SN-centered triple-network reorganization in carpal tunnel syndrome: A multimodal fMRI study of salience-driven network bias

Carpal tunnel syndrome (CTS), a median nerve compression disorder, offers a model of chronic afferent deprivation, yet its systems-level impact on intrinsic brain networks remains unclear. We tested a tri-network hypothesis that dysregulated interactions among the salience (SN), sensorimotor (SMN), and default mode (DMN) networks underlie persistent functional impairment in CTS. Resting-state fMRI data were acquired from 52 CTS patients and 30 matched healthy controls. We examined static and dynamic functional connectivity among SN, SMN, and DMN, directional effective connectivity using network-level models, and a state-resolved cross-network interaction index quantifying the relative engagement of SN with SMN versus DMN. CTS patients showed reduced static SMN-DMN coupling and enhanced SMN-SN coupling, and effective connectivity analyses revealed diminished excitatory influence from SMN to SN. Dynamic analyses identified four recurrent connectivity states, with CTS patients spending more time in a state marked by strong SN-SMN coupling and DMN suppression. The cross-network interaction index consistently demonstrated a shift toward preferential SN-SMN engagement across dynamic states. Together, these findings indicate a reproducible pattern of SN-centered reorganization in CTS, characterized by strengthened SN-SMN coupling and diminished integration with the DMN. This tri-network profile suggests that chronic afferent deprivation leads to dysregulated salience-mediated allocation of attentional and sensorimotor resources, contributing to persistent functional impairment, and that such large-scale network alterations may serve as mechanistic markers for patient stratification and potential therapeutic modulation.