Between-sex variability of resting state functional brain networks in amyotrophic lateral sclerosis (ALS)

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.

Accurate support vector machine identification of limb-onset amyotrophic lateral sclerosis using resting-state activity of regions within executive control network

“…Secondly, our cohort was very skewed, with 12 of the 14 limb-onset ALS patients being male. As RSN sex-differences have been reported in ALS (41) this is both a strength, as it improves the specificity of our cohort, but also a limitation, as it decreases the translatability of findings to females. Finally, our cerebellum RSN map showed poor similarity to previously described RSNs (26) and this may affect detecting effects in this region.…”

Resting state fMRI analysis of pseudobulbar affect in Amyotrophic Lateral Sclerosis (ALS): motor dysfunction of emotional expression

“…However, there are some shortcomings to be acknowledged, including some methodological issues, such as the relatively small sample size and the cross-sectional study design. Despite the small sample size, the population studied recalled the numbers of cohorts of patients with ALS investigated in previous neuroimaging analyses (Floeter et al, 2014 ; Hübers et al, 2016 ; Trojsi et al, 2021 ; Tu et al, 2021 ).…”

“…To extract RSN maps, single-subject, and group-level ICA were carried out on the preprocessed functional time series using 2 plug-in extensions of Brain Voyager QX (Goebel et al, 2006 ), respectively, implementing the fast ICA algorithm (Hyvärinen et al, 2001 ) and the self-organizing group ICA algorithm (Esposito et al, 2005 ). Furthermore, the ICASSO procedure (Himberg et al, 2004 ) was applied to the extraction of individual ICA components, according to previously described methods (Trojsi et al, 2021 ).…”

Repetitive Transcranial Magnetic Stimulation (rTMS) of Dorsolateral Prefrontal Cortex May Influence Semantic Fluency and Functional Connectivity in Fronto-Parietal Network in Mild Cognitive Impairment (MCI)

“…MR images were acquired on a 3T scanner equipped with a 32-channel parallel head coil (General Electric Healthcare, Milwaukee, WI, USA). The imaging protocol, according to a previous MRI analysis [65], included: three-dimensional T1-weighted sagittal images (gradient-echo sequence Inversion Recovery-prepared Fast Spoiled Gradient Recalled-echo, time repetition = 6.988 ms, TI = 650 ms, TE = 3.0 ms, flip angle = 9 • , voxel size = 1 × 1 × 1 mm 3 ; acquisition time = about 7 min) [66]; RS-fMRI was performed with a gradient-echo echo-planar imaging (GRE-EPI) sequence generating 320 T2*weighted volumes of 44 axial slices (time repetition = 1500 ms, echo time = 19 ms, FA = 90 • , voxel size = 3 × 3 × 3 mm 3 , matrix = 96 × 96, field of view = 288 mm, slice thickness = 3 mm, interslice gap = 0 mm; total acquisition time = ~8 min); T2-weighted fluid attenuation inversion recovery (FLAIR) was performed to exclude severe cerebrovascular disease according to standard clinical neuroradiological criteria on visual inspection by three experienced radiologists. During the functional scan, subjects were asked to simply stay motionless, awake, and relax and to keep their eyes closed.…”