Independent Contributions of Dorsolateral Prefrontal Structure and Function to Working Memory in Healthy Older Adults

Abstract

Age-related differences in dorsolateral prefrontal cortex (DLPFC) structure and function have each been linked to working memory. However, few studies have integrated multimodal imaging to simultaneously investigate relationships among structure, function, and cognition. We aimed to clarify how specifically DLPFC structure and function contribute to working memory in healthy older adults. In total, 138 participants aged 65-88 underwent 3 T neuroimaging and were divided into higher and lower groups based on a median split of in-scanner n-back task performance. Three a priori spherical DLPFC regions of interest (ROIs) were used to quantify blood-oxygen-level-dependent (BOLD) signal and FreeSurfer-derived surface area, cortical thickness, and white matter volume. Binary logistic regressions adjusting for age, sex, education, and scanner type revealed that greater left and right DLPFC BOLD signal predicted the probability of higher performing group membership (P values<.05). Binary logistic regressions also adjusting for total intracranial volume revealed left DLPFC surface area that significantly predicted the probability of being in the higher performing group (P = 0.017). The left DLPFC BOLD signal and surface area were not significantly associated and did not significantly interact to predict group membership (P values>.05). Importantly, this suggests BOLD signal and surface area may independently contribute to working memory performance in healthy older adults.

Keywords: cognitive aging; dorsolateral prefrontal cortex; multimodal neuroimaging; structural and functional magnetic resonance imaging; working memory.

Figure 1

2-back>0-back subtraction contrast depicting whole-brain BOLD activation patterns in regions within the working memory network, including the DLPFC (n = 138, family wise error; FWE < 0.05).

Figure 2

DLPFC surface created in FreeSurfer Analysis Suite v6.0. The spherical DLPFC ROIs were linearly registered to subject surfaces to extract cortical thickness and surface area values. S = Superior, I = Inferior, A = Anterior, P = Posterior. (A) Right DLPFC centered at MNI coordinates (44.53, 38.76, 24.43); (B) Left DLPFC; purple: centered at MNI coordinates (−37.75, 50.19, 13.6); blue: centered at MNI coordinates (−46.26, 22.71, 18.6).

Figure 3

The left DLPFC surface area by BOLD interaction did not significantly predict 2-back performance group. Follow-up regression analyses revealed that BOLD signal and surface area in this region are not significantly associated in either the higher or lower performers.