Fronto-striatal gray matter contributions to discrimination learning in Parkinson's disease

Claire O'Callaghan^1,2, Ahmed A. Moustafa³, Sanne de Wit⁴, James M. Shine⁵, Trevor W. Robbins⁶, Simon J. G. Lewis⁵ and Michael Hornberger^1,2,7,8*

• ¹Neuroscience Research Australia, Sydney, NSW, Australia
• ²Faculty of Medicine, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia
• ³School of Social Sciences and Psychology and the Marcs Institute for Brain and Behaviour, University of Western Sydney, Sydney, NSW, Australia
• ⁴Cognitive Science Center Amsterdam and Department of Clinical Psychology, University of Amsterdam, Amsterdam, Netherlands
• ⁵Parkinson's Disease Clinic, Brain and Mind Research Institute, University of Sydney, Sydney, NSW, Australia
• ⁶Department of Psychology, Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK
• ⁷ARC Centre of Excellence in Cognition and its Disorders, Sydney, NSW, Australia
• ⁸Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK

Discrimination learning deficits in Parkinson's disease (PD) have been well-established. Using both behavioral patient studies and computational approaches, these deficits have typically been attributed to dopamine imbalance across the basal ganglia. However, this explanation of impaired learning in PD does not account for the possible contribution of other pathological changes that occur in the disease process, importantly including gray matter loss. To address this gap in the literature, the current study explored the relationship between fronto-striatal gray matter atrophy and learning in PD. We employed a discrimination learning task and computational modeling in order to assess learning rates in non-demented PD patients. Behaviorally, we confirmed that learning rates were reduced in patients relative to controls. Furthermore, voxel-based morphometry imaging analysis demonstrated that this learning impairment was directly related to gray matter loss in discrete fronto-striatal regions (specifically, the ventromedial prefrontal cortex, inferior frontal gyrus and nucleus accumbens). These findings suggest that dopaminergic imbalance may not be the sole determinant of discrimination learning deficits in PD, and highlight the importance of factoring in the broader pathological changes when constructing models of learning in PD.