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A major contribution to our understanding of the aging brain comes either from studies comparing young with older adults or from studies investigating pathological aging and using the healthy aging older adults as control group. In consequence, we know relatively well, what distinguishes young from old brains or pathological aging from healthy but that does not mean that we really understand the structural and functional transformations characterizing the healthy aging brain. By analyzing task-free fMRI data from a large cross-sectional sample of 186 older adults (mean age = 70.4, 97 female), we aimed to elucidate age-related changes in the intrinsically active functional architecture of the brain in our study group covering an age range from 65 to 85 years. First, we conducted an intrinsic connectivity contrast analysis (ICC) in order to detect the brain regions whose degree of connectedness was significantly correlated with increasing age. Secondly, using connectivity analyses we investigated how the clusters highlighted by the ICC analysis functionally related to the other major resting-state networks. The most important finding was the right anterior insula's loss of connectedness in the older participants of the study group because of the region's causal role in the switching from the task-negative to the task-positive state of the brain. Further, we found a higher functional dedifferentiation of two of the brain's major intrinsic connectivity networks, the DMN, and the cingulo-opercular network, caused by a reduction of functional connection strength, especially in the frontal regions. At last, we showed that all these age-related changes have the potential to impair older adult's performance of working memory tasks.

Small Changes, But Huge Impact? The Right Anterior Insula's Loss of Connection Strength during the Transition of Old to Very Old Age