Nazeri Arash, Chakravarty M Mallar, Rotenberg David J, Rajji Tarek K, Rathi Yogesh, Michailovich Oleg V, Voineskos Aristotle N
Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8.
Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada M5T 1R8, Cerebral Imaging Centre, Douglas Institute, Verdun, Quebec, Canada H4H 1R3, Departments of Psychiatry and Biomedical Engineering, McGill University, Montreal, Quebec, Canada H3A 2B4.
J Neurosci. 2015 Jan 28;35(4):1753-62. doi: 10.1523/JNEUROSCI.3979-14.2015.
As humans age, a characteristic pattern of widespread neocortical dendritic disruption coupled with compensatory effects in hippocampus and other subcortical structures is shown in postmortem investigations. It is now possible to address age-related effects on gray matter (GM) neuritic organization and density in humans using multishell diffusion-weighted MRI and the neurite-orientation dispersion and density imaging (NODDI) model. In 45 healthy individuals across the adult lifespan (21-84 years), we used a multishell diffusion imaging and the NODDI model to assess the intraneurite volume fraction and neurite orientation-dispersion index (ODI) in GM tissues. We also determined the functional correlates of variations in GM microstructure by obtaining resting-state fMRI and behavioral data. We found a significant age-related deficit in neocortical ODI (most prominently in frontoparietal regions), whereas increased ODI was observed in hippocampus and cerebellum with advancing age. Neocortical ODI outperformed cortical thickness and white matter fractional anisotropy for the prediction of chronological age in the same individuals. Higher GM ODI sampled from resting-state networks with known age-related susceptibility (default mode and visual association networks) was associated with increased functional connectivity of these networks, whereas the task-positive networks tended to show no association or even decreased connectivity. Frontal pole ODI mediated the negative relationship of age with executive function, whereas hippocampal ODI mediated the positive relationship of age with executive function. Our in vivo findings align very closely with the postmortem data and provide evidence for vulnerability and compensatory neural mechanisms of aging in GM microstructure that have functional and cognitive impact in vivo.
在尸检研究中发现，随着人类年龄增长，新皮质广泛出现树突破坏的特征性模式，并伴有海马体和其他皮质下结构的代偿效应。现在，利用多壳层扩散加权磁共振成像（MRI）和神经突方向离散度与密度成像（NODDI）模型，能够研究年龄对人类灰质（GM）神经组织和密度的影响。在45名年龄跨度为成年期（21 - 84岁）的健康个体中，我们使用多壳层扩散成像和NODDI模型评估GM组织中的神经突内体积分数和神经突方向离散度指数（ODI）。我们还通过获取静息态功能磁共振成像（fMRI）和行为数据，确定了GM微观结构变化的功能相关性。我们发现新皮质ODI存在显著的年龄相关缺陷（最明显的是在额顶叶区域），而随着年龄增长，海马体和小脑中的ODI增加。在预测同一批个体的实际年龄方面，新皮质ODI比皮质厚度和白质分数各向异性表现更优。从具有已知年龄相关易感性的静息态网络（默认模式和视觉联合网络）中采样得到的较高GM ODI，与这些网络功能连接性增加相关，而任务阳性网络则倾向于无关联甚至连接性降低。额极ODI介导了年龄与执行功能的负相关关系，而海马体ODI介导了年龄与执行功能的正相关关系。我们的活体研究结果与尸检数据非常吻合，为GM微观结构老化的易损性和代偿性神经机制提供了证据，这些机制在活体中具有功能和认知影响。
