Abstract Alterations in the default mode network (DMN) are known to associated with aging and with neurological and psychiatric diseases. We assessed age-dependent changes in interactions within the DMN and between the DMN with other brain areas, and correlations of these interactions with a battery of neuropsychological tests to formulate a macroscopic model of ageing. Using a novel multivariate analysis method, enabling determination of directed pathways, on resting-state functional MRI data from fifty young and thirty-one old healthy individuals, we identified directed intra- and inter-DMN directed pathways that differed between the groups and used their correlations with neuropsychological tests to infer their behavioral meaning. Pathways connecting the DMN with visual and limbic regions in old subjects engaged at BOLD low frequency and involved the dorsal PCC. In young subjects, they were at high frequency and involved the ventral PCC. Pathways combining the sensorimotor (SM) and the DMN, were efferent in young subjects (DMN&lt;SM) and afferent in old subjects (DMN&gt;SM). Most inter-DMN pathways in the old subjects, correlated with reduced speed and working memory and, were DMN efferent (DMN&gt;). We suggest a macroscopic model of aging centered in the DMN. It suggests that the reduced sensorimotor efferent, probably brought about from reduced physical activity, and the increased need to control such activities by the mPFC, causes a higher dependency on external versus internal cues. This results in a shift from ventral to dorsal PCC of inter-DMN pathways. Consequently, the model combines physical activity with ageing.

Older age is associated with a shift from ventral to dorsal PCC in pathways connecting the DMN with visual and limbic areas and a directionality shift in pathways connecting the DMN with sensorimotor areas