For much of modern biology, the brain was treated as an island – walled off by the blood-brain barrier and guarded by its own microglial sentinels – while the body’s immune system fought its battles elsewhere. That picture is changing. We now know that the neuroimmune system doesn’t sit apart, but rather, is in constant dialogue with the rest of the body. Microglia still swallow threats at the front lines, but their signals ripple outward and back.

Prof. Asya Rolls, neuroimmunologist at the Department of Neuroscience, Tel Aviv University, has been one of the pioneers charting this hidden conversation. “I have always felt the mind–body connection very strongly in my own life, so I never doubted it must be biological,” she told us in our recent interview. “Every time I get sick right after submitting a grant (but never the day before), I can’t help but wonder how exactly that happens. That curiosity drove me to search for the biological mechanisms behind these experiences.” Her work has revealed that activating certain brain circuits, including those tied to reward, motivation, and expectation, can strengthen immune defenses. In mice, these circuits didn’t just nudge the immune system, they mobilized it, boosting both innate and adaptive responses, and even slowing tumor growth. She also discovered that the brain can store “immune memories” of past inflammation in the insular cortex, illuminating a brain-immune pathway that clarifies the psychosomatic component and helps explain why autoimmune diseases can flare unexpectedly in response to emotional triggers.

Now, with support from a Corundum Neuroscience grant, Prof. Rolls is taking the next step: mapping, in unprecedented detail, which brain regions are active during different inflammatory states – from gut inflammation to skin conditions – and how these regions are wired together. Using viral tracing and advanced imaging, her team aims to pinpoint “control hubs” that could be targeted with gentle neuromodulation and ultimately offer new treatment options for autoimmune and inflammatory diseases.

Reward Pathways as Immune Levers

Rolls’ lab has already shown that when the brain expects good news, the immune system gets the memo. By chemogenetically switching on dopamine neurons in the ventral tegmental area (VTA) – a key hub in the brain’s reward circuit that lights up with hope and positive expectation – they boosted immune activity in mice and slowed tumor growth. The activation strengthened both innate and adaptive responses: the activity of cytotoxic T cells and natural killer cells increased, sharpening the body’s ability to recognize and attack threats. This isn’t simply correlation: the reward pathway is a causal lever for mind-to-immune signaling. It also overlaps with circuitry implicated in placebo responses, where heightened activity tracks with expectation-driven improvements – hinting at a biologically grounded route from optimism to immunity.

That same lever matters for cancer. In melanoma and lung-carcinoma mouse models, activating the reward system reduced tumor burden. The effect ran through the sympathetic nervous system: ‘Fight-or-flight’ nerve signals (noradrenaline) to the bone marrow quieted, the cells that normally suppress immunity eased off, and tumor-killing T cells hit harder – with experiments confirming those myeloid-derived suppressor cells are a crucial link. “What is fascinating is that the brain tailors the response,” Prof. Rolls explains. “In bacterial infections, it communicates with the spleen, while in cancer, it targets the bone marrow. […] In a way, the brain is revealing new strategies the body has evolved to cope with different challenges.”

How does a dopamine signal in the midbrain reach the immune system at all? Dopamine itself can’t cross the blood-brain barrier, but the brain can signal the body through the sympathetic “fight-or-flight” nerves. When those peripheral sympathetic neurons were chemically switched off, turning on the VTA no longer boosted antibacterial defenses – pointing to the sympathetic nervous system as the pathway. This also fits with human placebo biology, where reward circuits are a hallmark, suggesting a concrete wiring route for how positive expectations can tune immunity.

The Immune Memory of Inflammation

Rolls’ team has also demonstrated that the brain doesn’t just sense inflammation, it remembers it. In mice, neurons in the insular cortex – an area that helps the brain track what’s happening inside the body – encoded specific inflammatory states. When those same neurons were switched back on later, the immune system replayed the original response, helping explain why autoimmune diseases can suddenly flare following emotional experiences.

In a gut-inflammation mouse model (DSS colitis), Rolls’ team first “tagged” the insula neurons active during disease. Reactivating just those tagged neurons reignited gut inflammation even without a new immunological trigger, while silencing the same region during illness reduced disease scores. The effect was specific: different neuron ensembles mapped to different inflammatory states, suggesting the brain stores distinct “immune memories,” not a generic sickness signal. “I think of it like any other meaningful memory,” says Prof. Rolls. “It exists to guide future behavior based on past experiences. But just like fear memories, if the imprint is too strong, it can be reactivated in the wrong context. That’s what happens in PTSD. Similarly, if the brain expects something to happen in the gut, it may trigger the immune response it remembers to be associated with a similar situation, even without a real threat. When this misfiring occurs, it can drive relapses.”

“I still don’t think we fully grasp how deep and far-reaching that effect is, and it keeps challenging me to think bigger about what memory means in a biological sense,” says Prof. Rolls.

I still don’t think we fully grasp how deep and far-reaching that effect is, and it keeps challenging me to think bigger about what memory means in a biological sense.

The insula is wired into autonomic control hubs that regulate organs and immune-active tissues. Through these pathways, patterns stored in the cortex can shape peripheral immune tone. Therapeutically, that suggests a new lever: quiet the maladaptive memory to calm the immune system – an approach that could complement existing treatments for inflammatory diseases once translated beyond mice.

Mapping the Neuroimmune Atlas

Now, Rolls is widening the map. “We are letting the functional anatomy mapping guide us,” says Prof. Rolls, “and so far, it keeps pointing us toward the hippocampal formation. This is exciting because the hippocampus is central to learning and memory, and exploring its role in immune regulation could reveal new dimensions of how the brain integrates experience with bodily defense.” Beyond the reward system and the insula, her lab is charting additional brain circuits that tune immunity – work aimed at a wiring diagram of neuroimmune control and a reference atlas. The goal is to pinpoint the nodes and pathways that bias immune tone and to flag candidate targets for future noninvasive modulation.

In parallel, the team is building a library of brain-activity signatures for specific inflammatory states – biomarkers that could sharpen diagnosis, track disease over time, and ultimately guide personalized treatment. The path is intentionally translational: start with noninvasive measurements, identify reliable signatures, and then test gentle neuromodulation strategies that complement, not replace, existing care.

Translating Mind-Body Control for Autoimmune Care

The next step is practical: map brain activity during distinct inflammatory states and use those patterns to guide gentle interventions. Because current treatments are powerful but blunt, we need a precise map of how brain states drive inflammatory cascades. “One of the key lessons we’ve learned is that it’s not enough just to activate the brain, you have to activate the right circuits,” says Prof. Rolls. Her team, in collaboration with Prof. Talma Hendler’s group, will pair noninvasive readouts – EEG and fMRI – with symptoms and standard clinical measures to identify reliable brain-activity signatures of flare and remission. Those signatures become targets for training: neurofeedback protocols that help patients nudge specific circuits toward patterns linked with a calmer immune tone. “What’s remarkable is that even now, when the signals we use are not yet fully refined, we already see an effect. That gives me a lot of optimism for where this field is heading,” says Prof. Rolls.

The aim is to complement current care for conditions where stress and emotion often tip the balance – rheumatoid arthritis, psoriasis, Crohn’s disease, type 1 diabetes, and more. Early human work will focus on safety and feasibility: can people learn these patterns? Does training shift brain activity as intended? And does that translate into fewer or milder flares? If so, clinicians gain two tools: clearer diagnostics and a noninvasive way to help stabilize immune dynamics, without changing medications unless the data say it helps.

A Step Towards Unlocking New Frontiers in Neuroscience and Human Health

With her CNS grant, Prof. Asya Rolls is pursuing a line of research that few have dared to explore – linking brain activity to immune system regulation. It’s the kind of work that could reframe how we approach autoimmune and inflammatory diseases and shift the conversation from symptom management to system-level recalibration. What excites her most is “the convergence of neuroscience, immunology, and technology.”

That ambition is exactly what investment in neuroscience innovations means at CNS: backing ideas that have the potential to change the rules entirely. For Prof. Rolls and her team, it’s an opportunity to follow the evidence wherever it leads – and perhaps open new doors for patients who have long been waiting for a different kind of answer.