Sex differences in resting-state EEG microstates and working memory in first-episode, medication-naïve major
Yuhang He1, Fengchun Wu2, Zhendong Zhang1
1Department of Psychiatry, The Affiliated Brain Hospital, Guangzhou Medical University, Guangzhou, 510370, China.
Background:
Cognitive impairment shows notable sex-related variability in major depressive disorder (MDD), yet the neurophysiological mechanisms underlying these differences remain unclear. Using resting-state EEG microstates as an index of large-scale neural dynamics, this study aimed to examine sex differences in microstate characteristics and their associations with cognitive function in MDD.
Methods:
A total of 197 first-episode, medication-naïve patients with MDD underwent resting-state EEG recording and cognitive assessment using the MATRICS Consensus Cognitive Battery. Microstate temporal parameters were extracted for canonical microstate classes (A-D). Between-group comparisons were conducted using independent-samples t-tests with false discovery rate (FDR) correction, and associations between microstate metrics and cognitive performance were examined using Spearman correlations.
Results:
Female patients showed significantly poorer WM performance compared with male patients (p_fdr = 0.015), despite comparable demographic and clinical features. Robust sex differences emerged in microstate coverage: males displayed greater coverage of microstates A and B, whereas females exhibited greater coverage of microstate C (all p_fdr < 0.05). Transition probabilities also differed, with males showing higher D → A and lower D → C transitions (both p_fdr = 0.012). Among the microstate metrics demonstrating sex differences, only microstate A coverage was significantly associated with WM performance (r = 0.153, p = 0.032).
Conclusions:
These findings reveal sex-specific alterations in intrinsic network dynamics in early-course MDD and suggest that differential engagement of sensory-attentional neural states may contribute to sex-linked vulnerability in WM dysfunction. Microstate parameters may serve as electrophysiological markers for identifying sex-dependent neurocognitive mechanisms in depression.
