A Touchscreen Motivation Assessment Evaluated in Huntington’s Disease Patients and R6/1 Model Mice.

A Touchscreen Motivation Assessment Evaluated in Huntington’s Disease Patients and R6/1 Model Mice.

Publication date: Mar 21, 2019

Apathy is pervasive across many neuropsychiatric disorders but is poorly characterized 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 behavior 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 behavior 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 behavior. 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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Heath, C.J., O’Callaghan, C., Mason, S.L., Phillips, B.U., Saksida, L.M., Robbins, T.W., Barker, R.A., Bussey, T.J., and Sahakian, B.J. A Touchscreen Motivation Assessment Evaluated in Huntington’s Disease Patients and R6/1 Model Mice. 06666. 2019 Front Neurol (10):

Concepts Keywords
Apathy Touchscreen
Breakpoint Narcissism
Genetic Emotions
Huntington Apathy
Mirror Abnormal psychology
Neurobiology Disease
Neuropsychiatric Pervasive neuropsychiatric disorders
Progressive Behavioural sciences
Species Human behavior
Symptom Saksida
Touchscreen
Wildtype

Semantics

Type Source Name
gene UNIPROT KCNK3
pathway BSID Translation
disease MESH Apathy

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