New brain training study could help explain the placebo effect


Increasing activity in a deep-brain region can boost the immune system’s response to vaccines—and people can be trained to do it themselves using the power of brain scans and positive thinking, according to a new study published on Monday in Nature Medicine. The findings could help explain the so-called placebo effect.

Researchers trained 34 participants using a technique called neurofeedback. Just as someone can be trained to lower their heart rate by watching a heart monitor in real time, people can learn how to activate certain parts of their brain while lying in a brain scanner. “We open a sort of window into an unconscious neural activity,” says Nitzan Lubianiker, co-lead author of the study and a neuroscientist at Yale University.

Participants were encouraged to try different mental strategies such as thinking of a positive memory or focusing on their body. And through real-time feedback, they learned to activate reward pathways in two deep-brain structures called the ventral tegmental area (VTA) and the nucleus accumbens.


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Two other groups of participants were trained to activate different brain regions or received no training at all. All the participants then received the hepatitis B vaccine. Researchers measured their immune systems’ response to the shot by checking the levels of hepatitis B antibodies in their blood two and four weeks later.

People who showed higher activity levels in their VTA had higher levels of antibodies in their blood. This suggests that the body mounted a stronger immune response when the VTA’s reward pathways were activated. The study “is one of the first to show that activity in a specific human brain region can correlate with downstream antibody responses,” says Isaac Chiu, an immunologist at Harvard University, who wasn’t involved in the research.

That said, there weren’t significant differences in antibody levels between the group that got the neurofeedback training focused on reward regions of the brain and the groups that didn’t. This may be because the nucleus accumbens, the other reward region that some participants learned to ramp up, didn’t have the same connection to immune response, muddying the results.

Participants who focused on positive expectations while in the brain scanner were more able to increase activity in the VTA, while concentrating on happiness or pleasure more broadly did not have the same effect.

The result could indicate a potential connection with the placebo effect, a phenomenon whereby a sham intervention shows positive results in people who expect the treatment to benefit them.

“There has to be some kind of a biological mechanism that explains how, when we expect something positive to happen, actually something changes in our body,” Lubianiker says. And while this study did not explicitly test the placebo effect, it does suggest our mind is connected to our immune system.

“This result showed the power of positivity. They utilized very modern and comprehensive methods, but the result is very simple,” says Kyungdeok Kim of Washington University in St. Louis, who was not involved in the study but co-authored an accompanying article about the results.

Researchers are still working to understand how the connection between the brain’s reward system and immune system works. Are brain signals transmitted to immune cells in the rest of the body via nerves, Chiu wonders, or some other mechanism?

It’s possible that the connection has deep evolutionary origins, hypothesizes Tamar Koren, a neuroimmunologist at Tel Aviv Sourasky Medical Center and co-lead author of the study. Reward signals may have evolved to encourage us to seek out food and mating—both of which can expose us to dangerous pathogens. It makes sense that, when we experience a feeling of reward, “we will also boost our immune response towards something that is potentially harmful for us,” she says.

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