Imaging Brain, Neurocognitive and Pubertal Maturation During Adolescence

描述(由申请人提供)：最近在理解与年龄相关的结构成熟变化方面取得了巨大进展，这些变化发生在儿童和青少年时期，但大脑结构的变异性非常大，即使在相同年龄段的人之间也是如此。文献表明，控制情感、情绪、编码信息的边缘结构的发育受到抵消，而边缘结构可能先于对冲动和风险评估提供调节控制的执行中心(额叶皮质)发育。目前对神经发育、神经内分泌、行为和环境因素几乎一无所知，这些因素可能与大脑结构和功能的变异性有关，也可能与青春期发生巨大变化的认知能力有关。在这个项目中，我们建议对120名9至15岁的典型发育青少年进行纵向研究，每隔两年扫描一次，并收集大脑成像(结构MRI、扩散张量成像和功能MRI，任务包括反应抑制、奖励处理、延迟折扣、面部情感处理)、神经认知(重点是执行功能和认知控制)、生理性成熟(使用Tanner分期)和荷尔蒙(使用唾液样本，皮质醇、睾酮、雌激素和脱氢表雄酮(DHEA))数据以及日常压力的测量。通过这些丰富的多模式成像、行为、认知和激素数据，我们将解决以下具体目标：1)区分激素依赖和非激素依赖对青春期神经发育的影响；2)评估大脑变化与认知行为指标(认知控制、执行功能、日常压力)和动机(例如奖励敏感性)之间的关系；以及3)评估大脑变化与青春期进程指标之间的关系的性别差异。据我们所知，这将是第一次通过使用功能和结构MRI的尖端综合多模式图像分析来纵向检查青少年的大脑发育，并将荷尔蒙与其他与年龄相关的环境和行为相关性区分开来，从而接受此类挑战的第一项研究。 与公共卫生相关：拟议中的研究在典型的发育中的儿童和青少年中使用集成的多模式神经成像、神经认知、压力和荷尔蒙纵向测量来研究青少年的大脑发育是至关重要的。青春期的开始是身体、情感和社会发生戏剧性变化的时期，也与抑郁症、自杀和药物滥用等精神病理的发生有关。为了提供一个框架，以了解青春期的风险如何改变青春期和成年期的病理结果，典型的大脑发育模型需要评估荷尔蒙和生理上的性成熟与仍在成熟的负责社会互动、情感状态和认知控制的神经系统之间的相互作用。

DESCRIPTION (provided by applicant): Enormous progress has been made recently in understanding the age-related structural maturational changes that occur in the human brain during childhood and adolescence, but variability in brain structure is very large, even among individuals of the same chronological age. The literature suggests an offset in development of limbic structures which control affect, emotion, encoding information, which may develop prior to the executive centers (frontal cortices) that provide regulatory control over impulses and risk assessment. Almost nothing is yet known about neurodevelopmental, neuroendocrine, behavioral and environmental factors that likely relate to variability in brain structure and function, and cognitive abilities that change so dramatically during adolescence. In this project, we propose to longitudinally study 120 typically developing adolescents between 9 and 15 years of age with 2-year scan intervals, and to collect brain imaging (structural MRI, diffusion tensor imaging and functional MRI with tasks of response inhibition, reward processing, delayed discounting, facial affect processing), neurocognitive (with emphasis on executive functioning and cognitive control), physical sexual maturation (using Tanners staging), and hormonal (cortisol, testosterone, estrogen and Dehydroepiandrosterone (DHEA) using saliva samples) data as well as measures of daily stress. With these rich multimodal imaging, behavioral, cognitive and hormonal data, we will address the following specific aims: 1) to distinguish hormone-dependent from non-hormone dependent neurodevelopmental effects in adolescence, 2) to evaluate relationships between brain changes and behavioral indices of cognition (cognitive control, executive functions, daily stress) and motivation (e.g., reward sensitivity), and 3) to evaluate gender differences in relationships between brain changes and indices of pubertal progression. To our knowledge, this will be the first study to undertake such challenges by using cutting-edge integrative multimodal image analyses of functional and structural MRI to examine, longitudinally, brain development in adolescents and to distinguish hormonal from other age-related environmental and behavioral correlates. PUBLIC HEALTH RELEVANCE: The proposed research to study adolescent brain development using integrated multimodal neuroimaging, neurocognitive, stress, and hormonal measures longitudinally in typically developing children and adolescents is of the utmost importance. The beginning of adolescence is a time of dramatic physical, emotional and social change, and is also associated with the onset of psychopathology such as depression, suicide, and substance abuse. To provide a framework for understanding how risks during adolescence can tip the balance toward pathological outcomes in youth and adulthood, models of typical brain development need to evaluate interactions between hormonal and physical sexual maturity and the still-maturing neural systems responsible for social interactions, affective states and cognitive control.