That’ll do pig, that’ll do. A common space approach to comparative neuroimaging extends the translational niche of the pig in euroscience

Abstract

The translation of preclinical findings into novel therapeutics is a process underwritten by evolutionary conservation. The conservation of structure and function across organ systems in the mammalian lineage has enabled findings to move from the bench to bedside, changing the modern medical practice. While the function of the cerebral cortex is conserved when viewed from this evolutionary perspective, the selective pressures which shape how a species fills its ecological niche also shape its cerebral cortex. Nevertheless, animal models have significantly contributed to our current knowledge of cortical function and structure. However, the time and cost-intensive methods used in classical neuroscience have limited the animal models available in neuroscience as compared to other biomedical research fields. Animal disease models may only emulate part of the natural human pathology, and some species are more apt at modeling specific aspects of disease than others. We call this the translational niche, and note it dependent on both the physiology and research methods available in a species. In the cerebral cortex, this role has been primarily left to rodents and non-human primates, as their cerebral cortex has been sufficiently studied to have identified common trends of cortical organization. These trends are used to interpret and contextualization the results found in each model, enabling them to produce findings relevant to clinical translation. To expand the experimental repertoire of available animal models capable of providing translational inference in neuroscience, we ask if Magnetic Resonance Imaging (MRI) can make up for lost ground and extend the translational niche of an animal already widely used in biomedical research; the domestic pig (sus scrofa). The pig has a long history of use in biomedical research, given its large body size, gyrencephalic brain, and similar metabolism. However, the availability of measures to characterize its cerebral cortex and knowledge of its cortical organization remain limited as compared to rodents and non-human primates. To overcome these limitations, we use anatomical, diffusion-weighted (DWI), and resting-state functional MRI (rs-fMRI) to build a common space capable of identifying conserved trends of cortical organization between the pig and human. In doing so, we first build the necessary tools to characterize the pig’s intrinsic cortical organization. We first identify 27 tracts similar and use these tracts to create a common space for horizontal translation between the pig and human. Having found sufficient conservation of the structural connectome to compare the pig and human, we ask if these findings extend to other modalities such as rsfMRI. Doing so, we find a common parcellation scheme of 9 pig resting-state networks with comparable structural connectivity and similar roles to their human counterparts within the pig’s macroscale cortical gradients. Leveraging these shared trends of cortical organization, we create a second common space between the pig and human that permitted us to quantitatively measure conserved cortical organization between the pig and human. This is only the beginning of expanding the pig’s translational niche in neuroscience. However, as the tools used to characterize the functional and structural connectome of the pig have been made using software that is easily adaptable to other species, we hope our work serves as a roadmap on how MRI can extend the translational niche of lesser studied animal models in neuroscience