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.

Public Health Relevance

Autistic spectrum disorder (ASD) is a developmental disorder that mainly affects communication and social interaction. It is well-known that sensory processing is abnormal in autism; in this project, we will investigate tactile processing abnormalities, in particular whether they are associated with lower levels of the neurotransmitter GABA, and whether they are related to altered signals in functional MRI.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH106564-03
Application #
9392582
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Gilotty, Lisa
Project Start
2016-01-18
Project End
2020-11-30
Budget Start
2017-12-01
Budget End
2018-11-30
Support Year
3
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
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Saleh, Muhammad G; Oeltzschner, Georg; Chan, Kimberly L et al. (2016) Simultaneous edited MRS of GABA and glutathione. Neuroimage 142:576-582

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