Apathy, effort-based decisions and brain integrity in Alzheimer’s and Parkinson’s diseases

Abstract Apathy, or loss of motivation, is a prominent syndrome accompanying both Alzheimer’s and Parkinson’s disease, in addition to other disorders. One approach to understanding motivational loss is to examine the processes underlying goal-directed behaviour. Weighing up rewarding outcomes against the effort costs required to obtain them – effort-based decision-making – is a core computation when deciding to act for outcomes. Whilst a growing body of evidence points to disruption of this computation in people with apathy, which underlying decision parameters drive this disruption, their neural associations, and whether these would generalise or differ across brain disorders has not been examined. People with amnestic mild cognitive impairment and probable Alzheimer's disease (aMCI/pAD) (n=37), Parkinson’s disease (PD) undergoing workup for deep brain stimulation (n=51), and healthy controls (n=21) performed a physical effort-based decision-making task (Apple gathering task), and caregiver-rated apathy scores were recorded. Following a model-free analysis of choice data, we utilised a stepwise model-based approach to explore the relationship between latent cognitive processes underlying effort-based decision-making, motivation and brain metrics. First, choices made and reaction times were analysed using drift diffusion modeling to uncover latent cognitive processes. Next, associations between apathy, diagnosis and these latent cognitive processes were examined using linear regression models. Finally, associations between latent cognitive processes altered in apathy and brain structure and connectivity in a priori regions were examined using linear mixed models. Model free analysis of choice data showed that apathy in both groups was associated with reduced incentivisation by lower rewards, whereas apathy was associated with increased sensitivity to high effort costs in PD, but reduced sensitivity to effort in aMCI/pAD. Drift diffusion modeling revealed that increased drift rate to reject offers as a function of changing effort levels was significantly associated with lower motivation in PD, but not aMCI/pAD, which was associated with lower fractional anisotropy in the pathways linking the dorsal anterior cingulate cortex and the striatum in PD. Additionally, apathy across participants was associated with bias towards rejecting offers, captured by the decision bias parameter. Furthermore, this bias was associated with increased functional connectivity in the dorsal attention network. In sum, apathy in both aMCI/pAD and PD is associated with alterations in effort-based decision making, but there are differences in these changes with disease type. Disease-specific processes and pathology remain relevant in determining the underlying causes of disrupted motivation, whilst a cross-cutting approach to apathy is still informative from a framework perspective.