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

评估 ADHD 4 特斯拉大脑生物化学的发展轨迹

• 批准号: 7797289
• 负责人: Jeffrey A Stanley
• 金额: $ 47.54万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-01-15 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7797289
• 关键词: 11 year old; 14 year old; Accounting; Address; Adolescence; Adolescent; Affect; Age; Anterior; Area; Attention; Attention deficit hyperactivity disorder; Basal Ganglia; Behavior; Behavioral; Bilateral; Biochemical; Biochemistry; Brain; Brain region; Child; Childhood; Cognition; Cognitive; Corpus striatum structure; Data; Dendrites; Development; Dorsal; Ethanolamines; Foundations; Frequencies; Functional disorder; Funding; Gender; Goals; Gray unit of radiation dose; Growth; Image; Lead; Left; Longitudinal Studies; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Medial; Membrane; Mental Health Services; Methods; Modeling; Motor; Neurodevelopmental Disorder; Neurons; Neuropil; Neuropsychological Tests; Parietal; Pathogenesis; Pathway interactions; Perception; Performance; Phospholipids; Phosphorous; Phosphorylcholine; Play; Prefrontal Cortex; Process; Protocols documentation; Public Health; Recruitment Activity; Regulation; Relative (related person); Resolution; Role; Short-Term Memory; Socioeconomic Status; Solid; Specificity; Spectrum Analysis; Surface; Synapses; System; Techniques; Testing; Thick; Time; Treatment outcome; Visit; Weight; Work; age group; base; executive function; follow-up; improved; in vivo; motivational processes; motor control; neurodevelopment; neuroimaging; neuropsychological; performance tests; phosphodiester; phosphoethanolamine; phosphomonoester; public health relevance; research study; ultra high resolution; white matter

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. PUBLIC HEALTH RELEVANCE 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 cause of this illness remains poorly understood, ADHD is increasingly seen as a neurodevelopmental disorder. This work promises to identify where in the brain and at what age certain alterations occur in children and adolescents with ADHD, and this information of changes with age can then potentially be used as a predictor of treatment outcome. .

描述（由申请人提供）：注意缺陷多动症（ADHD）是一个严重的公共卫生问题，影响3至9％的儿童，占儿童转诊至精神卫生服务的30％至40％之间。尽管这种疾病的发病机理仍然鲜为人知，但ADHD越来越被视为一种神经发育障碍，涉及抑制性调节，执行功能，动机过程，感知和运动控制。我们的长期目标是提高我们对小儿多动症中神经发育偏差的理解。该更新应用的目的是测试早期出现的纹状体的改变是否在后来发生的变化之前发生在较慢的发展前额叶区域，例如背外侧前额叶皮层（DLPFC）。 从童年到青春期，大脑会经历实质性的结构和功能变化，而差分时间与认知和行为的成熟相似。这种“微调”或成熟的认知性能的过程包括消除过度生产的神经元连接或突触，可以使用非侵入性神经影像学方法评估体内磷（31p）光谱法。从我们的第一循环中，在1.5特斯拉处获得的横截面31p光谱结果表明，基础神经节缺陷表明，树突状分支和突触形成和突触的形成不足，前额叶皮层缺陷，但仅在相对较老的儿童中，在相对较老的儿童中暗示了一个不足的过程。但是，要确定评估随着时间的推移的发展变化需要纵向测量。因此，这项研究的目的是获取纵向全脑3D多素体31p光谱和超高分辨率的解剖学MRI测量在4泰斯拉的儿童和青少年，有和没有多动症。那是基线加两次后续访问，相距12个月。使用高场MR系统可显着提高区域特异性和生化分辨率。将评估皮质表面形貌的偏差以及针对不同认知/行为领域的神经心理学指标。这项纵向研究的总体假设是，患有多动症的儿童将证明神经发育轨迹的区域偏差相对于健康对照，包括在较慢的DLPFC中，但直到DLPFC中发生在童年后期的DLPFC中的微调过程开始。意义：如果确认，这些研究将提供更直接的证据，证明针对纹状体的自下而上功能障碍的发育机制可能会损害ADHD儿童前额叶皮层中控制过程或执行功能的微调。此外，这些观察结果将建立与健康对照相比的小儿多动症中生化轨迹的基础，这可能导致改善对ADHD的评估和治疗。 公共卫生相关性注意力缺陷多动障碍（ADHD）是一个严重的公共卫生问题，影响3至9％的儿童，占儿童转诊至30％至40％的心理健康服务。虽然这种疾病的原因仍然鲜为人知，但ADHD越来越被视为神经发育障碍。这项工作有望确定患有多动症的儿童和青少年在大脑中以及在哪些年龄中发生某些变化的地方，然后可能会将这种变化随着年龄的变化的信息作为治疗结果的预测指标。 。