A new study highlights the brain’s role in immune health

The placebo effect, in which a patient’s subjective belief can affect the efficacy of treatment, was once maligned as dubious and unscientific, but is now recognised as a genuine, albeit poorly understood, therapeutic tool. In a study published this week in Nature Medicine, researchers have begun to lift the lid on its inner workings by demonstrating that positive expectations can boost the immune system’s response to vaccination.

Nitzan Lubianiker and Tamar Koren, a pair of neuroscientists at Tel Aviv University, wanted to understand the brain’s role in regulating immune health. They chose to focus their attention on the mesolimbic network, a brain region associated with reward-related behaviour and also known as an area linked to immune function in mice. To this end, they recruited 85 volunteers to undergo an advanced form of brain training, allowing each of them to exert some influence over neural processes usually outside conscious control.

Participants were shown representations in real time of their brain’s activity, converted into simple indicators such as changing numbers or a moving graph. Their goal, as explained by the experimenters, was to develop mental strategies, such as picturing an image or recalling a trip, which consciously directed neural activity to different brain regions. Each participant was encouraged to develop his or her own personalised approach. Over repeated sessions participants learnt, by trial and error, which strategies lit up which parts of the brain.

The researchers divided their volunteers into three groups. One trained to activate the brain’s reward system. A second trained to activate an unrelated brain network. The third received no target or training. Each group completed four sessions, in which those in training groups developed and refined their individual strategies to shift activity to the assigned region. Immediately after the final session, everyone received a hepatitis B vaccination as a standardised challenge to the immune system.

Blood samples taken before and after vaccination revealed a striking link between brain activity and immune response. Several parts of the mesolimbic network were activated during training, even in those not trying to do so. However, in all participants, activity in one particular region—the ventral tegmental area—displayed a positive correlation with levels of vaccine-induced antibodies. Following an analysis to rule out alternative explanations, the researchers suggest that this is the first direct evidence of a brain-immune regulatory system in humans.

To understand the psychology behind this, Dr Lubianiker, Dr Koren and their colleagues compared and categorised the various strategies adopted by participants. This analysis found that sustained activity in the ventral tegmental area was specifically linked to positive expectations—hopeful thoughts about the future—and that this connection strengthened through the training procedure. In contrast, general positive emotions, such as pleasure or love, did not display such a relationship.

The team’s research provides compelling evidence for the brain’s influence on physiology. A deeper understanding of this mind-body connection, they hope, could pave the way for new non-invasive procedures that boost immune health, with possible applications in cancer immunotherapy and against chronic inflammation.

This work may also help understanding of the biological mechanism of the placebo effect itself. Positive expectations have long been associated with placebo responses. Only now, though, have researchers observed the specific role of such emotions in activating the reward centre of the brain, and their downstream influence on immune response. More extensive trials are needed to establish the full implications of that for the placebo effect. But this demonstration of such a clear example of the link between brain and body means a potentially underused clinical tool is gaining a firmer scientific footing. ■