Effects of age on the structure of functional connectivity networks during episodic and working memory demand.

The aim of the study was to investigate age-related differences in large-scale functional connectivity networks during episodic and working memory challenge. A graph theoretical approach was used providing an exhaustive set of topological measures to quantify age-related differences in the network structure on various scales. In a single session, 10 young (22-30 years) and 10 senior (62-77 years) subjects performed an episodic and a working memory task during functional magnetic resonance imaging. Networks of functional connectivity were constructed by correlating the blood oxygenation level-dependent (BOLD) signal for every pair of voxels. Statistical network parameters yield a global characterization of the network topology, the quantification of the importance of specific regions, and shifts in local connectivity. An age-related increase in the density and size of the networks and loss of small-worldness was observed, related to an expanded distribution of brain activity during both memory demands in seniors, and a more specific and localized activity in young subjects. In addition, we found highly symmetrical neural networks in young subjects accompanied by a strong coupling between parietal and occipital regions. In contrast, seniors showed pronounced left-hemispheric asymmetry with decreased connectivity within occipital areas, but increased connectivity within parietal areas. Moreover, seniors engaged an additional frontal network strongly connected to parietal areas. In contrast to young subjects, seniors showed an almost identical structure of network connectivity during both memory tasks. The chosen network approach is explorative and hypothesis-free. Our results extend seed-based and BOLD-signal intensity focused studies, and support present hypotheses like compensation and dedifferentiation.