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

摘要 拟议研究的主要目标是首次审查 使用自然交叉培养设计的人脑网络。我们把与阅读相关的大脑网络， 特别是那些与语音和拼写处理有关的（以及语言-等等）， 初步在数学相关的过程），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。此外，本发明还提供了一种方法， 这些神经认知过程的损伤与特定的单词阅读学习障碍有关 (aka基于解码的阅读障碍[RD]或发展性阅读障碍），其终生患病率为5- 10%，后代患RD的风险增加4至8倍， 有RD的直系亲属。所提出的自然交叉培养设计解决了一个关键问题 关于代际效应的机制，即，无论是遗传（G），产前（PreE）或 出生后环境（PostE）起源。这是现在才有可能与广泛可用的体外 受精（IVF）。我们将在健康的家庭中获得认知测量、功能和结构MRI （三位一体）的步伐，即每幅土地每年30个家庭。我们将研究亲子关系，包括大脑- 大脑相关性，在四组IVF儿童中，这些儿童接受了不同的G/PreE/PostE贡献， 他们的养育父母以及第五组自然受孕的儿童（每组N=60个三合会， 8-11岁的儿童，一半有女儿，另一半有儿子）：（1）同源组，其中 通过试管婴儿受孕的后代由他们的遗传父母生育和抚养，因此暴露于母亲的影响。 和父亲的G/PreE/PostE影响;（2）供体卵子和（3）供体精子组，其中 后代是从捐赠的卵子/精子中受孕的，因此养育后代的母亲/父亲只有PreE/PostE，而没有 G，对后代的影响;（4）妊娠代孕组，其中后代是通过 非遗传的，非养育的母亲，因此养育父母只有G/PostE，但没有PreE的影响， 他们的后代;（5）自然受孕组，其中自然受孕的后代出生， 由他们的遗传父母抚养，因此受到母亲和父亲的G/PreE/PostE影响， 没有IVF的影响。父亲的PreE影响通常被认为是最小的。的具体目标 建议是：检查父母后代（二元）的相关性，检查环境和 遗传因素导致阅读和语言相关认知和神经生物学的共同差异 过程，检查父母的起源影响，并解离G，PreE和PostE的影响。一个成功 这一成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， 制定RD早期干预和预防策略。

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.