Effects of Inflammation on Hippocampus and Substantia Nigra Responses to Novelty in Healthy Human Participants

Effects of Inflammation on Hippocampus and Substantia Nigra Responses to Novelty in Healthy Human Participants

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...

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Main Authors: Harrison, Neil A, Cercignani, Mara, Voon, Valerie, Critchley, Hugo D
Format: Online
Language:English
Published: Nature Publishing Group 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264953/
id pubmed-4264953
recordtype oai_dc
spelling pubmed-42649532015-03-01 Effects of Inflammation on Hippocampus and Substantia Nigra Responses to Novelty in Healthy Human Participants Harrison, Neil A Cercignani, Mara Voon, Valerie Critchley, Hugo D Original Article 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. Nature Publishing Group 2015-03 2014-09-24 /pmc/articles/PMC4264953/ /pubmed/25154706 http://dx.doi.org/10.1038/npp.2014.222 Text en Copyright © 2015 American College of Neuropsychopharmacology http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission fromthe license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Harrison, Neil A
Cercignani, Mara
Voon, Valerie
Critchley, Hugo D
spellingShingle Harrison, Neil A
Cercignani, Mara
Voon, Valerie
Critchley, Hugo D
Effects of Inflammation on Hippocampus and Substantia Nigra Responses to Novelty in Healthy Human Participants
author_facet Harrison, Neil A
Cercignani, Mara
Voon, Valerie
Critchley, Hugo D
author_sort Harrison, Neil A
title Effects of Inflammation on Hippocampus and Substantia Nigra Responses to Novelty in Healthy Human Participants
title_short Effects of Inflammation on Hippocampus and Substantia Nigra Responses to Novelty in Healthy Human Participants
title_full Effects of Inflammation on Hippocampus and Substantia Nigra Responses to Novelty in Healthy Human Participants
title_fullStr Effects of Inflammation on Hippocampus and Substantia Nigra Responses to Novelty in Healthy Human Participants
title_full_unstemmed Effects of Inflammation on Hippocampus and Substantia Nigra Responses to Novelty in Healthy Human Participants
title_sort effects of inflammation on hippocampus and substantia nigra responses to novelty in healthy human participants
description 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.
publisher Nature Publishing Group
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264953/
_version_ 1613167136761446400

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