Neurite density but not myelination of specific fiber tracts links polygenic scores to general intelligence.

White matter is fundamental for efficient information transfer and thus crucial for intelligence. Previous studies demonstrated associations between fractional anisotropy and intelligence, but it remains unclear whether this relation is due to greater axon density, parallel, homogenous fiber orientation distributions, or greater myelination, as all influence fractional anisotropy. Using neurite orientation dispersion and density imaging and myelin water fraction imaging, we analyzed the microstructural architecture of intelligence in 500 healthy young adults. We were also interested whether specific white matter indices mediate the pathway linking genetic disposition for intelligence to phenotype. For the first time, we conducted mediation analyses investigating whether neurite density index, orientation dispersion index, and myelin water fraction of 64 white matter tracts mediate the effects of polygenic scores for intelligence on general intelligence (g). Our results showed that neurite density index, but not orientation dispersion index or myelin water fraction of white matter tracts, was significantly associated with g and that neurite density index of six fiber tracts mediated the relation between genetic variability and g. These findings are a crucial step toward decoding the neurogenetic underpinnings of general intelligence, as they identify that neurite density of specific fiber tracts relates polygenic variation to g, whereas orientation dispersion and myelination did not.