Molecular and cellular correlates of human cortical lateralization

Hemispheric specialization is a fundamental feature of human brain organization, with most individuals showing left hemisphere dominance for language and right hemisphere dominance for visuospatial attention. Although lateralized functions exist in other species, humans exhibit a pronounced, species-wide bias. Despite its evolutionary and functional significance, the molecular and cellular basis of this asymmetry remains unclear. Here, we identify neurochemical and cellular features associated with cortical lateralization. We show lateralized gradients in neurotransmitter receptor densities along the multimodal monoaminergic-cholinergic axis, alongside asymmetries in mitochondrial distribution and the prevalence of microglia and glutamatergic excitatory neurons. Integrating in vivo PET with post-mortem transcriptomic and cellular data, we delineate two cortical clusters: a left-lateralized language-related network and a right-lateralized visuospatial-related network. These findings reveal a biological substrate for lateralized cognition, with implications for evolution and neuropsychiatric disorders involving disrupted lateralization. Multimodal analyses reveal the molecular and cellular asymmetries underlying human cortical lateralization. Distinct neurotransmitter, mitochondrial, and cellular gradients support left-lateralized language and right-lateralized attention networks.