Reversal Learning in Pediatric Bipolar Disorder

描述（由申请人提供）：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，对儿童和青少年的BPD知之甚少。新的数据表明，BPD儿童在逆转学习中受损。这一过程需要行为适应不断变化的刺激-回报偶然性，并涉及腹侧前额叶皮层（vPFC）、腹侧纹状体和杏仁核。我的长期目标是了解大脑/行为的相互作用，情绪调节的核心，如何区分正常和精神病儿童，以制定更有效的诊断和治疗策略。对逆向学习的研究将有助于我在这方面的努力。 本申请的目的是（1）获得fMRI方法和实验设计方面的培训，（2）识别儿童BPD中受损逆转学习的神经学相关性，以及（3）基于本工作开发R 01应用程序。我的中心假设是，BPD儿童在逆转学习中有特定的损伤，这是由于包括vPFC、腹侧纹状体和杏仁核在内的神经回路功能障碍所致。为了验证这一假设，我将：（1）使用功能磁共振成像来识别正常儿童的逆转学习的底物;（2）确定BPD儿童在逆转学习过程中的功能神经解剖学和行为差异;（3）评估精神病对照组逆转学习缺陷的特异性。我将使用我们小组开发的“反应逆转”任务，用3特斯拉的功能磁共振成像和行为数据来评估逆转学习。这将是首批将行为功能障碍与严格定义的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儿童在逆转学习过程中额颞叶结构有选择性改变。 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，对儿科BPD的病理生理学更深入的了解将使儿科BPD领域超越基于ESTA的诊断，可能允许更准确或更早的诊断，从而降低患有这种衰弱性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.