Objective: To investigate the influence of reward and effort on behavior in PD patients with and without apathy, using a drift-diffusion model to analyze neuroimage and behavioral performance

Background: Loss of motivation (apathy) is particularly debilitating in individuals with Parkinson’s Disease (PD)¹. It manifests as a reduction of goal-directed behavior (GDB)². The most widely accepted approach to test GDB is via effort-based decision-making (EBDM) paradigms, in which individuals choose between exerting low or high effort for varying reward magnitudes^3-7. Previous work has focused on choice variation as a function of reward and effort, but the time taken to decide likely reflects neural processes of evidence accumulation and thus provides an important additional measure with which to probe underlying cognitive mechanisms of apathy.

Method: Participants with idiopathic PD underwent brain MRI (including multi-shell DWI). Apathy was measured by the Dimensional Apathy Scale (DAS). The effects of changing effort and reward on choice and decision time were assessed via the Apple Gathering Task (AGt), in which participants were given sequential offers of reward in return for exerting physical effort (Figure 1). Tractography was performed between frontal and subcortical regions previously associated with apathy to estimate fractional anisotropy (FA) for white matter tracts. We examined associations between 1) DAS and AGt measures, 2) FA with AGt measures, and 3) FA with DAS subdimensions.

Results: 26 participants were recruited (10F, 13 apathetic). After adjusting for age and motor disease severity, more severe apathy was correlated with v effort (likelihood of rejection with higher effort), ß = 0.27, p = 0.046 (Fig. 2). In contrast, negative correlations were observed between fronto-subcortical white matter FA and v effort, ß = -7.29, p = 0.019, suggesting that with lower white matter quality there is higher likelihood of rejection with higher effort (Fig. 3). Similarly, fronto-subcortical white matter FA and DAS were inversely correlated, ß =-2.56, p = 0.030 (Fig. 4).

Conclusion: Our findings suggest that fronto-subcortical white matter microstructural health, causing altered motivation for high effort, may underlie apathetic behaviors in PD. Future analysis in a larger cohort will investigate the mediation effects of white matter quality on behavioral and cognitive apathy measures.

References: 1. Aarsland D, Bronnick K, Ehrt U, et al. Neuropsychiatric symptoms in patients with Parkinson’s disease and dementia: frequency, profile and associated care giver stress. J Neurol Neurosurg Psychiatry. Jan 2007;78(1):36-42. doi:10.1136/jnnp.2005.083113
2. Levy R, Dubois B. Apathy and the functional anatomy of the prefrontal cortex-basal ganglia circuits. Cereb Cortex. Jul 2006;16(7):916-28. doi:10.1093/cercor/bhj043
3. Hartmann-Riemer M, Kirschner M, Kaiser S. Effort-based decision-making paradigms as objective measures of apathy in schizophrenia? Current Opinion in Behavioral Sciences. 2018/08/01/ 2018;22:70-75. doi:https://doi.org/10.1016/j.cobeha.2018.01.009
4. Treadway MT, Buckholtz JW, Schwartzman AN, Lambert WE, Zald DH. Worth the ‘EEfRT’? The effort expenditure for rewards task as an objective measure of motivation and anhedonia. PLoS One. Aug 12 2009;4(8):e6598. doi:10.1371/journal.pone.0006598
5. Bonnelle V, Manohar S, Behrens T, Husain M. Individual Differences in Premotor Brain Systems Underlie Behavioral Apathy. Cereb Cortex. Feb 2016;26(2):807-819. doi:10.1093/cercor/bhv247
6. Le Heron C, Plant O, Manohar S, et al. Distinct effects of apathy and dopamine on effort-based decision-making in Parkinson’s disease. Brain. 2018;141(5):1455-1469.
7. Le Heron C, Manohar S, Plant O, et al. Dysfunctional effort-based decision-making underlies apathy in genetic cerebral small vessel disease. Brain. 2018;141(11):3193-3210. doi:10.1093/brain/awy257

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MDS Abstracts - https://www.mdsabstracts.org/abstract/apathy-white-matter-microstructure-and-effort-based-decision-making-in-parkinsons-disease/