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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. 1 — a Experimental design of spine density measurements. Intergroup comparisons showed a surplus of dendritic spine density in Tsc2^+/− (+/−) mutant mice. Representative confocal images of Layer 5 dendritic spines in +/+ and +/− mice are also reported (unpaired t test, two-sided, t = 2.72, P = 0.021. n = 7 (+/+) and n = 5 (+/−) mice). b Voxelwise rsfMRI mapping revealed widespread increases in long-range connectivity in cortico-limbic and striatal areas of Tsc2^+/− mice (red–yellow, left). Global histogram analysis confirmed these findings, revealing a marked increase in the number of voxels showing stronger long-range rsfMRI connectivity in prefrontal and insular regions of Tsc2^+/− mice (right). c Spatial extension of the mouse default-mode network as probed using a seed region in the prefrontal cortex (PFC). Between-group comparisons (bottom) revealed prominent prefronto-cortical and striatal hyperconnectivity in Tsc2^+/− mice as compared to control littermates (red–yellow, bottom). Regional quantifications of this effects confirmed increased prefrontal rsfMRI connectivity with retrosplenial (RS, unpaired t test, two-sided, t = 3.40, P = 0.002) and striatal (CPu, unpaired t test, two-sided, t = 2.88, P = 0.006) areas in Tsc2^+/− mice. d Spatial extension of the mouse salience network as probed using a seed region in the anterior insular cortex (Ins). Between-group comparisons revealed foci of increased connectivity in prefrontal (PFC, unpaired t test, two-sided, t = 2.69, P = 0.011) and retrosplenial cortices (RS, unpaired t test, two-sided, t = 2.70, P = 0.009) of Tsc2^+/− mice (red–yellow, bottom). Regional quantifications of these effects confirmed increased connectivity between anterior insula and prefrontal and retrosplenial cortices in Tsc2^+/− mice. Error bars represent SEM. Cpu striatum, Ins insular cortex, PFC prefrontal cortex, RS retrosplenial cortex. *P < 0.05, **P < 0.01. n = 20 mice for each group in panel (b), (c), and (d). Source data are provided as a Source Data file.