The organization of brain functional connectivity (FC) has been shown to differ between sexes. Amyotrophic lateral sclerosis (ALS) is characterized by sexual dimorphism, showing sex-specific trends in site of onset, phenotypes, and prognosis. Here, we explored resting state (RS) FC differences within major large-scale functional networks between women and men in a sample of ALS patients, in comparison to healthy controls (HCs). A group-level independent component analysis (ICA) was performed on RS-fMRI time-series enabling spatial and spectral analyses of large-scale RS FC networks in 45 patients with ALS (20 F; 25 M) and 31 HCs (15 F; 16 M) with a focus on sex-related differences. A whole-brain voxel-based morphometry (VBM) was also performed to highlight atrophy differences. Between-sex comparisons showed: decreased FC in the right middle frontal gyrus and in the precuneus within the default mode network (DMN), in affected men compared to affected women; decreased FC in the right post-central gyrus (sensorimotor network), in the right inferior parietal gyrus (right fronto-parietal network) and increased FC in the anterior cingulate cortex and right insula (salience network), in both affected and non-affected men compared to women. When comparing affected men to affected women, VBM analysis revealed atrophy in men in the right lateral occipital cortex. Our results suggest that in ALS sex-related trends of brain functional and structural changes are more heavily represented in DMN and in the occipital cortex, suggesting that sex is an additional dimension of functional and structural heterogeneity in ALS.

大脑功能连接 (FC) 的组织已被证明在性别之间存在差异。肌萎缩侧索硬化症 (ALS) 的特征是性别二态性，在发病部位、表型和预后方面表现出性别特异性趋势。在这里，我们在 ALS 患者样本中探索了女性和男性之间主要大规模功能网络中的静息状态 (RS) FC 差异，与健康对照组 (HCs) 相比。对 RS-fMRI 时间序列进行组级独立成分分析 (ICA)，对 45 名 ALS（20 F；25 M）和 31 名 HC（15 F； 16 M），重点关注与性别有关的差异。还进行了基于全脑体素的形态测量 (VBM) 以突出萎缩差异。性别比较显示：与受影响的女性相比，受影响的男性在默认模式网络 (DMN) 内右额中回和楔前叶的 FC 降低；受影响和未受影响的右侧中央后回（感觉运动网络）、右侧顶下回（右侧额顶网络）的 FC 降低，前扣带皮层和右侧岛叶（突显网络）的 FC 增加男性与女性相比。在将受影响的男性与受影响的女性进行比较时，VBM 分析显示男性右侧枕叶皮质萎缩。我们的研究结果表明，在 ALS 中，与性别相关的大脑功能和结构变化趋势在 DMN 和枕叶皮层中表现得更为明显，这表明性别是 ALS 中功能和结构异质性的另一个维度。