ECNP Congress programme spotlight
How the brain influences immunity

Professor Asya Rolls is a psychoneuroimmunologist at the Technion – Israel Institute of Technology in Haifa, Israel, where she leads a laboratory which explores how the nervous system affects immune responses. Her work has highlighted how the brain’s reward system, which is implicated in the placebo response, affects anti-bacterial and anti-tumour immunity. More recently, her group discovered that the brain stores representations of past immune experiences and can use them to induce disease. Professor Rolls will present a plenary lecture, ‘The neuro-immune axis: how the brain influences immunity’, at the 36th ECNP Congress in Barcelona. She recently spoke to ECNP Press Officer, Tom Parkhill.

TP: Professor Rolls, what’s your connection to the ECNP?
AR: My work is relevant to many aspects of neuroscience and has a strong translational potential, so the ECNP is a good place to present the work to an audience with a wide range of interests. We aim to uncover a physiological perspective on the mind-body question – to understand what are the physiological mechanisms that allow mental and cognitive processes to be reflected in physiology. Mainly I’m looking in the context of the immune system and how it changes the immune response.

How did you start working in this field?
Well, I’m a person with strong psychosomatic responses! When I get stressed, I get sick. I can work to a deadline and be completely okay, but the next day I get sick. I feel this psychosomatic connection in myself very strongly, and I believe this was one of the attractions in understanding this connection. If you think about pharmacology, one of the strongest effects we have is the placebo effect, and too often in science, we won’t go near it. In epidemiology, we also see a strong connection between stress and disease emergence. And yet, it was almost as if these are not the kind of questions we can explore mechanistically. During my PhD I worked on how the immune system controls the brain, and we saw how changes in the immune system could change cognitive abilities and emotional status. And then I started wondering, what’s happening the other way around? But it was almost not a real scientific question.

So for my postdoc, I went to Stanford. Optogenetics had just been developed, and this allowed us to dissect the specific neuronal pathways and understand the role of brain activity in cognitive function. So when I started my lab at the Technion, I thought that I could use the same strategy to ask whether such brain activity can also affect physiology. We started with the first experiments with an attitude of “Maybe it’s insane, but let’s see if it works”. And it quickly became obvious that we were on to something, but of course, the real question is taking this big philosophical question and tying it down to specific brain activity.

Once you point it out it’s obvious. Everyone has their own personal experience. It seems to be an idea whose time has come.
Exactly. It’s very timely. A couple of months ago Nature sent a journalist to my lab to talk about our work and explore the whole field of psychosomatics. She produced a feature article that came out in February and it describes very well the state of the field.

I feel it’s an elephant in the room, we can’t continue ignoring it. Our current limitation is that we don’t understand the mechanisms, which limits our ability to integrate it into medicine. Once we can parse out the pathways – how a specific brain area induces a specific immune response, and how this information is delivered – then we can start harnessing this potential. We will be able to identify what goes awry in different immunological malfunctions and begin manipulating it. This field has enormous potential.

Many of the claims of the alternative health sector are based on the idea that your brain – and other things – can influence the body. Of course, many of these claims have little or no basis in fact, but that doesn’t mean that the brain is completely passive in terms of influencing the body.
Much of Eastern medicine is based on these aspects that we refer to as psychosomatic. Perhaps largely by chance, over years of trial and error, but also through strong intuition, they have identified these connections. Now we can see more studies trying to validate some of these techniques. Yet, the challenge is in translating these things that we know intuitively and by experience to modern medicine. This is especially relevant to psychiatry because many of psychiatric conditions are accompanied by major physiological changes and immune disorders. We have a tendency to break the problems down. It was a good practice since we did not have enough of the basic understanding of different systems, but now is a good time to start putting them together.

So how have you begun to pull out this evidence, how can you know that X causes Y?
We started by looking at brain areas that are involved in specific mental processes. For example, with the placebo effect you have positive expectations, and there is a brain area responsible for positive expectations, the reward system. This was our first study in mice, where we showed that if we activate the reward system, we boost anti-bacterial and anti-tumour immunity. For us this was a causal proof that specific brain activity that we know is increased while people are experiencing placebo has specific outcomes evident in the immune system. Later – this is more recent work – we also started asking how the brain monitors the state of the immune system. It doesn’t make sense that the brain would control the immune system without knowing what it controls. We started looking for evidence for the immune control by the brain, and one of the things that we found is that there is a representation of the immunological state in the insular cortex (this wasn’t new, it was known that the brain responds to inflammation). What we found surprising was that by just reactivating the information, namely the same neurons that were active during the inflammation, this manipulation could recapitulate the same inflammation. So, this was a proof that the brain can generate the disease. First that the brain stores memory-like representation of the inflammatory disease, and second, that it can actually initiate the inflammation. This feeds into a variety of conditions that we collectively refer to as psychosomatic disorders. Many diseases, like irritable bowel syndrome, Crohn’s disease, and other auto-immune conditions, are known to have a strong emotional trigger, but we don’t know why. Maybe, at least in part, the brain replays the original inflammatory state, resulting in flares of the disease.

Is this emotional content currently treated in these conditions?
There is increasing awareness that this is important, and there are more and more attempts to integrate psychological interventions or mindfulness interventions. But this is dependent on the specific clinical setting, and it’s not common practice. You will find it offered in some cases, but although there are many reports of beneficial effects of this kind of treatment, I don’t think it is a common practice. As long as we don’t understand the mechanisms, it’s hard to apply it broadly in medicine.

What are your next steps in your work, and how can you translate what you are doing into clinical practice?
Let me use an analogy. Imagine we have a piano, with an infinite number of tunes we can play. It can orchestrate the brain, the immune system, and our physiology in general, but our problem is that we still do not understand what the keys of the piano are, and how to create the harmonies. The keys are the different brain areas. Once we understand how different brain areas can influence physiology and how these brain areas are connected, then we can start playing the piano. We can do that by utilising many of the tools that are already available for targeted brain manipulation. This may allow us novel ways to treat auto-immune diseases, and even some cancers.

It even has an effect on cancer?
Oh yes, we have already shown that in the past. We showed that activation of the brain’s reward system boosts anti-tumour immune response by inducing some changes in the bone marrow, which is the site where immune cells are formed and programmed. It reduced the size of mouse tumours by 50%. These were B-16 melanoma, and Lewis lung carcinoma. Of course, these are models, and we need to be careful in interpreting them. These are two quite different tumour models. I don’t think that it would work in every cancer, but it may be relevant for some.

You have spoken about using such things as computer games or magnetic brain stimulation to treat somatic conditions?
That’s an example of the direction we can go. I think that once you know which brain areas you want to manipulate, you can do this in many different ways. If we acknowledge and understand these effects, then we can apply our knowledge to many fields of medicine, and this could lead to psychiatry being much more integrated into general medicine than we used to think. That’s what I’d like to see for the future, that psychiatry is fully integrated, central to general medicine.

Asya Rolls, Israel, will speak on Monday 9 October at 10.15-11.00 CEST (Central European Summer Time).
PL03 — The neuro-immune axis: how the brain influences immunity

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