A RECENT study has revealed that consciously generating positive expectations can influence the human immune system by engaging reward-related brain circuitry. Researchers conducted a preregistered, double-blind randomized controlled trial to test whether activation of the dopaminergic mesolimbic pathway, known for signalling positive outcomes, could enhance immune responses following vaccination.
Reward Mesolimbic Upregulation Links Brain and Immunity
Eighty-five healthy participants were randomised into three groups: reward mesolimbic upregulation via fMRI neurofeedback (n=34), non-mesolimbic control upregulation (n=34), and a no-neurofeedback control (n=17). Participants in the neurofeedback groups employed self-chosen mental strategies to increase activity in the reward circuitry before receiving the hepatitis B virus (HBV) vaccine. Both neurofeedback groups successfully increased reward mesolimbic activation.
Notably, higher ventral tegmental area (VTA) activation, but not nucleus accumbens or control region activity, correlated with larger post-vaccination increases in HBV antibody levels (r=0.31, P=0.018). Sustained VTA upregulation was associated with mental strategies focused on positive expectations. Despite these correlations, overall post-vaccination antibody levels did not differ significantly between groups, and no adverse events were reported.
Implications for Non-Invasive Immune Modulation
These findings provide evidence in humans that consciously generated positive expectations can engage the brain’s reward circuitry to modulate immune responses. Previous rodent studies have hinted at a link between the mesolimbic pathway and immune function, but this study demonstrates that deliberate mental strategies in humans can have measurable immunological effects.
The research has broad implications for non-invasive interventions to boost immune function, potentially complementing traditional vaccines and therapies. While the study did not observe significant differences in absolute antibody titres, the association between VTA activation and antibody response suggests that targeted neurofeedback could optimise immune responsiveness in future clinical applications.
Future studies are needed to explore the long-term effects of reward-based neurofeedback, identify which mental strategies are most effective, and determine clinical utility across diverse populations. This research paves the way for novel mind-body approaches in immunology, highlighting the powerful connection between mental states and physiological health.
Reference
Lubianiker et al. Upregulation of reward mesolimbic activity and immune response to vaccination: a randomized controlled trial. Nat Med. 2026; DOI:10.1038/s41591-025-04140-5.
