Spatiotemporal dedifferentiation of the global brain signal topography along the adult lifespan

Age-related variations in many regions and/or networks of the human brain have been uncovered using resting-state functional magnetic resonance imaging. However, these findings did not account for the dynamical effect the brain's global activity (global signal [GS]) causes on local characteristics, which is measured by GS topography. To address this gap, we tested GS topography including its correlation with age using a large-scale cross-sectional adult lifespan dataset (n = 492). Both GS topography and its variation with age showed frequency-specific patterns, reflecting the spatiotemporal characteristics of the dynamic change of GS topography with age. A general trend toward dedifferentiation of GS topography with age was observed in both spatial (i.e., less differences of GS between different regions) and temporal (i.e., less differences of GS between different frequencies) dimensions. Further, methodological control analyses suggested that although most age-related dedifferentiation effects remained across different preprocessing strategies, some were triggered by neuro-vascular coupling and physiological noises. Together, these results provide the first evidence for age-related effects on global brain activity and its topographic-dynamic representation in terms of spatiotemporal dedifferentiation. We revealed distinctive frequency and age effects in unimodal and multimodal regions, confirming that this separation constitutes the intrinsic structure of the global signal (GS) topography. We further demonstrated more homogeneous GS topography across frequencies in elderly brains, extending the traditional spatial dedifferentiation interpretation to the temporal dimension in aging brains, that is, the spatiotemporal dedifferentiation.image