Upregulation of reward mesolimbic activity and immune response to vaccination: a randomized controlled trial

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

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Gershman, S. J. & Uchida, N. Believing in dopamine. Nat. Rev. Neurosci. 20, 703–714 (2019).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Ben-Shaanan, T. L. et al. Activation of the reward system boosts innate and adaptive immunity. Nat. Med 22, 940–944 (2016).

Article 
CAS 
PubMed 

Google Scholar
 

Ben-Shaanan, T. L. et al. Modulation of anti-tumor immunity by the brain’s reward system. Nat. Commun. 9, 2723 (2018).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Kayama, T., Ikegaya, Y. & Sasaki, T. Phasic firing of dopaminergic neurons in the ventral tegmental area triggers peripheral immune responses. Sci. Rep. 12, 1447 (2022).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Costi, S. et al. Peripheral immune cell reactivity and neural response to reward in patients with depression and anhedonia. Transl. Psychiatry 11, 565 (2021).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Chat, I. K.-Y. et al. Goal-striving tendencies moderate the relationship between reward-related brain function and peripheral inflammation. Brain Behav. Immun. 94, 60–70 (2021).

Treadway, M. T. et al. Association between interleukin-6 and striatal prediction-error signals following acute stress in healthy female participants. Biol. Psychiatry 82, 570–577 (2017).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Sitaram, R. et al. Closed-loop brain training: the science of neurofeedback. Nat. Rev. Neurosci. 18, 86–100 (2017).

Article 
CAS 
PubMed 

Google Scholar
 

Lubianiker, N. et al. Process-based framework for precise neuromodulation. Nat. Hum. Behav. 3, 436–445 (2019).

Article 
PubMed 

Google Scholar
 

Lubianiker, N., Paret, C., Dayan, P. & Hendler, T. Neurofeedback through the lens of reinforcement learning. Trends Neurosci. 45, 579–593 (2022).

Article 
CAS 
PubMed 

Google Scholar
 

Klöbl, M. et al. Reinforcement and punishment shape the learning dynamics in fMRI neurofeedback. Front. Hum. Neurosci. 14, 304 (2020).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Oblak, E. F., Lewis-Peacock, J. A. & Sulzer, J. S. Self-regulation strategy, feedback timing and hemodynamic properties modulate learning in a simulated fMRI neurofeedback environment. PLoS Comput. Biol. 13, e1005681 (2017).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Zoefel, B., Huster, R. J. & Herrmann, C. S. Neurofeedback training of the upper alpha frequency band in EEG improves cognitive performance. NeuroImage 54, 1427–1431 (2011).

Article 
PubMed 

Google Scholar
 

Autenrieth, M., Kober, S. E., Neuper, C. & Wood, G. How much do strategy reports tell about the outcomes of neurofeedback training? A study on the voluntary up-regulation of the sensorimotor rhythm. Front. Hum. Neurosci. 14, 218 (2020).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Qiu, S. et al. Significant transcriptome and cytokine changes in hepatitis B vaccine non-responders revealed by genome-wide comparative analysis. Hum. Vaccin. Immunother. 14, 1763–1772 (2018).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Kirschner, M. et al. Ventral striatal hypoactivation is associated with apathy but not diminished expression in patients with schizophrenia. J. Psychiatry Neurosci. 41, 152–161 (2016).

Article 
PubMed 

Google Scholar
 

Ohmann, H. A., Kuper, N. & Wacker, J. Examining the reliability and validity of two versions of the Effort-Expenditure for Rewards Task (EEfRT). PLOS ONE 17, e0262902 (2022).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Gonen, T. et al. Human mesostriatal response tracks motivational tendencies under naturalistic goal conflict. Soc. Cogn. Affect. Neurosci. 11, 961–972 (2016).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Munshi, S. & Rosenkranz, J. A. Effects of peripheral immune challenge on in vivo firing of basolateral amygdala neurons in adult male rats. Neuroscience 390, 174–186 (2018).

Article 
CAS 
PubMed 

Google Scholar
 

Zhu, X. et al. Somatosensory cortex and central amygdala regulate neuropathic pain-mediated peripheral immune response via vagal projections to the spleen. Nat. Neurosci. 27, 471–483 (2024).

Article 
CAS 
PubMed 

Google Scholar
 

Boukezzi, S. et al. Exaggerated amygdala response to threat and association with immune hyperactivity in depression. Brain, Behav., Immun. 104, 205–212 (2022).

Article 
CAS 
PubMed 

Google Scholar
 

Yin, L. et al. Inflammation and decreased functional connectivity in a widely-distributed network in depression: Centralized effects in the ventral medial prefrontal cortex. Brain Behav. Immun. 80, 657–666 (2019).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Hui, M. & Beier, K. T. Defining the interconnectivity of the medial prefrontal cortex and ventral midbrain. Front. Mol. 15, 971349 (2022).

Jennings, J. H. et al. Distinct extended amygdala circuits for divergent motivational states. Nature 496, 224–228 (2013).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Glimcher, P. W. Understanding dopamine and reinforcement learning: the dopamine reward prediction error hypothesis. Proc. Natl Acad. Sci. 108, 15647–15654 (2011).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Lerner, T. N., Holloway, A. L. & Seiler, J. L. Dopamine, updated: reward prediction error and beyond. Curr. Opin. Neurobiol. 67, 123–130 (2021).

Article 
CAS 
PubMed 

Google Scholar
 

Niv, Y. Cost, benefit, tonic, phasic. Ann. N. Y. Acad. Sci. 1104, 357–376 (2007).

Article 
PubMed 

Google Scholar
 

Beeler, J. A. Tonic dopamine modulates exploitation of reward learning. Front. Behav. Neurosci. 4, 170 (2010).

Niv, Y., Daw, N. D., Joel, D. & Dayan, P. Tonic dopamine: opportunity costs and the control of response vigor. Psychopharmacology 191, 507–520 (2007).

Article 
CAS 
PubMed 

Google Scholar
 

Hahn, A. et al. Functional dynamics of dopamine synthesis during monetary reward and punishment processing. J. Cereb. Blood Flow. Metab. 41, 2973–2985 (2021).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Schmidt, *Clemens et al. Multimodal assessment of dopamine synthesis and bold- signaling in reward and punishment processing – a hybrid fpet/fmri study. Int. J. Neuropsychopharmacol. 28, i39–i40 (2025).

Article 
PubMed Central 

Google Scholar
 

Fields, H. L. & Margolis, E. B. Understanding opioid reward. Trends Neurosci. 38, 217–225 (2015).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Laurent, V., Morse, A. K. & Balleine, B. W. The role of opioid processes in reward and decision-making. Br. J. Pharmacol. 172, 449–459 (2015).

Article 
CAS 
PubMed 

Google Scholar
 

Bossong, M. G., Wilson, R., Appiah-Kusi, E., McGuire, P. & Bhattacharyya, S. Human striatal response to reward anticipation linked to hippocampal glutamate levels. Int. J. Neuropsychopharmacol. 21, 623–630 (2018).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Benedetti, F. & Amanzio, M. Mechanisms of the placebo response. Pulm. Pharmacol. Therapeutics 26, 520–523 (2013).

Article 
CAS 

Google Scholar
 

Zubieta, J.-K. & Stohler, C. S. Neurobiological mechanisms of placebo responses. Ann. N. Y. Acad. Sci. 1156, 198–210 (2009).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

MacInnes, J. J., Dickerson, K. C., Chen, N. & Adcock, R. A. Cognitive neurostimulation: learning to volitionally sustain ventral tegmental area activation. Neuron 89, 1331–1342 (2016).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Totah, N. K. B., Kim, Y. & Moghaddam, B. Distinct prestimulus and poststimulus activation of VTA neurons correlates with stimulus detection. J. Neurophysiol. 110, 75–85 (2013).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Howe, M. W., Tierney, P. L., Sandberg, S. G., Phillips, P. E. M. & Graybiel, A. M. Prolonged dopamine signalling in striatum signals proximity and value of distant rewards. Nature 500, 575–579 (2013).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Kahn, I. & Shohamy, D. Intrinsic connectivity between the hippocampus, nucleus accumbens, and ventral tegmental area in humans. Hippocampus 23, 187–192 (2013).

Article 
CAS 
PubMed 

Google Scholar
 

Cauda, F. et al. Functional connectivity and coactivation of the nucleus accumbens: a combined functional connectivity and structure-based meta-analysis. J. Cogn. Neurosci. 23, 2864–2877 (2011).

Article 
PubMed 

Google Scholar
 

Hammes, J. et al. Dopamine metabolism of the nucleus accumbens and fronto-striatal connectivity modulate impulse control. Brain 142, 733–743 (2019).

Article 
PubMed 

Google Scholar
 

Zunhammer, M., Gerardi, M. & Bingel, U. The effect of dopamine on conditioned placebo analgesia in healthy individuals: a double-blind randomized trial. Psychopharmacology 235, 2587–2595 (2018).

Article 
CAS 
PubMed 

Google Scholar
 

Kunkel, A. et al. Dopamine has no direct causal role in the formation of treatment expectations and placebo analgesia in humans. PLOS Biol. 22, e3002772 (2024).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Lange, T., Dimitrov, S., Bollinger, T., Diekelmann, S. & Born, J. Sleep after vaccination boosts immunological memory. J. Immunol. 187, 283–290 (2011).

Article 
CAS 
PubMed 

Google Scholar
 

Yu, X. et al. GABA and glutamate neurons in the VTA regulate sleep and wakefulness. Nat. Neurosci. 22, 106–119 (2019).

Article 
CAS 
PubMed 

Google Scholar
 

Schiller, M., Ben-Shaanan, T. L. & Rolls, A. Neuronal regulation of immunity: why, how and where? Nat. Rev. Immunol. 21, 20–36 (2021).

Article 
CAS 
PubMed 

Google Scholar
 

Castro, D. C. & Bruchas, M. R. A motivational and neuropeptidergic hub: anatomical and functional diversity within the nucleus accumbens shell. Neuron 102, 529–552 (2019).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

van Dongen, Y. C. et al. Anatomical evidence for direct connections between the shell and core subregions of the rat nucleus accumbens. Neuroscience 136, 1049–1071 (2005).

Article 
PubMed 

Google Scholar
 

Cloninger, C. R., Przybeck, T. R. & Svrakic, D. M. The tridimensional personality questionnaire: U.S. normative data. Psychol. Rep. 69, 1047–1057 (1991).

Article 
CAS 
PubMed 

Google Scholar
 

Costa, P. T. & McCrae, R. R. Normal personality assessment in clinical practice: the NEO Personality Inventory. Psychol. Assess. 4, 5 (1992).

Article 

Google Scholar
 

Torrubia, R., Avila, C., Moltó, J. & Caseras, X. The sensitivity to punishment and sensitivity to reward questionnaire (SPSRQ) as a measure of Gray’s anxiety and impulsivity dimensions. Personal. Individ. differences 31, 837–862 (2001).

Article 

Google Scholar
 

Treadway, M. T., Buckholtz, J. W., Schwartzman, A. N., Lambert, W. E. & Zald, D. H. Worth the ‘EEfRT’? The effort expenditure for rewards task as an objective measure of motivation and anhedonia. PloS one 4, e6598 (2009).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Knutson, B., Westdorp, A., Kaiser, E. & Hommer, D. FMRI visualization of brain activity during a monetary incentive delay task. Neuroimage 12, 20–27 (2000).

Article 
CAS 
PubMed 

Google Scholar
 

Kirschner, M. et al. Deficits in context-dependent adaptive coding of reward in schizophrenia. npj Schizophr. 2, 16020 (2016).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Murty, V. P. et al. Resting state networks distinguish human ventral tegmental area from substantia nigra. Neuroimage 100, 580–589 (2014).

Article 
PubMed 

Google Scholar
 

Koush, Y. et al. OpenNFT: an open-source Python/Matlab framework for real-time fMRI neurofeedback training based on activity, connectivity and multivariate pattern analysis. NeuroImage 156, 489–503 (2017).

Article 
PubMed 

Google Scholar
 

Lindquist, M. A. The statistical analysis of fMRI data. Statist. Sci. 23, (2008).

Hinds, O. et al. Computing moment-to-moment BOLD activation for real-time neurofeedback. NeuroImage 54, 361–368 (2011).

Article 
PubMed 

Google Scholar
 

Koush, Y., Zvyagintsev, M., Dyck, M., Mathiak, K. A. & Mathiak, K. Signal quality and Bayesian signal processing in neurofeedback based on real-time fMRI. NeuroImage 59, 478–489 (2012).

Article 
PubMed 

Google Scholar
 

Bagarinao, E., Matsuo, K., Nakai, T. & Sato, S. Estimation of general linear model coefficients for real-time application. NeuroImage 19, 422–429 (2003).

Article 
CAS 
PubMed 

Google Scholar
 

McCrae, R. R. & Costa, P. T. Empirical and theoretical status of the five-factor model of personality traits. SAGE Handb. Personal. Theory Assess. 1, 273–294 (2008).


Google Scholar
 

Esteban, O. et al. fMRIPrep: a robust preprocessing pipeline for functional MRI. Nat. Methods 16, 111–116 (2019).

Article 
CAS 
PubMed 

Google Scholar
 

Jenkinson, M., Beckmann, C. F., Behrens, T. E., Woolrich, M. W. & Smith, S. M. Fsl. Neuroimage 62, 782–790 (2012).

Article 
PubMed 

Google Scholar
 

Oldham, S. et al. The anticipation and outcome phases of reward and loss processing: a neuroimaging meta-analysis of the monetary incentive delay task. Hum. Brain Mapp. 39, 3398–3418 (2018).

Article 
PubMed 
PubMed Central 

Google Scholar
 

Woolrich, M. Robust group analysis using outlier inference. NeuroImage 41, 286–301 (2008).

Article 
PubMed 

Google Scholar
 

Beckmann, C. F., Jenkinson, M. & Smith, S. M. General multilevel linear modeling for group analysis in fMRI. NeuroImage 20, 1052–1063 (2003).

Article 
PubMed 

Google Scholar
 

Woolrich, M. W., Behrens, T. E. J., Beckmann, C. F., Jenkinson, M. & Smith, S. M. Multilevel linear modelling for FMRI group analysis using Bayesian inference. NeuroImage 21, 1732–1747 (2004).

Article 
PubMed 

Google Scholar
 

R Core Team, R. R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, 2020).

Chikhi, S., Matton, N., Sanna, M. & Blanchet, S. Mental strategies and resting state EEG: effect on high alpha amplitude modulation by neurofeedback in healthy young adults. Biol. Psychol. 178, 108521 (2023).

Article 
PubMed 

Google Scholar
 

Kober, S., Witte, M., Ninaus, M., Neuper, C. & Wood, G. Learning to modulate one’s own brain activity: the effect of spontaneous mental strategies. Front. Hum. Neurosci. 7, 695 (2013).

Article 
PubMed 
PubMed Central 

Google Scholar
 

McLaren, D. G., Ries, M. L., Xu, G. & Johnson, S. C. A generalized form of context-dependent psychophysiological interactions (gPPI): a comparison to standard approaches. NeuroImage 61, 1277–1286 (2012).

Article 
PubMed 

Google Scholar
 

Sescousse, G., Caldú, X., Segura, B. & Dreher, J.-C. Processing of primary and secondary rewards: a quantitative meta-analysis and review of human functional neuroimaging studies. Neurosci. Biobehav. Rev. 37, 681–696 (2013).

Article 
PubMed 

Google Scholar
 

Virtanen, P. et al. SciPy 1.0: fundamental algorithms for scientific computing in Python. Nat. Methods 17, 261–272 (2020).

Article 
CAS 
PubMed 
PubMed Central 

Google Scholar
 

Kühn, S. & Gallinat, J. Segregating cognitive functions within hippocampal formation: a quantitative meta-analysis on spatial navigation and episodic memory. Hum. Brain Mapp. 35, 1129–1142 (2014).

Article 
PubMed 

Google Scholar
 

Arsalidou, M. & Taylor, M. J. Is 2 + 2 = 4? Meta-analyses of brain areas needed for numbers and calculations. NeuroImage 54, 2382–2393 (2011).

Article 
PubMed 

Google Scholar
 

Hétu, S. et al. The neural network of motor imagery: an ALE meta-analysis. Neurosci. Biobehav. Rev. 37, 930–949 (2013).

Article 
PubMed 

Google Scholar
 

McNorgan, C. A meta-analytic review of multisensory imagery identifies the neural correlates of modality-specific and modality-general imagery. Front. Hum. Neurosci. 6, 285 (2012).