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

Biol Psychiatry. 2008 Jun 1;63(11):1022-9. doi: 10.1016/j.biopsych.2007.12.007. Epub 2008 Feb 1.


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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Brain Mapping
  • Cross-Over Studies
  • Double-Blind Method
  • Humans
  • Image Processing, Computer-Assisted
  • Inflammation / complications*
  • Inflammation / etiology
  • Inflammation / pathology*
  • Interleukin-6 / metabolism
  • Magnetic Resonance Imaging / methods
  • Male
  • Motor Skills Disorders / etiology*
  • Neuropsychological Tests
  • Oxygen / blood
  • Photic Stimulation / methods
  • Psychomotor Performance / physiology*
  • Reaction Time
  • Substantia Nigra / blood supply
  • Substantia Nigra / physiopathology*
  • Typhoid Fever / immunology
  • Vaccination / adverse effects


  • Interleukin-6
  • Oxygen