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bioRxiv · 10.64898/2025.12.22.695740

Real-time functional connectivity-based neurofeedback of the DLPFC-amygdala pathway during threat-exposure attenuates anxiety

Abstract

BackgroundAdaptive regulation of negative emotion is vital for mental health and dysregulations in this domain contribute to the major mental disorders, including anxiety and depression. On the neural level, efficient emotion regulation has been linked to functional communication between the dorsolateral prefrontal cortex (DLPFC) and the amygdala. Gaining voluntary control over this pathway may present an effective strategy for potentiating emotion regulation. ObjectiveAgainst this background, we developed a novel connectivity-based real-time fMRI (rt-fMRI) neurofeedback (NF) training that enables individuals to gain volitional control over the DLPFC-amygdala pathway during exposure to threatening stimuli. MethodsThe study employed a pre-registered, randomized, sham-controlled design with the experimental group (n = 22) receiving real-time NF information on connectivity between the right DLPFC and the amygdala during threat exposure and the sham control group (n = 23) receiving connectivity NF from a circuit not related to emotion regulation. The ability to maintain regulatory control in the absence of feedback was assessed after four NF runs. Primary outcomes included functional connectivity of the target pathway, as well as anxiety scores. ResultsThe results demonstrate that successful acquisition of self-regulation of the rDLPFC-amygdala top-down regulatory circuit in the experimental NF group facilitated attenuation of anxiety. ConclusionIn summary, our findings suggest that real-time fMRI neurofeedback (rtfMRI-NF) allows to volitionally enhance rDLPFC-amygdala connectivity, and in turn reduces negative emotional states, rendering the training a promising neurotechnology intervention for mental disorders.

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dong, w., Ferraro, S., Liu, D., Zhang, Y., Han, M., Mi, Y., Wang, J., Fu, K., Zhao, Z., Kendrick, K. M., Yao, D., Yao, S., Becker, B.. 2025-12-24. Real-time functional connectivity-based neurofeedback of the DLPFC-amygdala pathway during threat-exposure attenuates anxiety. https://doi.org/10.64898/2025.12.22.695740

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