Autism spectrum disorder (ASD) is a complex disorder of brain development characterized by difficulties in social interaction, communication, and repetitive behaviors and is often accompanied by disruptions of sensory processing. One recent and potentially unifying neurobiological explanation posits that ASD is caused by disruptions in the excitatory/inhibitory (E/I) balance within the brain. Consistent with the E/I explanation, recent genetic and neuroscience research in animal models suggest that inhibitory neurotransmitter gamma- aminobutyric acid (GABA) signaling may be significantly disrupted in ASD. However, the role of GABA in ASD remains largely untested in humans. We propose to test the hypothesis that changes in cortical levels of GABA give rise to over- and under- responsiveness of neural circuits leading to key sensory and motor symptoms of ASD. Critically, GABA signaling is highly amenable to pharmacological treatment. Thus, understanding how GABA signaling is altered in ASD will open up new pharmacological treatment possibilities. We will use state- of-the-art magnetic resonance spectroscopy (MRS) techniques to measure concentrations of GABA in adults with an ASD and neurotypical control subjects in visual, motor, and auditory cortices. We will use fMRI measures of evoked sensory and motor responses to characterize neural responsiveness in these regions along with clinical measures of sensory-sensitivity and motor-related symptoms. Finally, we will use fMRI to measure the strength of a well-established inhibitory neural circuit in the visual system: surround suppression. By elucidating the functioning of inhibitory signaling, our results will significantly advance understanding of the neurobiological causes of ASD.
This research will test the hypothesis that a dysfunction of inhibitory neural signaling underlies autism spectrum disorder (ASD) by measuring concentrations of the inhibitory neurotransmitter GABA and establishing its relationship to inhibitory neural circuits and clinical sensory and motor symptoms. Understanding the role of inhibitory signaling will allow the development of specific pharmacological treatments and thus have a direct impact on therapeutic interventions to help individuals with ASD.
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| Millin, Rachel; Kolodny, Tamar; Flevaris, Anastasia V et al. (2018) Reduced auditory cortical adaptation in autism spectrum disorder. Elife 7: |
