When the brain is not engaged in goal-directed activities and at rest, there are still measureable patterns of activity. One resting-state network, the default mode network (DMN) is responsible for a self-referential introspective state. There are many factors that influence normal changes in brain activity. The purpose of this review is to summarize differences in DMN functional connectivity in healthy individuals by age, sex, cognitive function, and analysis type to characterize what is "normal." Studies were systematically selected up to August 2016. Two reviewers independently used predetermined inclusion and exclusion criteria to identify relevant studies. Studies that provided sufficient information were included in a subsequent voxel-wise meta-analysis. Strength of DMN functional connectivity follows an inverse U-shape, where it is strongest in adulthood and lowest in children and elderly. Cognitive function is positively correlated with DMN functional connectivity. Females exhibit stronger intranetwork connectivity compared with males. Effects of analysis type were inconclusive and more studies need to incorporate complementing techniques. The voxel-wise meta-analysis was only conducted for the age factor. Findings supported an immature network in children compared with adults and a stronger network in adults compared with elderly. This is the first study to review differences of DMN functional connectivity in healthy individuals by age, sex, cognitive function, and analysis type. Findings add to the understanding of normal variance. Furthermore, defining a normal comparative base may allow for the identification of DMN change into pathology. This is important since it may allow for the detection of an intermediate risk phenotype and could serve as a biomarker for treatment response.
Keywords: age differences; default mode network; healthy controls; magnetic resonance imaging; sex differences.