Affect regulation and Beta Amyloid: Maturational Factors in Aging and Age-Related Pathology

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Our goal is to assess how affect regulation strategies are protective of cognitive and affective functioning in those who are at risk of suffering age-related disorders of mood and cognition. According to RFA MH-17-405, studies of maturational shifts in affect regulation often yield inconsistent findings and the neurobiological systems that support affect regulation remain largely untested. In this application, we propose to closely investigate the dynamics and mechanisms of two maturational trajectories that impact affect regulation: increasing age and beta-amyloid plaques within the brain. To date, most efforts have focused on age-related changes in valence regulation (e.g., the age-related positivity effect). Arousal is acknowledged as important, but very little is known about how older adults actively regulate their arousal states, or the proximal and longer- term consequences of such regulation attempts for risk of suffering age-related changes in mood and cognition. Recent findings from our team suggest that those who optimize for momentary comfort cultivate arousal-avoidance affect regulation trajectories, whereas those who optimize for mastery in memory and attention cultivate grit trajectories (the ability to tolerate momentary unpleasantness in the service of some goal that requires effort, which is often transiently experienced as an unpleasant aroused state). Our work also suggests that affect regulation is associated with both the structure and connectivity within two of the brain's core networks: the salience and default mode networks. In older adults, beta-amyloid (Aβ) plaques within these two networks are a key pathology—one of the two major molecular hallmarks of Alzheimer's disease (AD)— associated with elevated risk of cognitive decline, symptoms of depression, and dementia. With these observations in mind, our team will combine (a) innovative theory and methods from the study of normal maturational changes in situation-focused affect regulation, (b) structural, functional, and molecular brain imaging, and (c) innovative computational modeling of spatial and temporal dynamics in one large five year study designed to examine how arousal-regulation is associated with changing age and Aβ status. We will characterize situation-focused arousal regulation strategies and cognitive effort at various levels of difficulty using behavioral, experiential, and neurobiological levels of analysis, both in the behavioral lab and during brain scanning. Data analysis will involve constructing dynamic temporal trajectories across performance in each task to characterize arousal-avoidance and grit (i.e., tolerance of high arousal in the service of effort). We will characterize and compare arousal-avoiding and grit regulation trajectories in individuals who vary in age (from 40 to 90 years old), Aβ status, cognitive impairment, and mood symptomatology (distinguishing two types of symptoms: distress (negativity) and apathy (lack of effort or engagement). The findings from the proposed research will be used to develop a longer-term project to determine how the temporal dynamics of affect regulation predict developmental/maturational trajectories for mood disorders and cognitive impairment.