Kieslich, K. | Search bioRxiv

bioRxiv2024

A computational approach to understanding effort-based decision-making in depression

BackgroundMotivational dysfunction is a core feature of depression, and can have debilitating effects on everyday function. However, it is unclear which disrupted cognitive processes underlie impaired motivation, and whether impairments persist following remission. Decision-making concerning exerting effort to obtain rewards offers a promising framework for understanding motivation, especially when examined with computational tools which can offer precise quantification of latent processes. MethodsEffort-based decision-making was assessed using the Apple Gathering Task, where participants decide whether to exert effort via a grip-force device to obtain varying levels of reward; effort levels were individually calibrated and varied parametrically. We present a comprehensive computational analysis of decision-making, initially validating our model in healthy volunteers (N=67), before applying it in a case-control study including current (N=41) and remitted (N=46) unmedicated depressed individuals, and healthy volunteers with (N=36) and without (N=57) a family history of depression. ResultsFour fundamental computational mechanisms that drive patterns of effort-based decisions, which replicated across samples, were identified: overall bias to accept effort challenges; reward sensitivity; and linear and quadratic effort sensitivity. Traditional model-agnostic analyses showed that both depressed groups showed lower willingness to exert effort. In contrast with previous findings, computational analysis revealed that this difference was primarily driven by lower effort acceptance bias, but not altered effort or reward sensitivity. ConclusionsThis work provides insight into the computational mechanisms underlying motivational dysfunction in depression. Lower willingness to exert effort could represent a trait-like factor contributing to symptoms, and might represent a fruitful target for treatment and prevention.

neuroscience↗

bioRxiv2024

Depression in Parkinson's disease is associated with dopamine unresponsive reduced reward sensitivity during effort-based decision making

Willingness to exert effort for a given goal is dependent on the magnitude of the potential rewards and effort costs of an action. Such effort-based decision making is an essential component of motivation, in which the dopaminergic system plays a key role. Depression in Parkinsons disease (PD) is common, disabling and has poor outcomes. Motivational symptoms such as apathy and anhedonia, are prominent in PD depression and related to dopaminergic loss. We hypothesised that dopamine-dependent disruption in effort-based decision-making contributes to depression in PD. In the present study, an effort-based decision-making task was administered to 62 patients with PD, with and without depression, ON and OFF their dopaminergic medication across two sessions, as well as to 34 patients with depression and 29 matched controls on a single occasion. During the task, on each trial, participants decided whether to accept or reject offers of different levels of monetary reward in return for exerting varying levels of physical effort via grip force, measured using individually calibrated dynamometers. The primary outcome variable was choice (accept/decline offer), analysed using both logistic mixed-effects modelling and a computational model which dissected the individual contributions of reward and effort on depression and dopamine state in PD. We found PD depression was characterised by lower acceptance of offers, driven by markedly lower incentivisation by reward (reward sensitivity), compared to all other groups. Within-subjects analysis of the effect of dopamine medication revealed that, although dopamine treatment improves reward sensitivity in non-depressed PD patients, this therapeutic effect is not present in PD patients with depression. These findings suggest that disrupted effort-based decision-making, unresponsive to dopamine, contributes to PD depression. This highlights reward sensitivity as a key mechanism and treatment target for PD depression that potentially requires non-dopaminergic therapies.

neuroscience↗