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: 8596172
• 负责人: Kristina Andrea Uban
• 金额: $ 4.8万
• 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 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8596172
• 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; Performance; 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; 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）会改变特定大脑区域的结构和功能，这些改变与认知、行为和神经生理缺陷相对应；然而，对于区域间的结构和功能连接是如何改变的，我们知之甚少。进一步了解胎儿酒精谱系障碍（FASD）患者的发育轨迹是如何改变的，这对于专业干预措施的时机和设计，以及确定可能获得最大益处的敏感时期至关重要。最终，早期干预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（弥散张量成像）和功能（静息状态功能MRI）脑连接将使用多模态神经成像技术评估FASD青年和年龄匹配的对照组参与者。此外，尽管从动物模型中积累了证据，但对于FASD男孩和女孩的大脑发育和连接轨迹有何不同，我们还一无所知。PAE对改变激素系统的影响是否与FASD男孩和女孩的大脑异常有关，还有待调查。因此，目前的建议旨在使用多模态成像方法来评估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，激素将与大脑结构和功能连接的测量相结合。综合脑和激素测量将与认知表现测量相关（WISC-IV）。提出的研究结果对FASD患者中高发的认知、行为和精神健康问题具有启示意义。结果将有助于确定PAE对潜在神经网络的性别二态效应，以便为未来针对特定性别和特定神经网络损伤的干预和治疗策略提供信息。在关键的发育时期采取加强干预措施，可以通过预防/减少生命后期的一系列健康问题，帮助减轻卫生保健系统的负担。