Reconfiguration of brain network dynamics by paresthesia-based spinal cord stimulation in herpes zoster-associated neuralgia: evidence from EEG microstate analysis

BACKGROUND: Neuropathic pain is characterized by disrupted large-scale brain dynamics. While paresthesia-based spinal cord stimulation (SCS) offers superior efficacy compared to pharmacological interventions, its clinical potential is constrained by poorly understood central mechanisms. EEG microstate analysis provides a powerful framework for capturing rapid spatiotemporal brain dynamics, offering further insights to elucidate how SCS potentially reconfigures the organization of neural activity. METHODS: We recruited patients with acute and chronic herpes zoster-associated neuralgia (HZAN) to investigate the modulatory effects of SCS. Using a Group (acute vs. chronic) × Condition (SCS-on vs. SCS-off) interaction design, we evaluated topographies, temporal metrics, and microstate-based functional connectivity to comprehensively characterize condition-dependent brain dynamics. RESULTS: SCS significantly attenuated the temporal predominance (duration, coverage, and occurrence) of Microstate A (auditory/visual and arousal), accompanied by a reciprocal expansion of Microstate B (visual network). Transition dynamics were markedly reconfigured, specifically through increased transition probability from A to B and a decrease from C (salience) to A. Intriguingly, exploratory analysis indicated that the transition probability from A to B (SCS-off) was positively correlated with post-treatment VAS scores. Furthermore, microstate-based connectivity analysis captured four functional modulation trends: functional inflexibility, reversal, alignment, and shared modulation. Finally, frequency-specific Microstate-A subnetwork strength emerged as a robust predictor of SCS therapeutic efficacy, particularly in acute HZAN. CONCLUSIONS: Paresthesia-based SCS potentially functions as a systemic reconfigurator of large-scale brain dynamics. By modulating and reconfiguring the aberrant spatiotemporal architecture and connectivity, SCS holds the potential to nudge the brain away from pathological entrapment toward a more adaptive and flexible functional mode. These results underscore the potential of microstate-based metrics as non-invasive biomarkers for optimizing individualized neuromodulation in HZAN.