Glutamatergic signaling underlies brain structural organization for mathematical and reading abilities in children

The neurochemical mechanisms underlying individual differences in children's mathematical and reading abilities remain largely unknown. Here we investigate how neurotransmitter systems relate to brain structural organization supporting these abilities in two independent cohorts of children (N = 991). We mapped brain-wide structural phenotypes associated with academic performance onto a comprehensive PET atlas of 19 neurotransmitter receptors and transporters. Across both domains and cohorts, NMDA glutamatergic receptor distribution showed the most consistent associations with brain structural organization supporting academic abilities (replication Bayes factors >9e4 for mathematics; >4 for reading). NMDA receptor density corresponded with multiple functional networks for mathematical abilities but showed more spatially focused associations within visual networks for reading, suggesting both shared and domain-specific neurochemical mechanisms. Dopaminergic, cholinergic, serotonergic, and GABAergic systems showed weaker, non-replicable associations. These findings bridge molecular neurochemistry and macro-scale brain architecture supporting academic skills, identifying glutamatergic signaling as a candidate target for interventions addressing learning disabilities.