Kavroulakis Eleftherios, Simos Nicholas J, Maris Thomas G, Zaganas Ioannis, Panagiotakis Simeon, Papadaki Efrosini
Department of Radiology, School of Medicine, University of Crete, University Hospital of Heraklion, Heraklion, Greece.
Department of Electrical and Computer Engineering, Technical University of Crete, Chania, Greece.
Front Neurol. 2021 Mar 23;12:633500. doi: 10.3389/fneur.2021.633500. eCollection 2021.
To assess age-related changes in intrinsic functional brain connectivity and hemodynamics during adulthood in the context of the retrogenesis hypothesis, which states that the rate of age-related changes is higher in late-myelinating (prefrontal, lateral-posterior temporal) cerebrocortical areas as compared to early myelinating (parietal, occipital) regions. In addition, to examine the dependence of age-related changes upon concurrent subclinical depression symptoms which are common even in healthy aging. Sixty-four healthy adults (28 men) aged 23-79 years (mean 45.0, = 18.8 years) were examined. Resting-state functional MRI (rs-fMRI) time series were used to compute voxel-wise intrinsic connectivity contrast (ICC) maps reflecting the strength of functional connectivity between each voxel and the rest of the brain. We further used Time Shift Analysis (TSA) to estimate voxel-wise hemodynamic lead or lag for each of 22 ROIs from the automated anatomical atlas (AAL). Adjusted for depression symptoms, gender and education level, reduced ICC with age was found primarily in frontal, temporal regions, and putamen, whereas the opposite trend was noted in inferior occipital cortices ( < 0.002). With the same covariates, increased hemodynamic lead with advancing age was found in superior frontal cortex and thalamus, with the opposite trend in inferior occipital cortex ( < 0.002). There was also evidence of reduced coupling between voxel-wise intrinsic connectivity and hemodynamics in the inferior parietal cortex. Age-related intrinsic connectivity reductions and hemodynamic changes were demonstrated in several regions-most of them part of DMN and salience networks-while impaired neurovascular coupling was, also, found in parietal regions. Age-related reductions in intrinsic connectivity were greater in anterior as compared to posterior cortices, in line with implications derived from the retrogenesis hypothesis. These effects were affected by self-reported depression symptoms, which also increased with age.
为了在逆向发育假说的背景下评估成年期大脑内在功能连接性和血液动力学与年龄相关的变化，该假说指出，与早期髓鞘形成（顶叶、枕叶）区域相比，晚期髓鞘形成（前额叶、颞叶外侧后部）脑皮质区域与年龄相关的变化速率更高。此外，为了研究与年龄相关的变化对同时存在的亚临床抑郁症状的依赖性，这种症状即使在健康衰老过程中也很常见。对64名年龄在23 - 79岁（平均45.0岁，标准差 = 18.8岁）的健康成年人（28名男性）进行了检查。静息态功能磁共振成像（rs - fMRI）时间序列用于计算体素级内在连接性对比（ICC）图，反映每个体素与大脑其他部分之间功能连接的强度。我们进一步使用时间移位分析（TSA）来估计自动解剖图谱（AAL）中22个感兴趣区域（ROI）各自的体素级血液动力学超前或滞后情况。在对抑郁症状、性别和教育水平进行调整后，发现随着年龄增长ICC降低主要出现在额叶、颞叶区域和壳核，而在枕叶下部皮质则观察到相反的趋势（P < 0.002）。在相同的协变量下，随着年龄增长，前额叶上部皮质和丘脑的血液动力学超前增加，而枕叶下部皮质则呈现相反趋势（P < 0.002）。在顶叶下部皮质也有证据表明体素级内在连接性与血液动力学之间的耦合减少。在几个区域显示出与年龄相关的内在连接性降低和血液动力学变化——其中大多数是默认模式网络（DMN）和突显网络的一部分——同时在顶叶区域也发现了神经血管耦合受损。与后皮质相比，前皮质与年龄相关的内在连接性降低更大，这与逆向发育假说的推论一致。这些效应受到自我报告的抑郁症状的影响，抑郁症状也随着年龄增长而增加。
