Faculty, Staff and Student Publications
Publication Date
11-1-2024
Journal
Journal of Neuroscience Methods
Abstract
Background: Continuous myelination of cerebral white matter (WM) during adolescence overlaps with the formation of higher cognitive skills and the onset of many neuropsychiatric disorders. We developed a miniature-pig model of adolescent brain development for neuroimaging and neurophysiological assessment during this critical period. Minipigs have gyroencephalic brains with a large cerebral WM compartment and a well-defined adolescence period.
Methods: Eight Sinclair™ minipigs (Sus scrofa domestica) were evaluated four times during weeks 14-28 (40, 28 and 28 days apart) of adolescence using monocular visual stimulation (1 Hz)-evoked potentials and diffusion MRI (dMRI) of WM. The latency for the pre-positive 30 ms (PP30), positive 30 ms (P30) and negative 50 ms (N50) components of the flash visual evoked potentials (fVEPs) and their interhemispheric latency (IL) were recorded in the frontal, central and occipital areas during ten 60-second stimulations for each eye. The dMRI imaging protocol consisted of fifteen b-shells (b = 0-3500 s/mm2) with 32 directions/shell, providing measurements that included fractional anisotropy (FA), radial kurtosis, kurtosis anisotropy (KA), axonal water fraction (AWF), and the permeability-diffusivity index (PDI).
Results: Significant reductions (p < 0.05) in the latency and IL of fVEP measurements paralleled significant rises in FA, KA, AWF and PDI over the same period. The longitudinal latency changes in fVEPs were primarily associated with whole-brain changes in diffusion parameters, while fVEP IL changes were related to maturation of the corpus callosum.
Conclusions: Good agreement between reduction in the latency of fVEPs and maturation of cerebral WM was interpreted as evidence for ongoing myelination and confirmation of the minipig as a viable research platform. Adolescent development in minipigs can be studied using human neuroimaging and neurophysiological protocols and followed up with more invasive assays to investigate key neurodevelopmental hypotheses in psychiatry.
Keywords
Animals, Swine, Miniature, Evoked Potentials, Visual, Swine, White Matter, Diffusion Magnetic Resonance Imaging, Male, Female, Models, Animal, Photic Stimulation, Brain, Reaction Time, Diffusion weighted MRI, White matter, Miniature swine, Adolescent brain development, Visual pathways, Visual evoked components
DOI
10.1016/j.jneumeth.2024.110252
PMID
39159872
PMCID
PMC11983141
PubMedCentral® Posted Date
4-10-2025
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes