Thought as a health marker: linking dynamics of… (F32AG104234) – Project Grant to University Of Arizona

Abstract: The flow of human thought-how ideas linger, shift, and evolve-plays a critical role in mental health and well- being. Flexible thought transitions support adaptive emotion regulation and goal pursuit, whereas rigid or erratic patterns are linked to affective and cognitive dysfunction. Despite well-documented age-related changes in cognition, affect, and neural flexibility, little is known about how thought dynamics evolve across the adult lifespan or how they interact with mental well-being in older adulthood. This project investigates age-related differences in the dynamics of self-generated thought through two complementary studies leveraging an existing dataset including 162 older and 61 younger, cognitively unimpaired, adults who verbalized their ongoing thoughts in the scanner using a validated think-aloud paradigm. Study 1 characterizes age-related behavioral differences in thought dynamics using both discrete (topic boundaries) and continuous (large language model-based perplexity) measures. Study 1 will also explore how the unfolding of thoughts interacts with emotional valence, linking valence-related thought dynamics with the well-documented positivity bias in aging. This study aims to identify behavioral signatures of adaptive versus maladaptive thought patterns that may precede clinically diagnosed cognitive decline or emotional dysregulation. Study 2 examines the neural mechanisms underlying thought transitions across age groups, testing whether brain aging alters the neural architectures supporting dynamic thoughts. To further explore a mechanistic link between structural and functional change, a mediation analysis will test whether age-related differences in brain circuit recruitment are attributable to the structural integrity of the hippocampus. By delineating how aging alters the neural circuits supporting the thought flow, the results will provide a mechanistic understanding of how self-generated thought reflects neural health in older adults. Together, these studies will advance the "thought-as-a-health-marker" framework with implications in preclinical diagnosis and interventions. The fellowship provides advanced training in MRI analysis using state-of-the-art toolboxes and computational methods, as well as theoretical grounding in aging neuroscience under the expert mentorship of the sponsors. The training will take place at the university of arizona, an interdisciplinary environment with renowned expertise in aging research, equipped with cutting-edge imaging facilities and computational infrastructure. Thus, the proposed research and training will prepare the applicant for an independent research program that integrates computational and cognitive neuroscience to study self-generated thoughts with practical implications to promote mental well-being in older adulthood.

Thought as a health marker: linking dynamics of self-generated thoughts and neural health in aging

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