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

BACKGROUND: Earlier 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. METHODS: Eighty-five participants (41 males; 18-30 years (M = 23.0, SD = 2.4)) performed a mental effort-based decision-making task before, 2 h after, and 5 h 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 concentration levels were analyzed using partial correlation analyses. RESULTS: Plasma cytokine concentrations and fatigue were increased at 2 h post-LPS compared to baseline and 5 h post-LPS administration. Acceptance rates decreased for medium, but not for easy or hard effort levels at 2 h post-LPS versus baseline and 5 h post-LPS administration, irrespective of reward level. These reductions 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 cytokine concentrations. CONCLUSION: Fatigue 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.

Pitfalls in cytokine measurements - Plasma TGF-ß1 in chronic fatigue syndrome.

BACKGROUND: Serum TGF-ß1 concentrations are reported to be elevated in chronic fatigue syndrome (CFS). However, measurement of circulating cytokines is a complex procedure and control of pre-analytical procedures is essential. The objective of the current study was to measure circulating TGF-ß1 concentrations in CFS patients compared to healthy controls, taking into account differences in pre-analytical procedures. METHODS: Two cohorts of female CFS patients were included. In both studies patients were asked to bring a healthy, age-matched control. At baseline, TGF-ß1 levels were measured in plasma and additionally P-selectin, a marker of platelet activity, was determined in a subgroup of participants. RESULTS: 50 patients and 48 controls were included in cohort I, and 90 patients and 29 controls in cohort II. Within the cohorts there were no differences in TGF-ß1 concentrations. However, between the cohorts there was a large discrepancy, which appeared to be caused by differences in g-force of the centrifuges used. The lower g-force used in cohort II (1361 g) caused more platelet activation, reflected by higher p-selectin concentrations, compared to cohort I (p < 0.0001), which was confirmed in a second independent experiment. There was a correlation between TGF-ß1 and p-selectin concentrations (r 0.79, p < 0.0001). CONCLUSION: These results demonstrate that control of pre-analytical procedures is an essential aspect when measuring circulating cytokines. No evidence for enhanced TGF-ß1 in patients with CFS was found.

Reward learning deficits in Parkinson's disease depend on depression.

BACKGROUND: Depression is one of the most common and debilitating non-motor symptoms of Parkinson's disease (PD). The neurocognitive mechanisms underlying depression in PD are unclear and treatment is often suboptimal. METHODS: We investigated the role of striatal dopamine in reversal learning from reward and punishment by combining a controlled medication withdrawal procedure with functional magnetic resonance imaging in 22 non-depressed PD patients and 19 PD patients with past or present depression. RESULTS: PD patients with a depression (history) exhibited impaired reward v. punishment reversal learning as well as reduced reward v. punishment-related BOLD signal in the striatum (putamen) compared with non-depressed PD patients. No effects of dopaminergic medication were observed. CONCLUSIONS: The present findings demonstrate that impairments in reversal learning from reward v. punishment and associated striatal signalling depend on the presence of (a history of) depression in PD.

Widespread fMRI activity differences between perceptual states in visual rivalry are correlated with differences in observer biases.

When observing bistable stimuli, the percept can change in the absence of changes in the stimulus itself. When intermittently presenting a bistable stimulus, the number of perceptual alternations can increase or decrease, depending on the duration of the period that the stimulus is removed from screen between stimulus presentations (off-period). Longer off-periods lead to stabilization of the percept, while short off-periods produce perceptual alternations. Here we compare fMRI brain activation across percept repetitions and alternations when observing an intermittently presented ambiguously rotating structure from motion sphere. In the first experimental session, subjects were requested to voluntarily control the percept into either a repeating or an alternating perceptual regime at a single off-period. In a consecutive session, subjects observed the sphere uninstructed, and reported alternations and repetitions. The behavioral data showed that there were marked individual biases for observing the sphere as either repeating or alternating. The fMRI data showed activation differences between alternating and repeating perceptual regimes in an extensive network that included parietal cortex, dorsal premotor area, dorsolateral prefrontal cortex, supplementary motor area, insula, and cerebellum. However, these activation differences could all be explained by intersubject differences in the bias for one of the two perceptual regimes. The stronger the bias was for a particular perceptual regime, the less activation and vice versa. We conclude that widespread activation differences between perceptual regimes can be accounted for by differences in the perceptual bias for one of the two regimes.