Effects of in utero alcohol exposure on adolescent brain connectivity

子宫内酒精暴露对青少年大脑连接的影响

• 批准号: 8895226
• 负责人: Kristina Andrea Uban
• 金额: $ 5.42万
• 依托单位: CHILDREN'S HOSPITAL OF LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2016-08-22
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8895226
• 关键词: Adolescent; Affect; Age; Animal Model; Animals; Behavioral; Biological Neural Networks; Brain; Brain region; Circadian Rhythms; Cognitive; Development; Diffusion Magnetic Resonance Imaging; Dysmorphology; Early Intervention; Estradiol; Exhibits; Face; Female; Female Adolescents; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Functional Magnetic Resonance Imaging; Future; Gonadal Hormones; Health; Healthcare Systems; High Prevalence; Hippocampus (Brain); Hormones; Human; Hydrocortisone; Impaired cognition; Impairment; Individual; Intervention; Life; Measurement; Measures; Mental Health; Multimodal Imaging; Parietal; Participant; Pattern; Physiological; Problem behavior; Research Project Grants; Rest; Role; Severities; Sex Characteristics; Stress; Structure; System; Techniques; Testosterone; Time; Vulnerable Populations; Youth; behavior measurement; behavioral health; behavioral impairment; boys; cognitive performance; cohort; dehydroepiandrosterone; design; effective intervention; girls; improved; neuroimaging; neurophysiology; prevent; public health relevance; relating to nervous system; segregation; sex; treatment strategy; white matter

DESCRIPTION (provided by applicant): Prenatal alcohol exposure (PAE) alters the structure and function of specific brain regions, and these alterations correspond with cognitive, behavioral and neurophysiological deficits; however very little is known about how structural and functional connectivity among regions may be altered. Enhanced understanding of how developmental trajectories are altered in individuals with a Fetal Alcohol Spectrum Disorder (FASD) is essential for the timing and design of specialized interventions, and for identifying sensitive periods during which maximal benefits may be achieved. Ultimately, early interventions can help improve healthy development of brain networks, and produce a more beneficial developmental trajectory. Structural (diffusion tensor imaging) and functional (resting state functional MRI) brain connectivity will be assessed using multimodal neuroimaging techniques in FASD youth and age-matched control participants. Moreover, despite accumulating evidence from animal models, nothing is yet known about how these trajectories of brain development and connectivity differ between FASD boys and girls. It also remains to be investigated if the effects of PAE on altering hormone systems is involved with brain abnormalities in FASD boys and girls. Thus, the present proposal aims to use a multimodal imaging approach to assess sex differences in the effects of PAE on brain connectivity. The proposed research project will assess hormone function in PAE boys and girls, and hormones will be integrated with measures of structural and functional brain connectivity. Integrated brain and hormone measures will be correlated with measures of cognitive performance (WISC-IV). The proposed findings have implications for cognitive, behavioral and mental health problems that occur at a high prevalence among individuals with an FASD. Results will help identify sexually dimorphic effects of PAE on underlying neural networks in order to inform future intervention and treatment strategies targeted to a specific sex and specific impairments in neural networks. Enhanced interventions applied during key developmental time periods may help relieve the burden on health care systems by preventing/reducing a range of health problems later in life.

描述（由申请人提供）：产前酒精暴露（PAE）改变了特定大脑区域的结构和功能，这些改变与认知，行为和神经生理学缺陷相对应；然而，对于如何改变区域之间的结构和功能连通性知之甚少。对患有胎儿酒精谱系障碍（FASD）的个体的发展轨迹如何改变的发育轨迹的了解对于特殊干预措施的时间和设计至关重要，并且对于确定可以实现最大益处的敏感时期至关重要。最终，早期干预措施可以帮助改善大脑网络的健康发展，并产生更有益的发展轨迹。结构性（扩散张量成像）和功能性（静止状态功能MRI）将使用FASD青年和年龄匹配的对照参与者中的多模式神经成像技术评估大脑连接性。此外，尽管从动物模型中积累了证据，但FASD男孩和女孩之间的这些大脑发育和连通性的轨迹如何有所不同。如果PAE对FASD男孩和女孩的脑异常涉及改变激素系统的影响，这也尚待研究。因此，本提案旨在使用多模式成像方法来评估PAE对大脑连通性影响的性别差异。拟议的研究项目将评估PAE男孩和女孩的激素功能，激素将与结构和功能性脑连通性的度量相结合。综合的大脑和激素测量将与认知性能的度量（WISC-IV）相关。提出的发现对FASD患者的认知，行为和心理健康问题具有影响。结果将有助于确定PAE对基本神经网络的性二态影响，以告知针对神经网络特定性别和特定损害的未来干预和治疗策略。在关键发育期间采用的增强干预措施可以通过防止/减少生活中的一系列健康问题来帮助减轻医疗保健系统的负担。