Project ID NS-MH2023_14


Co Supervisor 1A IoPPN/Forensic and Neurodevelopmental ScienceWebsite

Co Supervisor 1B IoPPN/Forensic and Neurodevelopmental ScienceWebsite

Pharmacological challenges in Autism using multi-modal neuroimaging data from drug shiftability studies.

At present, there are no medications for treatment of Autism core or co-occurring symptoms. There is evidence that the neurobiological underpinnings of ASD include aberrations in brain growth, neuronal patterning, cortical connectivity and altered molecular pathways (e.g. serotonin and glutamate neurotransmitter systems. This PhD will investigate modulation of abnormalities from multiple perspectives (brain function, structure and pharmaco-challenge) with aim to create a medication stratification biomarker for translation of drugs to clinical trials. Our laboratory has been performing biomarker shiftability studies comparing brain in adults with and without autism. Specifically, the impact of acute doses of several medications, using multimodal imaging techniques, on resting and active brain functional connectivity, structure and chemistry (see figure). While each brain imaging modality reveals different aspect of the brain, this PhD will develop multivariate methods which use higher order statistics to combine diverse information to identify correspondence among data types. The PhD candidate will utilise our completed and ongoing multimodal pharmaco-challenge datasets to investigate this mapping.

Year 1: Study drugs and systems affected. Training in neuroimaging. Become familiar with team to learn and participate in subject recruitment, cognitive & autism testing and neuroimaging. Training in PhD skills (e.g. communication, teaching, academic writing and oral presentations) via departmental resources and/or Centre for Doctoral Studies.

Year 2: Investigate novel statistical techniques for multi-modal neuroimaging and decide on analytical pathway. Learn and begin pre-processing of data. Identify data sets (drug challenges) to analyse.

Year 3 -4: Data analysis then dissemination of results. Submission of PhD thesis.

One representative publication from each co-supervisor:

GABA B receptor modulation of visual sensory processing in adults with and without autism spectrum disorder: Huang, Q., Pereira, A. C., Velthuis, H., Wong, N., Ellis, C., Ponteduro, F., Dimitrov, M., Kowalewski, L., Lythgoe, D., Rotaru, D., Edden, R., Leonard, A., Ivin, G., Ahmad, J., Pretzsch, C., Daly, E., Murphy, D. & McAlonan, G., 5 Jan 2022, In: Science Translational Medicine. 14, 626

Modulation of atypical brain activation during executive functioning in autism: a pharmacological MRI study of tianeptine: Wichers, R. H., Findon, J. L., Jelsma, A., Giampietro, V., Stoencheva, V., Robertson, D. M., Murphy, C. M., Blainey, S., McAlonan, G., Ecker, C., Rubia, K., Murphy, D. G. M. & Daly, E. M., 19 Feb 2021, In: Molecular Autism. 12, 1, p. 14 14.