Neurobehavioral consequences of Mild Traumatic Brain Injury and addiction risk: a cotwin-control study

项目摘要/摘要 这项拟议研究的总体目标是确定儿童时期轻度的长期神经行为后果。 创伤性脑损伤(MTBI)对发育中的大脑的影响，并使用 严格的共生对照设计、纵向跟踪以及多模式和创新的神经成像工具和 神经行为评估。儿童期或青春期持续的MTBI，大脑持续的时期 发展和重组，是一个重大的公共卫生问题，因为其发病率高，持续时间长 与成瘾行为风险增加相关的神经行为后果。然而，在这方面的进展 了解mTBI的长期后遗症及其在成瘾中的作用受到许多重要因素的阻碍 方法学挑战：a)病例对照研究是相关的，不允许区分后果 先前存在的神经认知缺陷导致的脑外伤的风险可能增加；b)匹配病例和 控制是非常有问题的，因为大脑结构和基因的个体差异很大 脑损伤的功能和异质性；c)单一的神经成像方式只能提供有限的洞察 D)在横断面研究中，mTBI的影响可能与 物质使用的影响。拟议的研究将结合以下几个方面来解决这些阻碍进展的关键障碍 严谨和创新的方法：(1)双对控制设计，将为以下方面提供尽可能好的控制 MTBI病例--他们的无脑外伤病史的同卵同卵双胞胎，(Ii)多模式神经影像评估 利用核磁共振的高空间分辨率和脑电生理的高时间分辨率，以及(Iii) 对物质使用行为变化(开始、经常使用、物质使用)的纵向跟踪评估 障碍症状)。评估将包括结构、功能和弥散磁共振成像、定量梯度 回顾回声(QGRE)磁共振成像是一种新的神经成像技术，对大脑皮质细胞微结构敏感 神经生理学，包括静息状态脑电和事件相关脑电位(ERP)，方法是 对神经动力学的异常时序和同步性敏感。将致力于实现以下具体目标： 目标1：确定青春期早期mTBI的长期后果，并将其与先前存在的区别开来 使用双重对照设计的可能与mTBI风险相关的因素。我们假设，在mTBI中- 不协调的同卵双胞胎，有mTBI生前病史的双胞胎将显示大脑结构和 与无mTBI病史的同卵双胞胎相比，其神经心理功能和缺陷；目的 2：通过横断面和前瞻性研究，确定脑外伤是否与高血压风险升高有关。 上瘾的行为。更好地理解长期神经行为的机制 儿童期和青春期mTBI的后果有助于成瘾风险将通知更多的发展 有效的治疗和康复办法，以及预防药物使用和滥用以及精神疾病 有脑外伤病史的年轻人的疾病。

Project Summary/Abstract The overall goal of the proposed study is to identify long-term neurobehavioral consequences of childhood mild traumatic brain injury (mTBI) for the developing brain and examine their contribution to addiction risk using a rigorous cotwin-control design, longitudinal follow-up, and multimodal and innovative neuroimaging tools and neurobehavioral assessments. mTBI sustained during childhood or adolescence, periods of continuing brain development and reorganization, is a major public health problem due to its high prevalence and long-lasting neurobehavioral consequences associated with increased risk for addictive behaviors. However, progress in understanding long-term sequelae of mTBI and their role in addiction is hindered by a number of significant methodological challenges: a) case-control studies are correlative and do not allow to distinguish consequences of TBI from pre-existing neurocognitive deficits potentially increasing the risk for TBI; b) matching cases and controls is very problematic due to substantial (and largely heritable) individual variability in brain structure and function and heterogeneity of brain damage; c) single neuroimaging modalities provide only a limited insight into the consequences of mTBI; d) in cross-sectional studies, the effects of mTBI may be confounded with the effects of substance use. The proposed study will address these critical barriers to progress using a combination of rigorous and innovative approaches: (i) the co-twin control design that will provide the best-possible controls for mTBI cases - their monozygotic co-twins without TBI history, (ii) multimodal neuroimaging assessments leveraging high spatial resolution of MRI and high temporal resolution of brain electrophysiology, and (iii) a longitudinal follow-up assessment of changes in substance use behaviors (onset, regular use, substance use disorder symptoms). Assessment will include structural, functional, and diffusion MRI, quantitative Gradient Recalled Echo (qGRE) MRI, a novel neuroimaging technique sensitive to cortical cellular microstructure, brain neurophysiology including resting-state EEG, and event-related brain potentials (ERP), methods that are sensitive to abnormal timing and synchrony of neuronal dynamics. The following Specific Aims will be pursued: Aim 1: To identify long-term consequences of mTBI in early adolescence and distinguish them from pre-existing factors potentially associated with risk for mTBI using a cotwin control design. We hypothesize that, in mTBI- discordant monozygotic pairs, twins with lifetime history of mTBI will show alterations in brain structure and function and deficits in neuropsychological performance compared with their cotwins without mTBI history; Aim 2: To determine, both cross-sectionally and prospectively, whether mTBI is associated with elevated risk for addictive behaviors. A better understanding of the mechanisms by which long-lasting neurobehavioral consequences of childhood and adolescent mTBI contribute to addiction risk will inform the development of more efficient treatment and rehabilitation approaches, as well as prevention of substance use and abuse and mental illness in youth with a history of mTBI.