Enhanced Brain-Heart Connectivity as a Precursor of Reduced State Anxiety After Therapeutic Virtual Reality Immersion

State anxiety involves transient feelings of tension and nervousness in response to threats, which can escalate into anxiety disorders if persistent. Despite treatments, 30%-50% of individuals show limited improvement, and neurophysiological mechanisms of treatment responsiveness remain unclear, requiring the development of objective biomarkers. In this study, we monitored multimodal electrophysiological parameters: heart rate variability (high-frequency, low-frequency, LF/HF ratio), EEG beta and alpha relative power, and brain-to-heart connectivity in participants with real-life state anxiety. Participants underwent a therapeutic intervention combining virtual-reality immersion, hypnotic script, and a breath control exercise. Real-life state anxiety was captured using the STAI-Y1 scale before and after the intervention. We observed reduced anxiety immediately after the intervention in 16 out of 27 participants. While all participants, independently of their STAI-Y1 score, showed increased HRV low frequency power, only treatment-responders displayed increased overall autonomic tone (high and low frequency HRV), increased midline beta power and brain-to-heart connectivity. Notably, the LF/HF ratio showed a significant linear relationship with anxiety reduction, with higher ratios linked to greater therapeutic response. These findings suggest that increased cognitive regulation of brain-to-heart connectivity could serve as a biomarker for therapeutic efficacy, with elevated midline beta power facilitating improved cardiac tone in responders. Significance Statement Elevated state anxiety can escalate into debilitating disorders, such as generalized anxiety disorder, yet treatment efficacy remains inconsistent, and reliable biomarkers predicting therapeutic outcomes are lacking. This study identifies key neural and physiological markers linked to effective anxiety reduction following a virtual reality-based non-pharmacological intervention in healthy participants with increased state anxiety. Anxiety reduction is associated with increased midline beta power, heightened heart rate variability (LF/HF ratio), and enhanced brain-to-heart connectivity. These findings highlight the role of brain-to-heart modulation and autonomic nervous system functioning in therapeutic response. By highlighting these biomarkers, this research aims at advancing our understanding of anxiety treatment mechanisms and offering insights into the development of biomarker-driven, scalable interventions.