Mild exogenous inflammation blunts neural signatures of bounded evidence accumulation and reward prediction error processing in healthy male participants

Queirazza, F., Cavanagh, J. , Philiastides, M. G. and Krishnadas, R. (2024) Mild exogenous inflammation blunts neural signatures of bounded evidence accumulation and reward prediction error processing in healthy male participants. Brain, Behavior, and Immunity, (doi: 10.1016/j.bbi.2024.03.044) (PMID:38555987) (In Press)

Abstract

Background: Altered neural haemodynamic activity during decision making and learning has been linked to the effects of inflammation on mood and motivated behaviours. So far, it has been reported that blunted mesolimbic dopamine reward signals are associated with inflammation-induced anhedonia and apathy. Nonetheless, it is still unclear whether inflammation impacts neural activity underpinning decision dynamics. The process of decision making involves integration of noisy evidence from the environment until a critical threshold of evidence is reached. There is growing empirical evidence that such process, which is usually referred to as bounded accumulation of decision evidence, is affected in the context of mental illness. Methods: In a randomised, placebo-controlled, crossover study, 19 healthy male participants were allocated to placebo and typhoid vaccination. Three to four hours post-injection, participants performed a probabilistic reversal-learning task during functional magnetic resonance imaging. To capture the hidden neurocognitive operations underpinning decision-making, we devised a hybrid sequential sampling and reinforcement learning computational model. We conducted whole brain analyses informed by the modelling results to investigate the effects of inflammation on the efficiency of decision dynamics and reward learning. Results: We found that during the decision phase of the task, typhoid vaccination attenuated neural signatures of bounded evidence accumulation in the dorsomedial prefrontal cortex, only for decisions requiring short integration time. Consistent with prior work, we showed that, in the outcome phase, mild acute inflammation blunted the reward prediction error in the bilateral ventral striatum and amygdala. Conclusions: Our study extends current insights into the effects of inflammation on the neural mechanisms of decision making and shows that exogenous inflammation alters neural activity indexing efficiency of evidence integration, as a function of choice discriminability. Moreover, we replicate previous findings that inflammation blunts striatal reward prediction error signals.

• Item Type: Articles
• Additional Information: The study was funded by a clinical lecturer starter grant awarded to R.K. by the Academy of Medical Sciences. F.Q. was supported by the JMAS Sim Fellowship awarded by the Royal College of Physician of Edinburgh. M.G.P. was supported by a European Research Council grant (ERC, DyNeRfusion, 865003).
• Status: In Press
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Philiastides, Professor Marios and Cavanagh, Professor Jonathan and Queirazza, Dr Filippo and Krishnadas, Dr Rajeev

Creator Roles

Queirazza, F.: Writing – original draft, Visualization, Software, Resources, Methodology, Formal analysis, Writing – review and editing
Cavanagh, J.: Writing – review and editing
Philiastides, M. G.: Formal analysis, Methodology, Writing – review and editing
Krishnadas, R.: Conceptualization, Data curation, Funding acquisition, Resources, Writing – review and editing

• Authors: Queirazza, F., Cavanagh, J., Philiastides, M. G., and Krishnadas, R.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing; College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• Journal Name: Brain, Behavior, and Immunity
• Publisher: Elsevier
• ISSN: 0889-1591
• ISSN (Online): 1090-2139
• Published Online: 29 March 2024
• Copyright Holders: Copyright © 2024 The Authors
• First Published: First published in Brain, Behavior, and Immunity 2024
• Publisher Policy: Reproduced under a Creative Commons License