scholarly journals Dopamine-dependent loss aversion during effort-based decision-making

2019 ◽  
Author(s):  
Xiuli Chen ◽  
Sarah Voets ◽  
Ned Jenkinson ◽  
Joseph M. Galea

AbstractFrom psychology to economics there has been substantial interest in how costs (e.g., delay, risk) are represented asymmetrically during decision-making when attempting to gain reward or to avoid punishment. For example, in decision-making under risk, individuals show a tendency to prefer to avoid punishment than to acquire the equivalent reward (loss aversion). Although the cost of physical effort has received significant recent attention due to the evaluation of motor costs being crucial in our daily decisions, it remains unclear whether loss aversion exists during effort-based decision-making. On the one hand, loss aversion may be hardwired due to asymmetric evolutionary pressure on losses and gains and therefore exists across decision-making contexts. On the other hand, distinct brain regions are involved with different decision costs, making it questionable whether similar asymmetries exist. Here, we demonstrate that young healthy participants exhibit loss aversion during effort-based decision-making by exerting more physical effort in order to avoid punishment than to gain a same-size reward. Next, we show that medicated Parkinson’s disease (PD) patients show a reduction in loss aversion compared to age-matched controls. Behavioural and computational analysis revealed that people with PD exerted similar physical effort in return for a reward, but were less willing to produce effort in order to avoid punishment. Therefore, loss aversion is present during effort-based decision-making and can be modulated by altered dopaminergic state. This finding could have important implications for our understanding of clinical disorders that show a reduced willingness to exert effort in the pursuit of reward.Significance StatementLoss aversion – preferring to avoid punishment than to acquire equivalent reward – is an important concept in decision-making under risk. However, little is known about whether loss aversion also exists during decisions where the cost is physical effort. This is surprising given that motor cost shapes human behaviour, and a reduced willingness to exert effort is a characteristic of many clinical disorders. Here, we show that healthy individuals exert more effort to minimise punishment than to maximise reward (loss aversion). We also demonstrate that loss aversion is modulated by altered dopaminergic state by showing that medicated Parkinson’s disease patients exert similar effort to gain reward but less effort to avoid punishment. Therefore, dopamine-dependent loss aversion is crucial for explaining effort-based decision-making.

2016 ◽  
Author(s):  
Monique H.M. Timmer ◽  
Guillaume Sescousse ◽  
Rianne A.J. Esselink ◽  
Payam Piray ◽  
Roshan Cools

AbstractDepression, a common non-motor symptom of Parkinson’s disease (PD), is accompanied by impaired decision making and an enhanced response to aversive outcomes. Current strategies to treat depression in PD include dopaminergic medication. However, their use can be accompanied by detrimental side effects, such as enhanced risky choice. The mechanisms underlying dopamine-induced increases in risky choice are unclear. In the current study we adopt a clinical-neuroeconomic approach to investigate the effects of dopaminergic medication on loss aversion during risky choice in depressed and non-depressed PD. Twenty-three healthy controls, 21 depressed and 22 non-depressed PD patients were assessed using a well-established gambling task measuring loss aversion during risky choice. Patients were tested on two occasions, after taking their normal dopaminergic medication (ON) and after withdrawal of their medication (OFF). Dopaminergic medication decreased loss aversion to a greater extent in depressed than non-depressed PD patients. Moreover, we show that the degree to which dopaminergic medication decreases loss aversion correlated with current depression severity and with drug effects on depression scores. These findings demonstrate that dopamine-induced changes in loss aversion depend on the presence of depressive symptoms in PD.Significance statementDopaminergic medication that is used to treat motor and non-motor symptoms in patients with Parkinson’s disease is known to contribute to risky decision-making. The underlying mechanisms are unclear. The present study demonstrates that dopaminergic medication in Parkinson’s disease decreases loss aversion during risky choice, but only in depressed and not in non-depressed patients with Parkinson’s disease. These results advance our understanding of the mechanisms underlying dopamine-induced risky choice, while also identifying depression as an important factor that confers vulnerability to such dopamine-induced risky choice.Conflict of InterestThe authors declare no competing financial interests.


2021 ◽  
pp. 1-11
Author(s):  
Cristina Colón-Semenza ◽  
Daniel Fulford ◽  
Terry Ellis

Background: People with Parkinson’s disease (PwPD) are less active than their age-matched peers. Non-motor symptoms, specifically, deficient motivation, may influence decision-making for exercise due to the impaired mesolimbic dopaminergic pathway. Objective: The purpose of this study was to determine if effort-based decision-making for physical effort was different in PwPD compared to healthy controls. We sought to determine the relationship between effort-based decision making for exercise and a discrete motor task as well as the impact of components of motivation on decision-making for physical effort in PwPD. Methods: An effort-based decision-making paradigm using a discrete motor task (button pressing) and a continuous exercise task (cycling) was implemented in 32 PwPD and 23 healthy controls. Components of motivation were measured using the Apathy Scale and the Temporal Experience of Pleasure Scale- Anticipatory Pleasure scale. Results: The presence of Parkinson’s disease (PD) did not moderate decisions for either physical effort task. There was a moderate correlation between decisions for both tasks, within each group. The anticipation of pleasure and apathy were predictors of decisions for both physical effort tasks in PwPD, but not in healthy controls. Conclusion: PwPD responded similarly to effort and reward valuations compared to those without PD. Individuals were consistent in their decisions, regardless of the physical effort task. The anticipation of pleasure and apathy were significant predictors of decisions for exercise in PwPD only. Increased anticipation of pleasure, reduction of apathy, and the use of rewards may enhance engagement in high effort exercise among PwPD.


2009 ◽  
Vol 47 (8-9) ◽  
pp. 1901-1908 ◽  
Author(s):  
M. Delazer ◽  
H. Sinz ◽  
L. Zamarian ◽  
H. Stockner ◽  
K. Seppi ◽  
...  

2010 ◽  
Vol 23 (3) ◽  
pp. 131-143 ◽  
Author(s):  
Kirsten Labudda ◽  
Matthias Brand ◽  
Markus Mertens ◽  
Isabelle Ollech ◽  
Hans J. Markowitsch ◽  
...  

We aimed to study whether previously described impairment in decision making under risky conditions in patients with Parkinson's disease (PD) is affected by deficits in using information about potential incentives or by processing feedback (in terms of fictitious gains and losses following each decision). Additionally, we studied whether the neural correlates of using explicit information in decision making under risk differ between PD patients and healthy subjects. We investigated ten cognitively intact PD patients and twelve healthy subjects with the Game of Dice Task (GDT) to assess risky decision making, and with an fMRI paradigm to analyse the neural correlates of information integration in the deliberative decision phase. Behaviourally, PD patients showed selective impairment in the GDT but not on the fMRI task that did not include a feedback component. Healthy subjects exhibited lateral prefrontal, anterior cingulate and parietal activations when integrating decision-relevant information. Despite similar behavioural patterns on the fMRI task, patients exhibited reduced parietal activation. Behavioural results suggest that PD patients’ deficits in risky decision making are dominated by impaired feedback utilization not compensable by intact cognitive functions. Our fMRI results suggest similarities but also differences in neural correlates when using explicit information for the decision process, potentially indicating different strategy application even if the interfering feedback component is excluded.


2014 ◽  
Vol 254 ◽  
pp. 70-77 ◽  
Author(s):  
Jana K. Boller ◽  
Michael T. Barbe ◽  
K. Amande M. Pauls ◽  
Christiane Reck ◽  
Matthias Brand ◽  
...  

Author(s):  
Antonina Kouli ◽  
Marta Camacho ◽  
Kieren Allinson ◽  
Caroline H. Williams-Gray

AbstractParkinson’s disease dementia is neuropathologically characterized by aggregates of α-synuclein (Lewy bodies) in limbic and neocortical areas of the brain with additional involvement of Alzheimer’s disease-type pathology. Whilst immune activation is well-described in Parkinson’s disease (PD), how it links to protein aggregation and its role in PD dementia has not been explored. We hypothesized that neuroinflammatory processes are a critical contributor to the pathology of PDD. To address this hypothesis, we examined 7 brain regions at postmortem from 17 PD patients with no dementia (PDND), 11 patients with PD dementia (PDD), and 14 age and sex-matched neurologically healthy controls. Digital quantification after immunohistochemical staining showed a significant increase in the severity of α-synuclein pathology in the hippocampus, entorhinal and occipitotemporal cortex of PDD compared to PDND cases. In contrast, there was no difference in either tau or amyloid-β pathology between the groups in any of the examined regions. Importantly, we found an increase in activated microglia in the amygdala of demented PD brains compared to controls which correlated significantly with the extent of α-synuclein pathology in this region. Significant infiltration of CD4+ T lymphocytes into the brain parenchyma was commonly observed in PDND and PDD cases compared to controls, in both the substantia nigra and the amygdala. Amongst PDND/PDD cases, CD4+ T cell counts in the amygdala correlated with activated microglia, α-synuclein and tau pathology. Upregulation of the pro-inflammatory cytokine interleukin 1β was also evident in the substantia nigra as well as the frontal cortex in PDND/PDD versus controls with a concomitant upregulation in Toll-like receptor 4 (TLR4) in these regions, as well as the amygdala. The evidence presented in this study show an increased immune response in limbic and cortical brain regions, including increased microglial activation, infiltration of T lymphocytes, upregulation of pro-inflammatory cytokines and TLR gene expression, which has not been previously reported in the postmortem PDD brain.


2021 ◽  
pp. 1-7
Author(s):  
Sarah Jarrin ◽  
Abrar Hakami ◽  
Ben Newland ◽  
Eilís Dowd

Despite decades of research and billions in global investment, there remains no preventative or curative treatment for any neurodegenerative condition, including Parkinson’s disease (PD). Arguably, the most promising approach for neuroprotection and neurorestoration in PD is using growth factors which can promote the growth and survival of degenerating neurons. However, although neurotrophin therapy may seem like the ideal approach for neurodegenerative disease, the use of growth factors as drugs presents major challenges because of their protein structure which creates serious hurdles related to accessing the brain and specific targeting of affected brain regions. To address these challenges, several different delivery systems have been developed, and two major approaches—direct infusion of the growth factor protein into the target brain region and in vivo gene therapy—have progressed to clinical trials in patients with PD. In addition to these clinically evaluated approaches, a range of other delivery methods are in various degrees of development, each with their own unique potential. This review will give a short overview of some of these alternative delivery systems, with a focus on ex vivo gene therapy and biomaterial-aided protein and gene delivery, and will provide some perspectives on their potential for clinical development and translation.


Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 598
Author(s):  
Débora Masini ◽  
Carina Plewnia ◽  
Maëlle Bertho ◽  
Nicolas Scalbert ◽  
Vittorio Caggiano ◽  
...  

In Parkinson’s disease (PD), a large number of symptoms affecting the peripheral and central nervous system precede, develop in parallel to, the cardinal motor symptoms of the disease. The study of these conditions, which are often refractory to and may even be exacerbated by standard dopamine replacement therapies, relies on the availability of appropriate animal models. Previous work in rodents showed that injection of the neurotoxin 6-hydroxydopamine (6-OHDA) in discrete brain regions reproduces several non-motor comorbidities commonly associated with PD, including cognitive deficits, depression, anxiety, as well as disruption of olfactory discrimination and circadian rhythm. However, the use of 6-OHDA is frequently associated with significant post-surgical mortality. Here, we describe the generation of a mouse model of PD based on bilateral injection of 6-OHDA in the dorsal striatum. We show that the survival rates of males and females subjected to this lesion differ significantly, with a much higher mortality among males, and provide a protocol of enhanced pre- and post-operative care, which nearly eliminates animal loss. We also briefly discuss the utility of this model for the study of non-motor comorbidities of PD.


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