Cortical neurotransmitters dynamics in the Rasopathies

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Rasopathies such as Neurofibromatosis 1 (NF1) and Noonan syndrome (NS) are a group of rare genetic disorders that affect 1 in 1000 people. Much of the real-life impact of NF1/NS on children relates to learning and behavioural difficulties with long-term consequences on academic/occupational functioning. Problems with 'working memory' (WM) are particularly relevant for day-to-day functioning for listening to /remembering short-term information, following instructions, reasoning, and making decisions. Currently, there are no effective treatments for these difficulties. The aim of this doctoral study is to understand how brain push-pull neurotransmitters Glutamate and GABA fluctuate during learning. Research conducted in animal models of NF1/NS suggest that these neurotransmitters may underlie learning problems, but these mechanisms have not been investigated in humans. To achieve our aim, the study will recruit 30 children each with NF1, NS and healthy controls to the study. The student will use novel MRI methods called functional magnetic spectroscopy to quantify the ratio of Glutamate/GABA neurotransmitters at rest and the glutamate released in the brain during performance of a learning task. The study will investigate how the brain mechanisms in NF1/NS groups are different from controls. Understanding these mechanisms is important to allow design of appropriate interventions - for example non-invasive brain stimulation which can be used to modulate neuroplasticity. The project will be embedded within a wider project funded by NIHR Biomedical Research Centre and will benefit from access to administrative support and funding. The student will receive training in the design of functional MR experiments, clinical research skills, learning how to collect and analyze neuroimaging data. There is expertise within the supervisory team in psychiatry, cognitive neuroscience, computational modelling and neuroradiology. The supervisory team have a track record of scanning children with neurodevelopmental disorders.