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（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却知之甚少。加强对胎儿酒精谱系障碍 (FASD) 患者发育轨迹如何改变的了解对于专门干预措施的时机和设计以及确定可实现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。将使用多模式神经影像技术对 FASD 青少年和年龄匹配的对照参与者的结构（弥散张量成像）和功能（静息状态功能 MRI）大脑连接进行评估。此外，尽管从动物模型中积累了越来越多的证据，但对于 FASD 男孩和女孩之间的大脑发育和连接轨迹有何不同，我们仍一无所知。 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，还有待研究。因此，本提案旨在使用多模态成像方法来评估 PAE 对大脑连接影响的性别差异。拟议的研究项目将评估 PAE 男孩和女孩的激素功能，并将激素与大脑结构和功能连接的测量相结合。综合大脑和激素测量将与认知表现测量（WISC-IV）相关联。拟议的研究结果对 FASD 患者中高发的认知、行为和心理健康问题具有影响。结果将有助于确定 PAE 对潜在神经网络的性别二态性影响，以便为未来针对特定性别和神经网络特定损伤的干预和治疗策略提供信息。在关键发育时期加强干预措施可能有助于通过预防/减少以后生活中的一系列健康问题来减轻医疗保健系统的负担。