A failure of left temporal cortex to specialize for language is an early emerging and fundamental property of autism
A failure of left temporal cortex to specialize for language is an early emerging and fundamental property of autism
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DOI：
10.1093/brain/awr364
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发表时间：
2012-03-01
期刊：
影响因子：
14.5
通讯作者：
Courchesne, Eric
中科院分区：
文献类型：
--
作者：
Eyler, Lisa T.;Pierce, Karen;Courchesne, Eric
无法发展正常的语言理解能力是自闭症的早期预警信号，但这种特征缺陷背后的神经机制尚不清楚。这是因为在早期发育过程中几乎完全缺乏对自闭症大脑的功能研究。使用功能性磁共振成像，我们之前观察到，与正常发育的儿童相比，在一个小样本（n = 12）的2-3岁自闭症儿童中，对语言的异常侧化时间反应（即右侧激活更多，而不是预期的左侧）的趋势，这一发现在自闭症成人和青少年中也有报道。然而，尚不清楚是否会在更大的样本中观察到非典型偏侧性的发现，甚至在自闭症患者的更早年龄（例如一岁生日前后）观察到。这些问题的答案将为理解自闭症的神经功能缺陷如何展开提供基础，并为使用大脑激活模式作为自闭症功能性早期生物标志物的研究提供基础。为了开始研究这些问题，采用了前瞻性横断面设计，在自然睡眠期间讲睡前故事期间测量了大样本幼儿（n = 80）的大脑活动。 40 名患有自闭症谱系障碍的幼儿和 40 名年龄在 12 至 48 个月之间的正常发育幼儿参与了研究。任何在最终诊断之前参与成像实验的自闭症幼儿都会被跟踪，并在以后的年龄确认诊断。结果表明，后来被诊断为自闭症的高危幼儿表现出左半球对语音的反应不足，并且对语言的右侧颞叶皮层反应异常；这种缺陷随着年龄的增长而恶化，在 3 岁和 4 岁的自闭症儿童中最为严重。通常发育中的儿童表现出相反的发育趋势，随着年龄的增长，颞叶皮层反应会增强，而左偏激活会随着年龄的增长而维持。我们现在已经在两个不同的样本中证明了自闭症患者颞叶皮层语言处理的偏侧异常，其中包括后来被诊断为自闭症的大婴儿样本，这表明这种模式可能反映了自闭症的基本早期神经发育病理学。
Failure to develop normal language comprehension is an early warning sign of autism, but the neural mechanisms underlying this signature deficit are unknown. This is because of an almost complete absence of functional studies of the autistic brain during early development. Using functional magnetic resonance imaging, we previously observed a trend for abnormally lateralized temporal responses to language (i.e. greater activation on the right, rather than the expected left) in a small sample (n = 12) of sleeping 2-3 year olds with autism in contrast to typically developing children, a finding also reported in autistic adults and adolescents. It was unclear, however, if findings of atypical laterality would be observed in a larger sample, and at even earlier ages in autism, such as around the first birthday. Answers to these questions would provide the foundation for understanding how neurofunctional defects of autism unfold, and provide a foundation for studies using patterns of brain activation as a functional early biomarker of autism. To begin to examine these issues, a prospective, cross-sectional design was used in which brain activity was measured in a large sample of toddlers (n = 80) during the presentation of a bedtime story during natural sleep. Forty toddlers with autism spectrum disorder and 40 typically developing toddlers ranging in age between 12-48 months participated. Any toddler with autism who participated in the imaging experiment prior to final diagnosis was tracked and diagnoses confirmed at a later age. Results indicated that at-risk toddlers later diagnosed as autistic display deficient left hemisphere response to speech sounds and have abnormally right-lateralized temporal cortex response to language; this defect worsens with age, becoming most severe in autistic 3- and 4-year-olds. Typically developing children show opposite developmental trends with a tendency towards greater temporal cortex response with increasing age and maintenance of left-lateralized activation with age. We have now demonstrated lateralized abnormalities of temporal cortex processing of language in autism across two separate samples, including a large sample of young infants who later are diagnosed with autism, suggesting that this pattern may reflect a fundamental early neural developmental pathology in autism.