title: A Neurocomputational Account of How Inflammation Enhances Sensitivity to Punishments Versus Rewards.
abstract: Inflammation 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.
  
  
  
  Here, 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.
  
  
  
  Inflammation 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.
  
  
  
  Our 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.
authors.affiliation: Department of Psychiatry, Brighton and Sussex Medical School, Brighton; Sackler Centre for Consciousness Science, University of Sussex Brighton; Sussex Partnership National Health Service Foundation Trust, Brighton. Electronic address: n.harrison@bsms.ac.uk.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Harrison
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge; Cambridgeshire and Peterborough National Health Service Foundation Trust, Cambridge.
authors.forename: Valerie
authors.initials: V
authors.lastname: Voon
authors.affiliation: Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, University of Sussex, Brighton, United Kingdom.
authors.forename: Mara
authors.initials: M
authors.lastname: Cercignani
authors.affiliation: Department of Psychiatry, Brighton and Sussex Medical School, Brighton.
authors.forename: Ella A
authors.initials: EA
authors.lastname: Cooper
authors.affiliation: Motivation, Brain & Behavior Lab, Brain & Spine Institute, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Mathias
authors.initials: M
authors.lastname: Pessiglione
authors.affiliation: Department of Psychiatry, Brighton and Sussex Medical School, Brighton; Sackler Centre for Consciousness Science, University of Sussex Brighton; Sussex Partnership National Health Service Foundation Trust, Brighton.
authors.forename: Hugo D
authors.initials: HD
authors.lastname: Critchley
mesh_terms: D000328:Adult; D002540:Cerebral Cortex / Q000503:physiopathology*; D002755:Choice Behavior / Q000502:physiology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008959:Models, Neurological; D011337:Probability Learning; D011678:Punishment; D012054:Reinforcement, Psychology; D012201:Reward; D014435:Typhoid Fever / Q000517:prevention & control; D014611:Vaccination; D066328:Ventral Striatum / Q000503:physiopathology*; D055815:Young Adult
keywords: Depression; Imaging; Inflammation; Insula; Reward; Striatum