Resting-state functional connectivity reveals cortical compensatory reorganization in idiopathic REM sleep behavior...

Idiopathic REM sleep behavior disorder (iRBD) is a well-established prodromal manifestation of α-synucleinopathies, and patients without hyposmia may represent an early stage of the "body-first" Parkinson's disease (PD) subtype. This study aimed to investigate brain functional network alterations in hyposmia-free iRBD patients and validate the hypothesis of early cortical compensatory mechanisms.

Data were retrieved from the Parkinson's Progression Markers Initiative (PPMI) database. Thirty-seven hyposmia-free iRBD patients and 37 demographically matched healthy controls (HCs) were included. Degree centrality (DC) analysis to identify functional hub alterations, and seed-based functional connectivity (FC) analysis using differentially expressed DC regions as regions of interest.

Compared with HCs, iRBD patients exhibited significantly increased DC values in the left superior frontal gyrus. Seed-based FC analysis revealed enhanced connectivity between the Frontal_Sup_2_L and multiple cortical regions, including prefrontal subregions, temporal gyri, and sensorimotor areas. Within the iRBD group, the mean FC strength between the Frontal_Sup_2_L and its differentially connected brain regions was negatively correlated with RBDSQ scores (r = -0.360, p = 0.029).

Our findings suggest that hyposmia-free iRBD patients exhibit compensatory reorganization of brain functional networks centered on the left superior frontal gyrus, supporting the early cortical compensation hypothesis in the "body-first" α-synucleinopathy subtype. Stratification by both the presence and timing of hyposmia relative to RBD onset is critical for reconciling inconsistent rs-fMRI findings in iRBD.The DC value of the left Frontal_Sup_2_L and its FC with extensive cortical regions represent candidate imaging indicators for prodromal α-synucleinopathies, whose clinical utility requires prospective validation in larger independent cohorts with longitudinal designs.