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LR3-LI4 needling side and configuration are associated with phase-specific cortical activation and network organization: a functional near-infrared spectroscopy study in healthy adults.

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Title: LR3-LI4 needling side and configuration are associated with phase-specific cortical activation and network organization: a functional near-infrared spectroscopy study in healthy adults.
Authors: Xie Y; The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.; The Fifth Clinical College of Guangzhou Medical University, Guangzhou, China., Ouyang H; The Fifth Clinical College of Guangzhou Medical University, Guangzhou, China., Zhang X; The Fifth Clinical College of Guangzhou Medical University, Guangzhou, China., Zheng X; The Fifth Clinical College of Guangzhou Medical University, Guangzhou, China., Liang H; The Fifth Clinical College of Guangzhou Medical University, Guangzhou, China., Fu W; The Second Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.; Department of Acupuncture, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Source: Frontiers in neurology [Front Neurol] 2026 Aug 13; Vol. 17, pp. 1815369. Date of Electronic Publication: 2026 Aug 13 (Print Publication: 2026).
Publication Type: Journal Article; Randomized Controlled Trial
Language: English
Journal Info: Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101546899 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-2295 (Electronic) Linking ISSN: 16642295 NLM ISO Abbreviation: Front Neurol Subsets: MEDLINE
Imprint Name(s): Original Publication: [Lausanne : Frontiers Research Foundation, 2010]-
MeSH Terms: Acupuncture Therapy*/methods , Cerebral Cortex*/physiology , Cerebral Cortex*/diagnostic imaging , Functional Laterality*/physiology , Nerve Net*/physiology , Nerve Net*/diagnostic imaging , Acupuncture Points*, Dorsolateral Prefrontal Cortex/diagnostic imaging ; Dorsolateral Prefrontal Cortex/physiology ; Somatosensory Cortex/physiology ; Somatosensory Cortex/diagnostic imaging ; Adult ; Female ; Humans ; Male ; Young Adult ; Spectroscopy, Near-Infrared
Abstract: Background: Whether dominant-side, non-dominant-side, or bilateral acupuncture produces comparable cortical activation remains unresolved. This study compared phase-specific cortical hemodynamic responses across these configurations at LR3-LI4 using functional near-infrared spectroscopy (fNIRS).
Methods: In total, 53 healthy right-handed adults were randomized to dominant-side acupuncture (DS, n = 13), bilateral (BI, n = 15), non-dominant-side stimulation (NDS, n = 14), or sham (SH, n = 11). Cortical activity was measured across bilateral prefrontal, motor, and somatosensory regions during baseline, needle retention, and post-removal sessions. Functional connectivity and graph-theoretic metrics were analyzed as complementary network-level outcomes.
Results: During retention, DS showed greater left dorsolateral prefrontal cortex (DLPFC) and frontopolar area oxygenated hemoglobin (FPA HbO) activation than BI (DLPFC: mean difference = 0.110, 95% CI 0.036 to 0.184, p = 0.005; FPA: 0.146, 95% CI 0.044 to 0.248, p = 0.007) and SH (DLPFC: 0.070, p = 0.040; FPA: 0.114, p = 0.034). NDS showed limited prefrontal effects but greater right S1 activation than BI (mean difference = 0.179, 95% CI 0.079 to 0.279, p < 0.001). BI exhibited biphasic somatosensory responses, with initial right S1 deactivation during retention (t = -2.944, p = 0.010) followed by post-removal rebound (t = 3.188, p = 0.006). Functional connectivity analysis suggested configuration-specific associative patterns: DS showed dynamic frontoparietal-somatosensory coupling, BI showed delayed frontoparietal-motor connectivity enhancement, and NDS showed delayed cross-hemispheric sensorimotor coupling. All active groups showed enhanced bilateral FPA and right DLPFC-FPA connectivity compared with SH post-removal (F = 3.207, p = 0.031; F = 3.189, p = 0.031). Graph analysis further indicated phase-related network reorganization, with significant effects for global efficiency (FDR p = 0.021) and clustering coefficient (FDR p = 0.024).
Conclusion: In healthy right-handed adults, LR3-LI4 needling configuration was associated with distinct phase-specific cortical response patterns. DS was associated with greater retention-phase prefrontal HbO activation than BI; NDS showed a more somatosensory-dominant pattern, and BI showed attenuated retention-phase responses followed by post-removal network changes. These findings provide short-term neurophysiological evidence that the needling side may influence cortical responses, but they do not establish clinical superiority. Patient-based studies are needed to determine whether these cortical signatures predict therapeutic outcomes.
(Copyright © 2026 Xie, Ouyang, Zhang, Zheng, Liang and Fu.)
Competing Interests: The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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Contributed Indexing: Keywords: LR3-LI4; acupuncture; cortical activation; dominant-side needling; functional connectivity; functional near-infrared spectroscopy; laterality
Entry Date(s): Date Created: 20260828 Date Completed: 20260828 Latest Revision: 20260911
Update Code: 20260911
PubMed Central ID: PMC13518510
DOI: 10.3389/fneur.2026.1815369
PMID: 42661774
Database: MEDLINE
Description
ISSN:1664-2295
DOI:10.3389/fneur.2026.1815369