Abstract
BACKGROUND: Acupuncture is a widely used complementary therapy; however, the central mechanisms underlying its effects, particularly how stimulation at different specific acupoints modulates brain function in distinct or common ways, remain poorly understood. This gap persists due to a lack of large-sample, systematic comparative studies under a unified experimental paradigm. Task-based and resting-state functional magnetic resonance imaging (fMRI) offer powerful tools to capture both the instant and sustained neural responses to acupuncture. METHODS: We designed a randomized, single-blind, controlled trial. To achieve high statistical power and generalizability, 250 healthy participants will be enrolled. Each participant will undergo acupuncture at one of seven predefined acupoints (verum) and its corresponding non-acupoint (sham control) in two separate sessions, with a 1-week interval. Each session includes: (1) resting-state fMRI before and after needle manipulation, and (2) task-fMRI during the manipulation. The primary outcomes are fMRI-derived brain activity and functional connectivity patterns. Blinding assessment and the Modified Massachusetts General Hospital Acupuncture Sensation Scale-Chinese version (C-MMASS) will be collected to evaluate the credibility of sham control and the Deqi sensation. DISCUSSION: This study is novel in its comprehensive approach to mapping the neural correlates of multiple acupoints within a single, rigorous design. We anticipate that our results will provide the first systematic characterization of the "acupoint-brain functional network" map, elucidating both common activation patterns across acupoints and acupoint-specific differential responses. This will significantly contribute to understanding the functional neuroanatomy of acupuncture and provide high-level evidence for its mechanism of action, ultimately helping to bridge the gap between traditional practice and modern neuroscience. CONCLUSION: The findings of this trial are expected to establish a robust empirical foundation for the neural basis of acupuncture, offering insights that could validate clinical practice and guide future target-specific acupuncture applications. CLINICAL TRIAL REGISTRATION: Identifier ITMCTR2025000066.