SCIENTISTS have uncovered evidence that a person’s mental state may influence how well their body responds to a vaccine. A new study reports that when people increase activity in parts of the brain involved in motivation and expectation, their immune systems produce higher levels of protective antibodies after vaccination.
The research, published January 19 in Nature Medicine, connects this effect to the brain’s reward circuitry and the placebo response, which is the well-known phenomenon in which belief and expectation alone can trigger real physiological changes.
“This shows that placebo is not just an illusion,” said a neuroscientist at Tel Aviv University and senior author of the study, Talma Hendler. “It is a self-help mechanism of the brain, and here we demonstrate that it can support the immune system.”
Brain reward activity tied to antibody production
The team found that volunteers who showed higher activity in a key reward-related brain region, the ventral tegmental area (VTA), during training later produced more antibodies after receiving a hepatitis B vaccine. These increases were not caused by the vaccine itself alone, but were associated with how strongly the brain’s reward network was activated.
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A neuroscientist at Dartmouth College, Tor Wager, who was not involved in the research, called the work “the first human evidence directly linking brain reward systems to immune function.” However, he cautioned that the experiment was not designed to test whether vaccines become more effective in real-world settings and that larger trials will be needed.
Testing the brain–immune connection
Previous animal studies have shown that emotional and motivational states can influence immune responses. To test whether the same mechanisms exist in people, Hendler’s team recruited 85 healthy adults and trained them using neurofeedback, a technique that allows individuals to view and control their own brain activity in real time using imaging data, Science News reported.
Participants were randomly placed into three groups: one trained to increase activity in the brain’s reward network, another trained to activate a different network, and a third group that received no training.
After the final training session, all volunteers were given a hepatitis B vaccine. Blood samples were taken before vaccination and at two later time points to measure changes in antibody levels.
Expectations mattered most
When researchers compared brain activity with immune responses, they discovered that individuals who sustained higher activation in the VTA during training mounted stronger antibody responses.
They also examined what mental strategies worked best. Participants who focused on positive expectations, such as believing their efforts would help their body, were more successful at activating the VTA than those who relied on unrelated imagery or thoughts. This mental framing is closely linked to the placebo effect, where belief alone produces measurable health changes.
Why group differences were unclear
Interestingly, the study did not find clear immune differences between the three groups as a whole. According to Yale neuroscientist Nitzan Lubianiker, this is likely because both types of neurofeedback training inadvertently activated the VTA.
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At the time the study was designed, the researchers did not know the VTA would be the critical region. In addition, neurofeedback itself can feel rewarding, as participants receive visual signals when they succeed – a process that also stimulates the brain’s reward centers.
As an immunologist at Washington University, Jonathan Kipnis, noted in a commentary, “The immune effect appears to depend on how strongly individuals engage these brain circuits, not simply on which group they were assigned to.”
What comes next
The researchers are now conducting animal experiments to map how the VTA communicates with other brain regions that regulate immunity. Future human studies could use neurofeedback methods that specifically target this region, alongside control conditions that avoid activating it.
A psychoneuroimmunologist at UCLA, Michael Irwin, said such designs would help determine whether brain-based training could eventually be used to improve immune responses in clinical settings.
Wager added that replication is essential. “If these findings are confirmed,” he said, “they could change how we think about vaccination and the role of the brain in healing.”
