The DOI matches its Crossref record; 45 of the 48 references it cites were found in a registry or an index.
Peripheral Inflammation is Associated with Altered Substantia Nigra Activity and Psychomotor Slowing in Humans
Open accessAbstract
BackgroundSystemic infections commonly cause sickness symptoms including psychomotor retardation. Inflammatory cytokines released during the innate immune response are implicated in the communication of peripheral inflammatory signals to the brain.MethodsWe used functional magnetic resonance brain imaging (fMRI) to investigate neural effects of peripheral inflammation following typhoid vaccination in 16 healthy men, using a double-blind, randomized, crossover-controlled design.ResultsVaccination had no global effect on neurovascular coupling but markedly perturbed neural reactivity within substantia nigra during low-level visual stimulation. During a cognitive task, individuals in whom typhoid vaccination engendered higher levels of circulating interleukin-6 had significantly slower reaction time responses. Prolonged reaction times and larger interleukin-6 responses were associated with evoked neural activity within substantia nigra.ConclusionsOur findings provide mechanistic insights into the interaction between inflammation and neurocognitive performance, specifically implicating circulating cytokines and midbrain dopaminergic nuclei in mediating the psychomotor consequences of systemic infection. Systemic infections commonly cause sickness symptoms including psychomotor retardation. Inflammatory cytokines released during the innate immune response are implicated in the communication of peripheral inflammatory signals to the brain. We used functional magnetic resonance brain imaging (fMRI) to investigate neural effects of peripheral inflammation following typhoid vaccination in 16 healthy men, using a double-blind, randomized, crossover-controlled design. Vaccination had no global effect on neurovascular coupling but markedly perturbed neural reactivity within substantia nigra during low-level visual stimulation. During a cognitive task, individuals in whom typhoid vaccination engendered higher levels of circulating interleukin-6 had significantly slower reaction time responses. Prolonged reaction times and larger interleukin-6 responses were associated with evoked neural activity within substantia nigra. Our findings provide mechanistic insights into the interaction between inflammation and neurocognitive performance, specifically implicating circulating cytokines and midbrain dopaminergic nuclei in mediating the psychomotor consequences of systemic infection.
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![Figure 4 Effect of peripheral inflammation on neural reactivity during low-grade visual stimulation task. (A) Mean BOLD signal change (+SEM) during checkerboard stimulus in all voxels probabilistically assigned to Brodmann areas 17 and 18 for vaccine and placebo conditions. There was no significant interaction between mean activation to visual stimulation and inflammatory state in either BA17 (p = .11) or BA18 (p = .34), confirming no effect of inflammation on neurovascular coupling. (B) Interaction between task performance and inflammatory state shows a highly significant change in BOLD signal within the left substantia nigra during performance of flashing checkerboard task (p = .002 after whole brain family-wise error [FWE] correction at p = .05). BA, Brodmann area; BOLD, blood oxygenation level-dependent; FWE, family-wise error.](/paper-figures/e5544e107a4548e884a3a9d6c344e8fb/peripheral-inflammation-is-associated-with-altered-substantia-nigra-activity-and-figure-4.jpg)
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In the citing paper
“typhoid vaccination has been associated with altered neural activity in the substantia nigra, a part of the basal ganglia that is involved in motor planning and reward seeking”
From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Brydon, Harrison, Walker, Steptoe, & Critchley, 2008
In the citing paper
“Brydon et al. (2008) examined Stroop performance after typhoid vaccination, and found that individuals with higher vaccine-induced IL-6 levels had significantly slower reaction times across both incongruent and congruent trials.”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Brydon et al., 2008
In the citing paper
“Thus, inflammation did not impair inhibitory control, but rather led to an overall psychomotor slowing and/or decrease in motivation (Brydon et al., 2008).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Brydon et al., 2008
In the citing paper
“Studies across the endotoxin, typhoid vaccination, and IFN-α paradigms have consistently shown that exogenous stimulation of proinflammatory cytokines leads to reports of increased fatigue (Brydon et al., 2008; Capuron et al., 2002; Dowell et al., 2016; Eisenberger et al., 2010a; Grigoleit et al., 2011; Harrison et al., 2009; Moieni et al., 2015) and decreases in ratings of vigor (Dowell et al., 2”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Brydon et al., 2008
In the citing paper
“Further, greater IL-6 following typhoid vaccination was associated with slower response times on all trials of a color-word Stroop task (both congruent and incongruent trials) (Brydon et al., 2008).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Brydon et al., 2008
In the citing paper
“Notably, increases in IL-6 and decreases in motor speed were both associated with altered activation patterns (enhanced activation) in the substantia nigra (Brydon et al., 2008).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Brydon et al., 2008
In the citing paper
“This is exemplified by typhoid vaccine studies which can lead to increases in fatigue within 2–3 hours despite eliciting only mild, acute increases in inflammation (Brydon et al., 2008).”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Brydon et al., 2008
In the citing paper
“Mild, short-term increases in inflammation are sufficient to cause somatic symptoms, particularly fatigue.”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Brydon et al., 2008
In the citing paper
“depression and fatigue are the main side effects of treatment with IFN-α (111, 112).”
From Cytokine Research in Depression: Principles, Challenges, and Open Questions (2019) · cites this paper as [111]
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Metadata
- Authors
- Brydon, L., Harrison, N. A., Walker, C., Steptoe, A., & Critchley, H. D.
- Affiliations
- UCL Queen Square Institute of Neurology (GB)
- Wellcome Centre for Human Neuroimaging (GB)
- Brighton and Sussex Medical School (GB)
- Corresponding author
- Brydon, Lena
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2008-06
- Volume
- 63
- Issue
- 11
- Pages
- 1022-1029
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC2885493
- OpenAlex
- W2059416963
- Cited by
- 381
- References
- 48
- Citations by year
- 2026: 5 · 2025: 20 · 2024: 23 · 2023: 22 · 2022: 16 · 2021: 41 · 2020: 25 · 2019: 20 · 2018: 26 · 2017: 15 · 2016: 35 · 2015: 26 · 2014: 17 · 2013: 19 · 2012: 25
- FWCI
- 5.12
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Biological Psychiatry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Sussex Research Online (University of Sussex) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Funders
- Wellcome Trust
- British Heart Foundation
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- peripheral inflammation, substantia nigra, psychomotor retardation, typhoid vaccination, interleukin-6, sickness behavior, neuroinflammation, dopaminergic midbrain, reaction time, neurovascular coupling, systemic infection, cytokines
- MeSH terms
- Adolescent, Adult, Brain Mapping, Double-Blind Method, Humans, Image Processing, Computer-Assisted, Inflammation, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Oxygen, Photic Stimulation, Psychomotor Performance, Reaction Time, Substantia Nigra, Typhoid Fever, Vaccination, Interleukin-6, Cross-Over Studies, Motor Skills Disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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