Neurobiology of language function in adolescents exposed to cocaine in utero

子宫内接触可卡因的青少年语言功能的神经生物学

• 批准号: 8189669
• 负责人: Nicole Landi
• 金额: $ 22.35万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-30 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8189669
• 关键词: Adolescence; Adolescent; Affect; Age; Auditory; Behavioral; Brain-Derived Neurotrophic Factor; COMT gene; Candidate Disease Gene; Child; Childhood; Cognition; Cognitive; Complex; Comprehension; Development; Diffuse; Event-Related Potentials; Exposure to; Eye; Fetal Cocaine Exposure; Functional disorder; Genetic; Genetic Polymorphism; Genetic Variation; Goals; Impairment; Incidence; Infant; Language; Language Development; Language Disorders; Language Tests; Link; Long-Term Effects; Longevity; Longitudinal Studies; Measures; Nature; Neurobiology; Neurocognitive; Neurotoxins; Pattern; Performance; Pharmaceutical Preparations; Physiological; Process; Public Health; Relative (related person); Research; Retinal Cone; Sampling; Semantics; Speech; System; Temporal Lobe; Testing; Weight; auditory stimulus; brain behavior; cocaine exposure; criminal behavior; design; early childhood; endophenotype; in utero; language processing; neurodevelopment; neurophysiology; phonology; prefrontal lobe; pressure; relating to nervous system; response; skills; social; speech processing; standardize measure; stem; success; syntax

DESCRIPTION (provided by applicant): Prenatal cocaine exposure (PCE) can have broad effects on neural development and cognition, with language skills routinely being affected. Extant findings have revealed multiple deficits/delays in language function associated with PCE including: 1) delayed age for language acquisition 2) poorer receptive language 3) poorer expressive language (fewer words spoken) and 4) abnormal response to auditory stimuli. The specific pattern of findings observed indicates language processing deficits at multiple levels from low-level perceptual deficits (e.g., speech processing) to more metacognitive deficits (e.g., semantics, syntax, comprehension). What is unknown is whether these deficits stem from the same or different underlying neurobiological anomalies. Moreover, because extant studies have looked at infants and young children, the extent to which these profiles of language dysfunction change as system demands change, e.g., from phonological development (early childhood) to the understanding of complex semantic and syntactic relationships (late childhood and adolescence), is unknown. It is likely, given the teratogenic effect of PCE, that multiple systems are affected, but also that the observed impairments may differ as a function of changes in system demands associated with development and/or academic pressures. We hypothesize that the perceptual deficits observed are a result of anomalous development of auditory perceptual systems in the temporal lobe and that the higher-level language deficits observed are due to a more diffuse effect on prefrontal lobe function. Additionally, we predict a change in the relative weighting of the affected systems associated with development, which will result in an increase in metacognitve impairment for older children and adolescents. The proposed research will partner with an ongoing longitudinal study of PCE to examine the underlying neurobiology of language processing deficits in a well-characterized behavioral sample of PCE adolescents. Specifically, the goals of the proposed research are 1) to use event related potentials (ERP) to assess the neurocognitive language profiles of PCE adolescents and of control children who were not exposed to cocaine (NCE); 2) to examine the relationship between earlier behavioral performance (measured by standardized tests of language and cognitive skills) and these neurocognitive language profiles; and c) to link these brain-behavior patterns to polymorphisms in candidate genes that have been associated with perceptual or metacognitive skills (COMT and BDNF), in order to establish an endophenotype associated with poor language performance in PCE children. The research outlined in this proposal will have a direct impact our understanding of the relationship between prenatal cocaine exposure and the underlying neurobiology associated with impairments in critical language skills that are important for academic and social success. PUBLIC HEALTH RELEVANCE: Prenatal cocaine exposure (PCE) can alter normal neural development and affect the infant's cognitive and behavioral function throughout its lifespan, thus making it an important public health concern. A significant body of research has now identified poorer performance in PCE relative to non-exposed children across a number of cognitive tasks, with language skills routinely affected. The research outlined in this proposal aims to refine our understanding of the language impairments associated with PCE by identifying the neurobiological locus of these impairments and exploring the cognitive- developmental trajectories associated with language skills in PCE.

描述（由申请人提供）：产前接触可卡因（PCE）会对神经发育和认知产生广泛影响，语言技能通常会受到影响。现有的研究结果表明，与PCE相关的多种语言功能缺陷/延迟包括：1）语言习得年龄延迟2）接受性语言较差3）语言表达性较差（所说的单词较少）和4）对听觉刺激的异常反应。观察到的结果的具体模式表明多个级别的语言处理缺陷，从低级知觉缺陷（例如语音处理）到更多元认知缺陷（例如语义、语法、理解）。目前尚不清楚这些缺陷是否源于相同或不同的潜在神经生物学异常。此外，由于现有的研究关注的是婴儿和幼儿，因此随着系统需求的变化，例如从语音发育（幼儿期）到复杂语义和句法关系的理解（童年后期和青春期），这些语言功能障碍的情况发生变化的程度尚不清楚。考虑到 PCE 的致畸作用，多个系统可能会受到影响，而且观察到的损害可能会随着与发展和/或学业压力相关的系统需求的变化而有所不同。我们假设观察到的知觉缺陷是颞叶听觉知觉系统异常发育的结果，而观察到的高级语言缺陷是由于对前额叶功能的更分散的影响所致。此外，我们预测与发育相关的受影响系统的相对权重会发生变化，这将导致年龄较大的儿童和青少年的元认知障碍增加。拟议的研究将与正在进行的 PCE 纵向研究合作，以检查 PCE 青少年行为样本中语言处理缺陷的潜在神经生物学。具体来说，拟议研究的目标是 1) 使用事件相关电位 (ERP) 评估 PCE 青少年和未接触可卡因 (NCE) 的对照儿童的神经认知语言特征； 2）检查早期行为表现（通过语言和认知技能的标准化测试来衡量）与这些神经认知语言特征之间的关系； c) 将这些大脑行为模式与与知觉或元认知技能（COMT 和 BDNF）相关的候选基因的多态性联系起来，以便建立与 PCE 儿童语言表现不佳相关的内表型。该提案中概述的研究将直接影响我们对产前可卡因暴露与与关键语言技能损伤相关的潜在神经生物学之间关系的理解，这对学术和社会成功很重要。 公共卫生相关性：产前接触可卡因 (PCE) 会改变正常的神经发育，影响婴儿整个生命周期的认知和行为功能，因此成为重要的公共卫生问题。大量研究现已发现，在许多认知任务中，与未接触过 PCE 的儿童相比，PCE 的表现较差，语言技能也经常受到影响。本提案中概述的研究旨在通过确定这些障碍的神经生物学位点并探索与 PCE 中语言技能相关的认知发展轨迹，加深我们对与 PCE 相关的语言障碍的理解。