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Can positive expectations tune the immune system?

April 20, 2026
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When I was young, a teacher told me, “If you think good, you’ll feel good”. It stayed with me. Even as a child, I was fascinated by the mind-body link, and how thoughts shape our feelings. I notice this in myself too: when I’m anxious, I can get stomach aches or chest pain; when I’m happy, I feel lighter.

During my master’s degree, I learned about psychoneuroimmunology and the placebo effect, which gave language and scientific footing to these ideas. Placebo studies show that people can feel better even with an inactive treatment. The nocebo effect shows the opposite: people can feel worse after an inactive treatment (Wager 2015).

But how much can our thoughts influence our bodies, and could they even shape our immune function? A new randomised controlled trial by Lubianiker and colleagues aimed to address this using neurofeedback.

Neurofeedback gives real-time information about a person’s brain activity, often using MRI or EEG scans, so they can try to change it using mental strategies. Imagine a simple game where a balloon rises on a screen as your brain activity changes favourably. You try different mental strategies (e.g., thinking of a happy memory, imagining success) and the balloon changes based on your brain activity (Lubianiker 2022). Your brain gives you feedback, and you learn, little by little, how to change its activity. So, the authors asked themselves:

Can people learn to increase reward-related brain activity using neurofeedback, and does this relate to antibody responses after vaccination?

Can we learn to change our brain activity and influence the body? Neurofeedback offers a way to test that idea.

Can we learn to change our brain activity and influence the body? Neurofeedback offers a way to test that idea.

Methods

The authors conducted a preregistered, double-blind, randomised controlled trial in 85 healthy adults aged 18 to 45 years (mean age = 25 years; 51 female). Participants were randomised to one of three arms:

  1. Reward-mesolimbic neurofeedback (n=34)
  2. Control neurofeedback (n=34)
  3. No-neurofeedback control (n=17)

The study was powered to detect a moderate brain-immune correlation (r≈0.3). The intervention used fMRI neurofeedback to train participants to increase activity in the reward-related mesolimbic network, particularly the ventral tegmental area (VTA).

Participants used self-chosen mental strategies while receiving real-time feedback on brain activity. After multiple neurofeedback sessions, the final training session was followed immediately by a hepatitis B vaccination. Antibody levels were measured before and after vaccination, and a subset was assessed at 3 months.

The researchers also characterised participants’ mental strategies across 45 mental features to test whether specific psychological content, such as positive expectation, was linked to brain activity and immune response.

Results

Neurofeedback training

Both neurofeedback groups learned to increase activity in their target regions across the training, showing that participants were able to use brain feedback to change their own brain activity over time.

  • In the experimental group, this involved the reward-related mesolimbic network, including the VTA and bilateral nucleus accumbens (NAc).
  • In the control group, the assigned non-mesolimbic network was successfully up-regulated, suggesting that the neurofeedback approach worked across different brain systems, not just the target reward network.

Brain-immune response

Greater VTA up-regulation was associated with larger post-vaccination increases in hepatitis B antibody levels (r=0.31, P=0.018, n=60). This suggests that people who could more strongly engage this reward-related brain area tended to show a stronger immune response to vaccination. By contrast, NAc up-regulation showed no clear association with antibody response (r=0.19, P=0.365), nor did control-region up-regulation (r=0.11, P=0.559); indicating that the effect was not seen across all brain regions or networks tested.

The authors explored several alternative explanations for these findings:

  • General neurofeedback success did not explain the immune effect, as control regions showed no correlation with antibody changes.
  • Reward activity during feedback periods also did not correlate with antibody response (VTA: r=0.15, P=0.238).
  • Trait motivational measures (MID task, EEfRT, questionnaires) also showed no association with either VTA regulation or immune outcomes.
  • This suggests that baseline motivation or reward sensitivity did not explain the pattern of results.

Mental-strategy analysis

The mental-strategy analysis suggested that positive expectation became increasingly linked to sustained VTA activity over training. A mixed-effects model showed a strong interaction between the activity component and positive expectation (β=0.09, 95% CI [0.027 to 0.153], P=0.005), which strengthened at session 4 (β=0.128, 95% CI [0.037 to 0.218], P=0.006). This pattern suggests that the types of thoughts participants used during training became more closely tied to reward-related brain activity over time.

No significant group differences in post-vaccination antibody levels were found, meaning that average immune response was similar across the groups despite the observed brain–immune associations within individuals.

Neurofeedback training was associated with stronger activation of a key reward brain region, which in turn was linked to a stronger antibody response after vaccination.

Neurofeedback training was associated with stronger activation of a key reward brain region, which in turn was linked to a stronger antibody response after vaccination.

Conclusions

So, can positive expectations tune the immune system? Possibly, but not in a simple or universal way.

Greater VTA upregulation, along with positive expectation strategies, was linked to stronger antibody responses. However, the absence of group-level differences in antibody responses means that these findings remain mechanistic rather than providing clinical proof of benefit.

Taken together, these findings suggest that our expectations may not occur “just in our heads”. Instead, they may have measurable biological effects on the body, including the ability to influence immune responses; at least under carefully controlled experimental conditions.

Positive expectations and reward-related brain activity may be linked to immune responses, but evidence remains at the mechanistic level rather than showing clear clinical effects.

Positive expectations and reward-related brain activity may be linked to immune responses, but evidence remains at the mechanistic level rather than showing clear clinical effects.

Strengths and limitations

Strengths

There are several notable strengths of the current research, including:

  • Preregistered, double-blind RCT design with an active neurofeedback control group (not just a passive comparison). This strengthens confidence that the results are not due to expectancy effects or simple task repetition.
  • Targeted VTA neurofeedback via Monetary Incentive Delay (MID) task localisation, increasing the precision of measuring and training a key reward-related brain region.
  • Rigorous testing of alternative explanations of findings, including control regions, feedback effects, and trait motivation, none of which explained the observed effects, strengthening confidence in results.
  • Novel mental-strategy characterisation across 45 features, allowing the researchers to link positive expectation strategies to sustained VTA activity.
  • Clear power calculation based on detection of a moderate correlation (r=0.3).

Limitations

However, there are also important limitations to consider:

  • The main brain-immune finding was correlational (r=0.31) and thus, does not prove causation of VTA activity on antibody response.
  • No significant group × time interaction was found for antibody levels, suggesting that effects were not strong enough to translate into clear between-group differences.
  • Relatively small sample size (n=85 total, n=60 for correlations after exclusions).
  • Effects were found for VTA but not NAc, raising questions about how specific the effect is within the reward system.
  • Sample limited to healthy young adults only (mean age 25) and so, findings may not generalise to clinical/older populations.
  • Neurofeedback success may reflect individual differences in strategy learning, rather than being purely reflective of VTA regulation.
This study combined neurofeedback and vaccination to explore links between reward-related brain activity and immune responses, but findings were correlational and limited to healthy young adults.

This study combined neurofeedback and vaccination to explore links between reward-related brain activity and immune responses, but findings were correlational and limited to healthy young adults.

Implications for practice

The idea that a teacher’s simple words — “If you think good, you’ll feel good” — might actually connect to something as concrete as a change in antibody levels is no longer just childhood curiosity. Rather, it feels like a scientific bridge to mechanisms I’ve sensed my whole life across psychoneuroimmunology.

Lubianiker et al.’s study will not, on its own, change vaccination practice or lead us to prescribe neurofeedback for immune boosting. But it does add an important experimental piece to a larger puzzle.

Positive expectations appear to engage reward circuitry that may support immune responses, and the brain may amplify those expectation-driven benefits. However, it is unlikely that these will ever replace biological treatments.

Clinical implications

  • Take patient expectations seriously — they may influence more than just feelings of satisfaction.
  • The context around vaccination/treatment (e.g., hope, anticipation) may have biological relevance.
  • Consider psychological state when interpreting variations in vaccine responses.

Research implications

  • Replicate in larger, more diverse clinical samples (e.g., chronic illness, older adults, poor vaccine responders) is required.
  • Test causality: can VTA-specific neurofeedback cause improvements in immune outcomes?
  • Examine mechanisms: what biological pathways are involved (e.g., dopamine, opioids, autonomic, meningeal pathways)?
  • Explore positive expectation training without neurofeedback.

Personal reflection

This study resonates deeply with my own experiences of mind-body connection. Seeing that mind training – in this case, changes the VTA activation – is linked to higher antibody levels, lends scientific weight to what I’ve felt myself: thoughts leave traces in the body.

It’s exciting science that opens an enormous and important world of understanding about how our brain can change our immunity, and whether these pathways can be shaped through training to improve our health. This is not only to feel good emotionally, but to improve our bodies physically, too.

The implications of this study are interesting but preliminary. Real-world application still needs careful testing and replication.

The implications of this study are interesting, but preliminary. Real-world application still needs careful testing and replication.

Statement of interests

Estherina Trachtenberg has no involvement in the Lubianiker et al. study and no personal, professional, or financial relationships with its authors. She used AI-assisted tools to help with editing and clarifying the wording of this blog post, but all decisions about content, interpretation, and emphasis are her own.

Editor

Edited by Éimear Foley. AI tools assisted with language refinement and formatting during the editorial phase.

Links

Primary paper

Nitzan Lubianiker, Tamar Koren, Meshi Djerasi, Margarita Sirotkin, Neomi Singer, Itamar Jalon, Avigail Lerner, Roi Sar-el, Haggai Sharon, Moni Shahar, Hilla Azulay-Debby, Asya Rolls & Talma Hendler. (2026) Upregulation of reward mesolimbic activity and immune response to vaccination: a randomized controlled trial. Nature Medicine 32, 572-581. https://doi.org/10.1038/s41591-025-04140-5

Other references

Kim, K., Title, B., & Kipnis, J. (2026) Placebo effect influences vaccine responses. Nature Medicine 32, 416-417. https://doi.org/10.1038/s41591-025-04168-7

Wager, T. D. & Atlas, L. Y. The neuroscience of placebo effects: connecting context, learning and health. Nat. Rev. Neurosci. 16, 403–418 (2015). https://doi.org/10.1038/nrn3976

Lubianiker, N., Paret, C., Dayan, P., & Hendler, T. (2022). Neurofeedback through the lens of reinforcement learning. Trends in neurosciences, 45(8), 579–593. https://doi.org/10.1016/j.tins.2022.03.008

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