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.
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