widespread functional brain connectivity alterations in iRBD, including motor circuitry, despite normal motor function. Connectome alterations showed substantial resemblance with those observed in PD, underlining a close pathophysiological relationship of iRBD and PD.