Neural synchronydysfunction of gamma oscillations in autism

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自闭症中观察到的许多三联征缺陷的基础。在多个神经行为系统中广泛表达的有限数量的神经元水平缺陷可以为自闭症提供实质性的解释力。例如，异常的时间结合和弱中枢连贯可能与大脑功能和/或结构连通性的改变有关。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层计算模型中的内在gaba能活动有关，并且被认为在结合和中央相干中起重要作用。我们和其他人已经发表的数据表明，自闭症患者的伽马活动是异常的，可能反映了皮质GABA功能障碍。使用全头部脑磁图系统，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的新内表型的发展感兴趣，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，伽马同步缺陷可能是家族性的。40个有自闭症孩子的家庭将被招募，孩子的父母将在听觉实验中使用脑磁图测量伽马波段活动来评估。他们的数据将与匹配的成年人进行比较，这些成年人的孩子没有个人或家族史的自闭症谱系障碍。MEG测量的伽马功率和锁相将被测量，并与磁共振成像（MRI）数据的结构基础相关联，也与广泛的自闭症表型相关联。

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.