Compensatory Neural Networks for the Cognitive Control of Emotion in Youth at Risk for Bipolar Disorder

项目总结/摘要 父母患有双相情感障碍的后代（“高危青年”）患双相情感障碍的风险增加。 精神病理学这些高危青年中的许多人情绪不稳定，情绪变化频繁， 情绪状态，导致功能低下，增加情绪障碍的风险。但并非所有 有家族风险的个体会发展为精神障碍，在这个项目中，我们探讨了代偿性的 网络可以帮助解释风险的个体差异。有几条证据表明， 支持工作记忆（WM）的回路可能充当这样一个补偿网络， 特别是记忆容量（WMC）与更好的情绪调节和更少的情绪不稳定性有关。的 这个项目的目的是更好地了解情绪不稳定的神经回路，然后评估潜在的 双相情感障碍（BD）风险青年的补偿神经机制。我们建议首先评估 高危青年和健康青年腹侧核激活和功能连接（FxC）的差异 参与情绪认知重新评价的网络，以及这些网络中的个体差异是否 与高危青年的情绪不稳定程度相关。接下来，我们评估是否存在更大的WMC（和FxC）。 中央执行网络，中央WM）可能会补偿这些腹侧异常，因此可能是 与高危青少年的情绪不稳定性有关。为了探究这种关系的方向性， 我们在一组高危、不稳定的青少年中进行了WM训练的试点操作（5周）。鉴定 在问题青年中建立这样一个补偿网络将为在这些青年中采取预防措施提供一个目标， 并为未来的研究铺平道路，调查建设复原力的战略。 与本研究计划相一致，培训目标将为主要研究者提供一套技能 需要进一步追求这一研究路线：具体来说，在发展认知神经科学的培训， 在儿科人群中进行神经影像学研究， 神经成像数据。为了获得这项培训，PI组建了一个具有相关专业知识的导师团队 最值得注意的是，她的导师玛丽菲利普斯博士（BD神经影像学）和共同导师鲍里斯Birmaher博士 （与屋宇署进行青年研究）。她还设计了详细的培训计划，其中包括 与顾问，课程和研讨会的正式合作。研究和培训活动将 主要发生在匹兹堡大学，一个致力于儿科BD研究的机构， 以及情感和认知神经科学，以及支持职业发展的良好记录 初级教员。这项培训将建立在PI作为儿童精神病学家的现有背景之上， 统计学和临床神经科学的知识，为她提供必要的技能，成为一个 独立调查员她的长期研究目标是更好地描述神经发育 我们的目标是研究青少年BD的发展轨迹，并制定战略，在那些有障碍风险的人中建立复原力。

PROJECT SUMMARY / ABSTRACT Offspring of parents with bipolar disorder (“at-risk youth”) are at increased risk for the development of psychopathology. Many of these at-risk youth have elevated mood lability, frequent and severe changes in mood state, which contributes to poor functioning and increases risk for mood disorder. However, not all individuals at familial risk develop psychiatric disorders, and in this project we explore the compensatory networks that could help to explain individual differences in risk. Several lines of evidence indicate that neural circuitry supporting working memory (WM) might act as such a compensatory network, and that better working memory capacity (WMC) in particular is associated with better emotion regulation and less mood lability. The objective of this project is to better understand the neural circuitry of mood lability, and to then assess potential compensatory neural mechanisms in youth at risk for bipolar disorder (BD). We propose to first assess differences between at-risk and healthy youth in the activation and functional connectivity (FxC) of ventral networks involved in cognitive reappraisal of emotion, and whether the individual differences in these networks correlate with degree of mood lability in the at-risk youth. We next evaluate if a greater WMC (and FxC of the central executive network, central to WM) might compensate for these ventral abnormalities, and thus might be associated with less mood lability in at-risk youth. To provide a probe of the directionality of this relationship, we conduct a pilot manipulation of WM training (5 weeks) in a subset of at-risk, labile youth. Identification of such a compensatory network in at-risk youth would provide a target for preventive measures in these youth, and pave the way for future studies investigating strategies for building resilience. In concert with this research plan, training goals will provide the Principal Investigator with a skillset necessary to further pursue this line of research: specifically, training in developmental cognitive neuroscience, the implementation of neuroimaging studies in pediatric populations, and sophisticated analysis of neuroimaging data. To obtain this training, the PI has assembled a mentorship team with expertise in relevant areas, most notably, her mentor Dr. Mary Phillips (neuroimaging in BD) and co-mentor Dr. Boris Birmaher (implementation of studies of youth with BD). She has also designed a detailed training plan, which includes formal collaborations with consultants, coursework, and workshops. Research and training activities will primarily occur at the University of Pittsburgh, an institution with a commitment to research in pediatric BD, as well as affective and cognitive neuroscience, and a strong track record for supporting the career development of junior faculty. This training will build on the PI’s existing background as a child psychiatrist with a strong knowledge of statistics and clinical neuroscience, to provide her will the necessary skills to become an independent investigator. Her long-term research goal is to better characterize the neurodevelopmental trajectory of BD in youth, and develop strategies for building resilience in those who are at risk for disorder.