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White matter and latency of visual evoked potentials during maturation: A miniature pig model of adolescent
Peter Kochunov1, L Elliot Hong2, Ann Summerfelt3
1Faillace Department of Psychiatry and Behavioral Sciences at McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA; Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
Insights
Adolescent brain development in minipigs shows myelination correlating with cognitive maturation. This research validates minipigs as a model for studying brain development and psychiatric disorders.
Area of Science:
- Neuroscience
- Developmental Biology
- Comparative Medicine
Background:
- Adolescent brain development, particularly white matter myelination, is critical for cognitive function and is implicated in neuropsychiatric disorders.
- Miniature pigs offer a gyrencephalic brain and a distinct adolescent period, making them a suitable model for studying brain development.
Purpose of the Study:
- To establish and validate a miniature-pig model for adolescent brain development research.
- To assess white matter maturation using neuroimaging and neurophysiological techniques during adolescence.
Main Methods:
- Eight minipigs underwent repeated assessments between weeks 14-28 of adolescence.
- Flash visual evoked potentials (fVEPs) and diffusion MRI (dMRI) were used to evaluate white matter maturation.
- Key fVEP components (PP30, P30, N50, IL) and dMRI metrics (FA, KA, AWF, PDI) were recorded.
Main Results:
- A significant reduction in fVEP latency and interhemispheric latency (IL) was observed.
- These electrophysiological changes paralleled significant increases in fractional anisotropy (FA), kurtosis anisotropy (KA), axonal water fraction (AWF), and permeability-diffusivity index (PDI).
- fVEP latency changes correlated with whole-brain diffusion parameters, while IL changes related to corpus callosum maturation.
Conclusions:
- The correlation between reduced fVEP latency and increased diffusion parameters supports ongoing myelination in the minipig model.
- The study confirms the miniature pig as a viable research platform for adolescent brain development studies.
- Human neuroimaging and neurophysiological protocols can be applied to minipigs for investigating neurodevelopmental hypotheses in psychiatry.
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.
