Disruption of Brainstem Structural Connectivity in REM Sleep Behavior Disorder Using 7 Tesla Magnetic Resonance Imaging

Background Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is one of the earliest manifestations of alpha synucleinopathies. Brainstem pathophysiology underlying REM sleep behavior disorder has been described in animal models, yet it is understudied in living humans because of the lack of an in vivo brainstem nuclei atlas and to the limited magnetic resonance imaging (MRI) sensitivity. Objective To investigate brainstem structural connectivity changes in iRBD patients by using an in vivo probabilistic brainstem nuclei atlas and 7 Tesla MRI. Methods Structural connectivity of 12 iRBD patients and 12 controls was evaluated by probabilistic tractography. Two-sided Wilcoxon rank-sum test was used to compare the structural connectivity indices across groups. Results In iRBD, we found impaired (Z = 2.6, P < 0.01) structural connectivity in 14 brainstem nuclei, including the connectivity between REM-on (eg, subcoeruleus [SubC]) and REM sleep muscle atonia (eg, medullary reticular formation) areas. Conclusions The brainstem nuclei diagram of impaired connectivity in human iRBD expands animal models and is a promising tool to study and possibly assess prodromal synucleinopathy stages. (c) 2021 International Parkinson and Movement Disorder Society