White-matter degradation and dynamical compensation support age-related functional alterations in human brain

Abstract

Structural connectivity of the brain at different ages is analyzed using diffusion-weighted Magnetic Resonance Imaging (MRI) data. The largest decrease of the number and average length of streamlines is found for the long inter-hemispheric links, with the strongest impact for frontal regions. From the BOLD functional MRI (fMRI) time series we identify age-related changes of dynamic functional connectivity (dFC) and spatial covariation features of the FC links captured by metaconnectivity (MC). They indicate more constant dFC, but wider range and variance of MC. Finally we applied computational whole-brain network model based on oscillators, which mechanistically expresses the impact of the spatio-temporal structure of the brain (weights and the delays) to the dynamics. With this we tested several hypothesis, which revealed that the spatio-temporal reorganization of the brain with ageing, supports the observed functional fingerprints only if the model accounts for: (i) compensation of the individual brains for the overall loss of structural connectivity, and (ii) decrease of propagation velocity due to the loss of myelination. We also show that having these two conditions, it is sufficient to decompose the time-delays as bimodal distribution that only distinguishes between intra- and inter-hemispheric delays, and that the same working point also captures the static FC the best.