Peripheral inflammation is associated with altered substantia nigra activity and psychomotor slowing in humans

Background: 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. Methods: 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. Results: 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. Conclusions: 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.