Assessing Development Trajectories of the Brain Biochemistry in ADHD at 4 Tesla

描述(申请人提供)：注意力缺陷多动障碍(ADHD)是一种严重的公共卫生问题，影响3%至9%的儿童，占转诊至精神健康服务的儿童的30%至40%。虽然这种疾病的发病机制仍然知之甚少，但ADHD越来越被视为一种神经发育障碍，涉及抑制调节、执行功能、动机过程、感知和运动控制。我们的长期目标是增加我们对儿童ADHD神经发育偏差的了解。这一更新应用的目的是测试较早发育的纹状体的改变是否先于发育较慢的前额叶区域的改变，如背外侧前额叶皮质(DLPFC)。从童年到青春期，大脑经历了实质性的结构和功能变化，时间不同，这与认知和行为的成熟平行。这种“微调”或成熟认知能力的过程包括消除过度产生的神经元连接或突触，这可以使用非侵入性神经成像方法-体内磷(31P)光谱分析来评估。从我们的第一个资助周期中，在1.5特斯拉获得的体内横断面31P波谱结果显示，基底节缺陷表明树突分支和突触形成发育不足，前额叶皮质缺陷，但仅在相对较大的ADHD儿童中，表明微调的成熟过程未实现充分。然而，要确定地评估随着时间的发展变化，需要纵向测量。因此，本研究的目的是获取患有和不患有ADHD的儿童和青少年在4特斯拉的纵向全脑3D多体素31P波谱和超高分辨率解剖MRI测量；即基线加上相隔12个月的两次随访。使用高场磁共振系统显著提高了区域特异性和生化分辨率。将评估皮质表面地形图的偏差，并在每个时间点收集针对不同认知/行为领域的神经心理测量。这项纵向研究的总体假设是，ADHD儿童将表现出相对于健康对照组的神经发育轨迹的区域性偏差，包括发育较慢的DLPFC，但直到DLPFC的微调过程开始之前，DLPFC发生在童年后期。意义：如果得到证实，这些研究将提供更直接的证据，证明纹状体存在自下而上的功能障碍，可能会损害ADHD儿童前额叶皮质控制过程或执行功能的微调。此外，这些观察将为儿童ADHD与健康对照组对比的生化轨迹奠定基础，这可能导致对ADHD的评估和治疗的改进。

DESCRIPTION (provided by applicant): Attention Deficit Hyperactivity Disorder (ADHD) is a serious public health problem that affects between 3 to 9% of children and accounts for between 30 to 40% of child referrals to mental health services. While the pathogenesis of this illness remains poorly understood, ADHD is increasingly seen as a neurodevelopmental disorder implicating inhibitory regulation, executive function, motivational processes, perception and motor control. Our long-term goal is to increase our understanding of neurodevelopmental deviations in pediatric ADHD. The objective of this renewal application is to test whether alterations of the earlier developing striatum precede alterations that occur later in the slower developing prefrontal areas such as the dorsolateral prefrontal cortex (DLPFC). From childhood to adolescence, the brain undergoes substantive structural and functional changes with differential timing, which parallel the maturation of cognition and behavior. This process of "fine-tuning" or maturing cognitive performance includes the elimination of overproduced neuronal connections or synapses, which can be assessed using the noninvasive neuroimaging method, in vivo phosphorous (31P) spectroscopy. From our first-cycle of funding, the cross-sectional in vivo 31P spectroscopy results acquired at 1.5 Tesla show basal ganglia deficits suggesting an underdevelopment of dendritic branching and synaptic formations, and prefrontal cortex deficits but only in the relatively older ADHD children suggesting an underachieved maturational process of fine-tuning. However, to definitively assess developmental changes over time requires longitudinal measurements. Therefore, the aims of this study are to acquire longitudinal whole-brain 3D multi- voxel 31P spectroscopy and ultra-high resolution anatomical MRI measurements at 4 Tesla in children and adolescent with and without ADHD; that is baseline plus two follow-up visits 12-months apart. Using a high- field MR system dramatically improves the regional specificity and biochemical resolution. Deviations in cortical surface topography will be assessed as well as neuropsychological measures targeting different cognitive/behavioral domains will be collected at each time point. The overall hypothesis of this longitudinal study is that children with ADHD will demonstrate regional deviations in neurodevelopmental trajectories relative to healthy controls including in the slower developing DLPFC, but not until the onset of the fine-tuning processes in the DLPFC that occurs late in childhood. Significance: If confirmed, these studies will provide more direct evidence of a developmental mechanism targeting a bottom-up dysfunction in the striatum potentially impairing the fine-tuning of control processes or executive functions in the prefrontal cortex of children with ADHD. Additionally, these observations will establish a foundation of biochemical trajectories in pediatric ADHD contrasted against healthy controls, which may lead toward improved assessment and treatment of ADHD.