Dynamics of corticocortical brain functional connectivity relevant to therapeutic response to biologics in inflammatory arthritis

Abstract

ABSTRACTAberrant resting-state static functional connectivity of the brain regions, which could be evaluated by functional magnetic resonance imaging (fMRI), affects clinical courses in inflammatory arthritis (IA) including rheumatoid arthritis and spondyloarthritis. This static methods for assessing brain functional connections would be too simple to estimate the whole picture of resting-state brain function because it fluctuates over time. The effects of resting-state brain connectivity dynamics for clinical course are unknown in patients with IA. Therefore, we aimed to evaluate dynamic functional connectivity for clinical courses of IA in the context of therapeutic responsiveness to biologics using resting-state fMRI data of 64 patients with IA consisting of two cohorts. We determined representative whole-brain dynamic functional connectivity patterns by k-means++ cluster analysis, and evaluated the association of their occurrence probability and therapeutic outcomes with biologics. We determined four distinct clusters of dynamic functional connectivity in IA patients. In the first cohort, occurrence probability of the distinct cluster was associated with favorable therapeutic response in disease activity and patients’ global assessment. This finding was validated by the second cohort. The whole-brain functional coordination of the cluster indicated significantly increased corticocortical connectivity, and probabilistically decreased after therapy in treatment-effective patients compared to -ineffective patients. In conclusion, dynamic functional connectivity, in particular, frequent emergence of corticocortical connections was associated with clinical outcomes in patients with IA. The coherence of corticocortical interactions might affect modulation of pain, which would be relevant to therapeutic satisfaction.SUMMARYEffects of resting-state dynamic connectivity on clinical course of inflammatory arthritis regarding therapeutic responsiveness to biologics were assessed by functional magnetic resonance.Occurrence probability of corticocortical functional connectivity pattern was associated with favorable therapeutic response in disease activity and patients’ global assessment in inflammatory arthritis.