Fig. 3: Associations of regional synaptic loss with the brain network connectome.
a Schematic illustration of the model of network-associated synaptic loss. For a given index ROI (e.g., dark red), the SV2A-PET w score was modeled as the average of the w scores in the neighboring regions weighted by interregional connectivity. b The spatial association between the SV2A-PET w-score and averaged connectivity-weighted neighbor w-score was assessed against two null models accounting for autocorrelation (i.e., null spin) and network topology (i.e., null rewired). c As an example, the scatterplot shows the relationship between the group-average SV2A-PET w score in Aβ+ subjects (n = 91) and the functional connectivity-weighted neighbor w-score at the network sparsity of 25%, i.e., top 25% of connections with the strongest functional connectivity strength were preserved in the network. β and two-sided p value was derived from linear regression. The linear model fit is indicated with 95% confidence intervals. d The association was consistently significant compared to two null models (i.e., null spin and null rewired) when using functional connectivity matrix across different network sparsity (i.e., from 100% to 25%) and structural connectivity in Aβ+ subjects. *** indicates one-sided prewired or pspin < 0.001, without adjustment for multiple comparisons. e The model was assessed for each participant. The significance of the subject-level β-value distribution among Aβ+ individuals was assessed using two-sided one-sample t-tests, without adjustment for multiple comparisons. f The comparisons of subject-specific associations between CU Aβ- (n = 54) and Aβ+ subjects were conducted using linear regressions adjusting for age, sex, and education years (all two-sided p ≤ 0.001, uncorrected for multiple comparisons). Boxplots are displayed as median (center line) ± interquartile range (bounds) with whiskers including observations within the 1.5 interquartile range. ROI, region of interest. DMN, default mode network; FPCN, fronto-parietal control network; VAN, ventral attention network; DAN, dorsal attention network. Source data are provided in a Source data file.
