Israeli scientists have provided the first evidence that the brain can actively influence how well a vaccine works through a measurable, specific neural mechanism, Tel Aviv University announced. This new understanding of the connection between the brain and the body opens new possibilities for improving vaccine effectiveness through preparatory mental training.
The study, conducted by researchers from Tel Aviv University, the Technion, and Tel Aviv’s Ichilov Hospital, suggests that activating the brain’s reward system before vaccination can enhance antibody production. The findings were published in the peer-reviewed journal Nature Medicine.
Eighty-five healthy volunteers participated in the experiment. Some underwent brain training using functional MRI neurofeedback, a technique that allows individuals to observe their own brain activity in real time and learn how to regulate it.
The training focused on increasing activity in the Ventral Tegmental Area (VTA), a central hub of the brain’s reward system that plays a key role in motivation and the expectation of positive outcomes through dopamine release.
Immediately after the brain training, all participants received a hepatitis B vaccine. Researchers then tracked their immune responses using blood tests to measure levels of vaccine-specific antibodies.
The results showed that participants who successfully increased VTA activity produced significantly higher antibody levels following vaccination. The effect was also very specific. It was not observed when participants trained other brain regions used as controls, such as the hippocampus, nor in other parts of the reward system associated with pleasure or satisfaction rather than anticipation.
Human brain processes expectations, satisfaction from rewards
“The VTA is a core region in the reward brain system, secreting dopamine, and is responsible for processing expectations for and satisfaction from rewards, the main aspects of motivated behavior of all organisms,” Prof. Talma Hendler of Tel Aviv University told The Press Service of Israel. “In our study, we demonstrated that the wanting process was the leading factor through positive expectation.”
Hendler said the findings may have an evolutionary basis. “A possible evolutionary explanation is that the body prepares itself for possible physical risks when approaching the most motivating primary rewards, for example, food or sex, both of which involve exposure to infecting factors,” she explained to TPS-IL.
A detailed analysis of the mental strategies used during training showed that participants who focused on positive anticipation were the most successful at sustaining VTA activity. These strategies included imagining something rewarding about to happen, such as eating a favorite food or meeting a loved one, rather than focusing on the pleasant feeling that follows the reward.
“The most influential strategies involved expecting good things, rather than the feeling of pleasantness or satisfaction from the good thing,” Hendler told TPS-IL.
The researchers emphasized that the findings should not be interpreted as merely “positive thinking.” Instead, they point to a measurable neurobiological mechanism related to the placebo effect.
The placebo effect is a real physiological response in which a patient’s expectation of benefit triggers measurable changes in the brain and body, leading to symptom improvement even in the absence of an active medical ingredient.
“If we know the neural mechanism of the placebo effect, we could harness it for boosting existing treatments,” Hendler told TPS-IL, stressing that such approaches are meant to complement established medical interventions, not replace them.
The study also highlighted substantial individual differences in the extent to which reward-system activation influenced immune responses. According to Hendler, these differences likely stem from a combination of factors.
“All of these could be relevant, genetic, psychological, or lifestyle-related, and definitely prior experience, which also affects epigenetic and physiological tone,” she told TPS-IL.
Beyond vaccination, the findings may have implications for other areas of medicine, including cancer treatment and chronic illness. Hendler noted that similar mechanisms have already been demonstrated in animal studies.
“Indeed, in the animal model, it was demonstrated as affecting recovery from cancer and infections, but autoimmune disorders could also benefit, in the opposite direction of the system, downregulation,” she said.
The next phase of the research will focus on larger and more diverse populations, additional vaccines, and other neural pathways involved in immune regulation. “Most importantly, to first demonstrate that there is an effect on healing from a disorder or alleviating symptoms,” Hendler told TPS-IL.