Analytical overview

DF Dorothea L. Floris
ML Meng-Chuan Lai
TN Tanmay Nath
MM Michael P. Milham
AM Adriana Di Martino
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Using conjunction analyses, we explored whether atypical intrinsic brain properties in males with ASD showed significant spatial overlap with those exhibiting typical sex differences. Primary analyses used group difference Z-statistics maps from two published large-scale R-fMRI studies [1, 19]. Applying a more stringent statistical voxel-level threshold of Z ≥ 2.58 (cluster level p < 0.05) yielded highly similar findings as original results; see Additional file 1: Figure S1 for illustrative purposes. These studies were selected for their large sample sizes and for the representativeness of their findings in regard to typical sex differentiation (e.g., [79, 21, 22]) as well as ASD-related atypicalities [2, 2325] (for complete reviews, see [26]). Five R-fMRI metrics were examined which have been reported to reflect typical sex differences [79, 19] and ASD-related intrinsic brain properties [1, 24, 27, 28]: (1) regional homogeneity (ReHo) [29], (2) voxel-mirrored homotopic connectivity (VMHC) [30], (3) network degree centrality (DC) [31], (4) PCC-iFC, and (5) fractional amplitude of low frequency fluctuations (fALFF) [32] (for details on each measure, see Additional file 2: Supplementary methods). Validation and replication analytical strategies were conducted to address the possible confounds related to samples and preprocessing differences (Table 1).

Overview of analysis strategies

ABIDE Autism Brain Imaging Data Exchange, FCP 1000 Functional Connectome Project, GSP Brain Genomics Superstruct Project, ASD autism spectrum disorder, NT neurotypicals, M males, F females

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