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Development and therapeutic intervention of EEG abnormalities in early life in rodent models of autism and intellectual disability


About This PhD Project

Project Description

Project Code: 2020-SIDB-03

Autism (ASD) and intellectual disability (ID) are neurodevelopmental disorders which frequently appear early in the life cycle 1. Severe autism and intellectual disability are often comorbid with learning difficulties, motor deficits and epilepsy2,3. Electroencephalogram (EEG) recordings provide an unbiased measure of overall brain health and can be used to detect brain connectivity dysfunction, sleep deficits and seizures.

We have already identified EEG phenotypes such as sleep abnormalities and seizures in multiple genetic models of ASD, ID and epilepsy. One important question is to determine how early in development EEG abnormalities appear as this would identify biomarkers that we could attempt to therapeutically rescue. This would help inform us as to whether there are critical periods when these interventions are most effective in improving developmental outcomes, in accordance with aim 1 of the SIDB.

Our overall hypothesis is that, similarly to human patients, EEG deficits appear rapidly after birth in rodent models of ASD and ID and it is critical to treat these symptoms early in order to achieve improved normal developmental trajectories. In order to test this hypothesis, we will address the following key aims:

1) To establish EEG recordings in pups in order to assess whether there are physiological differences when compared to wild-type littermate controls.

2) To determine whether pharmacological treatments at these early life stages are effective in rescuing EEG abnormalities and whether these are effective in normalizing EEG signatures once animals reach adulthood.

3) To assess whether rescuing EEG phenotypes in early life influences behavioural measures of ASD and ID later in life.

References

1. Bosl W., Tierney A., Tager-Flusberg H., Nelson C. EEG complexity as a biomarker for autism spectrum disorder risk. BMC Med 2011;9. Doi: 10.1186/1741-7015-9-18.

2. Deonna T., Roulet-Perez E. Early-onset acquired epileptic aphasia (Landau-Kleffner syndrome, LKS) and regressive autistic disorders with epileptic EEG abnormalities: The continuing debate. Brain Dev 2010;32(9):746–52. Doi: 10.1016/j.braindev.2010.06.011.

3. Den Bakker H., Sidorov MS., Fan Z., Lee DJ., Bird LM., Chu CJ., et al. Abnormal coherence and sleep composition in children with Angelman syndrome: A retrospective EEG study. Mol Autism 2018;9(1):1–12. Doi: 10.1186/s13229-018-0214-8.

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