Asymmetric connectivity reduction and its relationship to “HAROLD” in aging brain

Hemispheric asymmetry reduction in older adults (HAROLD) has been frequently reported in studies of functional brain aging. It is commonly considered to be a plastic brain reorganization that provides compensation for declining unilateral neural efficiency. However, plastic functional alterations may also be associated with neural connectivity changes. Using activation and resting state functional magnetic resonance imaging (fMRI) as well as diffusion tensor imaging (DTI), we examined whether functional and structural connectivity related to prefrontal working memory function is asymmetrically reduced in the two hemispheres of the aging brain; and if yes, whether these asymmetric connectivity declines are correlated with asymmetry reduction in functional activation. With regions of interests defined by verbal working memory activations, it is revealed that although neural connectivity is generally reduced in the aging brain, prefrontal–parietal resting functional connectivity is better preserved in the left hemisphere while prefrontal DTI fiber pathways are better preserved in the right hemisphere. In addition, the laterality change of the functional activation is negatively correlated with that of the resting connectivity and positively correlated with that of the structural connectivity. These results reveal additional aspects of the neuronal alterations of aging and suggest a link between asymmetric connectivity reduction and HAROLD.