Heterogeneous Aging Effects on Functional Connectivity in Different Cortical Regions: A Resting-State Functional MRI Study Using Functional Data Analysis

Brain aging is a complex and heterogeneous process characterized by the selective loss and preservation of brain functions. This study examines the normal aging effects on the cerebral cortex by characterizing changes in functional connectivity using resting-state fMRI data. Previous resting-state fMRI studies on normal aging have examined specific networks of the brain, whereas few studies have examined cortical-cortical connectivities across the entire brain. To characterize the effects of normal aging on the cerebral cortex, we proposed the Pearson functional product-moment correlation coefficient for measuring functional connectivity, which has advantages over the traditional correlation coefficient. The distinct patterns of changes in functional connectivity within and among the four cerebral lobes clarified the effects of normal aging on cortical function. Besides, the advantages of the proposed approach over other methods considered were demonstrated through simulation comparisons. The results showed heterogeneous changes in functional connectivity in normal aging. Specifically, the elderly group exhibited enhanced inter-lobe connectivity between the frontal lobe and the other lobes. Inter-lobe connectivity decreased between the temporal and parietal lobes. The results support the frontal aging hypothesis proposed in behavioral and structural MRI studies. In conclusion, functional correlation analysis enables differentiation of changes in functional connectivities and characterizes the heterogeneous aging effects in different cortical regions.

脑衰老是一个复杂且具有异质性的过程，其特征为脑功能的选择性丧失与保留。本研究借助静息态功能磁共振成像（resting-state fMRI）数据刻画功能连接的变化，以此探究正常衰老对大脑皮层的影响。既往针对正常衰老的静息态功能磁共振成像研究多聚焦于大脑特定网络，鲜有研究覆盖全脑范围内的皮层-皮层连接。为刻画正常衰老对大脑皮层的影响，本研究提出采用皮尔逊函数积矩相关系数（Pearson functional product-moment correlation coefficient）来衡量功能连接，该方法相较于传统相关系数具备显著优势。四个脑叶内部及脑叶间功能连接的差异化变化模式，阐明了正常衰老对皮层功能的影响。此外，通过模拟对比实验，本研究验证了所提方法相较于其他参评方法的优越性。研究结果显示，正常衰老过程中功能连接存在异质性变化：具体而言，老年组的额叶与其余脑叶之间的跨脑叶连接呈增强趋势，而颞叶与顶叶之间的跨脑叶连接则出现减弱。本研究结果佐证了行为学与结构磁共振成像研究中提出的额叶衰老假说。综上，功能相关分析能够有效区分不同功能连接的变化特征，并刻画不同皮层区域衰老影响的异质性。