In 40 worms, 50 flies and 22 larval zebrafish, wiring explained 2-24% of the reliable pair-specific coupling after node and distance controls; the link was pair-specific, and only swimming changed it
Question: how much of the reliable pair-specific functional connectivity (FC) does wiring explain after node and distance effects, is that part truly pair-specific, and where does it change with brain state? Data: per-individual FC of C. elegans (40 worms, 119 neurons, Cook 2019 wiring), Drosophila (50 flies, 75 regions, FlyWire flow) and larval zebrafish (22 fish, 65 regions, mapZebrain projectome). Method: we removed node fixed effects, a distance spline and homologous pairs from group FC, and divided the split-half coupling of wiring with this pair-specific FC by the square root of its split-half reliability (rho = correlation with the noise-free pair FC). Checks: a network simulation, 200 strength- and distance-preserving surrogates, anisotropic geometry, rank-r node factors fit on other individuals, the Randi 2023 causal atlas, and paired state contrasts. Intervals are leave-one-individual-out jackknife 95% intervals. Results: in simulation, a noisier state cut the usual per-animal coupling by 62% while rho stayed at the truth. Pair-specific FC was reliable (split-half 0.88, 0.74, 0.81), but structure explained only 3%, 24% and 9% of it (rho of all structure 0.174, 0.485, 0.294; direct wiring 0.141, 0.392, 0.122). Surrogates reproduced only 8%, 18% and 0% of this coupling, so it is pair-specific; geometry changes moved rho by at most 0.03. Rank-3 node factors captured 62-78% of the reliable pair-specific FC; worm gap junctions (rho 0.164) and fly flow (0.284) still predicted the fine-grained rest. The worm causal atlas explained less than anatomy (rho 0.075 vs 0.171). Forward versus reversal (worm) and dark flashes (zebrafish) changed the pair pattern (cross-state rho 0.94 and 0.75) without a change of wiring coupling; rest versus walk (fly) changed neither, except a small decrease with global signal regression (0.031, CI 0.001-0.061). Swimming (14 fish) raised zebrafish coupling (direct 0.101 to 0.171, difference 0.070, CI 0.011-0.128; all structure 0.231 to 0.437), also after removal of the swim-evoked response. Limitations: connectomes and activity come from different animals; connectome error is not corrected; only 14 fish for swims; swim motion and gene co-expression were not controlled; some analyses were added after the first results.
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