NEUROMAGNETIC INVESTIGATION OF ADULTS WITH AUTISM

成人自闭症患者的神经磁学研究

• 批准号: 6296826
• 负责人: Martin Reite
• 金额: $ 18.24万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-13 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6296826
• 关键词: adult human (21+); autism; brain electrical activity; brain imaging /visualization /scanning; brain mapping; brain metabolism; cerebral cortex; clinical research; electroencephalography; evoked potentials; fragile X syndromes; human subject; magnetic resonance imaging; magnetoencephalography; memory; mental health epidemiology; mental retardation; neural information processing; somesthetic sensory cortex

Autism is a devastating developmental disorder with an incidence of approximately I in 1,000 live births. While strongly genetically determined, specific abnormalities remain to be determined, and the clinical picture is sufficiently diffuse to implicate pathology in multiple neural systems. Central to the syndrome is impaired social interaction, a severely restricted range of interests, and abnormalities of attention (hyper-attentiveness) and sensation (usually hyper- reactivity). We propose to utilize magnetoencephalographic (MEG) sensory evoked field (EF) data, EEG evoked potential (EP) data, and MRI anatomical data to specifically address early cortical processing of sensory information. We will study 1) 30 high functioning (IQ>50) autistic adults, 2) 30 IQ and age matched FraX patients, 3) 30 age matched MR subjects, and 4) 30 age matched normal adults. We will specifically: 1)Using MEG and EEG, we will quantify reactivity of primary auditory and somatosensory cortex to stimuli of varying intensity; 2) By localizing and quantifying very high frequency (VHF) MEG activity (600 Hz) from primary somato- sensory cortex we will directly measure cortical GABA-ergic inhibitory interneurone activity, which we hypothesize will be deficient in autistic subjects (and correlated with cortical hyper- reactivity); 3)Using an MEG auditory EF based goodness of fit metric, we will quantify the ability or autistic subjects to shift attention from one hemisphere to the other during a binaural auditory oddball task; 4) Using the amplitude of the 100 msec latency auditory EF (termed M100) as a function of auditory interstimulus interval (151) we will calculate tau, the time constant of the decay of the echoic memory trace, generated in Heschl's gyri. We hypothesize this will be prolonged in autistic subjects, relative to normals, Fra-X or MR groups; 5) Using the EEG EP based metric termed mismatch negativity (MMN) we hypothesize that autistic subjects will demonstrate evidence of an accentuated pre-attentive, automatic cortical feature detection processes; 6) Using an MEG EF metric of auditory cortex MEG alpha suppression during a tonal memory task, we hypothesize that autistic subjects will demonstrate evidence of greater alpha suppression than normals, supporting enhanced short term auditory memory storage, scanning and retrieval; 7) Using high resolution MR images of the brain we will relate MEG EF sources to specific cortical areas to determined if MEG and EEG based functional abnormalities are related to observed anatomical deficits in the cortex generating those signals.

自闭症是一种破坏性的发育障碍，其发病率为 大约每1000名活产儿中就有一名。虽然有很强的遗传性 已确定，具体异常情况仍有待确定，而 临床表现非常分散，足以牵连到 多个神经系统。该综合征的核心是社交功能受损 互动，严格限制的利益范围，以及反常 注意力(超注意力)和感觉(通常是超注意力) 反应性)。我们建议使用脑磁图(MEG) 感觉诱发电场(EF)数据、脑电诱发电位(EP)数据以及 专门针对早期皮质处理的MRI解剖学数据 感官信息。我们将研究30)高功能 (IQ&GT；50)自闭症成人，2)30名智商和年龄匹配的FRAX患者，3) 30例年龄匹配的MR受试者和30例年龄匹配的正常成人。 我们将具体：1)使用脑磁图和脑电，我们将量化 初级听觉和躯体感觉皮层对刺激的反应性 变化强度；2)通过非常高的局部化和量化 初级体感诱发频率(VHF)脑磁图活动(600赫兹) 感觉皮层我们将直接测量皮质GABA能 抑制神经元间活动，我们假设这将是 自闭症受试者缺乏(并与皮质功能亢进相关) 反应性)；3)使用基于拟合优度的MEG听觉EF 指标，我们将量化自闭症受试者的能力或转移 双耳听觉过程中从一个半球到另一个半球的注意 奇怪的任务；4)使用100毫秒延迟的幅度 听性EF(称为M100)是听性内刺激的函数 间隔(151)，我们将计算衰变的时间常数tau 回声记忆的痕迹，在赫施尔的脑回中产生。我们 假设在自闭症受试者中，这一时间将延长 法线、Fra-X或MR组；5)使用基于EEG EP的度量 称为失配负性(MMN)，我们假设自闭症患者 受试者将证明被强调的预先注意的证据， 自动皮质特征检测过程；6)使用MEG EF 音调期间听觉皮质脑磁α抑制的量度 记忆任务，我们假设自闭症受试者将展示 阿尔法抑制比正常更强的证据，支持 增强的短期听觉记忆存储、扫描和 检索；7)使用高分辨率的大脑磁共振图像，我们将 将MEG EF源与特定皮质区域相关联，以确定是否 基于脑磁图和脑电的功能异常与 观察到的大脑皮质解剖缺陷产生了这些信号。