Investigating dynamic brain functional redundancy as a mechanism of cognitive reserve

Julia Schwarz ^1* Franziska Zistler ¹ Adriana Usheva ¹ Anika Fix ¹ Sebastian Zinn ² Juliana Zimmermann ¹ Franziska Knolle ^3,4 Gerhard Schneider ¹ Rachel Nuttall ¹

• ¹ Department of Anesthesiology and Intensive Care, School of Medicine and Health, Technical University of Munich, Germany
• ² Department of Anesthesiology, Columbia University, New York, New York, United States
• ³ TUM-Neuroimaging Center, School of Medicine and Health, Technical University of Munich, Germany
• ⁴ Department of Neuroradiology, School of Medicine and Health, Technical University of Munich, Germany

Introduction: Individuals with higher cognitive reserve (CR) are thought to be more resilient to the effects of age-related brain changes on cognitive performance. A potential mechanism of CR is redundancy in brain network functional connectivity (BFR), which refers to the amount of time the brain spends in a redundant state, indicating the presence of multiple independent pathways between brain regions. These can serve as back-up information processing routes, providing resiliency in the presence of stress or disease. In this study we aimed to investigate whether BFR modulates the association between age-related brain changes and cognitive performance across a broad range of cognitive domains. Methods: An open-access neuroimaging and behavioral dataset (n=301 healthy participants, 18-89yrs) was analyzed. Cortical gray matter (GM) volume, cortical thickness and brain age, extracted from structural T1 images, served as our measures of life-course related brain changes (BC). Cognitive scores were extracted from principal component analysis performed on 13 cognitive tests across multiple cognitive domains. Multivariate linear regression tested the modulating effect of BFR on the relationship between age-related brain changes and cognitive performance.Results: PCA revealed three cognitive test components related to episodic, semantic and executive functioning. Increased BFR predicted reduced performance in episodic functioning when considering cortical thickness and GM volume as measures of BC. BFR significantly modulated the relationship between cortical thickness and episodic functioning. We found neither a predictive nor modulating effect of BFR on semantic or executive performance, nor a significant effect when defining BC via brain age.Discussion: Our results suggest that BFR could serve as a metric of CR when considering certain cognitive domains, specifically episodic functioning, and defined dimensions of BC. These findings potentially indicate the presence of multiple underlying mechanisms of CR.