Neural Substrates of Perseverative Thought Disengagement and Reward Learning in Early Adolescence: The Role of Puberty and Implications for Internalizing Symptoms

About This Grant

Childhood anxiety and depression (collectively, internalizing disorders) are a critical public health need. Early adolescence and the emergence of puberty is a pivotal moment wherein internalizing symptoms begin to rise, especially in girls. It is also a period when subcortical brain systems subserving motivated behaviors, including amygdala (negative emotions) and dorsal/ventral striatum (reward processing) increase in reactivity, and regu- latory capacity in the frontoparietal network (FPN) decreases. These cognitive-affective networks are linked to development of internalizing disorders, but the specific mechanisms remain poorly understood. The proposed project will investigate two such constructs that are impacted by these developing cognitive-affective brain net- works, perseverative thought disengagement and reward learning, in order to characterize their relationship to internalizing symptoms and the role of puberty in early-adolescent girls. Perseverative thought (PT) disengage- ment refers to the capacity to disengage from intrusive, repetitive and uncontrollable thoughts such as worries and rumination (i.e., PT), which are known contributors to internalizing symptoms in girls. Reward learning refers to the skills and strategies used to learn from rewards in the environment, which requires solving the explore/ex- ploit dilemma (whether to explore for new rewards or exploit known rewards). Using computational modeling of explore/exploit paradigms, deficits in uncertainty-directed exploration, or exploration aimed specifically at un- known parts of the environment, is linked to internalizing symptoms. Using a parallel structure, the Aims of this project will be to characterize the neural correlates of 1) PT disengagement and 2) uncertainty-directed explora- tion and their relationship to internalizing symptoms in 100 adolescent girls aged 9-14. As an Exploratory Aim, we will investigate relationships between the two constructs in these same participants. This project will take a transdiagnostic approach, recruiting girls on the basis of self-reported PT, as a risk factor for future internalizing symptoms. Girls will complete two study visits: an interview (conducted virtually) to determine topics of frequent PT, and an MRI visit to complete both PT disengagement and reward learning tasks. Functional MRI data will be analyzed using a general linear model (GLM)-based approach and internalizing symptoms will be measured transdiagnostically via questionnaire. Behavior from the explore/exploit (reward learning) task will be modeled using the previously-validated SCEPTIC model, fit to the data using Bayesian approaches, and related to fMRI data using frequentist multilevel models. The proposed training plan leverages a world-class research environ- ment with a team of highly skilled mentors and consultants to provide the candidate with area knowledge in adolescent neurodevelopment and puberty and training in computational modeling and Bayesian statistics. In line with NIMH’s Strategic Objectives, the proposed work will characterize neurodevelopmental processes po- tentially amenable to behavioral and neural intervention with life-long benefits in internalizing disorders.