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. 2021 Oct 19;12:6084. doi: 10.1038/s41467-021-26131-z

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© The Author(s) 2021

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — a Voxelwise long-range connectivity mapping showed prominent rsfMRI hyperconnectivity in the anterior insular cortex of children with ASD vs. TDs. Red–yellow represents the occurrence rate i.e., the number of datasets presenting rsfMRI overconnectivity (Cohen’s d > 0.2, left). Region-wise quantification confirmed that long-range rsfMRI connectivity of the anterior insular cortex is consistently increased in all seven sites of the ABIDE-I collection (Cohen’s d range, min = 0.06 [UM], max = 0.75 [SU], right). b Long-range rsfMRI connectivity mapping of the aggregated ABIDE datasets confirmed the presence of significant bilateral foci of functional hyperconnectivity in the insular cortex of ASD vs TD children (unpaired t test, two-sided, t = 3.04, P = 0.003). Error bars represent SEM. c Seed-based probing shows functional over-synchronization between anterior insula, and basal ganglia, and prefrontal cortices in children with ASD vs. TDs. Regional quantification confirmed increased rsfMRI connectivity between insula and PFC (unpaired t test, two-sided, t = 3.94, P < 0.001), precuneus (unpaired t test, two-sided, t = 3.26, P = 0.002), angular gyrus (unpaired t test, two-sided, t = 3.13, P = 0.002) and putamen (unpaired t test, two-sided, t = 4.33, P < 0.001) in ASD vs. TDs. PFC prefrontal cortex, PCUN precuneus, ANG angular gyrus, PUT putamen. Error bars represent SEM. d Network-based visualization of Tsc2-mTOR interactome used for gene enrichment. The pictured interactome is limited to 100 genes for visualization purposes. Tsc2 seed gene is highlighted in light blue and mTOR seed gene in orange. Nodes that belongs to “Reactome mTOR signaling” are in green, those that are part of the “KEGG mTOR signaling pathway” are in red, and those that belong to “GO:0032006 regulation of TOR signaling” are in blue (left). The ASD functional hyperconnected phenotype is enriched for genes that are part of the Tsc2-mTOR interactome and reported to be dysregulated in ASD. *P < 0.05, **P < 0.01. ***P < 0.001. Source data, including gene lists, are provided as a Source Data file.