Decoding Stress Resilience: The Role of Heart Rate Variability and Cross-Frequency Coupling During Mental Arithmetic Stress

• PAC differences emerged mainly between low- and high-stress conditions. • After FDR correction, only right F-P LG differed between HRV groups. • Low-HRV subjects showed higher ΔMI than high-HRV subjects in right F-P LG. • No significant inter-hemispheric differences remained after FDR correction. Stress triggers various physiological and neural responses, but phase-amplitude coupling (PAC) in the brain under stress remains underexplored. This study computed modulation indices (MIs) to quantify PAC between theta-alpha (4–13 Hz) and low-gamma (LG: 30–45 Hz) or high-gamma (HG: 55–95 Hz) oscillations in 29 subjects under baseline, low-stress, and high-stress conditions. Subjects were categorized into low-HRV and high-HRV groups based on the median split of the HF Norm during baseline to assess the impact of HRV on stress-induced neural coupling. MIs were analysed in fronto-frontal, fronto-parietal, parieto-frontal, and parieto-parietal networks in both hemispheres. Key findings include: (1) After adjustment for multiple comparisons, low-HRV individuals exhibited significantly larger stress-related changes in MIs than high-HRV individuals only in the right fronto-parietal ROI in the LG range; (2) no significant between-group differences were observed in the HG range after correction, although ΔMI tended to be higher in the low-HRV group across several hemisphere–network combinations; and (3) inter-hemispheric comparisons within HRV groups showed limited evidence of hemispheric asymmetry, with no significant left–right differences after adjustment. These findings suggest that lower HRV is associated with larger stress-related modulation of PAC in a spatially selective manner, particularly in the right fronto-parietal ROI within the LG range, while hemispheric effects appear modest. This study highlights HRV as a potential biomarker for stress susceptibility and emphasizes the ROI-specific influence of HRV on brain activity under stress.