3. Results
3.1. Demographic, neuropsychological and N-back task measurements
Table 1 presents the demographics, general cognitive status, and WM task performances of current study cohort. As shown in the table, the cohort showed relatively intact general cognitive function, with no significant age-related decline in MMSE scores (|r| < 0.1, p > 0.1). The WM task performances were remarkably affected by ageing, as significant age-related decreases in accuracy rate (AR) were found in all three task conditions (r = -0.325, 0.343, and 0.310 for 0-, 1-, and 2-back condition, respectively, all ps < 0.001), along with significantly longer reaction time (RT) in 0- and 1-back conditions (r = 0.222 and 0.208, and p = 0.003 and 0.008, respectively) in advanced age (Table 1).
3.2. Age effects on N-back task-evoked brain activity
Brain activities typically associated with WM tasks were found in the contrasts of “2-back - 0-back”, with positive regions mainly clustered in the lateral prefrontal and parietal lobes and negative areas located around the cingulate cortex and temporal lobe (Figure 1). Further regression models identified regions showing significant age-related alterations within the positive and negative areas, respectively. As the right inferior parietal lobule (rIPL, peak voxel coordinates: 48, -51, 45) presented an age-related decline in activity, the right anterior cingulate cortex (rACC, peak voxel coordinates: 3, 36, -3) showed an age-related increase (Figure 1, Table 2).
3.3. Age effects on the N-back task-based background functional connectivity
With the task-based background brain activity, task-based background FC maps were separately computed using the rIPL and rACC as seed regions (Figure S1). Significantly enhanced connectivity was then observed between the rIPL and those clustered in the right posterior cingulate cortex (rPCC, peak voxel coordinates: -3, -57, 30) with increasing age (Figure 2, Table 2). On the other hand, background connectivity between the rACC and the right precentral gyrus (rPreCG, peak voxel coordinates: 48, 9, 30), the left IPL (lIPL, peak voxel coordinates: -39, -48, 42) and the right angular gyrus (rAG, peak voxel coordinates: 42, -57, 54) were also found to be strengthened with ageing (Figure 2, Table 2). There were no other regions showing significant age-related alterations in functional connectivity with either ROI.
3.4. Brain activity, functional connectivity, and WM task performance
Relationships between brain activity, FC, and WM task performance were explored by linear regression models, controlling for the effects of age, gender, and years of education. As both AR and RT of 0-back were significantly associated with rIPL and rACC activities (for AR, | r | > 0.266, both p < 0.001; for RT, | r | > 0.174, p = 0.002, 0.028, respectively), only AR of 2-back was correlated with these activities (| r | > 0.241, p = 0.002, < 0.001, respectively). Then, after regressing out the effects of the activity in seed regions, we identified specific relationships between the rACC-lIPL connectivity and RT of 0-back (r = -0.170, p = 0.032), and between the rIPL-rPCC connectivity and AR of 2-back (r = 0.166, p = 0.037).
Since the AR of the 2-back and the RT of the 0-back were affected by both activity and connectivity, we subsequently conducted mediation analyses to inspect their roles in mediating ageing effects on task performance. The results showed that age-related impacts on the AR of 2-back were partly mediated by rIPL activity (indirect effect [IE] = -0.105, 95% CI [-0.173, -0.037]), as well as a trend of mediation of the AR of 2-back by the rIPL-rPCC connectivity (IE = 0.047, 95% CI [-0.002, 0.096]). Similarly, alterations in RT of 0-back during ageing were also fully mediated through the activity of the rACC (IE = 0.045, 95% CI [0.005, 0.085]) and partially mediated by the rACC-lIPL connectivity (IE = -0.057, 95% CI [-0.111, -0.002]). More importantly, the total of indirect effects of ageing on AR and RT, mediated by the two different functional measurements, were not significant (for AR of 2-back, sum of IE = -0.059, 95% CI [-0.143, 0.026]; for RT of 0-back, sum of IE = -0.012, 95% CI [-0.080, 0.056]; Figure 3).