Multimodal gradients of basal forebrain connectivity across the neocortex

Abstract

Cortical cholinergic projections originate from subregions of the basal forebrain (BF). To examine its organization in humans, we computed multimodal gradients of BF connectivity by combining 7 T diffusion and resting state functional MRI. Moving from anteromedial to posterolateral BF, we observe reduced tethering between structural and functional connectivity gradients, with the lowest tethering in the nucleus basalis of Meynert. In the neocortex, this gradient is expressed by progressively reduced tethering from unimodal sensory to transmodal cortex, with the lowest tethering in the midcingulo-insular network, and is also spatially correlated with the molecular concentration of VAChT, measured by [¹⁸F]fluoroethoxy-benzovesamicol (FEOBV) PET. In mice, viral tracing of BF cholinergic projections and [¹⁸F]FEOBV PET confirm a gradient of axonal arborization. Altogether, our findings reveal that BF cholinergic neurons vary in their branch complexity, with certain subpopulations exhibiting greater modularity and others greater diffusivity in the functional integration with their cortical targets.