Mapping Brain-Behavior relationships across the adult lifespan using multimodal MRI

Abstract

Aging is a complex and heterogeneous process, characterized by declines in physiological functions and an increased risk of neurodegenerative diseases. Although the underlying brain changes of aging have been defined, individual aging trajectories vary widely, leading to diverse functional outcomes that range from resilience to impairment. This variability complicates efforts to promote healthy aging. To better elucidate the neural underpinnings of this heterogeneity, my thesis systematically investigated brain morphometry and functional organization across three core functional domains: cognition, olfaction and fine motor function. Leveraging data from the large, population-based Rhineland Study, this work combines structural and functional MRI measurements to explore the neural basis of age-related functional declines. <br/> Specifically, I first characterized age-related brain network organization using resting-state fMRI and investigated its association with cognitive functions, exploring whether this relationship is affected by neuropathology. Second, by combining olfactory bulb volume with olfactory network functional connectivity, I studied how both peripheral and central pathways contribute to odor identification. Third, I applied structural MRI measurements, including cortical thickness and subcortical volumes, to explore the neuroanatomical basis of fine motor function. <br/> The findings revealed that while age is associated with dedifferentiation of brain functional networks, the beneficial effect of system segregation is conditional: segregated networks support faster processing speed only in individuals with a low burden of neuropathology. In the sensory domain, a novel automated method for quantifying olfactory bulb volume was developed and validated. Subsequent analyses demonstrated that olfactory decline is linked not only to smaller olfactory bulb but also to the disrupted functional connectivity of memory-related networks, especially in older adults. Finally, utilizing a digital spiral drawing test I investigated fine motor dexterity and found that it is supported by the maintenance of brain structural integrity, with performance associated not only with core motor regions but also with structures traditionally associated with cognition, such as the hippocampus. <br/> Collectively, these findings demonstrate the importance of using a multimodal imaging approach to investigate the heterogeneity of functional aging. The findings reveal that resilience across cognitive, sensory, and motor systems results from both intact brain structures and a balanced brain network organization. The identified structural and functional imaging biomarkers not only facilitate tracking age-related decline but also support the development of targeted therapeutic strategies against neurodegeneration and the promotion of healthy aging.