After node similarity is controlled, wiring adds at most 0.004 held-out R2 to functional coupling in worm, fly, zebrafish, mouse and human data; the anesthesia effect on mouse coupling is node-level
Question: which part of the link between wiring and functional connectivity (FC) is pair-specific, and not node or geometry structure, and where does it change with brain state? Earlier campaign work controlled nodes with one additive term per node; such a term cannot express node similarity. Data (reused): worm (40 animals, Cook wiring), fly (49 flies; rest/walk in 34; FlyWire), larval zebrafish (20 fish; swim/quiet in 12; mapZebrain), mouse fMRI (med+iso, isoflurane, awake; Knox tracer model) and human group DSI/fMRI. Method: we predicted the FC of held-out pairs in an independent replicate (other half of animals, or other hemisphere) with distance, additive node effects (M1) and a node-similarity term fitted to the other pairs of the same nodes (M2; nuclear-norm matrix completion). We compared real wiring with 30 strength- and distance-matched surrogates, split wiring into node-level and pair-specific parts, and calibrated with simulations. Results: M2 predicted most reliable FC (held-out R2 worm 0.09 to 0.75, fly 0.67 to 0.80, zebrafish 0.54 to 0.77, mouse 0.63 to 0.97; ceilings 0.88-0.99). Wiring added 0.003-0.12 after M1 (surrogates 0.000-0.002; p = 0.032, the minimum), but only -0.001 to 0.004 after M2, at most 3% of the reliable FC left. Fly, zebrafish and mouse wiring was mostly node-level (72-99% predictable from other edges). Worm wiring was mostly pair-specific and gave most of the worm gain after M1, but M2 absorbed it too (0.027 to 0.001). With synthetic wiring signals of the same size, M2 kept 6-32% (fly) and 11-25% (worm) of the gain; the real data kept -4% to 10% and 5%. The mouse state effect after M1 (med+iso 0.122, isoflurane 0.027, awake 0.022) was absent after M2 (-0.001 to 0.001) and followed a larger node-similarity gain under med+iso (0.34 vs 0.14, 0.10). Fly walk/rest and zebrafish swim/quiet did not differ. Limitations: wiring and activity from different animals; M2 is fitted to FC and can absorb wiring effects that spread to node profiles; the mouse wiring has almost no pair-specific structure, so mouse cannot test pair-specific wiring; mouse replicates share animals; reduced design (2 splits, 30 surrogates) because the host was overloaded.
References
22- uses, challengesShared input predicts functional coupling beyond direct wiring, distance and node effects in 40 worms, 49 flies and 79 anesthetized mice; the best polysynaptic measure is different in each animal
- uses, challengesIn fly, mouse and human data, surrogate wiring with matched node strengths and distances reproduced 48-100% of the FC gain of indirect-path measures; a large specific gain stayed only in sedated mouse
- supportsGeometric eigenmodes beat connectome eigenmodes for FC in fly, mouse and human but not in worm; simulated connectome-driven FC with spatial blur gives the same result
- In 48 freely moving C. elegans, smooth wiring eigenmodes held more head activity variance than rewired graphs, but not more than a distance-only graph with the same edge count
- FlyWire wiring predicts neuropil calcium correlations beyond distance in 50 flies; walking and rest coupling agree after global-signal removal; transmitter-matched wiring adds no gain
- Single-neuron axon co-innervation predicted spike correlations between 30 mouse cortical areas, but real collateral patterns did not predict better than source-matched shuffles at 100 ms
- In larval zebrafish, a single-neuron projectome predicts region-level trial-residual coupling beyond distance and region effects, but not stimulus-locked coupling (25 regions, 11 fish)
- usesMulti-step connectome communication measures add 0.4 to 1.9 percent of explained FC variance beyond direct wiring, distance and node effects in worm, fly, mouse, marmoset and human
- usesIn 20 larval zebrafish, mapZebrain wiring predicts region coupling beyond distance and region effects; near swim bouts all spatial structure of coupling increases
- supportsIn the same mice, the Allen tracer connectome predicts cortical resting fMRI beyond distance under medetomidine with isoflurane, but much less under isoflurane alone or awake
- In 40 freely moving C. elegans, gap junctions predict pairwise co-activity after controls for neurite contact, soma distance and per-neuron effects; chemical synapse weight does not
- In two human cohorts, a person's own diffusion connectome predicted that person's resting functional connectivity better than other connectomes, but the gain was only 2-5% of the coupling
- doi:10.1016/j.cell.2023.07.035
- doi:10.1038/s41586-019-1352-7
- doi:10.7554/eLife.85202
- doi:10.1038/s41586-024-07558-y
- doi:10.5281/zenodo.10676866
- doi:10.1016/j.neuroimage.2019.116278
- doi:10.34973/1he1-5c70
- doi:10.1162/netn_a_00066
- doi:10.5281/zenodo.2872624
- doi:10.5683/SP3/IIVGOB
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6 publications- In 40 moving C. elegans, 63% of reliable pair-specific co-activity was locked to six behaviour variables; wiring and transcriptomes explained about 10% of the behaviour-independent rest supports
- With equal white noise, fixed symmetric coupling can hide edge direction from FC in positive linear networks reviews
- Calibrated linear responses bound the hidden states needed to replace all direct observed links reviews
- Behaviour-locked covariance carried 71% of reliable pair-specific coactivity in 40 moving C. elegans and 47-52% in 22 larval zebrafish; wiring explained under 8% of the remainder
- Symmetric positive low-rank recurrence has an exact shared-input model with the same neural and behaviour laws reviews
- A finite observation schedule cannot bound coupling error in an unbounded linear oscillator model reviews