Fig. 3: Establishing data-derived WT- and AD-aging networks.

a We consider both the sum (all edges across two stages, left matrices) and intersect (common edges across two stages, right matrices) as a comprehensive and stringent definition of our data-driven aging networks for WT (top matrices) and AD (bottom matrices). Edges at chosen stages (Fig. 2) are highly overlapping (difference from null distribution, p <0.001) for both groups. Aging networks are displayed as connectomes (172 × 172 ROIs, see Fig. 1). Greater FC in older relative to younger mice is shown in red (upper right half matrices in connectomes). Greater FC in younger relative to older mice is shown in blue (lower left half matrices in connectomes). Data are also shown as vertical histograms of node degree (on the right of each matrix); node degree maps displayed on anatomical reference images (greyscale), and circle plots are shown in the bottom half of (a), for WT and AD (left and right respectively). All results have a statistical threshold (corrected, p <0.05) applied. b, c Fisher’s exact test (MATLAB) is used to assess (over/under) enrichment for edges within data-derived networks and the triple-network model: DMN, LCN, and SN, as well as their inter-network pairs (corrected, permutation test ×1000 iterations). These results are depicted using histogram diagrams for WT (b) and AD (c). Positive ( + ve) edges are shown in red (for older > younger) and negative (−ve, younger > older) are shown in blue, top and bottom of (b, c). Real data results are indicated with a grey vertical line and a black triangle. Null distribution is color-coded according to the network investigated (see Fig. 1a). A left-shift from the null distribution indicates under enrichment, a right-shift from the null distribution indicates over enrichment in the networks analyzed. Histograms indicate results from the sum. Significance is displayed as * for p <0.05, ** for p <0.01 and *** for p <0.001. Equivalent findings are uncovered for triple network representation when we use the sum or intersect definition. ENT entorhinal, HF hippocampal formation, RSP retrosplenial, TH thalamus, HY hypothalamus, SS somatosensory, CP caudoputamen, ACB nucleus accumbens, MO motor, VIS visual, ACA anterior cingulate, MB midbrain, PERI perirhinal, AUD auditory, TEa temporal association area, AI agranular insula, OLF olfactory, CBX cerebellar. Triple network color-coding: default-mode network (DMN) in green, salience network (SN) in pink, lateral-cortical network (LCN) in orange; regions in common across all three networks (light blue), regions shared by DMN and LCN (light purple) are also shown.