Upregulation of Reward Mesolimbic Activity via fMRI-Neurofeedback Improves Vaccination Efficiency in Humans

The placebo response is associated with a positive expectation of recovery. Recent studies in mice uncovered a potential underlying mechanism of placebo effects, by demonstrating the involvement of the dopaminergic mesolimbic pathway, previously implicated in reward expectation, in immune modulation. Yet, it is not known whether an analogous brain-immune regulatory mechanism exists in humans, and whether it employs conscious positive expectations. Here, we employed fMRI-neurofeedback to train healthy participants to increase their reward mesolimbic activity by using self-chosen mental strategies, followed by Hepatitis B Virus (HBV) vaccination. We found that stronger Ventral Tegmental Area (VTA) activity, but not control regions activation, was associated with higher post-vaccination HBV antibody titer. Interestingly, higher VTA activity before vaccination was associated with mental strategies characterized by positive expectation. Thus, our results establish a relationship between reward system activity, positive expectation and immunity in humans and reveal a potential neuropsychological mechanism for non-invasive immune modulation. https://clinicaltrials.gov/study/NCT03951870.