Alterations in Resting-State MR Functional Connectivity of the Central Autonomic Network in Multiple System Atrophy and Relationship with Disease Severity.

Abstract

The central autonomic network (CAN) plays a critical role in the body's sympathetic and parasympathetic control. However, functional connectivity (FC) changes of the CAN in patients with multiple system atrophy (MSA) remain unknown. To investigate FC alterations of CAN in MSA patients. Prospective. Eighty-two subjects (47 patients with MSA [44.7% female, 60.5 ± 6.9 years], 35 age- and sex-matched healthy controls [HC] [57.1% female, 62.5 ± 6.6 years]). 3-T, resting-state functional magnetic resonance imaging (rs-fMRI) using gradient echo-planar imaging (EPI), T1-weighted three-dimensional magnetization-prepared rapid gradient echo (3D MPRAGE) structural MRI. FC alterations were explored by using core modulatory regions of CAN as seeds, including midcingulate cortex, insula, amygdala, and ventromedial prefrontal cortex. Bartlett factor score (BFS) derived from a factor analysis of clinical assessments on disease severity was used as a grouping factor for moderate MSA (mMSA: BFS < 0) and severe MSA (sMSA: BFS > 0). For FC analysis, the one-way ANCOVA with cluster-level family-wise error correction (statistical significance level of P < 0.025), and post hoc t-testing with Bonferroni correction or Tamhane's T2 correction (statistical significance level of adjusted-P < 0.05) were adopted. Correlation was assessed using Pearson correlation or Spearman correlation (statistical significance level of P < 0.05). Compared with HC, patients with MSA exhibited significant FC aberrances between the CAN and brain areas of sensorimotor control, limbic network, putamen, and cerebellum. For MSA patients, most FC alterations of CAN, especially concerning FC between the right anterior insula and right primary sensorimotor cortices, were found to be significantly correlated with disease severity. FC changes were found to be more significant in sMSA group than in mMSA group when compared with HCs. MSA shows widespread FC changes of CAN, suggesting that abnormal functional integration of CAN may be involved in disease pathogenesis of MSA. 2 TECHNICAL EFFICACY: Stage 3.