This project aims to evaluate the familiality of a putative new endophenotype, dyscfunctional gamma-band phase locking, in the first degree relatives of people with autism. Magnetoencephalography (MEG) will be the primary measurement strategy. MRI scans will also be required.
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 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