Department of Neurology, Washington University in Saint Louis, St. Louis, MO 63110, USA.
Department of Radiology, Washington University in Saint Louis, Box 8225, 660 South Euclid Ave, St. Louis, MO 63110, USA; Knight Alzheimer Disease Research Center, Washington University in St. Louis, St. Louis, MO 63110, USA; Department of Psychological & Brain Sciences, Washington University, St. Louis, MO, USA.
Neuroimage. 2022 Nov 1;261:119511. doi: 10.1016/j.neuroimage.2022.119511. Epub 2022 Jul 30.
Prior studies of aging and Alzheimer disease have evaluated resting state functional connectivity (FC) using either seed-based correlation (SBC) or independent component analysis (ICA), with a focus on particular functional systems. SBC and ICA both are insensitive to differences in signal amplitude. At the same time, accumulating evidence indicates that the amplitude of spontaneous BOLD signal fluctuations is physiologically meaningful. We systematically compared covariance-based FC, which is sensitive to amplitude, vs. correlation-based FC, which is not, in affected individuals and controls drawn from two cohorts of participants including autosomal dominant Alzheimer disease (ADAD), late onset Alzheimer disease (LOAD), and age-matched controls. Functional connectivity was computed over 222 regions of interest and group differences were evaluated in terms of components projected onto a space of lower dimension. Our principal observations are: (1) Aging is associated with global loss of resting state fMRI signal amplitude that is approximately uniform across resting state networks. (2) Thus, covariance FC measures decrease with age whereas correlation FC is relatively preserved in healthy aging. (3) In contrast, symptomatic ADAD and LOAD both lead to loss of spontaneous activity amplitude as well as severely degraded correlation structure. These results demonstrate a double dissociation between age vs. Alzheimer disease and the amplitude vs. correlation structure of resting state BOLD signals. Modeling results suggest that the AD-associated loss of correlation structure is attributable to a relative increase in the fraction of locally restricted as opposed to widely shared variance.
先前关于衰老和阿尔茨海默病的研究使用基于种子的相关（SBC）或独立成分分析（ICA）评估静息状态功能连接（FC），重点关注特定的功能系统。SBC 和 ICA 都对信号幅度差异不敏感。同时，越来越多的证据表明自发 BOLD 信号波动的幅度在生理上是有意义的。我们系统地比较了基于协方差的 FC，它对幅度敏感，而基于相关的 FC 则不敏感，受影响的个体和来自两个参与者队列的对照者，包括常染色体显性阿尔茨海默病（ADAD）、晚发性阿尔茨海默病（LOAD）和年龄匹配的对照者。功能连接是在 222 个感兴趣区域上计算的，并且以投影到低维空间的组件的方式评估组间差异。我们的主要观察结果是：（1）衰老与静息状态 fMRI 信号幅度的全局丧失有关，这种丧失在静息状态网络中大致均匀。（2）因此，协方差 FC 测量值随年龄而下降，而相关性 FC 在健康老化中相对保留。（3）相比之下，有症状的 ADAD 和 LOAD 都会导致自发活动幅度的丧失以及严重退化的相关结构。这些结果表明，年龄与阿尔茨海默病之间存在双重分离，以及静息状态 BOLD 信号的幅度与相关性结构之间的分离。模型结果表明，与 AD 相关的相关性结构丧失归因于局部限制的分数相对于广泛共享的方差的相对增加。
