Sequence and Location of Cortical Activity When Infants Understand Words

描述（由申请人提供）：语言是人类经验的核心，但我们对其早期发育的神经基质知之甚少，因为现有的观察婴儿大脑活动的技术具有较低的解剖学或时间分辨率，与神经活动的间接关系，需要更多的行为成熟度，或沉积电离辐射。相比之下，脑磁图（MEG）是沉默的，婴儿耐受良好。脑磁图直接和即时测量神经元内电流潜在的认知信息处理。我们建议记录婴儿在文字处理过程中的全头部306通道脑磁图。通过限制源位于同一个体的皮层，在婴儿睡眠时进行MRI重建，可以获得良好的解剖学分辨率。我们最初的重点是大约14个月大的婴儿，他们通常能理解几十个单词，这是测试所需的最低限度。然后，我们将把这些方法扩展到18个月大的婴儿，他们迅速发展的表达性词汇允许将大脑反应与语言发展的个体差异联系起来。在基本任务中，婴儿听他们理解的单词，并听与每个单词的振幅、轮廓和频谱密度相匹配的噪音。在初步数据中，这种比较可靠地唤起了定位于经典语言区域的~400ms的MEG活动。在潜伏期和定位上，这种活动类似于成人词汇所诱发的N400m。通过测试婴儿N400m是否与成人N400m具有关键的认知特征，特别是对重复和语义启动的敏感性，将寻求证实这种同源性。语义启动将通过呈现一张图片，然后呈现一个与图片匹配或不匹配的听觉单词来检验。初步数据表明，婴儿N400m与成人N400m一样，存在语义一致性的抑制。本研究将建立婴儿词汇诱发神经活动的基本模式，将其从感觉反应中分离出来，并证明其与语义理解的关系。这将有助于揭示用于获得语言理解的神经回路和突触机制，并允许在有语言障碍风险的婴儿中进行测量。

DESCRIPTION (provided by applicant): Language is central to human experience, but we know very little regarding its neural substrate during early development because existing techniques for observing brain activity in infants have low anatomical or temporal resolution, an indirect relationship to neural activity, require more behavioral maturity, or deposit ionizing radiation. In contrast, magnetoencephalography (MEG) is silent and well tolerated by infants. MEG directly and instantaneously measures intraneuronal currents underlying cognitive information processing. We propose to record whole-head 306 channel MEG during word processing by infants. Good anatomical resolution will be obtained by constraining the sources to lie in the cortex of the same individual, reconstructed from MRI performed while the infant is asleep. Our initial focus is on ~14 month old infants, who typically understand a few tens of words, the minimum needed for testing. We will then extend these methods to ~18 month old infants, whose burgeoning expressive vocabularies permit correlation of brain responses with individual differences in language development. In the basic task, infants listen to words they understand, and to noise matched for amplitude, contour and spectral density to each word. In preliminary data, this comparison reliably evokes MEG activity at ~400ms localized to classical language regions. In latency and localization, this activity resembles the N400m evoked by words in adults. Confirmation of this homology will be sought by testing if the infant N400m shares key cognitive characteristics with the adult N400m, specifically sensitivity to repetition and semantic priming. Semantic priming will be examined by presenting a picture and then an auditory word which either matches the picture or not. Preliminary data indicates that the infant N400m, like the adult N400m, is depressed by semantic congruence. The proposed studies will establish a basic pattern of neural activity evoked by words in infants, dissociate it from sensory responses, and demonstrate its relationship to semantic understanding. This would help reveal the neural circuits and synaptic mechanisms used to acquire language understanding, and allow their measurement in infants at risk for language disorders. PUBLIC HEALTH RELEVANCE: Disorders of language acquisition are common and can severely limit psychosocial development. This research will develop a method to safely measure the brain activity underlying infant word-processing, to be used to study the neural basis of language development in both normal and atypically developing infants. Future applications of these methods may include the assessment of children at-risk for delayed language.