ENHANCED PARIETAL-CINGULATE CONNECTIVITY FOLLOWING ALTERED CORTICAL ACTIVATION IMPROVES WORKING MEMORY PERFORMANCE IN OLD AGE

Abstract

Substantial working memory (WM) decline in aging has been thought as one of the factors triggering the cognitive aging procedure, it is even more important when you consider the remarkable WM impairment in diseases like Alzheimer's disease (AD). In past few years, growing fMRI evidences have attributed the WM decline to cortical activation changes, especially in frontal and parietal regions. However, as the fact of cortical coordination in supporting cognitive process, task-based functional connectivity is thought to make direct and considerable contribution to WM alteration. Hence, we explore both the cortical activity and the background connectivity during WM tasks to explore their role in age-related WM decline. 166 participants who aged 55 to 86 years old, scored 24 or higher on MMSE and had at least 6 years of education were included. Neuropsychological profiles and nback task fMRI data were acquired from each participant. Task-related activation was examined on contrast images created by subtracting the 0-back images from the 2-back images, and the ROI-based background functional connectivity was calculated on the residual image obtained by regressing task-related signal and nuisance variables. General linear models were performed to explore the age effect on activation and connectivity, and their relationship with WM decline. Significant age-related decline was found in accuracy rate of nback tasks (0-, 1-, and 2-back), while reaction time was only remarkably increased in 0- and 1-back (p < 0.05). During the task, activation of right inferior parietal gyrus (IPG) and deactivation of left anterior cingulum gyrus (ACG) were attenuated with age (alphasim corrected p < 0.05), both mediating age impact on task performance. Further analyses on ROI-based functional connectivity revealed that connectivity between IPG and left middle cingulum gyrus (MCG), between ACG and left IPG and right angular gyrus (AG) were all enhanced during aging (alphasim corrected p < 0.05). More importantly, IPG-MCG and ACG-IPG connectivity could positively predicted individual's task performance, independent of task-related activation/deactivation alteration (p<0.05).