Mind over Matter

Ahead of the International Day of Women and Girls in Science, we sat down for an interview with Technion Professor Asya Rolls, a trailblazing scientist who leads a predominantly female research group that studies the effect of the brain on our body   

Soul, spirit, mind, consciousness – that something inside us that calls itself “me” – what power does it have over the inner workings of our body? Is it separate from the body, or part of it? Our body has shape, it occupies space. But what shape or form does our thought take? And if it is not a “thing” that exists in space, can it affect the physical?

If the mind is, to use Gilbert Ryle’s words, “the ghost in the machine,” the body being a machine whose nuts and bolts we study, then surely our thoughts, our state of mind, cannot affect its workings. And yet, the placebo effect – belief in the efficacy of a treatment alone causing it to have a positive effect – is taken into account in every medical study, and psychosomatic illnesses, while not fully understood, are well documented. How is that possible?

We sat down with Asya Rolls, Associate Professor in the Ruth and Bruce Rappaport Faculty of Medicine at the Technion, who started her career in our Faculty of Biology. Her Ph.D. was in neuroscience and immunology at the Weizmann Institute, and her postdoctoral work – in the Department of Psychiatry at Stanford University. The subject of how the mind affects the body always interested her, she says. Intuitively, it is a phenomenon observed in everyday life, and commonly accepted among medical practitioners. Good mood helps recovery, stress makes people ill. But scientifically, we didn’t really understand how that happened and what the mechanisms were. What kind of experiments can you conduct, what kind of models do you use to study this question?

Prof. Asya Rolls’ research group

The effect of the brain on the immune system

It is the emergence of new technology that made it possible to explore the connection between mind and body, and specifically, the aspect that interested Prof. Rolls most – the effect of the brain on the immune system. Recently developed methods allowed scientists to see with great precision what neurons are being activated in the brain at any given time, as well as to activate specific neurons themselves. This was the tool Prof. Rolls needed.

She made the mind-body problem the focus of her research. The results were novel, and at the same time so intuitive, that it was a wonder nobody had done this before. “I needed to see those results more than once before I believed common intuition had been right.” Asya Rolls says of her research. “I knew what we found, it seemed right, and that’s exactly why I had to doubt myself. It was very reassuring when groups started reproducing the same results.”

“I needed to see those results more than once before I believed common intuition had been right,” Prof. Rolls says. 

Now, she is more confident in the direction her study is taking, and her research opens the way to therapeutic applications and potential improvement to patients suffering from many different conditions.

The placebo effect: mice whose reward system had been activated fought off bacteria considerably better

A patient receives an inert tablet, such as a sugar pill. It’s not supposed to do anything at all, but the patient reports feeling better. This is the placebo effect. What helps the patient feel better if it is not the pill itself?

Previous studies found that taking a pill with the hope it will help you, activates the reward area in the brain. This is the same area that is responsible for our wanting and enjoying such activities as eating and sex – activities necessary for the body to survive and procreate. We perform the activity and are rewarded with a sense of wellbeing. In the case of the sugar-coated pill, the expected positive effect triggers the reward system.

Prof. Asya Rolls

“Feeling better” can mean many things for a patient. “Feeling” is still in the mind. Prof. Rolls sought to see effects on the body. To examine this, her group, in collaboration with Prof. Shai Shen Orr’s research group at the Technion, directly activated the reward system in mice, and then collected blood to test the ability of the mice’s immune system to combat disease. The results, published in Nature Medicine, were undeniable – mice whose reward system had been activated fought off bacteria considerably better. A positive experience, triggered directly in the brain, activated their immune system.

Keeping a positive outlook

“I was keeping a positive outlook,” a cancer survivor recently spoke of her journey to remission in an Israel Cancer Research Fund (ICRF) webinar. “I found the humor in situations, I reminded myself every day of all the things I could be grateful for.”

There is no doubt that this positive outlook helped her mentally. But did it help her physically as well? Prof. Rolls and her research group, in collaboration with Dr. Fahed Hakim (of the Rambam Health Care Campus) and Technion’s Dr. Michal Rahat, tested this question. Once again, stimulating the reward system produced a dramatic effect; tumors were significantly smaller in mice whose reward system was activated. A positive sensation in the brain caused their body to fight cancer with greater effectiveness. These results were published in Nature Communications.

Psychosomatic illnesses: can you switch off symptoms?

In a recent study, published in November 2021 in the prestigious journal Cell, Prof. Rolls’ group explored immune memory. There is an area in the brain called the insular cortex. It is responsible for interoception – the sense of the body’s internal state. This includes feelings like hunger or the need to relieve oneself, heart rate, sexual attraction. If information about an immune response is stored somewhere in the brain, it would make sense for the insular cortex to be involved.

Prof. Rolls’ students, in collaboration with Prof. Kobi Rosenblum of Haifa University, induced bowel inflammation in mice and were able to track which neurons in the insular cortex were activated. Then, they activated those neurons themselves. The neurons acted as a switch; turn them on, inflammation appears, turn them off, inflammation goes away, regardless of whether there is a real reason for inflammation.

Patients with irritable bowel syndrome suffer from repeated digestive tract symptoms that appear to be triggered at least in part by something in the brain – by stress, rather than by some physical cause. Until now, the phenomenon has been hard to explain, and consequently the condition is hard to diagnose and sometimes treated as malingering. Prof. Rolls’ findings support the patients’ experience, and also open the way to treatment – could their symptoms be switched off just like the mice’s symptoms?

Prof. Rolls (right), with graduate student Tamar Koren of her lab 

‘Remembering’ previous inflammations

Our body must constantly fight various enemies – bacteria, viruses, and more, Prof. Rolls explains. The better prepared the body is to combat, the better and faster it can defeat whatever comes. So, it’s better to activate the immune system not when the infection is already there, but when the body can reasonably expect it. Activities that particularly expose us to infection include eating and sexual intercourse. These are the same activities that activate the reward system. It makes evolutionary sense for the immune system to also be activated by this trigger, to call up the reserves and prepare for battle.

It is even more effective if the body, remembering where the last attack came from, could mobilize its troops to the same place for the next attack. Like a good military commander, the body does just that – it has the capacity to remember the location of a previous inflammation and activate the immune system in that location again.

Of course, activation of the immune system might be a false alarm, causing diseases such as irritable bowel syndrome. Understanding the mechanism should give us a key to developing treatment.

Healthy mind, healthy body?

If having a positive outlook helps the body fight cancer, are patients who suffer from prolonged sadness due to their condition guilty of not improving faster? If bowel inflammation comes from the brain, is it the patient’s fault that they have recurring episodes? Should we all “think happy thoughts” to make ourselves healthy, and is not being healthy punishment for thinking the “wrong” thoughts? If illness comes from the brain, is it malingering?

It cannot be stressed enough that this is not the case. These are findings in rodents that reveal new mechanisms in biology, but there is a long way to go before we can translate them to clinical reality. Even then, the implications of the lab findings won’t be so simplistic. Understanding the intricate connections between mind and body offers a way to help patients.

A conclusion that can be drawn from these studies is already mentioned by Galen and Maimonides in their writings, and one that we know intuitively to be true. It is not enough for the doctor to prescribe the correct pill. A doctor is not a plumber, nor a car mechanic. It is equally the doctor’s task to offer empathy and encouragement – to help the patient’s mind as well as body to get well.

Fostering interdisciplinary research

In addition to being a trailblazing scientist, Prof. Rolls — who was recently chosen as one of the most influential scientists in Israel for 2021 by Globes — is also a member of the Israel Young Academy. This organization aims to strengthen the relationships among Israeli academia, policymakers and society, to develop the abilities of young scholars in Israel and to promote research and scientific capabilities.

In this capacity, Prof. Rolls is responsible for multidisciplinarity. “The way academic studies are structured,” she says, “one specializes in an increasingly narrow field. One has to, in order to know it well. But this extreme specialization is also limiting – knowledge from a different field might help me answer a question, or better yet – ask a new one. We would like to offer scientists the opportunity to broaden their horizons.”

For a scientist whose research translates René Descartes’ mind-body problem into the field of physiology, this view is hardly surprising.

Story by Tatyana Haykin