Grant: Foundation Grant

One of the most pressing challenges in neuroscience is to understand how human perception, memory, and action, become dysfunctional with neurological and psychiatric disease. We use eye movements, and pupil dilation systems to study intact and impaired sensory, motor, and cognitive processes, employing behavioural testing, neuroimaging, neurophysiology and computational modeling. Our approach has the potential to revolutionize not only our understanding of the brain, but also the diagnosis and rehabilitation of patients with brain disorders and development of animal models for therapeutic drug testing. We study non-human primates (NHPs) and compare recordings from single neurons in crucial regions of the cerebral cortex and brainstem to determine how active vision is both coordinated and controlled. NHPs have similar sensory, motor, and cognitive systems as humans, thus the knowledge gained from detailed neurophysiological and behavioural experiments can be used to search for behavioural biomarkers in neurological and psychiatric patient groups. Knowledge gained from patients with Alzheimer's disease (AD) is now guiding a reverse translational effort: we are using our knowledge of patient pathology to generate and study a form of AD in NHPs. Because there has been great difficulty translating therapies that work in rodents to the specific human disease condition, shifting to NHPs with a brain similar to humans is crucial. In AD there is a build-up of toxic molecules in the brain called amyloid-beta oligomers (ABOs). We have shown that injection of these ABOs into the NHP brain leads to similar brain pathology as found in AD patients. We are now examining if there are changes in behaviour and cognition, and if so, how therapeutics can prevent or reverse those changes. The expected outcome of the proposed studies is the identification of a strategy that could slow AD progression and/or interrupt the onset of AD.