IMAGING THE AUTISTIC BRAIN BEFORE IT KNOWS IT HAS AUTISM

人类生命中没有其他时期能与神经功能的巨大和惊人的增长相提并论 能力是从新生儿到婴儿再到蹒跚学步儿童的过渡。在出生后的一两个月内，婴儿 开始微笑，在一岁生日前后开始说话。不久之后，他协调了演讲和 为了引起别人的注意而做出的手势。到他两岁的时候，他可以说简短的句子和 有丰富的社会情绪反应曲目。 在所有自闭症生物学中，最大的谜团是什么神经故障未能提供这一飞跃 社交、情感和语言能力。 唯一安全有效的直接观察人类神经功能的方法是功能磁共振成像。 虽然现在有数千项针对成熟人类的功能核磁共振研究，但没有一项功能核磁共振实验 试图发现这一令人难以置信的成就的神经功能基础在典型婴儿或其 自闭症婴儿的严重失败。 我们已经对典型的和自闭症幼儿进行了开创性的初步fMRI研究，为 首次发现了大脑中涉及对语言、社交和情感声音做出反应的区域。 我们以唯一可行的方式做到了这一点：当蹒跚学步的孩子处于自然睡眠状态，不动的时候。这种方法 映射神经功能和故障允许进行类似的测试，而不管 发育年龄或智力或行为能力的水平；所有年龄和功能水平的婴儿 同等学力。 因此，我们建议对12个月和24个月的自闭症高危婴儿进行首个此类功能磁共振研究。 我们提出的自然睡眠功能磁共振实验将是第一个描绘由社交， 自闭症、发育迟缓和典型发育中的婴儿的情绪和语言信息。 将识别异常的fMRI激活模式，以表征和预测社交情绪和 在临床评估和诊断中测量的语言行为缺陷核心B行为缺陷 在这三个领域，都是最先发出婴儿可能患有自闭症的危险信号，并通过我们的 研究中，我们将确定自闭症早期发展的第一批神经功能生物标志物。身份识别 这些自闭症早期发展的神经功能生物标志物将使我们能够通过与 核磁共振项目1、遗传项目3和4、治疗核心C和综合生物统计学核心D，以 执行有史以来第一次分析，一方面将建立大脑功能与 神经解剖学、基因表达和遗传多态、临床变量和治疗效果 在另一端。

No other period in human life matches the magnitude and astonishing increase in neural functional capacity as the transition from neonate to infant to toddler. Within a month or two following birth, the infant begins to smile and around first birthday begins to speak. Soon thereafter he coordinates speech and gesture in order to garner the attention of others. By the time he is two, he can speak in short sentences and has a rich repertoire of socio-emotional responding. Of all autism biology, the greatest mystery is what neural malfunction fails to provide this leap in social, emotional and language capacity. The only safe and powerful method for observing human neural function directly is functional MRI. While there are now thousands of fMRI studies in mature humans, not a single fMRI experiment has attempted to discover the neurofunctional bases of this incredible achievement in typical infants or its profound failure in the autistic infant. We have performed ground-breaking pilot fMRI studies of typical and autistic toddlers mapping for the first time the regions of the brain that are involved in responding to language, social and emotion sounds. We have done this in the only way feasible: while the toddler is in natural sleep and not moving. This method of mapping neural function and malfunction allows testing to be done comparably regardless of developmental age or level of mental or behavioral ability; infants at all ages and levels of functioning can be studied equivalently. We therefore propose the first-of-its-kind fMRI study of infants at-risk for autism at 12 and 24 months. Our proposed natural sleep fMRI experiments will be the first to map the neural systems activated by social, emotional and language information in the autistic, developmental^ delayed, and typically developing infant. Abnormal fMRI activation patterns will be identified that characterize and predict social emotional and language behavioral deficits as measured in clinical assessment and diagnosis Core B. Behavioral deficits in these three areas are among the first red flags signaling possible autism in the infant, and through our studies we will identify the first neurofunctional biomarkers of early development in autism. Identification of these neural functional biomarkers of early development in autism will enable us through collaboration with the MRI Project 1, genetic Projects 3 and 4, the Treatment Core C and the Integrated Biostatistics Core D, to perform the first ever analyses that will establish relationships between brain function on the one hand and neuroanatomy, gene expression and genetic polymorphisms, clinical variables and treatment effectiveness on the other.