Pubertal Maturation and Motivational Influences on Frontolimbic Systems

University Of Pittsburgh At Pittsburgh, Pittsburgh PA

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Abstract

DESCRIPTION (provided by applicant): There is a fundamental gap in understanding how puberty affects neural systems supporting emotion regulation in typically developing adolescents. Filling this gap is important to advance knowledge regarding neurodevelopmental markers of risk for mood disorders, which typically onset during adolescence particularly in girls. The long-term goal is to understand the development of frontolimbic-striatal systems in order to elucidate bio- markers of risk for mood disorders as well as periods of heightened plasticity to inform targeted brain-based neurobehavioral interventions. Given the importance of attentional biases in mood disorders, the objective in this particular application is to gain a deeper understanding of puberty-specific effects on frontolimbic systems responsible for attentional control in the context of emotional stimuli and the extent to which pubertal influences on reward systems can bolster the effects of incentives to enhance attentional control processes. The central hypothesis is that pubertal maturation coupled with elevated levels of sex hormones influence neural activity in and functional connectivity between prefrontal control and subcortical limbic regions contributing to a reduction in attentional control in the context of goal-irrelevant emotional stimuli. In parallel, they also influence activity in frontostriatal systems in ways that heighten sensitivity to reward and promote incentive-based learning. The rationale for the proposed research is that understanding the development of fronto-limbic-striatal systems during adolescence has the potential to translate into a mechanistic understanding of risk for mood disorders, which now afflict about one in every 10 young people at any given time, but also the creation of innovative de- velopmentally sensitive interventions. The specific aims are: 1) Determine in healthy adolescents how puberty influences neural activity in and functional connectivity between neural regions supporting attentional control in the context of emotional stimuli; 2) Determine in healthy adolescents the extent to which pubertal influences on reward systems will enhance reward-modulation of attentional control in the context of emotional stimuli. Exploratory analyses will examine pubertal influences on brain structure and how changes in neural indices across puberty relate to changes in levels of mood symptoms. A longitudinal design will be used to disentangle pubety- vs. age-related effects by recruiting groups of males and females matched on age but differing in pubertal status. Levels of sex hormones will be measured to determine individual differences in pubertal maturation. Frontolimbic function will be probed using an fMRI emotional working memory paradigm (with and without incentives) known to recruit prefrontal cortical regions, involved in attentional control, and subcortical limbic regions associated with emotion processing. This approach is innovative because it examines puberty-specific effects on frontolimbic-striatal systems implicated in emotion regulation. The proposed research is significant, because it can lead to the identification of neural markers of risk for mood disorders and inform future intervention studies grounded in knowledge from developmental neuroscience.