Neuro-Functional and Clinical Correlates of Emotional Dysregulation in Youth

Emotional Dysregulation (ED), characterized by heightened affective reactivity, irritability, and hyperarousal, represents a transdiagnostic vulnerability factor involved in a range of psychiatric conditions, particularly during childhood and adolescence. Despite its clinical significance, ED remains poorly defined within current nosographic systems highlighting the need for a neurodevelopmentally informed and mechanistically grounded understanding. This dissertation investigates the neurobiological and clinical substrates of ED through five complementary studies employing meta-analytic, neuroimaging, and behavioral methodologies. Study 1 conducts a large- scale coordinate-based meta-analysis of fMRI studies, identifying consistent patterns of brain hyper- and hypo-activation associated with ED across diagnostic categories. Study 2 utilizes a naturalistic fMRI paradigm to explore affective processing in adolescents with varying levels of ED across diagnostic groups. Study 3 aims to map emotion representations across specific cortical regions, examining their spatial organization through combined neuroimaging and behavioral paradigms in healthy children and adolescents. Study 4 investigates facial emotional expressions in youths with ED through automated affect coding during real-life clinical interviews. Study 5 explores the association between ED and sleep disturbances in a clinically heterogeneous sample, highlighting the role of circadian rhythm regulation. Together, these studies contribute to a comprehensive model of ED as a neurodevelopmental condition marked by disrupted top- down regulatory control and limbic hyperactivity. By integrating behavioral, cognitive, and regulatory domains within a transdiagnostic framework, this work supports the inclusion of ED as a core construct within dimensional psychiatric models such as the Research Domain Criteria and offers novel insights for biomarker-informed diagnosis and personalized intervention strategies.