Neural synchronydysfunction of gamma oscillations in autism

描述（由申请人提供）：已经提出，结构和功能神经元连接的一般异常可能是在自闭症中观察到的许多三联缺陷的基础。在神经元水平上，在多个神经行为系统中广泛表达的有限数量的缺陷可以为自闭症提供实质性的解释力。例如，异常的时间绑定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EEG和脑磁图（MEG）测量的伽马带振荡活动与动物和新皮层计算模型中的固有GABA能活动相关，并被认为在结合和中枢相干性中发挥重要作用。我们和其他人发表的数据表明，伽马活动在自闭症患者中是异常的，可能反映了皮质GABA功能障碍。使用全头脑磁图系统，我们将评估模式的听觉皮层同步与高精度的时间和频率。由于我们主要对自闭症新的内在表型的发展感兴趣，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，γ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，并在听觉实验中使用MEG测量伽马波段活动来评估儿童的父母。他们的数据将与匹配的成年人进行比较，这些成年人没有自闭症谱系障碍的个人或家族史。将测量伽马功率和锁相的MEG测量值，并将其与来自磁共振成像（MRI）数据的结构基础以及广泛的自闭症phrenotype的测量值相关联。 公共卫生相关性：有人提出，结构和功能神经元连接的一般异常可能是自闭症中观察到的许多三联缺陷的基础。在神经元水平上，在多个神经行为系统中广泛表达的有限数量的缺陷可以为自闭症提供实质性的解释力。例如，异常的时间绑定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。本申请的长期目标将是（1）检查这些问题的假定电生理学基础，EEG和MEG的伽马带中的神经元同步能力，（2）评估自闭症患者的一级亲属中诱发和诱导伽马功率和锁相因子的熟悉度，（3）在后续研究中，将这种缺陷与GABA能功能障碍和GABA受体候选基因联系起来，（4）评价直接靶向GABA功能的药物干预。在动物模型和新皮层的计算模型中，γ波段振荡活动与内在GABA能活动相关，并被认为在结合和中枢相干性中发挥重要作用

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