Functional reorganization of the prefrontal cortex in aging

1186 

Abstract Submission 

Ping Wang¹, Zi-Xuan Zhou¹, Peng Gao², Hai-Yan Hou³, Jia-Xin Zhang³, Hui-Jie Li³, Xi-Nian Zuo⁴

¹Beijing Normal University, Beijing, Beijing, ²Taiyuan University of Technology, Taiyuan, Shanxi, ³Institute of Psychology, Chinese Academy of Sciences, BEIJING, BEIJING, ⁴Xi-Nian Zuo, Professor, Beijing Normal University, Beijing, NA

Ping Wang  
Beijing Normal University
Beijing, Beijing

Zi-Xuan Zhou  
Beijing Normal University
Beijing, Beijing

Peng Gao  
Taiyuan University of Technology
Taiyuan, Shanxi

Hai-Yan Hou  
Institute of Psychology, Chinese Academy of Sciences
BEIJING, BEIJING

Jia-Xin Zhang  
Institute of Psychology, Chinese Academy of Sciences
BEIJING, BEIJING

Hui-Jie Li  
Institute of Psychology, Chinese Academy of Sciences
BEIJING, BEIJING

Xi-Nian Zuo  
Xi-Nian Zuo, Professor, Beijing Normal University
Beijing, NA

The posterior-to-anterior developmental trajectory of brain structure leads to posterior-to-anterior reorganization of brain function in aging (Grydeland et al., 2013), with the relative preserved prefrontal cortex compensating for decline in primary sensory cortex through increased functional activity (Davis et al., 2008). However, the prefrontal cortex itself undergoes differential subregional decline, with the rostral prefrontal cortex showing relative preservation throughout life (Bethlehem et al., 2022). We propose a posterior-to-anterior functional organization in the prefrontal cortex, with the preserved rostral prefrontal cortex compensating for decline in the dorsolateral prefrontal cortex, located in the middle and posterior regions and considered as the apex of the prefrontal cortex's functional hierarchy (Badre et al., 2018). To test this hypothesis, a gamified working memory training was conducted with older adults, targeting the dorsolateral prefrontal cortex, while the rostral prefrontal cortex is considered lack of involvement in working memory (Mansouri et al. 2017). If no functional reorganization occurs, the training would affect the dorsolateral prefrontal cortex and related brain regions, leaving the rostral prefrontal cortex unaffected. Conversely, if a posterior-to-anterior shift exists, the training would not only affect the dorsolateral prefrontal cortex but may also induce changes in the rostral prefrontal cortex.

We developed a gamified working memory intervention based on the classic n-back task and created an active control game with similar features. Seventy-six older adults were randomly assigned to either the working memory intervention group (n-back game) or the active control group (0-back control game). All participants completed 12 1-hour training sessions over 6 weeks. Structural magnetic resonance imaging (MRI) and resting-state functional MRI scans were conducted before and after the intervention. Cognitive assessments targeting working memory and other cognitive domains, such as processing speed, attention, visuospatial ability, episodic memory, and inhibition, were administered at pretest, posttest, and six months after the intervention. Changes in structure (cortical thickness, surface area and volume) and function (surface-based regional homogeneity and functional connectivity) of each subregion in prefrontal cortex, as well as changes in cognitive functions induced by the training was examined. The multivariate pattern classification analysis was conducted to test the consistency and discriminative power of changes induced by the intervention in both the structure and function of the prefrontal cortex, as well as working memory performance.

The results indicated that the working memory, inhibition, visuospatial processing, and episodic memory of older adults were all significantly improved after the intervention. The MRI analyses revealed thickening of the left frontal pole (part of rostral prefrontal cortex) in the prefrontal cortex and weakened regional homogeneity and functional connectivity with the left inferior temporal gyrus. Further statistical learning analytics showed that these neurocognitive changes might be the neurobiological mechanisms underlying the working memory improvements due to the current gamified digital working memory intervention.

The training-induced structural and functional changes observed in the frontal pole, rather than the typically assumed dorsolateral prefrontal cortex, suggest that the frontal pole may play a crucial role in working memory in aging. This finding implies a functional reorganization of the prefrontal cortex with increasing age. The current study provides preliminary evidence for a potential posterior-to-anterior functional shift within the prefrontal cortex, highlighting the importance of the rostral prefrontal cortex as a critical biomarker for maintaining normal cognitive function in older adults.

Working Memory ²

Aging ¹

Multivariate Approaches

Anatomical MRI

BOLD fMRI

Aging

Cognition

Cortex

FUNCTIONAL MRI

Machine Learning

Memory

MRI