Somatosensory Inhibitory Dysfunction in Autism Spectrum Disorder.

 描述(由申请人提供)：自闭症谱系障碍(ASD)是一组发育障碍，影响大约1%的儿童，患病率每年都在增加。ASD的特点是社交和沟通障碍，但人们越来越多地认识到感觉加工的改变是这种疾病的一个极其常见的特征。特别是，对触觉刺激的反应通常被观察到，例如，患有自闭症的儿童可能无法忍受持续的低水平刺激，例如典型发育中的儿童可能习惯的衬衫标签。越来越多的证据表明，对感觉刺激的反应改变不仅是自上而下控制和情绪处理改变的结果，也是由于GABA能抑制改变引起的初级躯体感觉皮层躯体感觉信息处理的改变。在这个建议中，我们建议使用触觉行为测试来研究和表征初级体感加工中的差异，fMRI来直接检测这种改变的加工的功能神经特征，而GABA的MRS来探索这种功能障碍的神经化学基础。这三种研究模式由ASD的躯体感觉GABA能功能障碍这一核心假说统一。这项建议建立在理查德·埃登博士(PI)、斯图尔特·莫斯托夫斯基博士(Co-PI)和Mark Tommerdahl博士(Co-PI)之间的密切合作基础上，以及显示ASD行为反应模式改变和主要躯体感觉区域GABA浓度下降的初步行为数据。在目标1中，我们将对72名8-12岁的ASD儿童进行触觉辨别和适应的心理物理测量，并以72名年龄、性别和智商匹配的典型发育儿童(TDC)为对照组，以探讨ASD是否存在行为差异。在目标2中，我们将比较GABA浓度的测量结果，并测试ASD中常见的异常触觉处理是否源于GABA能缺陷。在目标3中，我们将在触觉刺激过程中进行fMRI测量，以观察改变的体感加工的神经关联。

 DESCRIPTION (provided by applicant): Autism Spectrum Disorder (ASD) is a group of developmental disorders which affects approximately 1% of children, a prevalence rate that is increasing annually. ASD is characterized by social and communicative deficits, but there is increasing recognition of altered sensory processing as an extremely common feature of the disorder. In particular, responses to tactile stimuli are commonly observed, for example, a child with ASD may be unable to tolerate constant low level stimuli such as shirt tags which a typically developing child could habituate to. There is growing evidence that altered responses to sensory stimuli do not just result from altered top down control and emotional processing, but from altered processing of somatosensory information in primary somatosensory cortex due to altered GABAergic inhibition. In this proposal, we propose to use tactile behavioral testing to investigate and characterize differences in primary somatosensory processing, fMRI to directly detect the functional neural signature of this altered processing, and MRS of GABA to probe the neurochemical basis of the dysfunction. These three modes of investigation are unified by the core hypothesis of somatosensory GABAergic dysfunction in ASD. This proposal builds on a strong collaboration between Dr Richard Edden (PI), Dr Stewart Mostofsky (Co-PI) and Dr Mark Tommerdahl (Co-PI), and preliminary behavioral data showing altered patterns of behavioral responses in ASD and reduced GABA concentration in primary somatosensory areas. In Aim 1, we will perform psychophysical measures of tactile discrimination and adaptation in a group of 72 children with ASD between the age of 8 and 12 years with 72 ages, gender, and IQ-matched typically developing children (TDC) as the control group, to investigate whether there are behavioral differences in ASD. In Aim 2, we will compare measurements of GABA concentration and test whether the abnormal tactile processing commonly observed in ASD arises from a GABAergic deficit. In Aim 3, we will perform fMRI measurements during tactile stimulation to observe neural correlates of altered somatosensory processing.