Trial reportBiological psychiatry2016
A Neurocomputational Account of How Inflammation Enhances Sensitivity to Punishments Versus Rewards.
Trial report in Biological psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05866575 (Prediction of the Therapeutic Response in Depression Based on an Early Neuro-computational Modeling Assessment of Motivation), which is not on this map. Cited by 104 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Prediction of the Therapeutic Response in Depression Based on an Early Neuro-computational Modeling Assessment of Motivation
Who cites it
104 citing papers in PubMed, 1 synthesis or guideline pooled it, 182 citations in OpenAlex.
- Predictors of successful anti-inflammatory drug trials in patients with schizophrenia: A meta-regression and critical commentary.Brain, behavior, and immunity · 2023Pooled it
- Obesity, low-grade inflammation, and inflammatory response to immune challenge modulate willingness to expend effort for reward.Brain, behavior, and immunity · 2026Trial
- Inflammation-induced depressed mood and reward responsivity as a function of age in female adults: a randomized controlled trial of endotoxin.Translational psychiatry · 2025Trial
- A randomized proof-of-mechanism trial of TNF antagonism for motivational deficits and related corticostriatal circuitry in depressed patients with high inflammation.Molecular psychiatry · 2025Trial
- Sustained effects of repeated levodopa (L-DOPA) administration on reward circuitry, effort-based motivation, and anhedonia in depressed patients with higher inflammation.Brain, behavior, and immunity · 2025Trial
- Resting state functional connectivity changes following mindfulness-based stress reduction predict improvements in disease control for patients with asthma.Brain, behavior, and immunity · 2024Trial
- Functional connectivity in reward circuitry and symptoms of anhedonia as therapeutic targets in depression with high inflammation: evidence from a dopamine challenge study.Molecular psychiatry · 2022Trial
- Effects of stress-induced inflammation on reward processing in healthy young women.Brain, behavior, and immunity · 2020Trial
- The effect of a transient immune activation on subjective health perception in two placebo controlled randomised experiments.PloS one · 2019Trial
- Lipopolysaccharide Alters Motivated Behavior in a Monetary Reward Task: a Randomized Trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Trial
- Neurochemical drivers of effort: The roles of dopamine and beyond in physical and cognitive exertion.Neuroscience and biobehavioral reviews · 2026Review
- Synaptic effects of interleukin-6 on human iPSC-derived dopaminergic neurons.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Fluoxetine Reduces Hyperglycemia-Induced Facilitation of Fear Memory in Mice.Brain and behavior · 2026Article
- Ketone bodies mitigate against systemic inflammation-induced changes in brain energy metabolism and delirium-like deficits in aged mice.bioRxiv : the preprint server for biology · 2026Article
- Inflammatory models of depression in rodents and humans.Frontiers in psychiatry · 2026Review
- From Neural Circuits to Behavior: Examining the Central Role of Anhedonia in Major Depression.Advances in experimental medicine and biology · 2026Review
- The kynurenine pathway in depression and schizophrenia: convergent signals, divergent states, and clinical signatures.EXCLI journal · 2026Review
- Network-level organization of systemic inflammation reflects early Alzheimer's-like behavioral changes.Scientific reports · 2025Article
- The motivational drives of sickness: Acute changes in self-rated motivation during experimental endotoxemia assessed with the newly developed Motivation Scale of Sickness (MOSSick).Comprehensive psychoneuroendocrinology · 2025Article
- Network-Level Organization of Systemic Inflammation Reflects Early Alzheimer's-Like Behavioral Changes.Research square · 2025Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundInflammation rapidly impairs mood and cognition and, when severe, can appear indistinguishable from major depression. These sickness responses are characterized by an acute reorientation of motivational state; pleasurable activities are avoided, and sensitivity to negative stimuli is enhanced. However, it remains unclear how these rapid shifts in behavior are mediated within the brain.
methodsHere, we combined computational modeling of choice behavior, experimentally induced inflammation, and functional brain imaging (functional magnetic resonance imaging) to describe these mechanisms. Using a double-blind, randomized crossover study design, 24 healthy volunteers completed a probabilistic instrumental learning task on two separate occasions, one 3 hours after typhoid vaccination and one 3 hours after saline (placebo) injection. Participants learned to select high probability reward (win £1) and avoid high probability punishment (lose £1) stimuli. An action-value learning algorithm was fit to the observed behavior, then used within functional magnetic resonance imaging analyses to identify neural coding of prediction error signals driving motivational learning.
resultsInflammation acutely biased behavior, enhancing punishment compared with reward sensitivity, through distinct actions on neural representations of reward and punishment prediction errors within the ventral striatum and anterior insula. Consequently, choice options leading to potential rewards were less behaviorally attractive, and those leading to punishments were more aversive.
conclusionsOur findings demonstrate the neural mediation of a rapid, state-dependent reorientation of reward versus punishment sensitivity during inflammation. This mechanism may aid the adaptive reallocation of metabolic resources during acute sickness but might also account for maladaptive, motivational changes that underpin the association between chronic inflammation and depression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.