Research by Prof. Asia Rolls of Tel Aviv University shows that activating neural networks in the reward system changes immune system activity in various organs. Studies in mice have indicated an effect in dealing with infections, tumors and heart attacks, and the first study in humans has found a link between activating a specific area of the brain and the response to vaccination.
The connection between mental health and physical health has been known for years, but the biological mechanisms behind it are still not fully understood. One of the best-known expressions of this connection is The placebo effect: A measurable improvement in symptoms or physiological indicators following a treatment that does not necessarily contain an active substance, but which the patient expects to benefit from.
Even in everyday life, we are familiar with the phenomenon in which people manage to function during a stressful period, during an important project or towards a significant goal, and only after the stress is over do they fall ill. Such phenomena raise a fundamental question: how can thoughts, expectations and motivation affect bodily systems such as immune system?
The research group of Prof. Asia Rawls from the Faculty of Life Sciences at Tel Aviv University is trying to decipher the neural pathways that connect thebrain and the activity of the immune system. The goal of the research is not to show that thought alone can cure diseases, but to identify the mechanisms by which activity in specific areas of the brain alters the immune response in various organs.
The brain remembers the inflammation
In a previous study, Prof. Rawls' group showed that the brain may retain a neural representation of an inflammatory response that occurred in the body. The researchers identified groups of Neurons In the insular cortex that were active during intestinal inflammation.
When they reactivated the same neurons after the inflammation had subsided, an inflammatory response reappeared in the same organ, even though there was no new external factor that had created the disease. In contrast, suppressing the activity of those neurons reduced signs of inflammation in the intestine.
The findings indicated that the brain does not just receive reports of immune system activity. It may retain a kind of “memory” of the immune status and recreate certain patterns of physical response.
The current study focuses on the other direction of the connection: not just how the brain remembers illness, but how neural activity related to anticipation, motivation, and reward may alter the body's ability to cope with a health challenge.
How the reward system activates the body
The reward system It is a complex of neural networks involved in motivation, anticipation of a positive outcome, learning, and the feeling of pleasure. An important component of it is neurons that produce the neurotransmitter dopamine, including neurons in a region of the brain called the ventral tegmental area, or VTA.
These neurons project to many areas of the brain and influence behavior, decision-making, learning, and motivation. Prof. Rawls' research examines how different pathways within the reward system also affect systems outside the brain.
“Our working premise is that when there is a goal and motivation, we mobilize the body’s resources to achieve the goal, including our immune system,” explains Prof. Rawls. “Our goal is to understand how that reward system creates different immune responses depending on the challenge we are facing.”
This is not a uniform activation of the entire immune system. Studies show that the brain may activate different pathways depending on the organ and the type of threat. In one situation, the effect is focused on the bone marrow, in another on the liver, and in another on the spleen.
Targeted activation of neurons
To examine a causal relationship between brain activity and the immune response, researchers use methods that enable the activation of specific groups of nerve cells in mice.
One method is called chemogenetics. Researchers induce certain nerve cells to express a modified receptor that does not respond in the normal way to substances found in the body. A substance that activates the modified receptor is then injected, allowing targeted stimulation of selected nerve cells without activating the entire brain.
Using the method, it is possible to examine what happens when a specific neural connection is activated between two areas of the reward system, and then to examine whether there is a change in the immune system cells, the organs in which they are formed, or their ability to respond to disease.
“We saw that if we selectively activate dopamine neurons in the reward system in mice, we get a different immune system response when dealing with challenges such as cancer, Bacterial infections Or heart attacks,” says Rawls.
The bone marrow, liver, and spleen respond differently
In a study on cancer tumors, researchers activated the reward system in tumor-bearing mice. The activation altered the signals coming through the sympathetic nervous system to the bone marrow.
As a result, the activity of immunosuppressive cells produced in the bone marrow changed. These cells can, under certain conditions, weaken the immune system's ability to attack the tumor. Following the activation of the reward system, they became less suppressive, and the immune response against the tumor was strengthened.
However, these are studies in mouse models. Chemogenetic activation of neurons is a powerful and focused experimental action, which is not the same as the activity that occurs naturally in the human brain. Therefore, it should not be concluded from the experiment that a positive mood can stop cancer or change medical treatment.
Another study found that activating the reward system in mice after myocardial infarction affected the liver and immune system, encouraged blood vessel formation, and improved the process of heart tissue repair.
According to Rawls, the differences between the studies indicate that the brain has the ability to activate different physical targets: “Once the effect on the immune system was focused on the liver, once on the bone marrow and once on the spleen. The brain has the ability to know what is happening to the body and activate different targets.”
Can the system also be used in humans?
Studies in mice allow for the direct and precise activation of nerve cells, but such methods are not suitable for routine use in humans. Therefore, researchers are exploring non-invasive ways to influence these neural networks.
One option is biofeedback based on functional magnetic resonance imaging (fMRI). The participant lies inside a brain scanner and receives real-time feedback on activity in a specific area of their brain. By experimenting with different thought strategies, they gradually learn to increase activity in the desired network.
A joint study by Prof. Rawls and Prof. Thelma Handler of Tel Aviv University examined the possibility of teaching humans to increase activity in the mesolimbic reward pathway. The experiment involved 85 healthy subjects, who were subsequently vaccinated against hepatitis B.
The researchers found that subjects who were able to increase activity in the VTA region more tended to develop a greater increase in antibody levels after vaccination. Continued activity in this region was also associated with the use of cognitive strategies based on positive expectancy.
However, no significant difference was found in the average antibody levels between the experimental groups. Therefore, the study indicates a possible link between the ability to activate the neural pathway and the immune response, but does not yet prove that brain training consistently improves immune system activity.
Don't “think positive” instead of treatment
The studies do not justify the claim that diseases can be cured through the power of thought. Nor do they hold patients responsible for their bodies' failure to overcome an illness.
An infectious disease, a cancerous tumor, or a heart injury are complex biological conditions that require medical diagnosis and treatment. The reward system may be one of many factors that influence the immune response, along with genetics, age, medications, sleep, nutrition, exercise, and the characteristics of the disease itself.
The importance of the studies lies in identifying a possible biological mechanism by which neural activity affects organs and immune system cells. In the future, understanding these pathways may help develop complementary and targeted treatments, for example through magnetic stimulation, biofeedback, or other methods of non-invasively influencing the nervous system.
“I focus on basic research, trying to understand the essence of the connection between the mind and the physical – how different mental states affect our ability to cope with illness,” concludes Prof. Rawls.
“When we understand the networks involved in activating the immune system specifically in certain organs, we will be able to manipulate them to improve the immune response in a targeted manner. There are many tools today that can influence the activity of the nervous system from the outside, for example with magnetic stimulation of the brain. Perhaps in this way it will be possible to improve the fight against diseases.”
For the scientific article: Opening the scientific article
More on the subject on the science website
- Researchers were able to shrink cancerous tumors in mice by manipulating the reward region of the brain
- Can memory produce disease?
- A new study points to the importance of sleep for the success of bone marrow transplants
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