Douaud Gwenaëlle, Groves Adrian R, Tamnes Christian K, Westlye Lars Tjelta, Duff Eugene P, Engvig Andreas, Walhovd Kristine B, James Anthony, Gass Achim, Monsch Andreas U, Matthews Paul M, Fjell Anders M, Smith Stephen M, Johansen-Berg Heidi
Functional Magnetic Resonance Imaging of the Brain (FMRIB) Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom;
Research Group for Life-Span Changes in Brain and Cognition, Department of Psychology and.
Proc Natl Acad Sci U S A. 2014 Dec 9;111(49):17648-53. doi: 10.1073/pnas.1410378111. Epub 2014 Nov 24.
Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8-85 y) reveals a largely--but not only--transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer's disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer's disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer's disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.
有几种理论将人类的发育和衰老过程联系起来。例如,在神经科学领域,一种模型假定,与年龄相关的健康大脑退化反映了发育过程,即大脑中被认为较晚发育的区域也会较早退化。然而,大脑结构中健康衰老与发育之间这种联系的内在证据仍然难以捉摸。在这里,我们表明,对484名健康参与者(8至85岁)的大脑结构变异进行数据驱动分析,揭示了一个主要(但并非唯一)跨模态网络,其与年龄相关变化的寿命模式从本质上支持了这种反映发育和衰老的模型。我们进一步证明,这个大脑区域网络在青春期发育相对较晚,与大脑其他部分相比,在老年时显示出加速退化,它表征了对不健康发育和衰老过程易感性较高的区域,分别以精神分裂症和阿尔茨海默病为例。具体而言,这个网络虽然仅来自健康受试者,但在空间上重现了精神分裂症和阿尔茨海默病中观察到的大脑异常模式。在我们的大规模健康人群中,这个网络还与智力和情景记忆相关,而智力和情景记忆的损害是精神分裂症和阿尔茨海默病的关键症状。综上所述,我们的结果表明,在生命谱两端出现的这两种疾病中观察到的异常共同空间模式,可能受到它们各自不同病理过程在分别破坏健康大脑发育和衰老时的时间安排的影响。