Conole, E. L. S. | bioRxiv Science

bioRxiv2026

General cognitive function and the brain's structural connectome

General cognitive function ( g) reflects a broad capacity for flexible information processing, yet how brain-wide structural connectivity supports it remains unclear. In 38,824 individuals (26-84 years) across three cohorts, we show that g is supported by a widely distributed white matter network. Across streamline count, fractional anisotropy (FA), and mean diffusivity (MD), meta-analytic associations with g were widespread at global, nodal and edge levels, spanning all cerebral lobes and key subcortical structures and dependent on both inter- and intra-hemispheric connectivity, particularly ipsilateral long-range inter-lobar connections. White matter node-g associations spatially mirrored independent cortical morphometry-g associations, indicating convergence of grey and white matter contributions. Effect sizes increased with age: MD associations became more negative and FA more positive, especially in frontal regions. Edge-level findings replicated across cohorts and predicted g in a hold-out sample. These findings suggest g reflects a distributed structural communication backbone which becomes increasingly important with age.

neuroscience↗

bioRxiv2024

Brain maps of general cognitive function and spatial correlations with neurobiological cortical profiles

In this paper, we attempt to answer two questions: 1) which regions of the human brain, in terms of morphometry, are most strongly related to individual differences in domain-general cognitive functioning (g)? and 2) what are the underlying neurobiological properties of those regions? We meta-analyse vertex-wise g-cortical morphometry (volume, surface area, thickness, curvature and sulcal depth) associations using data from 3 cohorts: the UK Biobank (UKB), Generation Scotland (GenScot), and the Lothian Birth Cohort 1936 (LBC1936), with the meta-analytic N = 38,379 (age range = 44 to 84 years old). These g-morphometry associations vary in magnitude and direction across the cortex (|{beta}| range = -0.12 to 0.17 across morphometry measures) and show good cross-cohort agreement (mean spatial correlation r = 0.57, SD = 0.18). Then, to address (2), we bring together existing -and derive new -cortical maps of 33 neurobiological characteristics from multiple modalities (including neurotransmitter receptor densities, gene expression, functional connectivity, metabolism, and cytoarchitectural similarity). We discover that these 33 profiles spatially covary along four major dimensions of cortical organisation (accounting for 65.9% of the variance) and denote aspects of neurobiological scaffolding that underpin the spatial patterning of MRI-cognitive associations we observe (significant |r| range = 0.21 to 0.56). Alongside the cortical maps from these analyses, which we make openly accessible, we provide a compendium of cortex-wide and within-region spatial correlations among general and specific facets of brain cortical organisation and higher order cognitive functioning, which we hope will serve as a framework for analysing other aspects of behaviour-brain MRI associations.

neuroscience↗