Functional brain networks in REM sleep behavior disorder

Abstract

REM sleep behavior disorder (RBD) has a strong association with synucleinopathies. Prior studies of psychometrics have demonstrated subtle abnormalities of task-switching and visuospatial tasks in iRBD, similar to deficits in synucleinopathies. In this study, we used resting state functional connectivity MRI to assess the strength of brain networks and regions involved in attention, executive control, visual, auditory, and motor function. Ten individuals (6 male, 4 female) with polysomnogram-confirmed iRBD were compared to ten age- and sex-matched controls. All underwent brain MRI including two blood-oxygen level dependent (BOLD) sequences acquired resting awake with eyes closed. Following standard pre-processing and regression of noise signals, BOLD time series were extracted from pre-defined regions of interest (ROI). The correlation coefficient between BOLD time series of each pair of ROIs was Fisher-z transformed to obtain normally-distributed data, prior to constructing cross-correlation matrices. Correlation coefficients for ROI-pairs were averaged to assess the connectivity strength of each network. Paired t-tests were used to compare iRBD cases and controls. There were no significant differences between iRBD cases and controls in the strength of the executive control, attention, or default mode networks. However, there was a significant decrease in connectivity between visual cortex and attention network (iRBD 0.06 vs. Control 0.14, p = 0.02). Additionally, the iRBD group had almost no correlation between the visual and primary motor regions, significantly lower than the robust correlation in controls (iRBD 0.08 vs. Control 0.33, p = 0.008). Resting state functional connectivity MRI analysis demonstrates significantly reduced strength of connections between the visual regions and the attention network, and between the visual and motor regions. The strength of canonical cognitive networks—including the default mode, attention, and executive networks—and connectivity of other sensory and motor regions, was not different between iRBD cases and controls. These findings suggest that the decline in visuo-spatial performance in iRBD reflects a specific disconnection of the visual regions from their usual functional networks, rather than a generalized brain dysfunction. This has implications for understanding how and where synucleinopathies affect the brain at the earliest stages of disease. American Sleep Medicine Foundation Physician Scientist Training Award.