Abstract – Project 3 – Neuroscience Project The Neuroscience project will collect psychophysiological and MRI data from 300 MIDUS 3 respondents to derive measures of emotional reactivity and recovery in response to standardized positive and negative emotional stimuli. In addition, measures of resting state connectivity, structural MRI, and white matter connectivity measured with diffusion tensor imaging will provide additional indices of brain function and structure. Collectively these neuroscientifically-based measures will provide a unique opportunity to examine the neural pathways through which psychosocial factors are transduced and impact psychological function, health and well-being as we age. Among the several innovative features of this project, facial EMG will be acquired in the scanner to provide real-time, continuous, objective measures of emotional reactivity and recovery that will be used in conjunction with the imaging measures. Based upon findings from MIDUS 2, we predict that prolonged responding in the ventral striatum in response to positive incentives will be associated with higher levels of well-being and with lower levels of cortisol and with a biomarker and gene expression profile indicative of increased resilience. Functional connectivity between the different sectors of the prefrontal cortex and the amygdala and ventral striatum in resting state functional MRI are predicted to be associated with individual differences in well-being and with peripheral measures of stress biology. Increased functional connectivity between prefrontal cortex and these subcortical zones is predicted to be associated with a more resilient profile. Structural variations in key circuits will also be examined in relation to psychosocial factors and peripheral biology. The neuroscience project provides key measures of the neural bases and correlates of key emotion-related processes that are central to well-being and health and will enable MIDUS to provide a mechanistic account of how psychosocial factors are transduced and in turn impact neural circuits and peripheral biology in ways that modulate mental and physical health.