Fig. 3: LC-NE system contributed to the inverted U-shaped relationship between arousal and whole-brain FC.
A Hypothesis: A cluster of core regions bridge the arousal fluctuations and whole-brain FC dynamics. B Correlation between dynamic FC of each edge and the global one was defined as the sensitivity of arousal modulation. For each node, the sensitivity was calculated as the averaged sensitivity with other regions based on the corresponding brain parcellation. C Force-directed layout of the human arousal modulated sensitivity matrix. Line width represented the sensitivity of arousal modulation. Top 10% nodes with highest sensitivity were encircled in black. Cortical 7 functional network definition64 was adopted from Schaefer et. al. D Spatial distribution of nodes with top 10% sensitivity in human. Occupancy ratio was defined as the ratio of the voxel number of top 10% nodes to the total voxel number in each functional network. VIS visual, SomMot sensorimotor, DorsAtten dorsal attention. DR dorsal raphe, PB parabrachial nucleus. E Faster collapse of arousal modulated inverted U-shaped pattern on whole-brain FC after the orderly permutation than random permutations (n = 1000 times). The permutation was conducted across arousal bins for each node. Lower distance indicated a more similar inverted U-shaped pattern. F–H As in (C–E), but for mice. For better visualization in (F), we used 296 ROIs from Allen Mouse Brain CCFv3 instead of 7657 parcels. Cortical functional network definition33 was adopted from Zerbi et. al. SNr substantia nigra, VTA ventral tegmental area, BF basal forebrain, Mot motor, PFC prefrontal cortex. I Highest and significant spatial correlation between LC-NE anatomical projections and arousal-modulated spatial pattern (node). Anatomical projection maps were averaged cross-hemisphere for all cell types. Five cell-type specific anterograde axonal tracing were from the Allen Mouse Brain Connectivity Atlas. LC (NE), locus coeruleus (norepinephrine); BF (Ach), basal forebrain (acetylcholine); DR (5-HT), dorsal raphe (serotonin); VTA (DA), ventral tegmental area (dopamine); PMv (HA), hypothalamic ventral premammillary nucleus (histamine): experiment ID #511971714, #478491810, #114155190, #160539283, #157952068. Statistical significance of spatial correlation was determined using the spatial autocorrelation preserving shuffling (two-sided t-test, Details were shown in “Methods”). *, pspin < 0.05; ***, pspin < 0.005; n.s. no significance. Source data are provided as a Source Data file.
