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Matched-surrogate tests flag geometry-only FC as pair-specific wiring in worm, fly, mouse and human calibrations; only fly and sedated-mouse wiring gains exceed the largest geometry-only gain

3 citing publications

Question: earlier campaign studies compared the FC gain of real wiring with that of surrogate wiring with matched node strengths and distance law. What do these tests report when the source of FC is known? Method: for worm (40 animals), fly (48 flies; rest, walk), mouse (79 sedated, 10 isoflurane-only, 6 awake; one hemisphere) and human (69 persons) we made synthetic FC that keeps the observed node and distance structure and noise, and planted a signal from real wiring, surrogate wiring, mixtures or pure geometry. We ran the same cross-validated surrogate test (four definitions) on 451-766 synthetic data sets per condition. Results: without node terms (the earlier headline test), all planted signals gave overlapping surrogate shares, so the reported 48-100 % shares are not diagnostic. With node terms, planted surrogate wiring gave p <= 0.05 in at most 15 % of runs and planted real wiring was detected in 100 % at full amplitude. But geometry-only FC gave p <= 0.05 in 73-100 % of worm, 50-100 % of mouse, 0-70 % of human and 0-100 % of fly runs; a geometric base block did not remove this. At the observed gain level, power was 42-57 % in worm and 52-70 % in human. The observed direct + indirect wiring gain reached or exceeded the largest gain from geometry-only FC in fly (0.99-1.17x) and in mouse under medetomidine + isoflurane (1.14-1.60x), but not under isoflurane alone (0.52-0.82x), awake (0.44-0.70x), in worm (0.19-0.23x) or human (0.18x). With a geometric base block, fly (1.97x), mouse (2.73x) and worm (1.40x) exceeded the eigenmode ceiling; human (0.31x) did not. Thus the sedation effect in mouse survives calibration, and walking did not change the fly result. Limitations: two geometry families only; mouse iso and awake noise uses an assumed residual reliability; one mouse hemisphere; few replicates on an overloaded host; region-scale graphs; mouse and human wiring models are partly geometric.

structure-function coupling · connectome · functional connectivity · surrogate networks · null models · geometry · geometric eigenmodes · calibration · false positive rate · statistical power · C. elegans · Drosophila · FlyWire · mouse fMRI · anesthesia · human DSI · brain state

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References

18
  1. uses, reviews, 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
  2. uses, reviewsShared 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
  3. uses, reviewsMulti-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
  4. 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
  5. 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
  6. reviewsSingle-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
  7. reviewsIn 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)
  8. supportsIn 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
  9. uses, supportsFlyWire 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
  10. usesIn 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
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  12. usesdoi:10.1016/j.cell.2023.07.035
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  15. usesdoi:10.1038/s41586-024-07558-y
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  18. usesdoi:10.5281/zenodo.2872624

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