Autism Spectrum Disorder (ASD) is a group of developmental disorders which affects approximately 1% of children, a prevalence rate that is increasing annually. The molecular basis of ASD is likely to be complex and heterogeneous, but given the central role of the inhibitory neurotransmitter GABA in cognitive control, development and plasticity and a growing body of evidence linking GABAergic dysfunction to autism and autistic phenotypes, the GABA system is a strong potential area for ASD research. Recently, it has become possible to measure GABA concentration non-invasively in the brain using magnetic resonance spectroscopy (MRS), and in an extremely novel set of experiments we have shown that differences in regional GABA concentration among healthy subjects have measurable behavioral correlates. For example, GABA concentration in sensorimotor cortex correlates with performance at a somatosensory discrimination task (see below);this may have particular relevance for autism, as atypical response to tactile stimuli is a common (and diagnostic) feature of autism and one that can substantially impair behavioral function This proposal arises from a collaboration between Dr Richard Edden (PI) and Dr Stewart Mostofsky (Co-I) to apply the extremely novel pairing of MRS of GABA with somatosensory paradigms to investigate whether there is a measurable GABA deficit in autism, and whether this correlates with autism associated differences in somatosensory processing. The findings from examination of GABA MRS and its association with autistic behavior will provide a foundation for investigating novel treatment therapies, specifically use of medications that increase GABAergic activity.
In Aim 1, we will compare measurements of GABA concentration in a group of 20 children with ASD between the age of 8 and 12 years with 20 age-, gender-, and IQ-matched typically developing children (TDC) as the control group.
In Aim 2, we will perform psychophysical measures of tactile discrimination to investigate whether there are differences between children with ASD and TDC, and in Aim 3 we will test whether the abnormal tactile processing commonly observed in ASD arises from a GABAergic deficit.

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 whether tactile discrimination abnormalities are associated with lower levels of the neurotransmitter GABA.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21MH098228-02
Application #
8686958
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Gilotty, Lisa
Project Start
2013-07-01
Project End
2015-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Floris, Dorothea L; Barber, Anita D; Nebel, Mary Beth et al. (2016) Atypical lateralization of motor circuit functional connectivity in children with autism is associated with motor deficits. Mol Autism 7:35
Edden, Richard A E; Oeltzschner, Georg; Harris, Ashley D et al. (2016) Prospective frequency correction for macromolecule-suppressed GABA editing at 3T. J Magn Reson Imaging 44:1474-1482
Wodka, Ericka L; Puts, Nicolaas A J; Mahone, E Mark et al. (2016) The Role of Attention in Somatosensory Processing: A Multi-trait, Multi-method Analysis. J Autism Dev Disord 46:3232-41
Puts, Nicolaas A J; Wodka, Ericka L; Harris, Ashley D et al. (2016) Reduced GABA and altered somatosensory function in children with autism spectrum disorder. Autism Res :
Heba, Stefanie; Puts, Nicolaas A J; Kalisch, Tobias et al. (2016) Local GABA Concentration Predicts Perceptual Improvements After Repetitive Sensory Stimulation in Humans. Cereb Cortex 26:1295-301
Harris, Ashley D; Puts, Nicolaas A J; Barker, Peter B et al. (2015) Spectral-editing measurements of GABA in the human brain with and without macromolecule suppression. Magn Reson Med 74:1523-9
Puts, Nicolaas A J; Harris, Ashley D; Crocetti, Deana et al. (2015) Reduced GABAergic inhibition and abnormal sensory symptoms in children with Tourette syndrome. J Neurophysiol 114:808-17
Puts, Nicolaas A J; Wodka, Ericka L; Tommerdahl, Mark et al. (2014) Impaired tactile processing in children with autism spectrum disorder. J Neurophysiol 111:1803-11
Puts, Nicolaas A; Wodka, Ericka L; Tommerdahl, Mark et al. (2014) Reply to Dickinson and Milne. J Neurophysiol 112:1600-1