Project Summary Adolescents demonstrate a high need for emotion regulation [2-4], but often struggle to employ gold- standard regulatory strategies such as cognitive reappraisal due to underdeveloped lateral prefrontal neuroarchitecture (i.e. lateral prefrontal cortex (LPFC)), which plays a crucial role in cognitive control [5-8]. At the same time, adolescents are exquisitely sensitive to their peers [11,13-16]. Notably, neural regions linked to peer influence in adolescence, including ventral striatum (VS) and ventromedial prefrontal cortex (vmPFC), mature prior to LPFC. Thus, adolescents are uniquely poised to benefit from a social intervention designed to appropriate peer influence mechanisms towards enhancing emotion regulation efficacy. The goal of this R21 is to work with the developing brain, not against it, to utilize adolescent-emergent reward-related circuitry (VS, VMPFC) instead of LPFC to regulate emotion in adolescents. We will administer a novel paradigm during functional magnetic resonance imaging (fMRI) to examine whether adolescents (N = 50) and adults (N = 50) are more effective at down-regulating negative affect when a friend provides them with reinterpretations of negative stimuli (i.e. social reappraisal), as compared to when they reinterpret stimuli alone (i.e., cognitive reappraisal) [12]. Specifically, we will investigate whether social reappraisal is more effective and longer-lasting than cognitive reappraisal in down-regulating negative affect in adolescents and adults (Aim 1). We hypothesize that social reappraisal will be more effective and enduring than cognitive reappraisal in both groups, but that this effect will be larger in adolescents given their heightened sensitivity to peers. Furthermore, we will identify the neural mechanisms supporting social versus cognitive reappraisal and characterize age-related differences in these mechanisms (Aim 2). We will focus on examining activation in the amygdala, LPFC, VS, and VMPFC, as well as functional connectivity between these regions. We hypothesize that LPFC-amygdala connectivity will support cognitive reappraisal, which will be stronger in adults versus adolescents, whereas VS-amygdala and VMPFC-amygdala connectivity will support social reappraisal. While VS-amygdala connectivity is likely to be stronger in adolescents than adults, VMPFC- amygdala connectivity might not be given that this pathway is still developing during adolescence [21,76]. We expect that social reappraisal will have a more transformative and thus longer-lasting effect on amygdala- based representations of negative stimuli, particularly in adolescents, and will use representation similarity analysis to test this hypothesis. Examining the efficacy and neural underpinnings of social reappraisal in adolescents versus adults is an important step in advancing our understanding of how social contexts shape emotion regulation neurodevelopment, with the aim of improving adolescent health and laying the gro...