Abstract
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.
Highlights
Confirming the evidence of a pattern of widespread brain RS-fMRI abnormalities extended to both motor and extramotor resting-state functional networks (RSNs), such as sensorimotor network (SMN), FPNs and salience network (SLN), in both female and male patients compared to sex-matched healthy controls (HCs), revealed reduced functional connectivity (FC) in the default mode network (DMN) in the right middle frontal gyrus and in the precuneus and gray matter (GM) atrophy in the right lateral occipital cortex selectively in men with Amyotrophic lateral sclerosis (ALS) compared to women with ALS
Our findings might prove original while studying the brain FC effects of the known differences between males and females affected by ALS
Gender-related trends of FC changes are significantly represented in DMN, in terms of reduced FC in the posterior component of the network and increased fractional amplitude of low-frequency fluctuations (fALFF) in the slow-5 band in men with ALS compared to affected women
Summary
Different performances between sexes on various cognitive skills, including executive control (Gaillard et al 2021a), language (Wegesin 1998), spatial thinking (Zancada-Menendez et al 2016; Gur and Gur 2017), emotional processing (Whittle et al 2011) and social cognition (Gur and Gur 2017), have been explained in the last decades on the base of between-sex dissimilarities in brain function (Gaillard et al 2021b; Whittle et al 2011; Stevens and Hamann 2012; Volf et al 2010; Filippi et al 2013; Gur and Gur 2017) This evidence has supported the hypothesis that males and females. FC fMRI approaches found several brain regions whose spontaneous low-frequency fluctuations (< 0.1 Hz) of the blood oxygen level-dependent (BOLD) signal registered during RS correlate with each other Those regions are believed to be functionally connected (Biswal et al 2010; Greicius et al 2003; van den Heuvel and Hulshoff Pol 2010). The spectral composition of RS-fMRI signals, as quantified by the fractional amplitude of low-frequency fluctuations (fALFF) (Zou et al 2008) across four canonical frequency sub-bands (slow-5, 0.01–0.027 Hz; slow-4, 0.027–0.073 Hz; slow-3, 0.073–0.198 Hz; slow-2, 0.198–0.25 Hz) has been considered to further characterize the BOLD time-courses within the RSNs under pathological (neurodegenerative) conditions (Esposito et al 2013)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
