Effects of inflammation on hippocampus and substantia nigra responses to novelty in healthy human participants

Harrison, N.A. ORCID: https://orcid.org/0000-0002-9584-3769, Cercignani, M. ORCID: https://orcid.org/0000-0002-4550-2456, Voon, V. and Critchley, H.D. 2015. Effects of inflammation on hippocampus and substantia nigra responses to novelty in healthy human participants. Neuropsychopharmacology 40 (4) , pp. 831-838. 10.1038/npp.2014.222

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Abstract

Humans 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 the motivation 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.

Item Type:	Article
Status:	Published
Schools:	Cardiff University Brain Research Imaging Centre (CUBRIC) Medicine Psychology
Publisher:	Nature Publishing Group: Open Access Hybrid Model Option B
ISSN:	0893-133X
Last Modified:	25 Oct 2022 14:02
URI:	https://orca.cardiff.ac.uk/id/eprint/121450

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