Comparative mapping of functional and structural homologies in the pig and human brain

Comparative mapping of functional and structural homologies across humans, small animals, and nonhuman primates has been extensively pursued due to its strong translational relevance. However, these experimental models possess inherent limitations in fully recapitulating the complexity of human cortical organization. The porcine model has recently emerged as a promising alternative, given its neuroanatomical and physiological similarities to the human brain.

Despite these advantages, systematic cross-species characterization of functional and structural homologies between humans and pigs remains largely understudied. In the present study, we acquired resting-state functional MRI and diffusion MRI data from pigs and analyzed them alongside corresponding human datasets to investigate cross-species correspondence in large-scale brain organization. First, to enhance functional network alignment across species, group independent component analysis was performed separately within each species to identify intrinsic large-scale functional networks.

Our results demonstrated that multiple canonical human resting-state networks are represented in the porcine brain, including sensorimotor, default mode, cerebellar, frontal, and central executive networks. Moreover, we observed significant cross-species concordance in intrinsic functional architecture across multiple distributed networks, both in spatial distribution and temporal patterns, indicating homologous large-scale brain organization between pigs and humans. Second, we conducted comparative structural analyses using diffusion MRI-based fiber tractography, color-encoded fractional anisotropy maps, and structural connectivity analyses to examine and compare white matter organization in pigs and humans.

Cross-species comparison revealed substantial similarities in major white matter pathways and their spatial organization, supporting structural correspondence at the level of tract geometry. Together, these findings underscore the translational value of the porcine model as a robust and neurobiologically relevant platform for investigating human brain function, structural organization, and related neurological disorders. This work was supported by the National Science Foundation (Grant 2112455), the National Institutes of Health (Grants R01MH123610 and R01MH119251 to V.

Calhoun), and the National Institutes of Health, National Institute of Neurological Disorders and Stroke (Grants 1R21NS131526 and 1R21NS123732 to E. These authors contributed equally: Qun Zhao, Vince D. Tri-Institutional Center for Translational Research in Neuroimaging and Data Science, Georgia State University, Georgia Institute of Technology, Emory University, Atlanta, GA, USA Department of Physics and Astronomy, University of Georgia, Athens, GA, USA Ishfaque Ahmed, Morgan H.

Laballe & Qun Zhao Bio-Imaging Research Center, University of Georgia, Athens, GA, USA Department of Animal and Dairy Sciences, University of Georgia, Athens, GA, USA Moria F. West Regenerative Bioscience Center, University of Georgia, Athens, GA, USA Biomedical and Translational Sciences Institute, University of Georgia, Athens, GA, USA Neuroscience Institute, Georgia State University, Atlanta, GA, USA School of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA, USA Departments of Neurology and Pediatrics, Emory University, Atlanta, GA, USA Correspondence to Qiang Li, Qun Zhao or Vince D. The authors declare no competing interests.