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

Area of Science:

• Neuroscience
• Autonomic Neuroscience
• Neuromodulation

Background:

• Post-brain injury autonomic dysfunction is linked to frontal-vagal network (FVN) dysregulation.
• Current methods lack noninvasive tools for functional mapping and targeted neuromodulation of the FVN.
• The left dorsolateral prefrontal cortex (DLPFC) is hypothesized as a key FVN hub.

Purpose of the Study:

• To characterize autonomic impairment after brain injury.
• To confirm the left DLPFC as an FVN hub.
• To validate a closed-loop intermittent theta-burst stimulation coupled with heart rate variability monitoring (iTBS-HRV) paradigm for FVN assessment.

Main Methods:

• Integrated structural MRI-guided optical neuronavigation with real-time HRV biofeedback.
• Compared HRV metrics (RMSSD, HF, LF/HF, SDNN) in 59 brain-injured patients and 30 controls.
• Conducted randomized crossover iTBS trials targeting left vs. right DLPFC and a closed-loop iTBS-HRV intervention study.

Main Results:

• Brain-injured patients exhibited severe autonomic dysfunction, with reduced vagal tone (RMSSD) and global variability (SDNN).
• Left frontal lesions worsened sympathovagal imbalance (increased LF/HF).
• Left DLPFC iTBS selectively enhanced vagal modulation (increased HF, decreased LF/HF), confirming its hub function, though patients showed blunted HRV responses.

Conclusions:

• The dual-modality iTBS-HRV framework effectively maps FVN dysfunction.
• This approach enables targeted neuromodulation of the left DLPFC hub in brain-injured individuals.
• This study validates a novel noninvasive method for assessing and treating autonomic dysfunction after brain injury.