Mander Bryce A, Zhu Alyssa H, Lindquist John R, Villeneuve Sylvia, Rao Vikram, Lu Brandon, Saletin Jared M, Ancoli-Israel Sonia, Jagust William J, Walker Matthew P
Sleep and Neuroimaging Laboratory, Department of Psychology, University of California, Berkeley,
Department of Psychiatry and Human Behavior, University of California, Irvine, Orange, California 92868.
J Neurosci. 2017 Nov 29;37(48):11675-11687. doi: 10.1523/JNEUROSCI.3033-16.2017. Epub 2017 Oct 30.
Sleep spindles promote the consolidation of motor skill memory in young adults. Older adults, however, exhibit impoverished sleep-dependent motor memory consolidation. The underlying pathophysiological mechanism(s) explaining why motor memory consolidation in older adults fails to benefit from sleep remains unclear. Here, we demonstrate that male and female older adults show impoverished overnight motor skill memory consolidation relative to young adults, with the extent of impairment being associated with the degree of reduced frontal fast sleep spindle density. The magnitude of the loss of frontal fast sleep spindles in older adults was predicted by the degree of reduced white matter integrity throughout multiple white matter tracts known to connect subcortical and cortical brain regions. We further demonstrate that the structural integrity of selective white matter fiber tracts, specifically within right posterior corona radiata, right tapetum, and bilateral corpus callosum, statistically moderates whether sleep spindles promoted overnight consolidation of motor skill memory. Therefore, white matter integrity within tracts known to connect cortical sensorimotor control regions dictates the functional influence of sleep spindles on motor skill memory consolidation in the elderly. The deterioration of white matter fiber tracts associated with human brain aging thus appears to be one pathophysiological mechanism influencing subcortical-cortical propagation of sleep spindles and their related memory benefits. Numerous studies have shown that sleep spindle expression is reduced and sleep-dependent motor memory is impaired in older adults. However, the mechanisms underlying these alterations have remained unknown. The present study reveals that age-related degeneration of white matter within select fiber tracts is associated with reduced sleep spindles in older adults. We further demonstrate that, within these same fiber tracts, the degree of degeneration determines whether sleep spindles can promote motor memory consolidation. Therefore, white matter integrity in the human brain, more than age per se, determines the magnitude of decline in sleep spindles in later life and, with it, the success (or lack thereof) of sleep-dependent motor memory consolidation in older adults.
睡眠纺锤波促进年轻人运动技能记忆的巩固。然而，老年人睡眠依赖的运动记忆巩固能力较差。目前尚不清楚为何老年人的运动记忆巩固无法从睡眠中获益的潜在病理生理机制。在此，我们证明，相对于年轻人，老年男性和女性的夜间运动技能记忆巩固能力较差，损伤程度与额叶快速睡眠纺锤波密度降低的程度相关。老年人额叶快速睡眠纺锤波丧失的程度可通过连接皮层下和皮层脑区的多个白质束中白质完整性降低的程度来预测。我们进一步证明，选择性白质纤维束的结构完整性，特别是右侧放射冠后部、右侧毯状核和双侧胼胝体的结构完整性，在统计学上调节了睡眠纺锤波是否促进运动技能记忆的夜间巩固。因此，已知连接皮层感觉运动控制区域的白质束内的白质完整性决定了睡眠纺锤波对老年人运动技能记忆巩固的功能影响。与人类大脑衰老相关的白质纤维束的退化似乎是影响睡眠纺锤波皮层下 - 皮层传播及其相关记忆益处的一种病理生理机制。许多研究表明，老年人睡眠纺锤波表达减少，睡眠依赖的运动记忆受损。然而，这些改变的潜在机制尚不清楚。本研究表明，特定纤维束内与年龄相关的白质退化与老年人睡眠纺锤波减少有关。我们进一步证明，在这些相同的纤维束内，退化程度决定了睡眠纺锤波是否能够促进运动记忆巩固。因此，人类大脑中的白质完整性，而非年龄本身，决定了晚年睡眠纺锤波下降的幅度，以及老年人睡眠依赖的运动记忆巩固的成功与否（或反之）。
