Acute prefrontal hemodynamic responses to Xingnao Kaiqiao acupuncture in healthy participants and patients with prolonged disorders of consciousness

Background/objectives Xingnao Kaiqiao (XNKQ) acupuncture is used clinically in prolonged disorders of consciousness (pDOC), but the cortical processes underlying its acute effects remain incompletely characterised. We used bedside functional near-infrared spectroscopy (fNIRS) with a superficial non-acupoint sham comparator to examine acute prefrontal hemodynamic responses in pDOC patients and healthy controls. Methods Forty-five pDOC patients (25 minimally conscious state; 20 unresponsive wakefulness syndrome) and 127 healthy volunteers were enrolled; 124 healthy volunteers were retained for complete-case analysis. Participants received real XNKQ acupuncture or superficial sham needling at adjacent non-acupoints. fNIRS recorded oxyhaemoglobin (HbO) across three 8-min windows: pre-acupuncture (Before), steady-state needle retention (During), and post-acupuncture (After). Regional HbO was the principal analysis; connectivity-derived network, temporal, and baseline-association analyses were exploratory. Results In healthy participants, real acupuncture produced greater HbO responses than sham across all four regions and the global prefrontal average (Cohen’s d = 0.62–1.20; all q ≤ 0.0011). In pDOC patients, the response was smaller and regionally restricted: the dorsolateral prefrontal cortex (DLPFC; d = 0.80, q = 0.0397) and global HbO ( d = 0.98, q = 0.0191) remained significant after false discovery rate (FDR) correction, whereas the frontopolar area (PFA) was borderline ( q = 0.0576), and the sensorimotor cortex and inferior frontal area (IFA) were not significant. Baseline-adjusted analyses showed the same general pattern. No connectivity-derived network contrast survived FDR correction. Baseline-to-change correlations were negative but mathematically coupled. Conclusion Real XNKQ acupuncture was associated with greater acute prefrontal HbO responses than superficial non-acupoint needling. The effect was broad in healthy participants and more restricted in pDOC patients. These findings demonstrate an acute hemodynamic response, not clinical efficacy, preserved awareness, or strict acupoint specificity. Network and baseline association findings remain exploratory. Patient protocol registration Chinese Clinical Trial Registry, https://www.chictr.org.cn , identifier ChiCTR2400090915 (registered 15 October 2024).