Reward insensitivity is associated with dopaminergic deficit in rapid eye movement sleep behaviour disorder.
Barber TR., Muhammed K., Drew D., Bradley KM., McGowan DR., Klein JC., Manohar SG., Hu MTM., Husain M.
Idiopathic rapid eye movement sleep behaviour disorder (iRBD) is now established as an important marker of the prodromal stage of Parkinson's disease and related synucleinopathies. However, although dopamine transporter (DaT) SPECT has been used to demonstrate the presence of nigro-striatal deficit in iRBD, quantifiable correlates of this are currently lacking. Sensitivity to rewarding stimuli is reduced in some people with Parkinson's disease, potentially contributing to aspects of the neuropsychiatric phenotype in these individuals. Further, a role for dopaminergic degeneration is suggested by the fact that reward insensitivity can be improved by dopaminergic medications. iRBD patients present a unique opportunity to study the relationship between reward sensitivity and early dopaminergic deficit in the unmedicated state. Here, we investigate whether a non-invasive, objective measure of reward sensitivity might be a marker of dopaminergic status in prodromal Parkinson's, by comparing with SPECT/CT measurement of dopaminergic loss in the basal ganglia. Striatal dopaminergic deficits in iRBD are associated with progression to Parkinsonian disorders. Therefore, identification of a clinically measurable correlate of this degenerative process might provide a basis for the development of novel risk stratification tools. Using a recently developed incentivised eye-tracking task, we quantified reward sensitivity in a cohort of 41 patients with idiopathic RBD and compared this with data from 40 patients with Parkinson's and 41 healthy controls. iRBD patients also underwent neuroimaging with DaT SPECT/CT. Overall, reward sensitivity, indexed by pupillary response to monetary incentives, was reduced in iRBD cases compared to controls, and was not significantly different to that in Parkinson's patients. However, in iRBD patients with normal DaT SPECT/CT imaging, reward sensitivity was not significantly different to healthy controls. Across all iRBD cases, a positive association was observed between reward sensitivity and dopaminergic SPECT/CT signal in the putamen. These findings demonstrate a direct relationship between dopaminergic deficit and reward sensitivity in patients with iRBD and suggest that measurement of pupillary responses could be of value in models of risk stratification and disease progression in these individuals.