Rich-club reorganization and related network disruptions are associated with the symptoms and severity in classic trigeminal neuralgia patients.

Background: Alterations in white matter microstructure and functional activity have been demonstrated to be involved in the central nervous system mechanism of classic trigeminal neuralgia (CTN). However, the rich-club organization and related topological alterations in the CTN brain networks remain unclear.

Methods: We simultaneously collected diffusion-tensor imaging (DTI) and resting state functional magnetic resonance imaging (rs-fMRI) data from 29 patients with CTN (9 males, mean age = 54.59 years) and 34 matched healthy controls (HCs) (12 males, mean age = 54.97 years) to construct structural networks (SNs) and functional networks (FNs). Rich-club organization was determined separately based on each group's SN and different kinds of connections. For both network types, we calculated the basic connectivity properties (network density and strength) and topological properties (global/local/nodal efficiency and small worldness). Moreover, SN-FN coupling was obtained. The relationships between all those properties and clinical measures were evaluated.

Results: Compared to their FN, the SN of CTN patients was disrupted more severely, including its topological properties (reduced network efficiency and small-worldness), and a decrease in network density and strength was observed. Patients showed reorganization of the rich-club architecture, wherein the nodes with decreased nodal efficiency in the SN were mainly non-hub regions, and the local connections were closely related to altered global efficiency and whole brain coupling. While the cortical-subcortical connections of feeder were found to be strengthened in the SN of patients, the coupling between networks increased in all types of connections. Finally, disease severity (duration, pain intensity, and affective alterations) was negatively correlated with coupling (rich-club, feeder, and whole brain) and network strength (the rich-club of the SN and local connections of the FN). A positive correlation was only found between pain intensity and the coupling of local connections.

Conclusions: The SN of patients with CTN may be more vulnerable. Accompanied by the reorganization of the rich-club, the less efficient network communication and the impaired functional dynamics were largely attributable to the dysfunction of non-hub regions. As compensation, the pain transmission pathway of feeder connections involving in pain processing and emotional regulation may strengthen. The local and feeder sub-networks may serve as potential biomarkers for diagnosis or prognosis.