Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Apathy is a debilitating and under-recognized condition that has a significant impact in many neurodegenerative disorders. In Parkinson's disease, it is now known to contribute to worse outcomes and a reduced quality of life for patients and carers, adding to health costs and extending disease burden. However, despite its clinical importance, there remains limited understanding of mechanisms underlying apathy. Here we investigated if insensitivity to reward might be a contributory factor and examined how this relates to severity of clinical symptoms. To do this we created novel ocular measures that indexed motivation level using pupillary and saccadic response to monetary incentives, allowing reward sensitivity to be evaluated objectively. This approach was tested in 40 patients with Parkinson's disease, 31 elderly age-matched control participants and 20 young healthy volunteers. Thirty patients were examined ON and OFF their dopaminergic medication in two counterbalanced sessions, so that the effect of dopamine on reward sensitivity could be assessed. Pupillary dilation to increasing levels of monetary reward on offer provided quantifiable metrics of motivation in healthy subjects as well as patients. Moreover, pupillary reward sensitivity declined with age. In Parkinson's disease, reduced pupillary modulation by incentives was predictive of apathy severity, and independent of motor impairment and autonomic dysfunction as assessed using overnight heart rate variability measures. Reward sensitivity was further modulated by dopaminergic state, with blunted sensitivity when patients were OFF dopaminergic drugs, both in pupillary response and saccadic peak velocity response to reward. These findings suggest that reward insensitivity may be a contributory mechanism to apathy and provide potential new clinical measures for improved diagnosis and monitoring of apathy.

Type

Journal article

Journal

Brain : a journal of neurology

Publication Date

24/07/2016

Addresses

1 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK 2 Department of Experimental Psychology, University of Oxford, Oxford, UK kinan.muhammed@ndcn.ox.ac.uk.