Abstract
Functional MRI neurofeedback (NF) allows humans to self-modulate neural patterns in specific brain areas. This technique is regarded as a promising tool to translate neuroscientific knowledge into brain-guided psychiatric interventions. However, its clinical implementation is restricted by unstandardized methodological practices, by clinical definitions that are poorly grounded in neurobiology, and by lack of a unifying framework that dictates experimental choices. Here we put forward a new framework, termed ‘process-based NF’, which endorses a process-oriented characterization of mental dysfunctions to form precise and effective psychiatric treatments. This framework relies on targeting specific dysfunctional mental processes by modifying their underlying neural mechanisms and on applying process-specific contextual feedback interfaces. Finally, process-based NF offers designs and a control condition that address the methodological shortcomings of current approaches, thus paving the way for a precise and personalized neuromodulation.
This is a preview of subscription content, access via your institution
Relevant articles
Open Access articles citing this article.
-
Depressive symptoms reduce when dorsolateral prefrontal cortex-precuneus connectivity normalizes after functional connectivity neurofeedback
Scientific Reports Open Access 16 February 2022
-
Alpha activity neuromodulation induced by individual alpha-based neurofeedback learning in ecological context: a double-blind randomized study
Scientific Reports Open Access 16 September 2021
-
The DecNef collection, fMRI data from closed-loop decoded neurofeedback experiments
Scientific Data Open Access 23 February 2021
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 per month
cancel any time
Subscribe to this journal
Receive 12 digital issues and online access to articles
$119.00 per year
only $9.92 per issue
Rent or buy this article
Get just this article for as long as you need it
$39.95
Prices may be subject to local taxes which are calculated during checkout



Change history
05 June 2019
The original and corrected figures, and the Editorial Summary, are shown in the accompanying Publisher Correction.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
30 April 2019
The original and corrected text is shown in the accompanying Publisher Correction.
References
Sitaram, R. et al. Nat. Rev. Neurosci. 18, 86–100 (2017).
Casey, B. J. et al. Nat. Rev. Neurosci. 14, 810–814 (2013).
Freedman, R. et al. Am. J. Psychiatry 170, 1–5 (2013).
Sulzer, J. et al. Neuroimage 76, 386–399 (2013).
Fovet, T., Jardri, R. & Linden, D. Curr. Pharm. Des. 21, 3384–3394 (2015).
Thibault, R. T., MacPherson, A., Lifshitz, M., Roth, R. R. & Raz, A. Neuroimage 172, 786–807 (2017).
Cuthbert, B. N. & Insel, T. R. BMC Med. 11, 126 (2013).
Kaiser, T. & Feng, G. Nat. Med. 21, 979–988 (2015).
Menon, V. Trends Cogn. Sci. 15, 483–506 (2011).
Barrett, L. F. & Satpute, A. B. Curr. Opin. Neurobiol. 23, 361–372 (2013).
Berridge, K. C. & Kringelbach, M. L. Neuron 86, 646–664 (2015).
Insel, T. R. & Cuthbert, B. N. Science 348, 499–500 (2015).
Detke, M. J., Lu, Y., Goldstein, D. J., Hayes, J. R. & Demitrack, M. A. J. Clin. Psychiatry 63, 308–315 (2002).
Hypericum Depression Trial Study Group. J. Am. Med. Assoc. 287, 1807–1814 (2002).
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (5th ed.) (American Psychiatric Publishing, 2013).
Pizzagalli, D. A. Annu. Rev. Clin. Psychol. 10, 393–423 (2014).
Nestler, E. J. & Carlezon, W. A. Jr. Biol. Psychiatry 59, 1151–1159 (2006).
Whitton, A. E., Treadway, M. T. & Pizzagalli, D. A. Curr. Opin. Psychiatry 28, 7–12 (2015).
Snaith, R. P. et al. Br. J. Psychiatry 167, 99–103 (1995).
Knutson, B., Westdorp, A., Kaiser, E. & Hommer, D. Neuroimage 12, 20–27 (2000).
Knutson, B., Bhanji, J. P., Cooney, R. E., Atlas, L. Y. & Gotlib, I. H. Biol. Psychiatry 63, 686–692 (2008).
Lutz, K. & Widmer, M. Neurosci. Neuroecon. 3, 33–35 (2014).
World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines (WHO, 1992).
Kringelbach, M. L. & Berridge, K. C. Trends Cogn. Sci. 13, 479–487 (2009).
Salamone, J. D., Yohn, S. E., López-Cruz, L., San Miguel, N. & Correa, M. Brain 139, 1325–1347 (2016).
Nusslock, R. & Alloy, L. B. J. Affect. Disord. 216, 3–16 (2017).
Calhoun, V. D., Miller, R., Pearlson, G. & Adalı, T. Neuron 84, 262–274 (2014).
Goodkind, M. et al. JAMA. Psychiatry 72, 305–315 (2015).
Sha, Z., Wager, T. D., Mechelli, A. & He, Y. Biol. Psychiatry 85, 379–388 (2018).
Etkin, A., Büchel, C. & Gross, J. J. Nat. Rev. Neurosci. 16, 693–700 (2015).
Schachar, R., Mota, V. L., Logan, G. D., Tannock, R. & Klim, P. J. Abnorm. Child Psychol. 28, 227–235 (2000).
Verdejo-García, A., Lawrence, A. J. & Clark, L. Neurosci. Biobehav. Rev. 32, 777–810 (2008).
Hampshire, A. & Sharp, D. J. Trends Cogn. Sci. 19, 445–452 (2015).
Wager, T. D. et al. N. Engl. J. Med. 368, 1388–1397 (2013).
López-Solà, M. et al. Pain 158, 34–47 (2017).
Rosenberg, M. D. et al. Nat. Neurosci. 19, 165–171 (2016).
Chang, L. J., Gianaros, P. J., Manuck, S. B., Krishnan, A. & Wager, T. D. PLoS Biol. 13, e1002180 (2015).
Sarkheil, P. et al. Behav. Brain Res. 281, 326–332 (2015).
Paret, C. et al. Soc. Cogn. Affect. Neurosci. 11, 952–960 (2016).
Nicholson, A. A. et al. Hum. Brain Mapp. 38, 541–560 (2017).
Cohen Kadosh, K. et al. Neuroimage 125, 616–626 (2016).
Megumi, F., Yamashita, A., Kawato, M. & Imamizu, H. Front. Hum. Neurosci. 9, 160 (2015).
Ramot, M., Grossman, S., Friedman, D. & Malach, R. Proc. Natl Acad. Sci. USA 113, E2413–E2420 (2016).
Yamada, T. et al. Int. J. Neuropsychopharmacol. 20, 769–781 (2017).
Ramot, M. et al. eLife 6, e28974 (2017).
Koush, Y. et al. Neuroimage 81, 422–430 (2013).
Koush, Y. et al. Cereb. Cortex 27, 1193–1202 (2017).
Jacob, Y., Or-Borichev, A., Jackont, G., Lubianiker, N. & Hendler, T. Network based fMRI neuro-feedback for emotion regulation; proof-of-concept. in International Workshop on Complex Networks and their Applications 1250–1260 (Springer, 2017).
Haynes, J. D. Neuron 87, 257–270 (2015).
Norman, K. A., Polyn, S. M., Detre, G. J. & Haxby, J. V. Trends Cogn. Sci. 10, 424–430 (2006).
LaConte, S. M. Neuroimage 56, 440–454 (2011).
LaConte, S. M., Peltier, S. J. & Hu, X. P. Hum. Brain Mapp. 28, 1033–1044 (2007).
Shibata, K. Science 334, 1413–1414 (2011).
Watanabe, T., Sasaki, Y., Shibata, K. & Kawato, M. Trends Cogn. Sci. 21, 997–1010 (2017).
Cortese, A., Amano, K., Koizumi, A., Kawato, M. & Lau, H. Nat. Commun. 7, 13669 (2016).
Koizumi, A. et al. Nat. Hum. Behav. 1, 0006 (2016).
Taschereau-Dumouchel, V. et al. Proc. Natl Acad. Sci. USA 115, 3470–3475 (2018).
Fair, D. A. et al. PLOS Comput. Biol. 5, e1000381 (2009).
Cohen Kadosh, K., Cohen Kadosh, R., Dick, F. & Johnson, M. H. Cereb. Cortex 21, 1389–1394 (2011).
Johnson, M. H., Grossmann, T. & Cohen Kadosh, K. Dev. Psychol. 45, 151–159 (2009).
Cohen-Kadosh, K. & Johnson, M. H. Trends Cogn. Sci. 11, 367–369 (2007).
Caria, A., Sitaram, R. & Birbaumer, N. Neuroscientist 18, 487–501 (2012).
Phan, K. L. et al. Neuroreport 15, 527–532 (2004).
Emmert, K. et al. Neuroimage Clin. 14, 97–104 (2017).
Ninaus, M. et al. Front. Hum. Neurosci. 7, 914 (2013).
Meir-Hasson, Y. et al. PLoS One 11, e0154968 (2016).
Dehghani-Arani, F., Rostami, R. & Nadali, H. Appl. Psychophysiol. Biofeedback 38, 133–141 (2013).
Buyukturkoglu, K. et al. PLoS One 10, e0135872 (2015).
Paret, C. et al. Front. Behav. Neurosci. 8, 299 (2014).
Paret, C. et al. Neuroimage 125, 182–188 (2016).
Sokunbi, M. O., Linden, D. E., Habes, I., Johnston, S. & Ihssen, N. Front. Behav. Neurosci. 8, 392 (2014).
Ihssen, N., Sokunbi, M. O., Lawrence, A. D., Lawrence, N. S. & Linden, D. E. J. Brain Imaging Behav. 11, 915–924 (2017).
Young, K. D. et al. Am. J. Psychiatry 174, 748–755 (2017).
Kober, S. E., Witte, M., Ninaus, M., Neuper, C. & Wood, G. Front. Hum. Neurosci. 7, 695 (2013).
Marxen, M. et al. Front. Hum. Neurosci. 10, 183 (2016).
Mueller, C. et al. J. Neurosci. Methods 209, 290–298 (2012).
Mishra, J., Anguera, J. A. & Gazzaley, A. Neuron 90, 214–218 (2016).
Cavazza, M. et al. Integrating virtual agents in BCI neurofeedback systems. in Proceedings of the 2014 Virtual Reality International Conference 25 (ACM, 2014).
Mathiak, K. A. et al. Front. Behav. Neurosci. 9, 136 (2015).
Bohil, C. J., Alicea, B. & Biocca, F. A. Nat. Rev. Neurosci. 12, 752–762 (2011).
Morina, N., Ijntema, H., Meyerbröker, K. & Emmelkamp, P. M. Behav. Res. Ther. 74, 18–24 (2015).
Opriş, D. et al. Depress. Anxiety 29, 85–93 (2012).
Rizzo, A. & Shilling, R. Eur. J. Psychotraumatol. 8, 1414560 (2017).
Wiederhold, B. K. et al. IEEE Trans. Inf. Technol. Biomed. 6, 218–223 (2002).
Vourvopoulos, A., Cardona, J.E.M. & Badia, S.B.i. Optimizing motor imagery neurofeedback through the use of multimodal immersive virtual reality and motor priming. in 2015 International Conference on Virtual Rehabilitation (ICVR) 228–234 (2015).
Othmer, S. & Kaiser, D. Cyberpsychol. Behav. 3, 415–420 (2000).
Benedetti, F. Neuron 84, 623–637 (2014).
Goldman, R. I., Stern, J. M., Engel, J. Jr. & Cohen, M. S. Neuroreport 13, 2487–2492 (2002).
Emmert, K. et al. Neuroimage 124, 806–812 (2016). Pt A.
Paret, C. et al. Hum. Brain Mapp. 39, 3018–3031 (2018).
Harmelech, T., Friedman, D. & Malach, R. J. Neurosci. 35, 2588–2595 (2015).
Sulzer, J. et al. Neuroimage 83, 817–825 (2013).
Greer, S. M., Trujillo, A. J., Glover, G. H. & Knutson, B. Neuroimage 96, 237–244 (2014).
Alegria, A. A. et al. Hum. Brain Mapp. 38, 3190–3209 (2017).
Doya, K. Curr. Opin. Neurobiol. 10, 732–739 (2000).
Corbetta, M. & Shulman, G. L. Nat. Rev. Neurosci. 3, 201–215 (2002).
Ridderinkhof, K. R., Ullsperger, M., Crone, E. A. & Nieuwenhuis, S. Science 306, 443–447 (2004).
Schabus, M. Brain 140, e64 (2017).
Emmert, K. et al. Brain Imaging Behav. 11, 712–721 (2017).
Scheinost, D. et al. Front. Behav. Neurosci. 8, 338 (2014).
Weber, E., Köberl, A., Frank, S. & Doppelmayr, M. Appl. Psychophysiol. Biofeedback 36, 37–45 (2011).
Ninaus, M. et al. Biol. Psychol. 110, 126–133 (2015).
Halder, S. et al. Front. Hum. Neurosci. 7, 105 (2013).
Kirsch, M., Gruber, I., Ruf, M., Kiefer, F. & Kirsch, P. Addict. Biol. 21, 982–992 (2016).
MacInnes, J. J., Dickerson, K. C., Chen, N. K. & Adcock, R. A. Neuron 89, 1331–1342 (2016).
Linden, D. E. J. et al. PLoS One 7, e38115 (2012).
Sherwood, M. S., Kane, J. H., Weisend, M. P. & Parker, J. G. Neuroimage 124, 214–223 (2016). Pt A.
Grech, R. et al. J. Neuroeng. Rehabil. 5, 25 (2008).
Congedo, M., Lubar, J. F. & Joffe, D. IEEE Trans. Neural Syst. Rehabil. Eng. 12, 387–397 (2004).
Yao, J. & Dewald, J. P. Neuroimage 25, 369–382 (2005).
Valdes-Sosa, P. A. et al. Hum. Brain Mapp. 30, 2701–2721 (2009).
Laufs, H., Daunizeau, J., Carmichael, D. W. & Kleinschmidt, A. Neuroimage 40, 515–528 (2008).
Ben-Simon, E., Podlipsky, I., Arieli, A., Zhdanov, A. & Hendler, T. PLoS One 3, e3984 (2008).
de Munck, J. C. et al. Neuroimage 35, 1142–1151 (2007).
Mantini, D., Perrucci, M. G., Del Gratta, C., Romani, G. L. & Corbetta, M. Proc. Natl Acad. Sci. USA 104, 13170–13175 (2007).
Meir-Hasson, Y., Kinreich, S., Podlipsky, I., Hendler, T. & Intrator, N. Neuroimage 102, 128–141 (2014).
Keynan, J. N. et al. Biol. Psychiatry 80, 490–496 (2016).
Cohen, A. et al. Front. Robot. AI 3, 52 (2016).
Keynan, J. N. et al. Nat. Hum. Behav. 3, 52–73 (2018).
Goldway, N. et al. Neuroimage 186, 758–770 (2018).
Klovatch-Podlipsky, I., Or-Borichev, A., Sar-El, R., Lubianiker, N. & Hendler, T. Front. Hum. Neurosci. https://doi.org/10.3389/conf.fnhum.2016.220.00018 (2016).
Holmes, E. A. & Mathews, A. Clin. Psychol. Rev. 30, 349–362 (2010).
Sepulveda, P. et al. Hum. Brain Mapp. 37, 3153–3171 (2016).
Scharnowski, F. et al. Biol. Psychol. 108, 85–97 (2015).
Johnson, K. A. et al. J. Neuroimaging 22, 58–66 (2012).
Hellrung, L. et al. Neuroimage 166, 198–208 (2018).
Acknowledgements
K.C.K., T.H., and D.E.J.L. are members of the BRAINTRAIN consortium, a Collaborative Project supported by the European Commission under the Health Cooperation Work Programme of the 7th Framework Programme, under Grant Agreement no. 602186. T.H. thanks the following grants: US Department of Defense grant agreement no. W81XWH-11–2–0008; Mafat, IDF, I-Core cognitive studies grant agreement no. 693210; the Israeli Ministry of Science, Technology and Space (Grant No. 3-11170); Kamin Program of the Israel Innovation Authority (Grant No. 59143); and the Sagol Network for Brain Research. N.L. thanks JOY Ventures Foundation. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors thank E. Gregorian for her contribution to the graphic illustration depicted in Fig. 1.
Author information
Authors and Affiliations
Contributions
All authors contributed to the writing of the manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Lubianiker, N., Goldway, N., Fruchtman-Steinbok, T. et al. Process-based framework for precise neuromodulation. Nat Hum Behav 3, 436–445 (2019). https://doi.org/10.1038/s41562-019-0573-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41562-019-0573-y
This article is cited by
-
Real-time fMRI neurofeedback: the promising potential of brain-training technology to advance clinical neuroscience
Neuropsychopharmacology (2023)
-
Depressive symptoms reduce when dorsolateral prefrontal cortex-precuneus connectivity normalizes after functional connectivity neurofeedback
Scientific Reports (2022)
-
Alpha activity neuromodulation induced by individual alpha-based neurofeedback learning in ecological context: a double-blind randomized study
Scientific Reports (2021)
-
The DecNef collection, fMRI data from closed-loop decoded neurofeedback experiments
Scientific Data (2021)
-
Bacomics: a comprehensive cross area originating in the studies of various brain–apparatus conversations
Cognitive Neurodynamics (2020)