Pubertal Maturation and Motivational Influences on Frontolimbic Systems

描述（由申请人提供）：在理解青春期如何影响支持典型发育青少年情绪调节的神经系统方面存在根本性差距。填补这一空白对于推进有关情绪障碍风险的神经发育标志物的知识非常重要，情绪障碍通常在青春期发作，特别是在女孩中。 长期目标是了解额缘-纹状体系统的发育，以阐明情绪障碍风险的生物标志物以及可塑性增强的时期，从而为有针对性的基于大脑的神经行为干预提供信息。考虑到注意力偏差在情绪障碍中的重要性，本申请的目的是更深入地了解青春期对负责情绪刺激背景下注意力控制的额边缘系统的影响，以及青春期对奖励系统的影响在多大程度上可以增强激励措施的效果，以增强注意力控制过程。核心假设是青春期成熟加上性激素水平的升高影响了前额叶控制和皮质下控制之间的神经活动和功能连接。 在目标无关情境中，边缘系统区域对注意力控制的减少有贡献 情感刺激与此同时，它们也影响额纹状体系统的活动， 提高对奖励敏感性并促进以奖励为基础的学习。这项研究的基本原理是，了解青春期额叶-边缘-纹状体系统的发展有可能转化为对情绪障碍风险的机械理解，现在每10个年轻人中就有一个在任何给定时间受到影响，而且还创造了创新的对情绪敏感的干预措施。具体目标是：1）确定在健康青少年青春期如何影响神经活动和神经区域之间的功能连接，支持在情绪刺激的背景下的注意力控制; 2）确定在健康青少年青春期对奖励系统的影响将在多大程度上增强在情绪刺激的背景下注意力控制的奖励调制。探索性分析将研究青春期对大脑结构的影响，以及青春期神经指标的变化如何与情绪症状水平的变化相关。纵向设计将用于通过招募年龄匹配但青春期状态不同的男性和女性组来解开青春期与年龄相关的影响。将测量性激素水平，以确定青春期成熟的个体差异。额叶边缘功能将使用功能磁共振成像情绪工作记忆范式（有和没有激励），已知招募前额叶皮层区域，参与注意力控制，和皮层下边缘区与情绪处理相关的探测。这种方法是创新的，因为它研究了青春期特有的影响额缘纹状体系统涉及情绪调节。这项研究意义重大，因为它可以识别情绪障碍风险的神经标志物，并为未来基于发展神经科学知识的干预研究提供信息。

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.