Functional magnetic resonance imaging studies of acupuncture at ST36: a coordinate-based meta-analysis
Zhang et al. · Frontiers in Neuroscience · 2023
Evidence Level
STRONGOBJECTIVE
Identify and map the brain regions activated by acupuncture at the ST-36 point (Zusanli) through meta-analysis of neuroimaging studies
WHO
542 healthy participants from 27 independent studies
DURATION
Analysis of studies published through August 2021
POINTS
ST-36 (Zusanli) - located 3 cm below the knee joint on the anterior aspect of the leg
🔬 Study Design
ST-36 acupuncture
n=542
Needle stimulation at the ST-36 point during functional MRI
📊 Results in numbers
Left cerebellar activation
Bilateral Rolandic operculum activation
Right supramarginal gyrus activation
Heterogeneity between studies
Number of studies included
Percentage highlights
📊 Outcome Comparison
Brain regions activated
This study scientifically demonstrates that acupuncture at the ST-36 point (located in the leg, below the knee) activates specific brain regions related to movement, perception, and pain regulation. The results provide a scientific basis for the traditional use of this point in the treatment of various health problems.
Article summary
Plain-language narrative summary
Acupuncture, the ancient Chinese practice that involves the insertion of needles at specific points on the body, has been gaining growing scientific recognition for its therapeutic benefits. Among the most commonly used points is Zusanli (ST-36), located three centimeters below the knee joint on the anterior aspect of the leg. This point is traditionally used in the treatment of various conditions, ranging from gastrointestinal problems to cognitive disorders and pain. With the development of modern neuroscience, functional magnetic resonance imaging (fMRI) has allowed researchers to observe how acupuncture affects the human brain in real time.
However, individual studies on the ST-36 point presented inconsistent results, making it difficult to understand the neural mechanisms involved in this therapy.
To clarify these issues, researchers conducted a comprehensive meta-analysis, combining data from multiple functional MRI studies on acupuncture at the ST-36 point. The objective was to create a reliable "brain map" of this acupuncture point, identifying which areas of the brain are consistently activated when ST-36 is stimulated. The researchers followed a rigorous protocol, previously registered in scientific databases, to ensure transparency and methodological quality. They performed extensive searches in multiple databases through August 2021, including studies in different languages.
The inclusion criteria were rigorous: only studies that used fMRI to investigate the effects of acupuncture on the human brain, involving exclusively healthy participants, with true (non-sham) acupuncture at the ST-36 point, and that reported precise three-dimensional brain coordinates. For analysis, they employed an advanced statistical technique called SDM-PSI (Seed-based d mapping with permutation of subject images), considered state-of-the-art in neuroimaging meta-analyses.
The analysis included 27 studies involving 542 healthy participants. The results revealed a consistent pattern of brain activation when the ST-36 point was stimulated. The main areas activated included the bilateral cerebellum (an important structure for motor coordination and cognitive functions), the bilateral Rolandic operculum (region involved in processing bodily sensations and body awareness), the right supramarginal gyrus (area related to temporal perception, attention, and memory), and specific lobes of the cerebellum. Interestingly, the analysis showed low heterogeneity between studies, indicating that these results are consistent and reliable.
There was no evidence of publication bias, strengthening the validity of the findings.
To better understand the significance of these brain activations, the researchers investigated the functional characteristics of the identified areas. They discovered that stimulation of ST-36 is mainly associated with functions related to action and perception, including motor control, cognition, learning, memory, and body awareness. The cerebellum, for example, not only coordinates movements but also participates in cognitive and emotional processing, in addition to playing an important role in visceral pain, which explains why ST-36 is traditionally used for digestive problems. The Rolandic operculum processes signals that integrate external and internal sensations, contributing to body awareness and self-perception.
The right supramarginal gyrus is involved in complex cognitive functions such as temporal perception, episodic memory, and emotion recognition.
A particularly important discovery was the distinction between brain activations related to the painful sensation of the needle versus specific therapeutic effects of acupuncture. The researchers identified that some activated areas (such as the cerebellum, insula, and superior temporal cortex) are part of the pain neural network, reflecting the physical stimulation of the needles. However, other regions (including the right inferior frontal gyrus, left superior temporal gyrus, and specific areas of the cerebellum) represent networks unrelated to pain, suggesting specific therapeutic mechanisms of acupuncture. This differentiation is crucial for understanding how acupuncture produces therapeutic benefits beyond simple sensory stimulation.
The clinical implications of these findings are promising for patients and health care professionals. The brain mapping of ST-36 provides a solid scientific basis for its therapeutic use, especially in conditions involving motor function, cognitive processes, learning and memory problems, as well as issues related to body awareness. For patients, this means greater confidence in the efficacy of acupuncture based on concrete neurobiological evidence. For professionals, these results can guide more precise and informed therapeutic decisions.
The identification of specific patterns of brain activation also paves the way for more personalized therapies, where the choice of acupuncture points can be based on specific neurological goals.
The study has important limitations that should be considered. The included studies varied in experimental design, analytical methods, and software used, although the low heterogeneity suggests that this did not significantly compromise the results. The analysis focused exclusively on healthy participants, limiting generalization to populations with specific diseases. In addition, the relatively small number of studies included requires caution when interpreting the results.
The lack of rigorous control over sham acupuncture designs also reduces the reliability of conclusions about the specificity of the effects.
This research represents a significant advance in the scientific understanding of acupuncture, providing the first comprehensive and reliable brain map of the ST-36 point. The results demonstrate that acupuncture produces specific and consistent patterns of brain activation, validating its neurobiological mechanisms. Looking ahead, these findings lay the foundation for the development of more precise and personalized acupuncture therapies. The possibility of mapping other acupuncture points using similar methodologies may eventually create a complete brain atlas of acupuncture, revolutionizing clinical practice by allowing treatments based on specific neurological targets.
Future studies should include larger samples, more rigorous designs, and investigation of clinical populations to expand and validate these promising findings.
Strengths
- 1Large combined sample of 542 participants
- 2Rigorous methodology with low heterogeneity between studies
- 3Use of advanced meta-analysis technique (SDM-PSI)
- 4Clear identification of specific neural networks vs. pain-related networks
- 5Pre-registered protocol ensuring methodological transparency
Limitations
- 1Differences in experimental designs and analytical methods between studies
- 2Included only healthy participants, limiting clinical applicability
- 3Lack of adequate control with sham acupuncture
- 4Limited number of studies for some specific analyses
- 5Variability in stimulation parameters between studies
Expert Commentary
Dr. Marcus Yu Bin Pai
MD, PhD · Pain Medicine · Physical Medicine and Rehabilitation · Medical Acupuncture
▸ Clinical Relevance
The neurofunctional characterization of ST-36 by fMRI consolidates what we have already observed empirically in practice: this point exerts influence on circuits that go far beyond local nociception. The consistent activation of the cerebellum, the bilateral Rolandic operculum, and the right supramarginal gyrus across 27 studies with 542 participants and zero heterogeneity places ST-36 at a level of neurobiological evidence that is difficult to ignore. For the physiatrist who works with motor rehabilitation, chronic visceral pain, or post-injury cognitive deficits, these findings help justify the choice of the point on neurophysiological criteria, not merely tradition. The distinction the authors make between pain-related networks and specific therapeutic networks — such as the right inferior frontal gyrus and cerebellar areas distinct from those activated by the simple needle prick — is the data point that most directly informs the decision to include ST-36 in protocols for cognitive-motor rehabilitation, irritable bowel syndrome, and multimodal management of chronic pain.
▸ Notable Findings
Zero heterogeneity across the 27 studies is the most striking methodological finding: this level of consistency is rarely seen in neuroimaging meta-analyses, a notoriously noisy field. This suggests that the ST-36 activation pattern is robust enough to survive variations in protocol, equipment, and software across laboratories. From a neurophysiological perspective, cerebellar involvement deserves special attention: its participation is not restricted to motor coordination but encompasses emotional processing, visceral integration, and cognitive modulation — which creates a coherent explanatory platform for the broad spectrum of traditional indications of the point. The identification of non-nociceptive brain networks activated by ST-36, dissociated from the response to the needle prick itself, is the most compelling argument in favor of effect specificity and opens the way to thinking of acupuncture as a neuromodulatory intervention with defined targets, analogous to the concept of transcranial electrical stimulation at functional targets.
▸ From My Experience
In my practice in the pain and rehabilitation service, ST-36 features in virtually all the protocols I design for chronic visceral pain, fibromyalgia with a cognitive component, and post-stroke rehabilitation with spasticity. I usually observe perceptible clinical response — improvement in fatigue, sleep quality, or reduction in painful episodes — from the third or fourth session onward, with a functional plateau typically between the eighth and twelfth session. From that point on, I work with monthly maintenance. I routinely combine ST-36 with supervised aerobic exercise and, when there is an evident central component, with electrical stimulation at the point itself at a frequency of 2 Hz for endorphinergic modulation. What the article formalizes in neuroimaging is what we have been seeing clinically: patients with motor dysfunction associated with pain respond differently than patients with purely nociceptive pain. I have learned to value this distinction in the history-taking to calibrate the therapeutic expectation — and now I have a substrate of brain networks to explain this to the resident.
Full original article
Read the full scientific study
Frontiers in Neuroscience · 2023
DOI: 10.3389/fnins.2023.1180434
Access original articleScientific Review

Marcus Yu Bin Pai, MD, PhD
CRM-SP: 158074 | RQE: 65523 · 65524 · 655241
PhD in Health Sciences, University of São Paulo. Board-certified in Pain Medicine, Physical Medicine and Rehabilitation, and Medical Acupuncture. Scientific review and curation of every entry in this library.
Learn more about the author →Medical disclaimer: This content is for educational purposes only and does not replace consultation, diagnosis, or treatment by a qualified professional. Some information may be assisted by artificial intelligence and is subject to inaccuracies. Always consult a physician.
Content reviewed by the medical team at CEIMEC — Integrated Centre for Chinese Medicine Studies, a reference in Medical Acupuncture for over 30 years.
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