Intergenerational Neuroimaging of Language and Reading Networks Using a Natural Cross-Fostering Design

使用自然交叉培养设计的语言和阅读网络的代际神经影像

• 批准号: 10403943
• 负责人: FUMIKO HOEFT
• 金额: $ 64.52万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-10 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10403943
• 关键词: Address; Age; Animal Experimentation; Animal Model; Animals; Behavioral; Behavioral Research; Biological; Biological Models; Black race; Brain; Brain region; Child; Cognitive; Complex; Conceptions; Daughter; Development; Developmental reading disorder; Dorsal; Early Intervention; Environmental Risk Factor; Exposure to; Family; Family member; Fathers; Fertilization in Vitro; Formulation; Fostering; Foundations; General Population; Genetic; Genetic study; Gestational surrogate; Human; Individual Differences; Intervention; Investigation; Knowledge; Language; Learning Disorders; Magnetic Resonance Imaging; Mathematics; Measures; Mediating; Mothers; Neurobiology; Neurocognitive Deficit; Newborn Infant; Orthography; Outcome; Parents; Pathway interactions; Pattern; Phenotype; Prevalence; Prevention strategy; Procedures; Process; Protocols documentation; Publishing; Reading; Reading Disorder; Research; Risk; Sex Differences; Site; Son; Time; Translations; Triad Acrylic Resin; aged; base; behavioral phenotyping; design; egg; intergenerational; language processing; multimodal neuroimaging; neurodevelopment; neuroimaging; non-genetic; novel strategies; offspring; phonology; postnatal; prenatal; prenatal influence; protective factors; recruit; relating to nervous system; sex; skills; sperm cell; success; trait; transmission process

ABSTRACT The main objective of the proposed research is to examine, for the first time, intergenerational transmission of human brain networks using a natural cross-fostering design. We take reading-related brain networks, in particular those related to phonological and orthographic processing (as well as in language- and more preliminarily in math-related processes), as model systems because of the potentially differential impact of genetic and environmental factors on these networks and corresponding behavioral phenotypes. In addition, impairment of these neurocognitive processes is associated with specific learning disorder of word reading (aka decoding-based reading disorder [RD] or developmental dyslexia) that has a lifetime prevalence of 5- 10%, and an increased risk of the offspring developing RD by 4 to 8 times the general population with an immediate family member with RD. The proposed natural cross-fostering design addresses a critical question about the mechanisms of intergenerational effects, i.e., whether they are genetic (G), prenatal (PreE) or postnatal environmental (PostE) in origin. This is only now possible with the widespread availability of in-vitro fertilization (IVF). We will obtain cognitive measures, and functional and structural MRI, in healthy families (triads) at a pace of 30 families per site per year. We will examine parent-offspring correlations, including brain- brain correlations, across four groups of IVF children that receive distinctive G/PreE/PostE contributions from their rearing parents as well as a fifth group of naturally conceived children (N=60 triads per group, with children of ages 8-11, half with daughters and the other half with sons): (1) the HOMOLOGOUS group in which offspring conceived through IVF are borne and reared by their genetic parents, thus being exposed to maternal and paternal G/PreE/PostE influences; (2) the DONOR EGG and (3) DONOR SPERM groups, in which offspring are conceived from donor eggs/sperm, and hence rearing mothers/fathers only have PreE/PostE, not G, influence on their offspring; (4) the gestational SURROGACY group in which offspring are borne through non-genetic, non-rearing mothers, and hence rearing parents only have G/PostE but no PreE influences over their offspring; and (5) the NATURAL conception group in which naturally conceived offspring are borne and reared by their genetic parents, thus being exposed to maternal and paternal G/PreE/PostE influences and without the influence of IVF. Fathers’ PreE influence is typically considered minimal. The specific aims of the proposal are: to examine parent-offspring (dyad) correlations, to examine the extent to which environmental and genetic factors contribute to shared variance in reading- and language-related cognitive and neurobiological processes, to examine parent-of-origin effects, and to dissociate G, PreE and PostE influences. A successful outcome will establish a new paradigm for studying genetic and environmental influences on brain networks, and ultimately provide us with important information about risk/protective factors, windows of opportunity to intervene, and development of early intervention and preventive strategies of RD.

抽象的 本研究的主要目的是首次检验代际传播 人脑网络采用自然交叉培养设计。我们采用与阅读相关的大脑网络 特别是那些与语音和拼写处理（以及语言等）相关的 初步在数学相关过程中），作为模型系统，因为 这些网络的遗传和环境因素以及相应的行为表型。此外， 这些神经认知过程的损害与特定的单词阅读学习障碍有关 （又名基于解码的阅读障碍 [RD] 或发育性阅读障碍），终生患病率为 5- 10%，并且后代患 RD 的风险增加为普通人群的 4 至 8 倍 患有 RD 的直系亲属。拟议的自然交叉培育设计解决了一个关键问题 关于代际效应的机制，即它们是遗传的（G）、产前的（PreE）还是 产后环境（PostE）起源。随着体外技术的广泛应用，这现在才成为可能 受精（IVF）。我们将在健康家庭中获得认知测量以及功能和结构 MRI （三合会），每年每个地点 30 个家庭。我们将检查亲子相关性，包括脑- 四组 IVF 儿童的大脑相关性，这些儿童接受了独特的 G/PreE/PostE 贡献 他们的抚养父母以及第五组自然受孕的孩子（每组 N = 60 个三合会，其中 8-11岁的儿童，一半有女儿，另一半有儿子）：（1）同源组，其中 通过体外受精（IVF）孕育的后代由其遗传父母生育和抚养，因此暴露于母体 以及父亲的 G/PreE/PostE 影响； (2) 供卵组和 (3) 供体精子组，其中 后代是由捐赠的卵子/精子孕育而成，因此养育的母亲/父亲只有 PreE/PostE，没有 G、对后代的影响； (4) 妊娠代孕群体 非遗传、非抚养母亲，因此抚养父母只有 G/PostE，但没有 PreE 影响 他们的后代； (5) 自然受孕组，其中自然受孕的后代出生，并且 由其亲生父母抚养，因此受到母系和父系 G/PreE/PostE 的影响， 不受IVF的影响。父亲对学前教育的影响通常被认为是微乎其微的。该计划的具体目标 建议是：检查亲子（二元）相关性，检查环境和 遗传因素导致与阅读和语言相关的认知和神经生物学的共同差异 过程，检查亲本效应，并分离 G、PreE 和 PostE 影响。一个成功的 结果将为研究遗传和环境对大脑网络的影响建立一个新的范式， 并最终为我们提供有关风险/保护因素、机会之窗的重要信息 干预，并制定 RD 的早期干预和预防策略。