Translatable EEG biomarkers of intellectual disability in pre-clinical mouse models of fragile X syndrome and tuberous sclerosis complex

The neurodevelopmental psychiatric disorders fragile X syndrome and tuberous sclerosis complex both have known synaptic plasticity and excitatory/inhibitory balance phenotypes. Efficacious drug treatments have been developed but they are not ideal for human use.

This project will introduce new electroencephalogram biomarkers of known neuronal events, including synaptic plasticity, activity of two different GABAergic inhibitory neuronal subclasses and burst firing, which can be experimentally constrained in primary visual cortex by habituation to simple visual stimuli and presentation of novelty. The immediate goal of the project is to show that cortical dysfunction is severe enough to be evident in these biomarkers in pre-clinical mouse models of two highly penetrant, single gene causes of fragile X syndrome and tuberous sclerosis complex. We will also demonstrate that altered biomarkers can be remedied which could lead to new drug treatments for the disorders.

This seed study will lead to larger studies using genetic and invasive experimental tools to deeply understand processes of learning and memory in mice, and to understand their dysfunction in genetically defined neurodevelopmental psychiatric disorders. We also wish to translate the use of these biomarkers into human subjects for patient stratification and assessment of response to treatment.