Department of Psychiatry, University of Wisconsin-Madison, 6001 Research Park Boulevard, Madison, WI 53719, United States.
Department of Medical Physics, University of Wisconsin-Madison, 1111 Highland Avenue, Madison, WI 53705, United States.
Neuroimage. 2021 May 1;231:117825. doi: 10.1016/j.neuroimage.2021.117825. Epub 2021 Feb 5.
White matter (WM) development early in life is a critical component of brain development that facilitates the coordinated function of neuronal pathways. Additionally, alterations in WM have been implicated in various neurodevelopmental disorders, including psychiatric disorders. Because of the need to understand WM development in the weeks immediately following birth, we characterized changes in WM microstructure throughout the postnatal macaque brain during the first year of life. This is a period in primates during which genetic, developmental, and environmental factors may have long-lasting impacts on WM microstructure. Studies in nonhuman primates (NHPs) are particularly valuable as a model for understanding human brain development because of their evolutionary relatedness to humans. Here, 34 rhesus monkeys (23 females, 11 males) were imaged longitudinally at 3, 7, 13, 25, and 53 weeks of age with T1-weighted (MPnRAGE) and diffusion tensor imaging (DTI). With linear mixed-effects (LME) modeling, we demonstrated robust logarithmic growth in FA, MD, and RD trajectories extracted from 18 WM tracts across the brain. Estimated rate of change curves for FA, MD, and RD exhibited an initial 10-week period of exceedingly rapid WM development, followed by a precipitous decline in growth rates. K-means clustering of raw DTI trajectories and rank ordering of LME model parameters revealed distinct posterior-to-anterior and medial-to-lateral gradients in WM maturation. Finally, we found that individual differences in WM microstructure assessed at 3 weeks of age were significantly related to those at 1 year of age. This study provides a quantitative characterization of very early WM growth in NHPs and lays the foundation for future work focused on the impact of alterations in early WM developmental trajectories in relation to human psychopathology.
脑白质（WM）的早期发育是大脑发育的关键组成部分，有助于神经元通路的协调功能。此外，WM 的改变与各种神经发育障碍有关，包括精神障碍。由于需要了解出生后数周内 WM 的发育情况，我们在灵长类动物生命的第一年期间，描述了 WM 微观结构在整个新生猕猴大脑中的变化。这是灵长类动物的一个时期，在这个时期，遗传、发育和环境因素可能对 WM 微观结构产生持久的影响。非人类灵长类动物（NHPs）的研究特别有价值，因为它们与人类在进化上的亲缘关系，是理解人类大脑发育的模型。在这里，34 只恒河猴（23 只雌性，11 只雄性）在 3、7、13、25 和 53 周龄时进行了 T1 加权（MPnRAGE）和弥散张量成像（DTI）的纵向成像。通过线性混合效应（LME）建模，我们证明了 FA、MD 和 RD 轨迹的对数增长，这些轨迹是从大脑中 18 个 WM 束中提取出来的。FA、MD 和 RD 的估计变化率曲线表现出最初的 10 周快速 WM 发育期，然后生长速度急剧下降。原始 DTI 轨迹的 K-均值聚类和 LME 模型参数的等级排序显示出 WM 成熟的明显后向前和内向外梯度。最后，我们发现 3 周龄时 WM 微观结构的个体差异与 1 岁时的差异显著相关。这项研究提供了 NHPs 中非常早期 WM 生长的定量特征，并为未来专注于早期 WM 发育轨迹改变与人类精神病理学之间关系的工作奠定了基础。
