Abstract
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.
Highlights
Systemic infections commonly cause sickness symptoms including psychomotor retardation
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, implicating circulating cytokines and midbrain dopaminergic nuclei in mediating the psychomotor consequences of systemic infection
Summary
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. Volunteers who had received typhoid vaccine in the past 3 years or any other vaccine in the previous 6 months were excluded. Participants were advised not to consume caffeinated beverages or alcohol and to refrain from excessive exercise during the 12 hours prior to testing. They were advised not to take aspirin, ibuprofen, or antibiotics for 14 days prior to testing. All participants gave their informed consent, and the study was approved by the joint University College London/ University College London Hospital Committee on the Ethics of Human Research
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