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. 2020 Dec 20;46(6):1194–1206. doi: 10.1038/s41386-020-00916-0

Fig. 5. Effect of PCP on functional connectivity, and its antagonization by xanomeline.

Fig. 5

A–D PCP increases brain functional connectivity. A Effect of PCP on global and local brain connectivity. Red/yellow reflects increase in connectivity strength (t > 3, p < 0.05, cluster correction; Veh, N = 9; PCP N = 10). B Seed–correlation mapping highlighted increased connectivity in cortical and subcortical networks of PCP-treated animals. On the left column of each panel, correlation with the seed of interest is reported for vehicle-treated animals (n = 9; t > 2.7, p < 0.05, cluster corrected). The right column of each panel indicates the corresponding connectivity difference in PCP-treated animals (red/yellow indicates connectivity increase in PCP-treated group with respect to control, z > 2; veh, n = 9; PCP, n = 10; p < 0.05, cluster corrected). C–D Quantification of Local connectivity and long-range connectivity in selected brain regions (mean ± SEM, student t test, **p < 0.01, FDR corrected). E–I Xanomeline attenuates PCP-induced long-range functional connectivity changes in the mouse brain. E Modulatory effect of xanomeline on PCP-induced local and global connectivity (Xan-PCP vs. veh-PCP, t ± 3, p < 0.05, cluster corrected). F, G Quantification of local connectivity and long-range connectivity in volumes of interest (mean ± SEM, student t test, xan-PCP vs. veh-PCP, ***p < 0.01, FDR corrected; §p < 0.05, uncorrected). H Seed-based probing of rsfMRI networks. On the left column of each panel, correlation with the seed of interest is reported for control (vehicle pretreated) subjects (N = 9; t > 2.7, p < 0.05, cluster corrected). The right column of each panel indicates the corresponding connectivity difference in xanomeline-pretreated animals (blue indicates significant connectivity decrease in xanomeline-PCP group (N = 10) with respect to control vehicle-PCP, (N = 10) Z > 2, p < 0.05, cluster corrected). I Quantification of interhemispheric rsfMRI connectivity (mean ± SEM, student t test, xan-PCP vs. veh-PCP. **p < 0.01, FDR corrected). Au auditory cortex, mPFC medial prefrontal cortex, Cg cingulate cortex, Rs retrosplenial cortex, Th thalamus, vHC ventral hippocampus, SS primary, somatosensory cortex, CPu striatum, Mid midbrain, pCtx parietal cortex, M1 primary motor cortex, Nacc nucleus accumbens, dHC dorsal hippocampus. PFC prefrontal cortex, pHC posterior hippocampus, V1 primary visual cortex, Pt posterior parietal association cortex.