Ageing is the main risk factor for most neurodegenerative diseases and results in complex transformations of the human brain function.

138 controls were recruited and divided into two groups according to age: 55 young (20-30 years [YC]) and 83 old (41-84 years [OC]). SFC analysis aims to characterize regions that connect to specific seed brain areas at different levels of link-step distances. Eight well-known hubs of the human connectome were selected as seeds: middle frontal gyrus, rostral anterior and posterior cingulate cortex, precuneus, inferior parietal, middle temporal and lingual gyri and pericalcarine cortex. Whole-brain two-sample t-test comparisons between groups were performed.

At one-link step distance, in older controls, all the seed regions displayed decreased regional–local functional connectivity with superior frontal and medial orbital frontal gyri, rostral anterior and isthmus cingulate cortex, precuneus and middle and inferior temporal gyri relative to young controls; across intermediate link-steps, a reduced connectivity was observed between all seed regions and frontal and parietal lobes. By contrast, at the first link-step distance, young controls showed lower connectivity only between few seed regions (middle frontal gyrus, anterior and posterior regions of cingulate cortex and precuneus) and precentral, paracentral and lateral occipital gyri compared to older controls. At intermediate link-step distances, increased connectivity with sensorimotor regions was found in older relative to younger controls.