Sex-specific alterations in brain network topology in methamphetamine use disorder: A graph theory-based fMRI study

Methamphetamine use disorder (MUD) imposes severe neurological and societal challenges, yet the sex-specific alterations in brain network topology remain poorly understood.

Resting-state fMRI data were acquired from 78 patients with MUD (49 male, 29 female) and 65 demographically matched healthy controls (HCs). Functional connectivity matrices were constructed using RESTplus V1.30, and graph metrics (global efficiency, nodal centrality) were computed using GRETNA V2.0.0. Group comparisons (MUD vs. HCs; male vs. female) and correlation analyses with Barratt Impulsiveness Scale scores were conducted, applying false discovery rate correction.

Compared to HCs, patients with MUD exhibited disrupted nodal metrics across multiple brain regions, including bilateral anterior-inferior triangular regions, right gyrus rectus, left cuneus, bilateral supplementary motor areas, bilateral parietal regions, and occipital lobes, without significant alterations in global network metrics. Furthermore, significant sex-related main effects were observed in widespread brain areas, involving key nodal metrics such as degree centrality, local efficiency, clustering coefficient, and nodal efficiency. Female patients with MUD demonstrated higher global network measures and showed more extensive nodal metric differences compared to males. These findings highlight distinct sex-dependent network alterations in MUD and emphasize the need for sex-stratified therapeutic approaches targeting specific network vulnerabilities.

This study provides evidence of sexually dimorphic network pathology in MUD, revealing that females exhibit widespread front-parietal-occipital disruptions, whereas males demonstrate relative network preservation. These findings underscore the importance of sex-stratified therapeutic strategies targeting network-specific vulnerabilities in MUD.