Puberty-related development of fronto-amygdala circuitry in anxious youth: A multimodal neuroimaging study with ultra-high resolution MRI scanner (7T) - Supplement

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Abstract Pediatric anxiety disorders are an area of critical public health need. The past two decades have seen substantial increases in both incidence and prevalence of anxiety psychopathology,1,2 trends which were amplified by the COVID-19 epidemic and have recently been declared an emergency.3 Early adolescence and the emergence of puberty is a pivotal moment wherein trajectories of anxiety symptoms begin to rise, especially in girls.4,5 It is also a period of puberty-associated neuroplastic changes in brain networks associated with emotion regulation and cognitive control.6,7 The parent R01 for this supplement investigates these puberty-related neurodevelopmental mechanisms through the lens of an important brain circuit, vmPFC-amygdala connectivity, and its relationship to threat reactivity, a known factor in anxiety disorders.8–10 This project proposes to extend the aims of the parent R01 to another known factor, perseverative thought (PT), a transdiagnostic construct comprising negative, repetitive thinking. PT in the form of worry and rumination has been associated with anxiety for decades.11 Although PT can vary in different aspects, a hallmark of pathological PT is its uncontrollability.12–14 Thus, the ability to disengage from PT is a potential factor of resilience. Recent years have seen interest in interventions targeting PT, which enhance PT disengagement skills and appear effective against anxiety and depressive symptoms.15 However, the neural mechanisms of real-time disengagement from PT in adolescence remain unknown. The study of neurodevelopmental mechanisms of PT disengagement therefore has substantial potential to improve treatment efficacy and identify new neurobiologically-informed treatment targets. The aim of the proposed project is to initiate a developmental study of PT disengagement by adapting a paradigm previously published in adults16 for use in adolescents. Aim 1 proposes minor adaptations of the task and behavioral pilot testing (N=30) to ensure understandability and tolerability in adolescents, then extending to a neuroimaging context (N=30) to confirm its tolerability. Aim 2 proposes analyses of the pilot data and their relationship to gender and symptomatology. The Candidate will expand her extant fMRI data analytic skills through a training plan including formal didactics and supervision from the study PI. This project will benefit from the parent PI’s extensive experience in neurodevelopment and psychopathology and the wealth of mentorship and resources at the University of Pittsburgh. It will further the Candidate’s goals of becoming an independent investigator by supporting research activities during the final year of clinical fellowship and generating pilot data and testable hypotheses for a K23 award proposal. Benchmarks for this award include presentations at scientific conferences and transition to a T32 postdoctoral fellowship as the next steps towards a faculty position and independence as a physician-scientist.