Lambregts, B. I. H. M. | Search bioRxiv

bioRxiv2024

Fatigue >12 weeks after coronavirus disease (COVID) is associated with reduced reward sensitivity during effort-based decision making

BackgroundFatigue and depressive mood is inherent to acute disease, but a substantial group of people report persisting disabling fatigue and depressive symptoms long after a COVID infection. Acute infections have shown to change decisions to engage in effortful and rewarding activities, but it is currently unclear whether fatigue and depressive symptoms similarly affect decision making during acute and persistent phases of a COVID infection. Here, we investigated whether fatigue and depressive mood are associated with altered weighting of effort and reward in decision-making during different timepoints after COVID infection. MethodsWe conducted an online cross-sectional study between March 2021 and March 2022. 242 Participants (18-65 years) with COVID <4 weeks ago (n=62), COVID >12 weeks ago (n=81), or no prior COVID (self-reported) (n=90) performed an effort-based decision-making task, in which they decided whether they wanted to exert physical effort (ticking boxes on screen, 5 levels) for reward (money to be gained in a voucher-lottery, 5 levels). State fatigue and depressive mood was measured by the Profile of Mood States (POMS) prior to the task. We used multilevel binomial regression analysis to test whether fatigue and depressive mood were related to acceptance rates for effort and reward levels and whether this differed between the groups. ResultsCompared with no COVID and COVID <4 weeks groups, the COVID >12 weeks group reported higher state fatigue scores (mean{+/-}SD: 20{+/-}7 vs. 14{+/-}7 and 12{+/-}6 POMS-score, respectively; both p<0.001) and was less sensitive to rewards (Reward*Group: OR: 0.35 (95%CI 0.20, 0.62), p<0.001 and OR: 0.38 (95%CI 0.20, 0.72), p=0.003). In the COVID >12 weeks group, fatigue was more negatively associated with reward sensitivity compared with the COVID <4 weeks group (Reward*Fatigue*Group: OR 0.47 (95%CI 0.25, 1.13), p=0.022) and the no COVID group (Reward*Fatigue*Group: OR 0.48 (95%CI 4.01, 0.92), p=0.029). No group differences were observed for the relationship between fatigue and effort sensitivity. No group differences were observed for the relationship between depressive mood and effort or reward sensitivity. Higher age, lower BMI, unhealthy lifestyle, and worrying during the acute phase of COVID each predicted decreased reward sensitivity in the >12 weeks group (Age*Reward: OR 0.30 (95%CI 0.19, 0.48), p<0.001; BMI*Reward: OR 1.43 (95%CI 1.01, 2.00), p=0.047); Lifestyle*Reward: OR 1.50 (95%CI 1.06, 2.14), p=0.022; Worrying*Reward: OR 0.59 (95%CI 0.38, 0.94), p=0.025, respectively). ConclusionThe finding that fatigue is related to lower reward sensitivity >12 weeks after COVID, suggesting potential reward deficits in post-covid fatigue. These findings are in line with previous observations that long-term inflammation can induce dysregulations in neural reward processing, which should be further investigated in future studies. HighlightsO_LIWe tested if fatigue and mood were related to altered decision making post-COVID C_LIO_LIParticipants post-COVID >12wks ago were more fatigued and less reward sensitive C_LIO_LIPost-COVID-related fatigue was associated with reduced reward sensitivity C_LIO_LIPost-COVID-related depressive mood was not associated with altered decision making C_LIO_LIHigher age, unhealthy lifestyle, and worrying predicted reward deficits C_LI

neuroscience↗

bioRxiv2023

Fatigue during acute systemic inflammation is associated with reduced mental effort expenditure while task accuracy is preserved

BackgroundEarlier work within the physical domain showed that acute inflammation changes motivational prioritization and effort allocation rather than physical abilities. It is currently unclear whether a similar motivational framework accounts for the mental fatigue and cognitive symptoms of acute sickness. Accordingly, this study aimed to assess the relationship between fatigue, cytokines and mental effort-based decision making during acute systemic inflammation. MethodsEighty-five participants (41 males; 18-30 years (M=23.0, SD=2.4)) performed a mental effort-based decision-making task before, 2 hours after, and 5 hours after intravenous administration of 1 ng/kg bacterial lipopolysaccharide (LPS) to induce systemic inflammation. Plasma concentrations of cytokines (interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)) and fatigue levels were assessed at similar timepoints. In the task, participants decided whether they wanted to perform (i.e., accepted) arithmetic calculations of varying difficulty (3 levels: easy, medium, hard) in order to obtain rewards (3 levels: 5, 6 or 7 points). Acceptance rates were analyzed using a binomial generalized estimated equation (GEE) approach with effort, reward and time as independent variables. Arithmetic performance was measured per effort level prior to the decisions and included as a covariate. Associations between acceptance rates, fatigue (self-reported) and cytokine concentrations levels were analyzed using partial correlation analyses. ResultsPlasma cytokine concentrations and fatigue were increased at 2 hours post-LPS compared to baseline and 5 hours post-LPS administration. Acceptance rates decreased for medium, but not for easy or hard effort levels at 2 hours post-LPS versus baseline and 5 hours post-LPS administration, irrespective of reward level. This reduction in acceptance rates occurred despite improved accuracy on the arithmetic calculations itself. Reduced acceptance rates for medium effort were associated with increased fatigue, but not with increased cytokines. ConclusionFatigue during acute systemic inflammation is associated with alterations in mental effort allocation, similarly as observed previously for physical effort-based choice. Specifically, willingness to exert mental effort depended on effort and not reward information, while task accuracy was preserved. These results extend the motivational account of inflammation to the mental domain and suggest that inflammation may not necessarily affect domain-specific mental abilities, but rather affects domain-general effort-allocation processes.

neuroscience↗