Faillace 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.
Faillace Department of Psychiatry and Behavioral Sciences at McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
J Neurosci Methods. 2024 Nov;411:110252. doi: 10.1016/j.jneumeth.2024.110252. Epub 2024 Aug 17.
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.
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/mm) 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).
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.
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.
大脑白质（WM）在青春期的持续髓鞘化与高级认知技能的形成和许多神经精神疾病的发病有关。我们开发了一种小型猪的青春期脑发育模型，用于在这个关键时期进行神经影像学和神经生理学评估。小型猪的大脑具有回旋脑结构，具有较大的大脑 WM 隔室和明确的青春期。
8 头 Sinclair™小型猪（Sus scrofa domestica）在青春期的第 14-28 周（40、28 和 28 天）期间进行了 4 次评估，使用单眼视觉刺激（1 Hz）诱发的脑电和 WM 的扩散 MRI（dMRI）。在每个眼的 10 次 60 秒刺激中，记录了闪光视觉诱发电位（fVEP）的前正 30 毫秒（PP30）、正 30 毫秒（P30）和负 50 毫秒（N50）成分的潜伏期及其半球间潜伏期（IL），在前额、中央和枕区。dMRI 成像方案包括 15 个 b-壳（b = 0-3500 s/mm），每个壳有 32 个方向，提供了包括各向异性分数（FA）、径向峰度、峰度各向异性（KA）、轴突水分数（AWF）和通透性扩散指数（PDI）在内的测量结果。
在同一时期，fVEP 测量的潜伏期和 IL 显著降低（p < 0.05），同时 FA、KA、AWF 和 PDI 显著升高。fVEPs 的纵向潜伏期变化主要与整个大脑扩散参数的变化有关，而 fVEP IL 的变化与胼胝体的成熟有关。
fVEPs 的潜伏期降低与大脑 WM 的成熟之间的良好一致性被解释为髓鞘化持续进行的证据，并证实小型猪是一种可行的研究平台。可以使用人类神经影像学和神经生理学方案研究小型猪的青春期发育，并进行更具侵袭性的检测，以研究神经精神疾病中的关键神经发育假说。
