Neural synchronydysfunction of gamma oscillations in autism

自闭症伽马振荡的神经同步功能障碍

基本信息

批准号：
8197005
负责人：
DONALD C. ROJAS
金额：
$ 26.51万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-12-01 至 2013-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8197005
关键词：
Adult Affect Age Animal Model Attention Auditory Auditory area Autistic Disorder Binding Biological Brain Candidate Disease Gene Cerebral cortex Child Cognitive Computer Simulation Cortical Desynchronizations Cortical Synchronization Data Development Electroencephalography Enrollment Family Family history of Family member First Degree Relative Frequencies Functional disorder Future GABA Receptor Gender Genetic Goals Head Image Individual Intervention Laboratories Literature Magnetic Resonance Imaging Magnetoencephalography Measurement Measures Methods Neocortex Neurons Noise Parents Pattern Performance Persons Phase Phenotype Play Power Sources Publishing Recording of previous events Role Sampling Signal Transduction Source Stimulus System Techniques Thick Time Triad Acrylic Resin autism spectrum disorder central coherence design developmental disease endophenotype follow-up gamma-Aminobutyric Acid interest magnetic field neurobehavioral proband public health relevance relating to nervous system research study selective attention sensor translational study

项目摘要

DESCRIPTION (provided by applicant): It has been proposed that general abnormalities in structural and functional neuronal connectivity may underlie many of the triad of deficits observed in autism. A limited number of deficits at the neuronal level, widely expressed in multiple neurobehavioral systems could provide substantial explanatory power in autism. For example, abnormal temporal binding and weak central coherence may be related to alterations in brain functional and/or structural connectivity. Gamma band oscillatory activity, as measured using EEG and magnetoencephalography (MEG), has been associated with intrinsic GABAergic activity in animal and computational models of the neocortex and is thought to play an important role in binding and central coherence. We and others have published data demonstrating that gamma activity is abnormal in people with autism, possibly reflecting a cortical GABA dysfunction. Using a whole-head MEG system, we will assess patterns of auditory cortical synchronization with high precision in both time and frequency. As we are primarily interested in the development of new endophenotypes for autism, we will study parents of affected individuals as well as probands. Preliminary evidence from our laboratory indicates that a gamma- synchronization deficit may be familial. Forty families who have children with autism will be enrolled and the parents of the children will be assessed using MEG measures of gamma-band activity in auditory experiments. Their data will be compared to matched adults with no personal or family history of autism spectrum disorders their children. MEG measures of gamma power and phase-locking will be measured and associated with their structural underpinnings from magnetic resonance imaging (MRI) data and also with measures of the broad autism phrenotype. PUBLIC HEALTH RELEVANCE: It has been proposed that general abnormalities in structural and functional neuronal connectivity may underlie many of the triad of deficits observed in autism. A limited number of deficits at the neuronal level, widely expressed in multiple neurobehavioral systems could provide substantial explanatory power in autism. For example, abnormal temporal binding and weak central coherence may be related to alterations in brain functional and/or structural connectivity. The long term goals of this application will be (1) to examine a putative electrophysiological underpinning of such problems, neuronal synchronization ability in the gamma band of the EEG and MEG, (2) to evaluate the familiality of evoked and induced gamma power and phase- locking factor in first degree relatives of people with autism, (3) in follow-up studies associate such deficits with GABAergic dysfunction and GABA receptor candidate genes and (4) evaluate pharmacological interventions that directly target GABA function. Gamma band oscillatory activity has been associated with intrinsic GABAergic activity in animal and computational models of the neocortex and is thought to play an important role in binding and central coherence

描述（由申请人提供）：有人提出，结构和功能神经元连接的普遍异常可能是在自闭症中观察到的许多三联缺陷的基础。神经元水平上有限数量的缺陷在多个神经行为系统中广泛表达，可以为自闭症提供重要的解释力。例如，异常的时间结合和弱的中央一致性可能与大脑功能和/或结构连接的改变有关。使用脑电图和脑磁图 (MEG) 测量的伽马带振荡活动与动物和新皮质计算模型中的内在 GABA 能活动相关，并且被认为在结合和中枢一致性方面发挥着重要作用。我们和其他人发表的数据表明，自闭症患者的 γ 活性异常，可能反映了皮质 GABA 功能障碍。使用全头脑磁图系统，我们将在时间和频率上高精度地评估听觉皮层同步模式。由于我们主要对自闭症新内表型的发展感兴趣，因此我们将研究受影响个体的父母以及先证者。我们实验室的初步证据表明伽马同步缺陷可能是家族性的。将招募 40 个有自闭症儿童的家庭，并使用听觉实验中伽马带活动的 MEG 测量对孩子的父母进行评估。他们的数据将与他们的孩子没有自闭症谱系障碍个人或家族史的匹配成年人进行比较。将测量伽马功率和锁相的 MEG 测量值，并将其与磁共振成像 (MRI) 数据的结构基础以及广泛的自闭症表型测量值相关联。公共健康相关性：有人提出，结构和功能神经元连接的普遍异常可能是自闭症中观察到的许多三联症缺陷的基础。神经元水平上有限数量的缺陷在多个神经行为系统中广泛表达，可以为自闭症提供重要的解释力。例如，异常的时间结合和弱的中央一致性可能与大脑功能和/或结构连接的改变有关。该应用的长期目标是 (1) 检查此类问题的假定电生理学基础、EEG 和 MEG 伽马带中的神经元同步能力，(2) 评估诱发和诱导伽马功率和相位的家族性- 自闭症患者一级亲属的锁定因素，(3) 在后续研究中将此类缺陷与 GABA 能功能障碍和 GABA 受体候选基因联系起来，以及 (4) 评估直接针对 GABA 的药物干预措施功能。伽马带振荡活动与动物和新皮质计算模型中的内在 GABA 能活动相关，并且被认为在结合和中枢一致性中发挥重要作用