File(s) under permanent embargo
Effects of inflammation on hippocampus and substantia nigra responses to novelty in healthy human participants
journal contribution
posted on 2023-06-08, 20:16 authored by Neil Harrison, Mara Cercignani, Valerie Voon, Hugo CritchleyHugo CritchleyHumans are naturally inquisitive. This tendency is adaptive, aiding identification of potentially valuable novel outcomes. The dopaminergic substantia nigra (SN) is implicated in the drive to explore novel stimuli and situations. However, infection and inflammation inhibit themotivation to seek out novelty. This likely serves to limit exposure to uncertain, potentially detrimental outcomes when metabolic resources are limited. Nevertheless, the neural mechanisms through which inflammation constrains novelty seeking are poorly understood. We therefore scanned 16 healthy participants (6 male, mean 27.2±7.3 years), using fMRI, once following experimental inflammation (intramuscular (i.m.) typhoid vaccination) and once after placebo (i.m. saline), with the aim of characterizing effects of inflammation on neural processing of novel and familiar place, and face stimuli. We specifically tested the effects of inflammation on the hypothesized roles of SN and hippocampus in novelty processing. Typhoid vaccination evoked a nearly threefold increase in circulating pro-inflammatory cytokine (interleukin-6) levels 3 h after injection, indicating induction of mild systemic inflammation. Enhanced hippocampal responses to novel (compared with familiar) stimuli were observed following both vaccine and placebo, consistent with intact central novelty detection. However, the normal bilateral reactivity of SN to stimulus novelty was significantly attenuated following inflammation. Correspondingly, inflammation also markedly impaired novelty-related functional coupling between the SN and hippocampus. These data extend previous findings of SN sensitivity to mild inflammation associated with changes in psychomotor responding, and suggest that inflammation-induced blunting of SN responses to hippocampal novelty signals may represent a plausible mechanism through which inflammation impairs motivational responses to novelty.
History
Publication status
- Published
File Version
- Published version
Journal
NeuropsychopharmacologyISSN
0893-133XPublisher
Nature Publishing GroupExternal DOI
Issue
4Volume
40Page range
831-838Department affiliated with
- Clinical and Experimental Medicine Publications
Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2015-03-09First Compliant Deposit (FCD) Date
2015-03-09Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC