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Israeli scientists figure out why your brain imagines you're sick

Gid'on Lev 11-14 minutes 11/14/2021

Psychosomatic activity is one of the most powerful and significant expressions of the effect of the mind on the body. An uncomfortable emotional state – stress or depression, for instance – leads to the onset of physiological symptoms or illness. As long as the trouble is left unattended, psychology suggests, there is a reasonable chance of it being expressed in the body.

This is how the New Zealand-French psychoanalyst Joyce McDougall described the phenomenon: “Grief that has no vent in tears, makes other organs weep.”

There is ample evidence of the existence of the phenomenon, but its cause remains unclear. How does an emotional state or thought create an illness?

A new study published in the journal Cell on Monday identifies a specific area of the brain that can generate psychosomatic phenomena, and it even offers an explanation for the mechanism behind the phenomenon.

The research, conducted in the Haifa laboratory of Prof. Asya Rolls from the Technion’s Rappaport Faculty of Medicine, focused on an area of the brain called the insula (aka insular cortex), which plays a vital role in the perception of internal physical and psychological conditions such as body temperature, respiration, heart rate, pain and hunger.

Microscopic images from the study.

Microscopic images from the study.Credit: Nitzan Zohar/Technion

It is an area that is particularly sensitive to the changes the body undergoes, Rolls tells Haaretz, and is therefore linked to numerous other systems.

The new study probed the link between the insula and the intestine, which was chosen due to its being a nerve-rich organ. (The digestive system has about half a billion neurons, which is even more than the spinal cord.)

Rolls and her colleagues tested this link by means of a lab experiment on mice. They found that in the brains of mice suffering from inflamed intestines, a specific area of the insula was activated.

After the mice had recovered, a smaller group of cells in the insula (those active during the original inflammation) were proactively activated. This proactive step led to the development of a new inflammation. In other words, brain activity created a symptom.

Conversely, repression of the same area triggered a reduction in the inflammation response. Both the activation and repression were conducted using a method of genetic manipulation that makes it possible to activate specific cells.

The experiment gives rise to a hypothesis that groups of neurons in the brain can store and export information related to the immune system – i.e., they have immunological memory.

Until now, this sort of memory has been attributed solely to the immune system: During the initial encounter with bacteria, virus or immunization preparation, the system learns the attributes of the foreign invader and retains them in its memory cells. This way, the next time it identifies these factors, the system can respond to the same disease with greater speed and efficiency.

Prof. Asya Rolls from the Technion’s Rappaport Faculty of Medicine.

Prof. Asya Rolls from the Technion’s Rappaport Faculty of Medicine.Credit: Rami Shllush

The new study demonstrated, for the first time, that immunological memory also exists outside of the immune system – in the brain.

Rolls says that as part of the research, she met with clinical psychologists at Rambam Health Care Campus, Haifa, who told her about people suffering from post-traumatic stress disorder, and whose trauma is related to a physical event such as fever or pain. In such instances, when the patient is in a state of stress, that same physical event reoccurs.

“There are lots of ways in which the psychosomatic effect manifests itself: You think of the experience of an illness and it takes form; you hear about someone who fell ill with the coronavirus and you develop a cough,” she explains. “In the study, we proved that the brain can actually produce illnesses, and we showed that it does so on the basis of a type of past memory. The brain preserves information about an illness you once had, and can reactivate it.”

'There are lots of ways in which the psychosomatic effect manifests itself, such as you hear about someone who has coronavirus and you develop a cough'

An illustration of an ill person.

Credit: Nuthawut Somsuk / Getty Images /

Surprising find

Dr. Yoav Livneh of the Department of Brain Sciences at the Weizmann Institute of Science, Rehovot, researches the interaction between the insula and the body. “It’s clear to us that the brain affects the immune system. We know of studies that demonstrated how devout people who pray may cope better with cancer immunologically,” he says.

“Scientists try to understand how the brain does this through experiments on model organisms. This new study is very elegant because it succeeds in demonstrating the brain’s effect on the immune system in a causal and bidirectional manner. In other words, the same immune response is both activated and reduced by means of specific manipulation of a small group of cells in the brain.”

The fact that stress causes disease is well known, but it’s also known that stress inhibits the immune system. Until now, it was unclear how it causes inflammation – a situation in which the immune system works actively in an attempt to defend itself from a foreign invader.

According to Rolls, when the initial results of the experiment came in, many researchers in her field were surprised, as it was unclear why the brain remembers immune system responses.

Tamar Koren, a Ph.D. candidate working in Prof. Rolls' lab.

Tamar Koren, a Ph.D. candidate working in Prof. Rolls' lab.Credit: Rami Shllush

She suggests the following explanation: The faster the immune system reacts, the better it will be at fighting off the pathogen. Therefore, if an encounter with a pathogen is expected, there’s a benefit to activating the system even before the encounter occurs.

“If I ingest bacteria every time I drink from a well, it is worth my while preparing my immune system even as I’m making my way toward the well. The brain prepares us to face challenges we’ll come across – and most of the time this works really well and we don’t pay any attention to it. But if the body thinks a foreign pathogen is about to invade it and sends the immune system cells to deal with it but there’s nothing there, it may still develop inflammation, which can cause damage on its own.”

As an example, Rolls suggests we think of backpackers returning from a trip to the Far East with a parasite in their digestive system. Years later, even though the parasite has long been eliminated, in situations where the ex-travelers find themselves in an emotionally distressing situation, they suffer from stomachaches and diarrhea – the symptoms of the original illness.

Rolls believes the brain interprets the emotional situation as a signal that it is expecting to come up against something dangerous. The signal thus activates the immune system, via the insula. At that point, symptoms appear in the sensitive tissue that suffered the trauma in the past: for instance, the tissue affected by the parasite in the backpackers’ bodies, or the pathogen in the case of the mice in the experiment.

“Activation of the insula alone is not enough,” Rolls points out. “In order for symptoms to develop, the reacting tissue [in the mice] must have previously undergone inflammation. The immune system produces an identical reaction to the one produced following exposure to a pathogen, except it’s not there. Therefore, this means that the symptom is the product of the immune system and not the pathogen.”

Livneh, who was not involved in the new study, researches the insula in other contexts, related to internal bodily sensations in general. The insula is located in the cerebral cortex, he says. In other words, it is the interface between cognition and body.

Students in Prof. Rolls' lab at the Technion.

Students in Prof. Rolls' lab at the Technion.Credit: Rami Shllush

He cites the famous experiments of physiologist Ivan Pavlov, in which a dog began to salivate at the sound of a bell after said sound had been associated with receiving food. “Pavlov received the Nobel Prize in part because he demonstrated that along with the secretion of saliva, digestive juices are also secreted even before the food has entered the dog’s body.

“Based on that, it follows that the brain prepares the body for expected changes. Subsequent studies demonstrated that the body deals less effectively with the absorption of sugar after eating if this mechanism is eliminated,” Livneh says.

He explains that because processes within the body take place relatively slowly, the body would not cope well if it responded solely reactively (because it would always respond too late). This is why the brain evolved in such a way as to allow itself to prepare the body for future anticipated changes.

In the new study, Livneh says, the researchers present an immune system version of Pavlov’s experiments with dogs: There is a specific memory in the brain of an immunological response, and once an emotional or cognitive signal is given, it prepares the immune system in advance for a new threatening situation.

The placebo effect

Rolls stresses that there is a huge gap between a discovery found in mice and the situation in people, and we should be very cautious when interpreting her research. Nevertheless, she notes that the findings can help us understand psychosomatic phenomena and to take a different approach to them.

“This is a new scientific approach to these diseases,” she says. “Today, we often treat them by suppressing the entire immune system. But if we understand that there’s a part of the brain that produces an area-specific response of the immune system, it might be possible to suppress only this area and thereby reduce the intensity of the disease.”

A petri dish used as part of the experiment.

A petri dish used as part of the experiment.Credit: Rami Shllush

She says one approach would be conducted via the neurofeedback system, in which patients learn to control specific parts of the brain. “The entire placebo concept is psychosomatic,” Rolls explains. “As early as the ancient Greeks, it was noted that when it came to dealing with diseases, the individual’s personality was often more important than the disease itself.”

Livneh notes that among mammals, the insula is an evolutionarily conserved area, i.e., it exists in the brains of various mammals, and there are the same functional connections between the insula and the body in all of them. “Among mammals, the same region of the brain, the insula, engages more or less in the same basic functions,” he says. “In this sense, the study is very relevant to human beings.”

Rolls and her partners mapped the nerves in the insula, and identified links of different groups of cells in this area with various body organs. They also found that every specific cell group is capable of producing different types of inflammation in the organ with which it was linked.

“We don’t know how exactly the brain does it, but it’s clear it can produce very precise reactions,” Rolls says. “There’s a hidden healing potential in the brain – and we’re not using it. We give medication and it produces side effects because it interferes with specific physiological pathways and isn’t in sync with the other processes in the body. The brain, though, can produce the most precise manipulation, which would also be synchronized with the rest of the body.”

Rolls notes that the study, which was funded by the European Union, was led by doctoral student Tamar Koren in collaboration with Prof. Kobi Rosenblum of the Sagol Department of Neurobiology at the University of Haifa, and Dr. Fahed Hakim, medical director of the EMMS Nazareth Hospital.

Hakim, she says, brought a clinical perspective to the research. “He’s a huge expert on psychosomatic illnesses, because he has the number one patient,” Rolls laughs, pointing at herself. “Ultimately, the motivation to conduct research is often personal.”