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

<div><p>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.</p></div

Histograms of the normal aging effects on inter-lobe functional connectivities.

<p>The distribution curves indicate that inter-lobe connectivities of the frontal lobe tend to increase with age, whereas those among posterior lobes tend to decrease with age.</p

Cortical-Cortical Connectivity (CCC) matrices for the young (top) and the elderly (bottom) groups.

<p>The colors on the upper triangular matrices indicate the average individual-centered functional connectivity intensity of the ROI pairs. The gray square elements on the lower triangular matrices indicate ROI pairs with statistically significant nonzero correlations.</p

Paired differences of the brain connectivity matrices between the young and the elderly groups ().

<p>The colors on the upper triangular matrix indicate the PFCorr difference of the ROI pairs. The significantly different ROI pairs are shown on the lower triangular matrix, with negative values marked in blue and positive values marked in red.</p

Resting-state fMRI preprocessing.

<p>Resting-state fMRI preprocessing.</p

Performance comparison of the estimated functional correlations based on bias, standard error and mean square error for Scenario 1 and Scenario 2.

<p>Performance comparison of the estimated functional correlations based on bias, standard error and mean square error for Scenario 1 and Scenario 2.</p

The uncorrected (top panel) and corrected (bottom) <i>p</i>-values (upper triangular matrix) of testing the paired difference of the Pearson Functional Correlations between the young and the elderly groups, (elderly–young).

<p>The ROI pairs with significant difference are marked in blue for negative values and in red for positive values in the lower triangular matrix.</p

The distinguished normal ageing effects across the cortical lobes.

<p>E: elderly group; Y: young group; E-Y: ageing effects (elderly group subtracts young group). Connectivity 1 denotes the connectivity from the frontal lobe to posterior lobes; Connectivity 4, 5, 6 are the interlobe connectivities among the posterior lobes: Connectivity 4 connects the temporal and occipital lobes, Connectivity 5 connects the parietal and occipital lobes, and Connectivity 6 connects the temporal and parietal lobes.</p