Somatosensory Inhibitory Dysfunction in Autism Spectrum Disorder.



 DESCRIPTION (provided by applicant): Autism Spectrum Disorder (ASD) is a group of developmental disorders which affects approximately 1% of children, a prevalence rate that is increasing annually. ASD is characterized by social and communicative deficits, but there is increasing recognition of altered sensory processing as an extremely common feature of the disorder. In particular, responses to tactile stimuli are commonly observed, for example, a child with ASD may be unable to tolerate constant low level stimuli such as shirt tags which a typically developing child could habituate to. There is growing evidence that altered responses to sensory stimuli do not just result from altered top down control and emotional processing, but from altered processing of somatosensory information in primary somatosensory cortex due to altered GABAergic inhibition. In this proposal, we propose to use tactile behavioral testing to investigate and characterize differences in primary somatosensory processing, fMRI to directly detect the functional neural signature of this altered processing, and MRS of GABA to probe the neurochemical basis of the dysfunction. These three modes of investigation are unified by the core hypothesis of somatosensory GABAergic dysfunction in ASD. This proposal builds on a strong collaboration between Dr Richard Edden (PI), Dr Stewart Mostofsky (Co-PI) and Dr Mark Tommerdahl (Co-PI), and preliminary behavioral data showing altered patterns of behavioral responses in ASD and reduced GABA concentration in primary somatosensory areas. In Aim 1, we will perform psychophysical measures of tactile discrimination and adaptation in a group of 72 children with ASD between the age of 8 and 12 years with 72 ages, gender, and IQ-matched typically developing children (TDC) as the control group, to investigate whether there are behavioral differences in ASD. In Aim 2, we will compare measurements of GABA concentration and test whether the abnormal tactile processing commonly observed in ASD arises from a GABAergic deficit. In Aim 3, we will perform fMRI measurements during tactile stimulation to observe neural correlates of altered somatosensory processing.