What type of study is this?

This is a Randomized Controlled Trial study.

What question did this study set out to answer?

To characterize autonomic impairment and validate left DLPFC as an FVN hub using iTBS and HRV monitoring.

January 6, 2026

Left DLPFC as a Frontal–Vagal Hub in Post-Brain Injury Dysregulation: iTBS Evidence From Dual-Modality Neuronavigation

TCTingting ChenGuangzhou Sport University TZT. D. ZhangSouthern Medical University JZJimin ZhangSouthern Medical University

Key Points

To characterize autonomic impairment and validate left DLPFC as an FVN hub using iTBS and HRV monitoring.
Exploratory analysis integrating data from three investigations using dual-modality neuronavigation.
HRV analysis comparing 59 brain-injured patients to 30 healthy controls for autonomic profiling.
Randomized crossover trial comparing effects of left vs. right DLPFC stimulation on HRV in 15 participants.
Patients exhibited severe autonomic dysfunction with reduced vagal tone and global variability compared to controls.
Left DLPFC iTBS selectively enhanced vagal modulation, confirming its function as a lateralized hub.

Abstract

Background Post-brain injury autonomic dysfunction, mediated by frontal–vagal network (FVN) dysregulation, lacks noninvasive tools for functional mapping and targeted neuromodulation. Objective To characterize autonomic impairment after brain injury, testify left dorsolateral prefrontal cortex (DLPFC) as an FVN hub, and validate a closed-loop intermittent theta-burst stimulation coupled with heart rate variability monitoring (iTBS–HRV) paradigm for FVN assessment. Methods This exploratory, secondary analysis integrated data from 3 coordinated investigations conducted using a dual-modality platform that combined structural magnetic resonance imaging (MRI)-guided optical neuronavigation with real-time HRV biofeedback: (1) autonomic profiling through HRV analysis comparing 59 brain-injured patients with 30 healthy controls; (2) A randomized crossover trial using MRI-neuronavigation iTBS to compare left versus right DLPFC stimulation effects on HRV in 15 participants; and (3) a translation study applied closed-loop iTBS–HRV intervention in 17 patients to quantify FVN responsivity. Key HRV metrics: root-mean-square of successive RR intervals differences (RMSSD; vagal tone), (high-frequency HF), low-frequency (LF)/HF (sympathovagal balance), and standard deviation of RR intervals (SDNN; global variability). Results Patients showed severe autonomic dysfunction with reduced vagal tone (RMSSD: 18.6 ms vs 36.7 ms, P < .001) and global variability (SDNN: 21.3 ms vs 50.9 ms, P < .001). Left frontal lesions exacerbate sympathovagal imbalance (LF/HF ↑2.40, P < .05). Left DLPFC iTBS selectively enhanced vagal modulation (ΔHF%: +2.73, P < .01; ΔLF/HF: −1.60, P < .001), confirming lateralized hub function, while patients exhibited attenuated HRV responses (ΔRMSSD: 0.50 ms vs 3.34 ms in controls, P < .01). Conclusion The dual-modality iTBS–HRV framework provides an effective approach for mapping FVN dysfunction and targeting the left DLPFC hub for neuromodulation after brain injury.

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