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

轻度创伤性脑损伤和成瘾风险的神经行为后果：一项 cotwin 对照研究

• 批准号: 10803512
• 负责人: Andrey P. Anokhin
• 金额: $ 69.83万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10803512
• 关键词: Addictive Behavior; Adolescence; Adolescent; Age; Anxiety; Behavior; Behavioral; Brain; Brain Injuries; Case/Control Studies; Childhood; Cognition; Corpus Callosum; Correlative Study; Cross-Sectional Studies; Data Analyses; Development; Diffusion Magnetic Resonance Imaging; Discrimination; Electroencephalography; Electrophysiology (science); Equation; Etiology; Event; Female; Functional Magnetic Resonance Imaging; Goals; Heritability; Heterogeneity; High Prevalence; Impulsivity; Knowledge; Link; Magnetic Resonance Imaging; Mediating; Mental Health; Mental disorders; Methodology; Methods; Modality; Modeling; Monozygotic twins; Neurocognitive Deficit; Neurons; Neuropsychology; Pathway interactions; Performance; Prevention; Psychopathology; Public Health; Recording of previous events; Rehabilitation therapy; Reporting; Resolution; Rest; Risk; Risk Factors; Role; Self Medication; Structure; Substance Use Disorder; Substance abuse problem; Symptoms; Techniques; Testing; Thick; Trauma; Twin Multiple Birth; Youth; addiction; adverse outcome; case control; cognitive function; comorbidity; coping; design; early adolescence; early onset substance use; emotion regulation; follow up assessment; follow-up; functional disability; gray matter; high risk; individual variation; innovation; insight; long-term sequelae; mild traumatic brain injury; mind control; multimodal neuroimaging; multimodality; negative affect; neural; neurobehavioral; neurodevelopment; neuroimaging; neurophysiology; novel; physical conditioning; prospective; risk sharing; stress reactivity; substance abuse prevention; substance use; substance use prevention; temporal measurement; tool; white matter

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.

项目摘要/摘要 拟议的研究的总体目标是确定儿童温和的长期神经行为后果 用于发育中的大脑的创伤性脑损伤（MTBI），并检查其对成瘾风险的贡献 严格的Cotwin-Control设计，纵向随访以及多模式和创新的神经影像学工具和 神经行为评估。 MTBI在童年或青春期，持续大脑时期 开发和重组，由于其高流行且持久而是一个主要的公共卫生问题 神经行为的后果与增加上瘾行为的风险有关。但是，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 方法论上的挑战：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的TBI可能会增加TBI的风险； b）匹配案例和 由于大脑结构和 脑损伤的功能和异质性； c）单个神经影像模式仅提供有限的见解 MTBI的后果； d）在横断面研究中，MTBI的影响可能与这些影响混淆 使用物质。拟议的研究将解决这些关键障碍，以结合 严格且创新的方法：（i）将为最有可能的控件提供的共同双重控制设计 MTBI病例 - 他们的单卵双重二线，没有TBI病史，（ii）多模式神经影像学评估 利用MRI的高空间分辨率和大脑电生理学的高时间分辨率和（iii）A 对物质使用行为变化的纵向随访评估（发病，定期使用，使用物质 疾病症状）。评估将包括结构，功能和扩散MRI，定量梯度 召回回声（QGRE）MRI，一种对皮质细胞微结构敏感的新型神经影像学技术 神经生理学包括静息状态脑电图和事件相关的大脑电位（ERP），方法是 对神经元动力学的异常时间和同步敏感。将追求以下具体目标： 目标1：确定MTBI在青春期早期的长期后果，并将其与预先存在 使用Cotwin控制设计可能与MTBI风险相关的因素。我们假设在mtbi中 不一致的单卵双对，具有MTBI寿命的双胞胎将显示大脑结构和 与没有MTBI病史的Cotwins相比，神经心理表现的功能和缺陷；目的 2：在横截面和前瞻性上确定MTBI是否与较高的风险有关 上瘾的行为。更好地理解持久神经行为的机制 童年和青少年MTBI的后果导致成瘾风险促进了更多的发展 有效的治疗和康复方法，以及预防药物使用和滥用以及精神 有MTBI史的年轻人的疾病。