Causal Brain Network Alterations Across Disease Stages in Herpes Zoster and Postherpetic Neuralgia

Herpes zoster (HZ) and postherpetic neuralgia (PHN), which are common chronic pain disorders, can cause long-term pain and negative emotions accompanied by structural brain changes; however, their temporal dynamics and causal relationships remain unknown.

This study employed causal structural covariance network (CaSCN) analysis was used to explore gray matter volume (GMV) alterations across disease stages and their causal relationships. CaSCN refers to directed causal influences between brain regions based on structural covariance.

This study employed a cross-sectional observational design. In this study, 157 treatment-naïve first-episode HZ and PHN patients (53 acute HZ, 53 subacute HZ and 52 chronic PHN) were enrolled, along with 85 sex- and age-matched healthy controls (HCs). Voxel-based morphometry (VBM) was applied to analyze high-resolution T1-weighted magnetic resonance images and measure GMV in each participant. On the basis of the results of the intergroup comparisons, the left pericalcarine cortex and bilateral thalamus (voxel-level p < 0.001, cluster-level p < 0.05) presented significant differences and were selected as seed regions for subsequent CaSCN analysis.

Compared with healthy controls, patients with HZ and PHN presented stage-specific GMV changes, and areas such as the left pericalcarine cortex and bilateral thalamus presented GMV changes at the time of onset; causal structure analysis revealed that the left pericalcarine cortex and bilateral thalamus presented significant positive causal effects on the left middle occipital gyrus, left middle temporal gyrus, left angular gyrus, left cerebellum, right inferior temporal gyrus, left medial superior frontal gyrus, left cusai lobe and other brain regions.

This study revealed dynamic patterns of GMV changes over time in HZ and PHN patients by CaSCN analysis, providing new perspectives for understanding the neuroimaging mechanisms of HZ and PHN and clarifying the causal relationships of brain structural alterations during disease progression.