Reversal Learning in Pediatric Bipolar Disorder

描述(申请人提供)：双相情感障碍(BPD)是美国成年人发病率和死亡率的主要来源，每年花费超过240亿美元；然而，对儿童和青少年BPD的了解要少得多。新出现的数据显示，BPD儿童在反转学习方面存在障碍。这一过程需要行为适应不断变化的刺激-奖赏偶发事件，并参与腹侧前额叶皮质(VPFC)、腹侧纹状体和杏仁核。我的长期目标是了解大脑/行为交互是情绪调节的核心，如何区分正常儿童和精神疾病儿童，以便开发更有效的诊断和治疗策略。反转学习的研究将有助于我在这方面的努力。 该应用程序的目标是(1)获得fMRI方法和实验设计方面的培训，(2)确定儿童BPD患者逆转学习受损的神经学相关性，以及(3)在此工作的基础上开发R01应用程序。我的中心假设是，由于vPFC、腹侧纹状体和杏仁核周围神经回路的功能障碍，BPD儿童在反转学习方面存在特定的障碍。为了验证这一假设，我将：(1)使用功能磁共振成像来确定正常儿童反转学习的底物；(2)确定BPD儿童在反转学习过程中的功能、神经解剖学和行为差异；(3)评估精神对照组中反转学习缺陷的特异性。我将使用我们小组开发的“反应反转”任务，用3个特斯拉的fMRI和行为数据来评估反转学习。这将是第一批将行为障碍与患有严格定义的BPD儿童的大脑异常联系起来的研究之一。从这些研究中，我希望确定BPD儿童在反转学习过程中额颞部结构有选择性的改变。 这项拟议的工作将对儿童心理健康产生积极影响，促进我们对儿童和青少年BPD的潜在大脑/行为异常的了解。反过来，对儿童BPD的更好的病理生理学了解将使儿童BPD的领域超越基于症状的诊断，潜在地允许更准确或更早的诊断，从而降低患有这种衰弱疾病的儿童和青少年的发病率和死亡率。

DESCRIPTION (provided by applicant): Bipolar disorder (BPD) in a major source of morbidity and mortality for adults in America, with more than $24 billion spent annually; however, far less is known about BPD in children and adolescents. Emerging data shows that BPD children are impaired in reversal learning. This process requires behavioral adaptation to changing stimulus-reward contingencies and engages the ventral prefrontal cortex (vPFC), ventral striatum, and amygdala. My long-term goal is to understand how brain/behavior interactions, central to emotion regulation, differentiate normal from psychiatrically ill children, in order to develop more effective diagnostic and treatment strategies. The study of reversal learning will facilitate my efforts in this respect. The objectives of this application are to (1) acquire training in fMRI methods and experimental design, (2) identify neurological correlates of impaired reversal learning in pediatric BPD, and (3) develop an R01 application based on this work. My central hypothesis is that BPD children have specific impairments in reversal learning due to dysfunction in a neural circuit encompassing the vPFC, ventral striatum, and amygdala. To test this hypothesis, I will: (1) use fMRI to identify substrates of reversal learning in normal children; (2) determine functional neuroanatomical and behavioral differences in BPD children during reversal learning; (3) evaluate the specificity of reversal learning deficits in psychiatric controls. I will use the "response reversal" task developed by our group to evaluate reversal learning with 3 Tesla fMRI and behavioral data. This will be among the first studies to link behavioral dysfunction to brain abnormalities in children with strictly defined BPD. From these studies, I expect to determine that BPD children have selective alterations in fronto-temporal structures during reversal learning. The proposed work will positively impact child mental health advancing our knowledge of the underlying brain/behavior abnormalities mediating BPD in children and adolescents. In turn, greater pathophysiological understanding of pediatric BPD will move the field of pediatric BPD beyond symptom-based diagnosis, potentially allowing more accurate or earlier diagnosis, thus reducing the morbidity and mortality in children and adolescents suffering from this debilitating disorder.