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

摘要 这项拟议研究的主要目标是第一次检查艾滋病的代际传播。 人脑网络使用自然的交叉培养设计。我们把与阅读相关的大脑网络放在 特别是与语音和拼写处理有关的那些(以及语言方面的--等等 初步用于与数学相关的过程)，作为模型系统，因为潜在的差异影响 遗传和环境因素对这些网络和相应的行为表型的影响。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%，后代患RD的风险增加4至8倍 患有RD的直系亲属。拟议的自然交叉养育设计解决了一个关键问题 关于代际影响的机制，即它们是遗传的(G)、产前的(Pree)还是 出生后环境(POST)的起源。只有现在，随着体外培养技术的广泛应用，才有可能做到这一点 受精(试管婴儿)。我们将在健康家庭中进行认知测量以及功能和结构核磁共振检查 (黑社会)以每年每个地点30个家庭的速度进行。我们将研究亲子关系，包括大脑- 四组接受不同G/PRE/POST贡献的体外受精儿童的大脑相关性 他们的养育父母以及第五组自然受孕的儿童(N=60个三合一，每组有 8-11岁的儿童，一半生女儿，另一半生儿子)：(1)同源组，其中 通过试管受精受孕的后代由他们的遗传父母生育和抚养，因此接触到母体 和父亲G/Pree/POST的影响；(2)供体卵子；(3)供体精子组，其中 后代是从捐赠者的卵子/精子中受孕的，因此养育子女的母亲/父亲只有PRE/POST，而不是 对后代的影响；(4)通过代孕生育后代的妊娠代孕群体 非遗传的、非养育的母亲，因此养育的父母只有G/POST，而没有Pree的影响 其后代；(5)生育自然受孕后代的自然受孕群体，以及 由他们的遗传父母抚养，因此暴露在母亲和父亲的G/Pree/Post的影响下 不受体外受精的影响。父亲对普里的影响通常被认为是微乎其微的。《公约》的具体目标 建议是：检查父母-子女(二联体)的相关性，检查环境和 遗传因素导致阅读和语言相关的认知和神经生物学方面的共同差异 过程，以检验父母的起源效应，并分离G，PRE和POST的影响。一位成功的 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/保护因素的重要信息、机会之窗 RD的早期干预和预防策略的制定。

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.