title: Peripheral inflammation acutely impairs human spatial memory via actions on medial temporal lobe glucose metabolism.
abstract: BACKGROUND
  Inflammation impairs cognitive performance and is implicated in the progression of neurodegenerative disorders. Rodent studies demonstrated key roles for inflammatory mediators in many processes critical to memory, including long-term potentiation, synaptic plasticity, and neurogenesis. They also demonstrated functional impairment of medial temporal lobe (MTL) structures by systemic inflammation. However, human data to support this position are limited.
  
  
  METHODS
  Sequential fluorodeoxyglucose positron emission tomography together with experimentally induced inflammation was used to investigate effects of a systemic inflammatory challenge on human MTL function. Fluorodeoxyglucose positron emission tomography scanning was performed in 20 healthy participants before and after typhoid vaccination and saline control injection. After each scanning session, participants performed a virtual reality spatial memory task analogous to the Morris water maze and a mirror-tracing procedural memory control task.
  
  
  RESULTS
  Fluorodeoxyglucose positron emission tomography data demonstrated an acute reduction in human MTL glucose metabolism after inflammation. The inflammatory challenge also selectively compromised human spatial, but not procedural, memory; this effect that was independent of actions on motivation or psychomotor response. Effects of inflammation on parahippocampal and rhinal glucose metabolism directly mediated actions of inflammation on spatial memory.
  
  
  CONCLUSIONS
  These data demonstrate acute sensitivity of human MTL to mild peripheral inflammation, giving rise to associated functional impairment in the form of reduced spatial memory performance. Our findings suggest a mechanism for the observed epidemiologic link between inflammation and risk of age-related cognitive decline and progression of neurodegenerative disorders including Alzheimer's disease.
authors.affiliation: Department of Psychiatry, Brighton and Sussex Medical School, Falmer, United Kingdom; Sackler Centre for Consciousness Science, University of Sussex, Falmer, United Kingdom. Electronic address: n.harrison@bsms.ac.uk.
authors.forename: Neil A
authors.initials: NA
authors.lastname: Harrison
authors.affiliation: Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, The Netherlands.
authors.forename: Christian F
authors.initials: CF
authors.lastname: Doeller
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Valerie
authors.initials: V
authors.lastname: Voon
authors.affiliation: Institutes of Cognitive Neuroscience and Neurology, University College London, London, United Kingdom.
authors.forename: Neil
authors.initials: N
authors.lastname: Burgess
authors.affiliation: Department of Psychiatry, Brighton and Sussex Medical School, Falmer, United Kingdom; Sackler Centre for Consciousness Science, University of Sussex, Falmer, United Kingdom.
authors.forename: Hugo D
authors.initials: HD
authors.lastname: Critchley
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D016207:Cytokines / Q000378:metabolism; D004311:Double-Blind Method; D019788:Fluorodeoxyglucose F18; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000523:psychology*; D008297:Male; D008569:Memory Disorders / Q000378:metabolism*; D049268:Positron-Emission Tomography; D065852:Spatial Memory / Q000502:physiology*; D013702:Temporal Lobe / Q000378:metabolism*; D014436:Typhoid-Paratyphoid Vaccines / Q000009:adverse effects; D055815:Young Adult
chemical_list: D016207:Cytokines; D014436:Typhoid-Paratyphoid Vaccines; D019788:Fluorodeoxyglucose F18
keywords: Alzheimer’s disease; PET; imaging; inflammation; memory; parahippocampus