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Investigating the neurobehavioral basis of sensory behavior in ASD

Principal Investigator:

Autism Spectrum Disorder (ASD) is a group of developmental disorders which affects approximately 1% of children. One of the prominent associated symptoms of ASD is abnormal sensory behaviors. While these behaviors limit the child’s and family’s functioning, the underlying causes of these behaviors have not yet been explored. The present project aims to investigate the neurobehavioral basis of abnormal sensory behavior in ASD. Within the same sample of children (with and without autism), we will examine the relationship between basic sensory perception (e.g., differences in the way things feel), attention (e.g., ability to shift attention from one stimulus to another), language (e.g., vocabulary knowledge and expression), neurotransmitter functioning (as measured through Magnetic Resonance Spectroscopy: MRS), and abnormal sensory behaviors. We aim to clarify these relationships to inform treatment and intervention targets and goals. We hypothesize that compared to typically developing (TD) controls, children with autism will:

1) be rated by their parents as having deficits in sensory behavior;
2) perform at a different level on measures of sensory perception; and 3) show differences in gamma-Aminobutryic acid (GABA) concentration in the sensorimotor cortex.

Additionally, it is hypothesized that differences in the strength of correlations between measures of sensory perception and processing, GABA concentration, behavior, language, and attention will be observed between children with ASD and TD controls.

The molecular basis of ASD is likely to be complex and heterogeneous, but given the central role of the inhibitory neurotransmitter GABA in neuroplasticity mechanisms critical to behavioral and cognitive development, 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 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 somotosensory discrimination task; 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 function in school, family and social situations.

This project is a collaboration between Ericka Wodka, Ph.D., ABPP-CN (KKI/JHU), Richard Edden, Ph.D. (JHU), Nicholaas Puts, Ph.D. (JHU), and Dr Stewart Mostofsky, M.D. (KKI/JHU) to apply the extremely novel design examining multiple aspects of abnormal sensory behavior in ASD. Simultaneously measuring cognitive, neurochemical, and behavioral aspects of abnormal sensory behavior is ASD will clearly define processes that could serve as intervention targets (that could potentially be more easily, efficiently, or effectively addressed), including behavioral interventions or the pairing of MRS of GABA with somatosensory behavioral 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 it association with autistic behavior will provide a foundation for investigating novel treatment therapies, specifically use of medications that impact GABAergic activity.


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