Dynamic reconfiguration of directed effective connectivity between attention networks and the default mode network in knee osteoarthritis: a combined resting-state and non-noxious thermal stimulation functional magnetic resonance imaging study

Background: Chronic pain is understood as a disturbance of large-scale brain-network organization involving systems that coordinate internally and externally oriented processing. In knee osteoarthritis (KOA), altered connectivity involving attention networks and the default mode network (DMN) has been reported, but directed organization and reconfiguration during non-noxious somatosensory input remain unclear.

Methods: In this cross-sectional neuroimaging study, 148 patients with KOA and 36 healthy controls (HCs) underwent resting-state fMRI followed by non-noxious knee thermal-stimulation fMRI. Directed effective connectivity (EC) was estimated separately for the resting-state and thermal-stimulation runs using regression dynamic causal modeling and summarized within the Yeo 7-network framework. Between-group analyses assessed directed network organization at rest and stimulation-related reconfiguration, defined as thermal-stimulation minus resting-state connectivity (ΔEC = ECthermal - ECrest). Network in-degree, out-degree, and exploratory clinical associations were examined.

Results: Compared with HC, KOA patients exhibited reduced directed inputs to the dorsal attention network (DAN) from multiple networks and increased directed drive toward the DMN at rest. During thermal stimulation, KOA patients showed greater increases in directed connectivity toward the DAN but attenuated DAN→DMN connectivity changes. Core edge-level effects were robust in sensitivity analyses. Degree analyses supported altered input-output profiles of the DAN and DMN. Exploratory associations with pain severity and functional impairment did not survive false-discovery-rate correction.

Conclusions: KOA was characterized by altered directed interactions between attention networks and the DMN at rest, together with atypical reconfiguration from rest to non-noxious somatosensory stimulation. These findings are consistent with altered coordination between externally oriented attention and internally oriented processing.