Parent Project Summary Emotions are central to human functioning, guiding thought and action from the earliest to the latest days of life1–3. Emotional experiences change over the adult life span, with older adults shifting their motivational goals towards optimizing emotional regulation and reporting positive emotions more often that their younger counterparts1–3. However, affective symptoms, such as anxiety, mood instability, and apathy are common conditions among older adults and may herald incipient neuropsychiatric disorders4,5. Social behavior and human emotions are shaped by the intimate, dynamic interactions between the autonomic nervous system (ANS)6–8 and the salience network9–11, a distributed brain network12,13 critical for homeostatic regulation and emotions14–17 anchored by the anterior cingulate and fronto-insular cortices9–11,18. Loneliness – the subjective experience of feeling socially isolated – has recently been identified as a major modifiable risk factor for cognitive decline and worsening of social-emotional well-being in older adults 19–22. Loneliness, which has gained increasing relevance due to the ongoing COVID-19 pandemic23,24, has been shown to spread among social networks through a contagious process 19–22 , to predict low life satisfaction, depressive symptoms, cognitive impairments, and Alzheimer’s disease dementia among older persons19–22. The overarching goal of the parent project is to better understand the neural underpinning of social-emotional functioning in older adults and to elucidate the impact of loneliness on these neural systems. More specifically, two aims are at the core of the parent grant: (1) to elucidate whether distinct emotional stimuli induce dissociable signatures of salience network and autonomic activity in older adults, and (2) to assess the impact of loneliness on neural systems supporting social-emotional functions in older adults. Towards these aims, we will recruit 40 lonely and 40 non- lonely older adults based on their scores on the 3-item UCLA loneliness scale (5 or above indicate loneliness). All participants will be assessed with simultaneous functional MRI and autonomic physiology recordings, both during resting-state conditions and during an emotional reactivity task. Advanced computational methods designed to unravel the dynamic nature of neural activity will be used to derive neural signatures of activity that differentiate among emotion states and to assess how these neural systems are affected by loneliness in older adults.