Hu Kun, Van Someren Eus J W, Shea Steven A, Scheer Frank A J L
Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2490-4. doi: 10.1073/pnas.0806087106. Epub 2009 Feb 6.
Human motor control systems orchestrate complex scale-invariant patterns of activity over a wide range of time scales (minutes to hours). The neural mechanisms underlying scale-invariance are unknown in humans. In rats, the master circadian pacemaker [suprachiasmatic nucleus (SCN)] is crucially involved in scale-invariant activity fluctuations over multiple time scales from minutes to 24 h. Aging and Alzheimer's disease (AD) are associated with progressive dysfunction of the SCN. Thus, if the SCN is responsible for the scale-invariant activity fluctuations in humans, we predict disturbances of scale-invariant activity fluctuations in elderly humans and even more pronounced disturbances in elderly humans with AD. To test these hypotheses, we studied spontaneous daytime activity patterns in 13 young adults (mean +/- SD: 25.5 +/- 6.1 y); 13 elderly people with early-stage AD (68.5 +/- 6.1 y) matched with 13 elderly controls (68.6 +/- 6.1 y); and 14 very old people with late-stage AD (83.9 +/- 6.7 y) matched with 12 very old controls (80.8 +/- 8.6 y). In young adults, activity exhibited robust scale-invariant correlations across all tested time scales (minutes to 8 h). The scale-invariant correlations at 1.5-8 h declined with age (P = 0.01) and were significantly reduced in the elderly (P = 0.04) and very old controls (P = 0.02). Remarkably, an age-independent AD effect further reduced the scale-invariant correlations at 1.5-8 h (P = 0.04), leading to the greatest reduction of the scale-invariant correlations in very old people with late-stage AD-resembling closely the loss of correlations at large time scales in SCN-lesioned animals. Thus, aging and AD significantly attenuate the scale invariance of activity fluctuations over multiple time scales. This attenuation may reflect functional changes of the SCN.
人类运动控制系统在广泛的时间尺度（从几分钟到几小时）上协调复杂的尺度不变活动模式。人类中尺度不变性背后的神经机制尚不清楚。在大鼠中，主昼夜节律起搏器[视交叉上核（SCN）]在从几分钟到24小时的多个时间尺度上的尺度不变活动波动中起着关键作用。衰老和阿尔茨海默病（AD）与SCN的进行性功能障碍有关。因此，如果SCN负责人类的尺度不变活动波动，我们预测老年人中尺度不变活动波动会受到干扰，而患有AD的老年人中这种干扰会更加明显。为了验证这些假设，我们研究了13名年轻成年人（平均±标准差：25.5±6.1岁）、13名患有早期AD的老年人（68.5±6.1岁，与13名老年对照者（68.6±6.1岁）匹配）以及14名患有晚期AD的非常老年人（83.9±6.7岁，与12名非常老年对照者（80.8±8.6岁）匹配）的白天自发活动模式。在年轻成年人中，活动在所有测试的时间尺度（从几分钟到8小时）上表现出强大的尺度不变相关性。1.5 - 8小时的尺度不变相关性随年龄下降（P = 0.01），在老年人（P = 0.04）和非常老年对照者（P = 0.02）中显著降低。值得注意的是，与年龄无关的AD效应进一步降低了1.5 - 8小时的尺度不变相关性（P = 0.04），导致患有晚期AD的非常老年人中尺度不变相关性的最大降低，这与SCN损伤动物在大时间尺度上相关性的丧失非常相似。因此，衰老和AD显著减弱了多个时间尺度上活动波动的尺度不变性。这种减弱可能反映了SCN的功能变化。
