Common Connectivity Phenotypes in Rapid Eye Movement Sleep Behavior Disorder and Parkinson’s Disease: The Search for an Intermediate Phenotype

Rapid eye movement sleep behavior disorder (RBD) is often prodromal to Parkinson’s disease (PD). Thus there should be detectable in vivo functional signatures shared between RBD and PD that aid in disease classification. To assess common in-vivo phenotypes, resting state data was collected on a 3T clinical MRI platform and a novel functional connectivity magnetic resonance imaging (fcMRI) approach, which combined independent component analysis (ICA) and graph theory, was used to evaluate deficits in interconnectivity among 15 PD, 14 RBD and 13 control participants. Whole brain and network-level analyses revealed the largest deficits in network connectivity in PD compared with controls, with less severe differences between RBD and controls. Importantly, the network-level analysis demonstrated decreased network interconnectivity, with the greatest aberrant networks in PD, and a subset in RBD. Additionally, a disease classification algorithm predicted PD cases by being trained on RBD cases with 0.87 sensitivity and 0.68 specificity. The functional alterations in cortical networks in RBD extended beyond the brainstem. These findings demonstrate progressive reductions in connectivity between brain networks, with less severe deficits in RBD than PD. Moreover, RBD phenotypes can be used to predict PD status in a cross-sectional sample, which suggests RBD is an intermediate phenotype.