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Peer-reviewedCC BY-NC-NDCommunications Biology

Molecular and cellular correlates of human cortical lateralization

  • Loïc Labache1,2
  • Alex Fornito3,4
  • Xi-Han Zhang5
  • Avram J. Holmes6
6 affiliations
  1. 1Department of Psychiatry, Brain Health Institute, Rutgers University, Piscataway, NJ, USA. [email protected]
  2. 2Department of Psychology, Yale University, New Haven, CT, USA. [email protected]
  3. 3Center for Youth Mental Health, University of Melbourne, Melbourne, VIC, Australia
  4. 4Orygen, Parkville, VIC, Australia
  5. 5Department of Psychology, Yale University, New Haven, CT, USA
  6. 6Department of Psychiatry, Brain Health Institute, Rutgers University, Piscataway, NJ, USA
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Abstract

Hemispheric specialization is a fundamental characteristic of human brain organization, where most individuals exhibit left-hemisphere dominance for language and right-hemisphere dominance for visuospatial attention. While some lateralized functions are evident in other species, the human brain displays a strong, species-wide bias. Despite the evolutionary and functional significance of these asymmetries, their molecular and cellular foundations remain poorly understood. Here, we identify key neurochemical and cellular asymmetries that underpin cortical lateralization. Specifically, we demonstrate lateralized gradients in neurotransmitter receptor densities, particularly along the multimodal monoaminergic-cholinergic axis, as well as asymmetries in mitochondrial distribution and the spatial prevalence of microglia and glutamatergic excitatory neurons. Using a multimodal approach that integrates in vivo functional MRI, PET imaging, and post-mortem transcriptomic and cellular data, we delineate two distinct cortical clusters: a left-lateralized network centered on language processing and a right-lateralized network supporting visuospatial attention. These results highlight a biologically embedded substrate for lateralized cognition that may inform both evolutionary theory and our mechanistic understanding of neuropsychiatric illnesses characterized by disrupted lateralization.

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Cite

BibTeXRIS
BibTeX
@article{labache2026molecular,
  title = {{Molecular and cellular correlates of human cortical lateralization}},
  author = {Loïc Labache and Alex Fornito and Xi-Han Zhang and Avram J. Holmes},
  journal = {Communications Biology},
  year = {2026},
  month = jun,
  doi = {10.1038/s42003-026-10508-1},
  url = {https://doi.org/10.1038/s42003-026-10508-1},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Molecular and cellular correlates of human cortical lateralization
AU  - Loïc Labache
AU  - Alex Fornito
AU  - Xi-Han Zhang
AU  - Avram J. Holmes
PY  - 2026
DA  - 2026/06/18
JO  - Communications Biology
DO  - 10.1038/s42003-026-10508-1
UR  - https://doi.org/10.1038/s42003-026-10508-1
AB  - Hemispheric specialization is a fundamental characteristic of human brain organization, where most individuals exhibit left-hemisphere dominance for language and right-hemisphere dominance for visuospatial attention. While some lateralized functions are evident in other species, the human brain displays a strong, species-wide bias. Despite the evolutionary and functional significance of these asymmetries, their molecular and cellular foundations remain poorly understood. Here, we identify key neurochemical and cellular asymmetries that underpin cortical lateralization. Specifically, we demonstrate lateralized gradients in neurotransmitter receptor densities, particularly along the multimodal monoaminergic-cholinergic axis, as well as asymmetries in mitochondrial distribution and the spatial prevalence of microglia and glutamatergic excitatory neurons. Using a multimodal approach that integrates in vivo functional MRI, PET imaging, and post-mortem transcriptomic and cellular data, we delineate two distinct cortical clusters: a left-lateralized network centered on language processing and a right-lateralized network supporting visuospatial attention. These results highlight a biologically embedded substrate for lateralized cognition that may inform both evolutionary theory and our mechanistic understanding of neuropsychiatric illnesses characterized by disrupted lateralization.
SN  - 2399-3642
ER  -