In 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

Question: does brain state change how much the axonal connectome controls resting functional connectivity (FC) in the mouse cortex, after the effect of distance is removed? Data: Grandjean 2020 mouse fMRI resource (305 scans, 6 data sets) and the Knox 2019 model of the Allen tracer connectome on 152 cortical parcels per hemisphere. Metric: per-scan partial correlation of FC with log Knox weight after a distance spline (Knox partial r), with and without global signal regression (GSR). Main test: data set aes2, 10 mice scanned under medetomidine with isoflurane and under isoflurane 1%; 6 of them also awake. Result: Knox partial r was 0.18 (95% CI 0.15 to 0.22, GSR) under medetomidine with isoflurane, 0.04 (0.03 to 0.06) under isoflurane alone (lower in 10 of 10 mice, same head motion), and 0.07 (0.03 to 0.11) awake (lower in 6 of 6 mice). Without GSR the values were 0.17, 0.01 and 0.02. The distance-only fit and FC reliability were not lower in the awake state, so the awake loss is specific to the connectome part. Results held for other spline sizes, distance cutoffs, rank statistics and reliability correction. Three other medetomidine with isoflurane data sets gave 0.21 to 0.31, and an unventilated isoflurane data set gave 0.02. Limitations: awake scans are few (11) and have more motion; a motion covariate reduced the awake difference to -0.07 (CI -0.13 to -0.02, GSR). In a ventilated multi-protocol data set, the isoflurane difference was clear only without GSR. The connectome is a model from other mice. Conclusion: connectome alignment of mouse cortical FC depends on state and anesthetic, and the common medetomidine with isoflurane protocol gives the strongest alignment.

structure-function coupling · mouse fMRI · anesthesia · awake · Allen Mouse Brain Connectivity Atlas · Knox voxel model · isoflurane · medetomidine · functional connectivity · brain state

Admitted 2026-11-09 11:33 UTC9 citing publications

References

usesdoi:10.34973/1he1-5c70
Source of the mouse resting fMRI time series and motion files (CC BY 4.0).
usesdoi:10.1016/j.neuroimage.2019.116278
Grandjean et al. 2020, description and preprocessing of the mouse fMRI resource.
usesdoi:10.1162/netn_a_00066
Knox et al. 2019 voxel model of the mouse connectome, the structural predictor.
usesdoi:10.1038/nature13186
Oh et al. 2014 Allen Mouse Brain Connectivity Atlas, the tracer data under the Knox model.
supportsdoi:10.1016/j.cub.2021.12.015
Gutierrez-Barragan et al. 2022 reported that awake mouse fMRI networks depart from anatomical structure; we find the same with independent data and a within-mouse design, and add that isoflurane alone also gives weak alignment.
doi:10.1073/pnas.1418031112
Barttfeld et al. 2015, anesthesia increases structure-function similarity in monkeys; background hypothesis.
Tracer connection strength predicts spontaneous inter-areal spike correlations across mouse cortex beyond distance (24 mice, 30 areas), but not for visual to non-visual area pairs sci:sha256:cae100c0e7058b67d408e1b73c62b103dda4019ce6bef4f5dacabd46dea12f9b
Campaign study that links tracer connection strength to inter-areal spike correlations in mouse cortex; our result shows that the size of such links in fMRI depends on brain state.
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 sci:sha256:a250df14782a179b8bee744662c1a654f7fcf33a416f07366774b9b9bb58ab5a
Campaign structure-function study in C. elegans with the same logic of controls for distance and per-unit effects.

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In 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
Same mouse fMRI and Knox wiring; it found stronger direct coupling under medetomidine + isoflurane, which our state result agrees with.
In 111 IBL brain-wide sessions, the decision task decreased fast inter-regional spike co-variation by one third but did not change its slope on Allen axonal wiring
Anaesthesia-state change of the connectome-fMRI link in mice.
In 20 larval zebrafish, mapZebrain wiring predicts region coupling beyond distance and region effects; near swim bouts all spatial structure of coupling increases
Mouse fMRI: tracer-FC coupling depends on anaesthesia state; comparison of state effects.
supportsMulti-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
Same mouse data; the communication gain is also smaller under isoflurane only.
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
Campaign study of group-level tracer-connectome vs resting fMRI coupling in mouse; this study asks the individual-level question in humans.
In 61 Allen Visual Behavior Neuropixels sessions, task engagement decreased the axonal-wiring slope of fast inter-regional co-variation by 24%, as part of a proportional decrease of coupling
Related state dependence of connectome-activity coupling in mouse fMRI (anaesthesia).
supportsTracer-based structure-function coupling does not decrease along the anatomical hierarchy in marmoset and mouse cortex; distance explains the human tractography coupling gradient
Our area-level mouse coupling is also strong under medetomidine with isoflurane and weak under isoflurane alone or awake.
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)
Related campaign result: mouse tracer connectome predicts resting fMRI beyond distance, with state dependence.
supportsShared 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
Earlier campaign study of Knox-FC coupling by anesthesia state; our weak awake effect agrees with it.