Altered Neuronal Networks in Infantile Epileptic Spasms Syndrome: Investigation of Cross-Channel Interactions and Relapse

Objective: In infantile epileptic spasms syndrome (IESS), relapse following initial effective adrenocorticotropic hormone (ACTH) treatment presents a significant challenge, involving complex neuronal oscillation interactions. Phase-amplitude coupling (PAC) is widely used to characterize rhythmic activity interactions under pathological conditions. However, the potential impact of cross-brain region PAC at different frequencies on long-term prognosis remains unclear. Methods: This study employed cross-channel PAC analysis based on noise-assisted multivariate empirical mode decomposition (NA-MEMD) to intricately analyze the neurodynamic mechanisms of IESS relapse. Results: In processing nonlinear and non-stationary signals, the simulation analysis of cross-channel PAC further validated the superiority of the NA-MEMD method, demonstrating its advantages in mode alignment and effective suppression of mode mixing, compared to the ensemble empirical mode decomposition (EEMD) method, thereby reducing spurious coupling. The EEG results of IESS patients showed that, compared to the nonrelapse group, the relapse group of IESS patients exhibited a significant increase in cross-channel PAC intensity at relatively lower frequencies and a decrease at higher frequencies. Further network topology analysis indicated that the relapse group showed higher levels of modularity in the high-frequency band, accompanied by lower clustering coefficients, reduced betweenness centrality, and decreased global efficiency. Conclusion: The NA-MEMD-based cross-channel PAC analysis demonstrates potential as a tool for assessing relapse-related connectivity patterns and prognosis in IESS. Significance: This work offers a novel perspective on the early identification of long-term outcomes in non-structural IESS patients.