Tracer-based structure-function coupling does not decrease along the anatomical hierarchy in marmoset and mouse cortex; distance explains the human tractography coupling gradient

Human tractography studies report that structure-function coupling decreases from sensory to association cortex. We tested this with tracer connectomes and removed the distance effect. For each cortical area, we calculated the rank partial correlation between resting FC and tracer input weight after a spline of centroid distance. Marmoset: 55 injected areas (Marmoset Brain Connectivity Atlas), awake fMRI of 31 animals. Mouse: 36 areas (Knox model of Allen tracer data), Grandjean 2020 fMRI of 79 mice under medetomidine with isoflurane, plus small awake and isoflurane sets. Tracer inputs predicted FC beyond distance (median partial r 0.40 in marmoset, 0.64 in mouse; 96% and 92% of areas positive). Coupling did not decrease along the anatomical hierarchy from laminar tracer data (marmoset SLN levels rho = 0.06, spatial-null p = 0.76; mouse Harris 2019 score rho = 0.08, p = 0.85; at 141 mouse parcels rho = +0.25). Along FC gradient 1, marmoset coupling decreased (rho = -0.53, p = 0.003), but this gradient separates visual from auditory and frontal areas and correlates weakly with the SLN hierarchy (rho = 0.35); in mouse the sign changed with preprocessing and state. We then re-analysed the published human result (Vazquez-Rodriguez 2019, 1000 Lausanne nodes). Our regional R2 (distance, path length, communicability) matched the published R2 (rho = 0.77) and decreased along the published gradient (rho = -0.39, p = 0.01). Distance alone gave the same decrease (rho = -0.52, p = 0.002). The network gain beyond distance did not decrease (rho = +0.13, p = 0.30). In 69 persons at 219 nodes the result was the same. Limitations: coupling is correlational; distance removal can remove true structural effect; marmoset structure covers only injected areas; mouse structure is a model; the awake mouse set has 6 animals; no macaque fMRI; the human reproduction is not exact.

structure-function coupling · tract tracing · cortical hierarchy · resting-state fMRI · marmoset · mouse · human connectome · distance · FC gradient · laminar hierarchy · spatial autocorrelation null · Knox connectome