John Sweeney, Ph.D. of the University of Cincinnati and Craig Erickson, M.D., of Cincinnati Children’s Hospital Medical Center will conduct neurophysiological and pharmacological investigations closely paralleling the mouse-model work in Projects 1 and 2.
They will use highly similar auditory cortex studies using auditory evoked ERP/EEG (electroencephalogram) measures as used in Project 2 to verify the clinical relevance of the mouse-model work, to further understand the nature of sensory processing problems in patients with FXS, and to test the effect of novel therapies on brain function.
A novel class of sounds called “chirp-modulated sweeps” will be used to identify frequency-specific deficits in evoked cortical responses.
A mechanistic investigation using pharmacological probes with FXS subjects will determine the role of ERK, MMPs, and glutamate/GABA signaling in causing neurophysiological abnormalities in sensory processing, and evaluate the potential of drug targeting these mechanisms to correct cortical hyperexcitability and sensory sensitivities.
These experiments will synergize with and inform the human translational relevance of parallel studies in mouse auditory cortex (Project 1 and Project 2).
- Ethridge L. E., White S. P., Mosconi M. W., Wang J., Byerly M. J., Sweeney J. A. Reduced habituation of auditory evoked potentials indicates cortical hyper-excitability in Fragile X Syndrome. Translational Psychiatry6, e787, (2016).
- Ouyang M., Cheng H., Mishra V., Gong G., Mosconi M. W., Sweeney J., Peng Y., Huang H. Atypical age-dependent effects of autism on white matter microstructure in children of 2-7 years. Hum Brain Mapp 37, 819-32, (2016).
- Najjar F., Owley T., Mosconi M. W., Jacob S., Hur K., Guter S. J., Sweeney J. A., Gibbons R. D., Cook E. H., Bishop J. R. Pharmacogenetic study of serotonin transporter and 5HT2A genotypes in Autism. J Child Adolesc Psychopharmacol 25, 467-74, (2015).
- Mosconi M. W., Mohanty S., Greene R. K., Cook E. H., Vaillancourt D. E., Sweeney J. A. Feedforward and feedback motor control abnormalities implicate cerebellar dysfunctions in autism spectrum disorder. J Neurosci 35, 2015-25, (2015).
- Amodeo D. A., Jones J. H., Sweeney J. A., Ragozzino M. E. Risperidone and the 5-HT2A receptor antagonist M100907 improve probabilistic reversal learning in BTBR T+tf/J mice. Autism Res 7, 555-67, (2014).