A Touchscreen Motivation Assessment Evaluated in Huntington's Disease Patients and R6/1 Model Mice.
Heath, Christopher J
Phillips, Benjamin U
Frontiers in neurology
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Heath, C. J., O'Callaghan, C., Mason, S., Phillips, B. U., Saksida, L., Robbins, T., Barker, R., et al. (2019). A Touchscreen Motivation Assessment Evaluated in Huntington's Disease Patients and R6/1 Model Mice.. Frontiers in neurology, 10 858. https://doi.org/10.3389/fneur.2019.00858
Apathy is pervasive across many neuropsychiatric disorders but is poorly characterised mechanistically, so targeted therapeutic interventions remain elusive. A key impediment has been the lack of validated assessment tools to facilitate translation of promising findings between preclinical disease models and patients. Apathy is a common symptom in Huntington’s disease. Due to its established genetic basis and the availability of defined animal models, this disease offers a robust translational framework for linking motivated behaviour with underlying neurobiology and an ideal context in which to evaluate a quantitative, translational apathy assessment method. In this study we therefore aimed to demonstrate the validity of using touchscreen-delivered progressive ratio tasks to mirror apathy assessment in Huntington’s disease patients and a representative mouse model. To do this we evaluated Huntington’s disease patients (n=23) and age-matched healthy controls (n=20), and male R6/1 mice (n=23) and wildtype controls (n=29) for apathy-like behaviour using touchscreen-delivered progressive ratio tasks. The primary outcome measure of the assessment was breakpoint, defined as the highest number of touchscreen responses emitted before task engagement ceased. Patients and R6/1 mice were both found to exhibit significantly reduced breakpoints relative to their respective control groups, consistent with apathy-like behaviour. This performance was also not associated with motoric differences in either species. These data demonstrate the utility of touchscreen-delivered progressive ratio tasks in detecting clinically relevant motivational deficits in Huntington’s disease. This approach may offer a platform from which clinically relevant mechanistic insights concerning motivation symptoms can be derived and provide an effective route for translation of promising preclinical findings into viable therapeutic interventions.
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External DOI: https://doi.org/10.3389/fneur.2019.00858
This record's URL: https://www.repository.cam.ac.uk/handle/1810/295088
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