Effects of in utero alcohol exposure on adolescent brain connectivity

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，这些变化与认知、行为和神经生理缺陷相对应；然而，人们对区域之间的结构和功能连接如何改变知之甚少。加强对胎儿酒精谱系障碍(FASD)患者的发育轨迹如何改变的了解，对于确定专门干预措施的时机和设计，以及确定可获得最大益处的敏感期至关重要。最终，早期干预可以帮助促进大脑网络的健康发展，并产生更有益的发展轨迹。结构(扩散张量成像)和功能(静息状态功能磁共振)脑连接将使用多模式神经成像技术在FASD青年和年龄匹配的对照组参与者中进行评估。此外，尽管从动物模型中积累了证据，但关于FASD男孩和女孩之间大脑发育和连接的这些轨迹如何不同，目前还不清楚。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，也有待调查。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男孩和女孩的荷尔蒙功能，荷尔蒙将与结构和功能大脑连接的测量相结合。综合的大脑和荷尔蒙测量将与认知表现测量(WISC-IV)相关。建议的发现对认知、行为和精神健康问题有影响，这些问题在FASD患者中高发。结果将有助于确定PAE对潜在神经网络的性二型性影响，以便为未来针对神经网络中特定性别和特定损伤的干预和治疗策略提供信息。在关键的发展时期加强干预措施，可通过预防/减少日后的一系列健康问题，帮助减轻保健系统的负担。

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.