Real-time functional magnetic resonance imaging (rt-fMRI) has revived the translational perspective of neurofeedback (NF)1. Particularly for stress management, targeting deeply located limbic areas involved in stress processing2 has paved new paths for brain-guided interventions. However, the high cost and immobility of fMRI constitute a challenging drawback for the scalability (accessibility and cost-effectiveness) of the approach, particularly for clinical purposes3. The current study aimed to overcome the limited applicability of rt-fMRI by using an electroencephalography (EEG) model endowed with improved spatial resolution, derived from simultaneous EEG–fMRI, to target amygdala activity (termed amygdala electrical fingerprint (Amyg-EFP))4,5,6. Healthy individuals (n = 180) undergoing a stressful military training programme were randomly assigned to six Amyg-EFP-NF sessions or one of two controls (control-EEG-NF or NoNF), taking place at the military training base. The results demonstrated specificity of NF learning to the targeted Amyg-EFP signal, which led to reduced alexithymia and faster emotional Stroop, indicating better stress coping following Amyg-EFP-NF relative to controls. Neural target engagement was demonstrated in a follow-up fMRI-NF, showing greater amygdala blood-oxygen-level-dependent downregulation and amygdala–ventromedial prefrontal cortex functional connectivity following Amyg-EFP-NF relative to NoNF. Together, these results demonstrate limbic specificity and efficacy of Amyg-EFP-NF during a stressful period, pointing to a scalable non-pharmacological yet neuroscience-based training to prevent stress-induced psychopathology.
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Scientific Reports Open Access 06 June 2023
Amygdala downregulation training using fMRI neurofeedback in post-traumatic stress disorder: a randomized, double-blind trial
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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We thank I. Rashap, D. Torjeman, Y. Roll, S. Dushy, I. Teshner, N. Shani, L. Frumer, T. Yeheskely, R. Bashan, L. Wiezman, O. Shani, A. Greental, T. Jacoby and M. Halevy for assisting in this study. This project was supported by 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 funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
T.H., N.I. and Y.M.-H. are inventors of related patent applications entitled ‘Method and system for use in monitoring neural activity in a subject’s brain’ (US20140148657 A1, WO2012104853 A3 and EP2670299 A2). This does not alter the authors’ adherence to all Nature Human Behaviour policies.
Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Figures 1–7, Supplementary Tables 1–6, Supplementary Methods, Supplementary References
An illustration of NF training guided by the animated scenario. Real-time modulations in the Amyg–EFP signal are reflected by audiovisual changes in the unrest level of a virtual 3D scenario (a typical hospital waiting room), manifested as the ratio between characters sitting down and those loudly protesting at the counter. The video shows an example both for down- and up-regulation training; however, in the current study, only down-regulation training was conducted. The participant consented to appear in the video. Video reproduced from ref. 26
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Keynan, J.N., Cohen, A., Jackont, G. et al. Electrical fingerprint of the amygdala guides neurofeedback training for stress resilience. Nat Hum Behav 3, 63–73 (2019). https://doi.org/10.1038/s41562-018-0484-3
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