Brain Activities Responding to Acupuncture at ST-36 (Zusanli) in Healthy Subjects: A Systematic Review and Meta-Analysis of Task-Based fMRI Studies
Huang et al. · Frontiers in Neurology · 2022
Evidence Level
STRONGOBJECTIVE
To investigate brain activity in response to acupuncture at ST-36 (Zusanli) in healthy individuals using functional magnetic resonance imaging
WHO
401 healthy right-handed participants (199 men and 202 women)
DURATION
Studies with varying needle retention times (0.5 to 5 minutes)
POINTS
ST-36 (Zusanli) — located in the tibialis anterior muscle, four finger-widths below the inferior margin of the patella
🔬 Study Design
True acupuncture
n=401
Manual acupuncture or electroacupuncture at ST-36 with deqi sensation
Controls
n=180
Sham acupuncture, control points, or tactile stimulation
📊 Results in numbers
Activated brain regions
Right inferior frontal gyrus
Left superior temporal gyrus
Right median cingulate gyrus
📊 Outcome Comparison
Brain activation (number of voxels)
This study showed that acupuncture at ST-36 activates specific brain areas related to pain processing, language, and mood regulation. Electroacupuncture produces more extensive activations than manual acupuncture, and needle retention time influences the brain response, particularly in the olfactory cortex.
Article summary
Plain-language narrative summary
# Acupuncture at ST-36: What Neuroscience Reveals About Its Effects on the Brain
A recent high-quality scientific study investigated how acupuncture at ST-36 (known as "Zusanli") affects the brain in healthy individuals, using functional magnetic resonance imaging technology. This research represents an important advance in our scientific understanding of the neurological mechanisms of acupuncture, an ancient practice of traditional Chinese medicine that has been gaining increasing recognition in modern medicine.
ST-36 is one of the most important and widely used acupuncture points in clinical practice. Located in the leg, approximately four finger-widths below the inferior border of the patella and one finger-width lateral to the anterior border of the tibia, this point is traditionally used to strengthen the spleen and stomach, regulate the meridians, and improve overall body vitality. In contemporary medicine, acupuncture at this point has been applied for pain management, improvement of cognitive function, cerebral circulation, and regulation of gastrointestinal disorders.
The primary objective of this research was to identify and precisely map which brain regions are activated when ST-36 is stimulated by acupuncture in healthy individuals. The researchers conducted a systematic review and meta-analysis, considered the gold standard of scientific research, pooling data from sixteen independent studies that used functional magnetic resonance imaging to observe brain activity during acupuncture sessions. This methodology allows combining results from multiple studies, increasing the reliability of conclusions and providing a more comprehensive view of the neurological effects of acupuncture.
In total, data from 401 healthy right-handed participants were analyzed, including 199 men and 202 women, from studies conducted in different countries including the United States, China, Korea, and Germany. The researchers used an advanced technique called seed-based d mapping with permutation of subject images, which allows identifying with high statistical precision which brain areas show greater activity during acupuncture stimulation. Additionally, subgroup analyses were performed to compare the effects of traditional manual acupuncture with electroacupuncture, as well as analyses to understand how needle retention time influences brain activity.
The results revealed that acupuncture at ST-36 consistently activates three main brain regions. The first is the opercular part of the right inferior frontal gyrus, an area involved in language processing and communication. The second activated region is the left superior temporal gyrus, fundamental for auditory processing and language comprehension. The third area corresponds to the right median cingulate gyrus, an important region for emotional processing and mood regulation.
Interestingly, the researchers found that needle retention time during the acupuncture session has a positive correlation with activation of the left olfactory cortex, suggesting that longer sessions may have specific neurological effects related to olfactory processing.
The subgroup analyses revealed important differences between stimulation modalities. Electroacupuncture, which combines traditional needles with low-intensity electrical stimulation, was shown to activate more extensive brain areas compared to traditional manual acupuncture. Specifically, electroacupuncture activated additional regions such as the left medial orbital superior frontal gyrus, right superior temporal gyrus, and left anterior thalamic projections. This finding suggests that different acupuncture techniques may have distinct neurological mechanisms, which has important implications for treatment personalization.
To better understand the functional significance of these brain activations, the researchers mapped the identified regions onto large-scale neural networks. The results showed that the areas activated by acupuncture at ST-36 belong primarily to the auditory network, anterior salience network, and posterior salience network. Using functional decoding techniques, it was possible to determine that these regions are associated with pain processing, secondary somatosensory stimulation, auditory and speech processing, and mood regulation. These findings provide a solid neurological basis for the therapeutic effects traditionally attributed to acupuncture at ST-36.
The clinical implications of these findings are significant for both patients and healthcare providers. For patients considering acupuncture as a therapeutic option, this study provides robust scientific evidence that acupuncture produces measurable and specific neurological effects in the brain. This is particularly relevant for the treatment of pain-related conditions, language disorders, and mood disturbances — areas where the identified brain regions play crucial roles. The finding that different acupuncture techniques activate different neural patterns also suggests that treatments can be optimized according to the specific needs of each patient.
For healthcare providers, these results offer valuable insights into the mechanisms of action of acupuncture, aiding evidence-based clinical decision-making. The identification of specific neural networks activated by acupuncture may help explain why this therapy is effective for certain conditions and guide the development of more precise treatment protocols. Furthermore, the understanding that needle retention time influences brain activity may lead to optimizations in treatment parameters.
It is important to acknowledge the limitations of this study for appropriate interpretation of the results. The relatively small number of included studies and total participants represents a methodological limitation. In addition, the research could not adequately assess the effects of the deqi sensation — that specific sensation of heaviness, tingling, or propagation that patients frequently report during acupuncture and which is considered fundamental to therapeutic efficacy in traditional Chinese medicine. The lack of standardized tools to quantify this sensation across the different studies made a more precise analysis of this aspect difficult.
Another important consideration is that the included studies were conducted over an extensive period during which neuroimaging techniques and analysis software evolved significantly, which may have introduced variability in the results. Additionally, although the study focused on healthy individuals to establish the basic neurological effects of acupuncture, the results may differ in populations with specific clinical conditions.
In conclusion, this study represents an important milestone in the scientific understanding of the neurological mechanisms of acupuncture. The results demonstrate that acupuncture at ST-36 produces consistent and specific brain activations in regions associated with pain processing, language, and emotional regulation. These findings not only scientifically validate the neurological effects of acupuncture but also open pathways for more precise and personalized clinical applications. For patients and professionals interested
Strengths
- 1First meta-analysis with a large sample (401 participants) of fMRI studies of ST-36
- 2Robust analysis using advanced brain mapping techniques (SDM-PSI)
- 3Consistent identification of three main activated brain regions
- 4Subgroup analysis comparing manual acupuncture vs. electroacupuncture
- 5Mapping onto large-scale functional brain networks
Limitations
- 1Heterogeneity in stimulation techniques across studies
- 2Lack of standardization in assessment of the deqi sensation
- 3Relatively small number of included studies (16 studies)
- 4Different software and neuroimaging processing techniques
- 5Possible bias due to the use of the same subjects for different stimulations
Expert Commentary
Prof. Dr. Hong Jin Pai
PhD in Sciences, University of São Paulo
▸ Clinical Relevance
The ability to precisely map brain responses to ST-36 stimulation represents a concrete advance for clinical acupuncture practice. By demonstrating that needling this point consistently recruits the right inferior frontal gyrus, left superior temporal gyrus, and right median cingulate gyrus — regions linked to pain processing, sensory integration, and emotional regulation — the meta-analysis provides a neurobiological substrate for clinical decisions that previously relied exclusively on tradition and accumulated experience. In practice, this guides the selection of ST-36 in scenarios such as chronic musculoskeletal pain, mood disorders with somatic components, and functional gastrointestinal disorders. The distinction between electroacupuncture and manual acupuncture — with the former producing more extensive activations, including thalamic projections and orbital frontal regions — has direct implications for choosing the modality according to the therapeutic objective of the case, making acupuncture prescription more rational and grounded in neuroscience.
▸ Notable Findings
The most striking finding of this meta-analysis is the consistency of the three activated regions across 401 participants distributed across 16 international studies, with robust statistical significance levels. The recruitment of the right median cingulate gyrus is particularly revealing: this structure integrates affective processing and pain modulation, offering a plausible explanation for the analgesic and anxiolytic effects clinically attributed to ST-36. Equally noteworthy is the positive correlation between needle retention time and activation of the left olfactory cortex — a finding that opens perspectives on how technical parameters influence specific brain circuits. The subgroup analysis revealing that electroacupuncture additionally accesses the anterior thalamus and orbital frontal regions suggests differentiated mechanisms of action between modalities, something that classical meridian theory could never anticipate, but that neuroimaging now allows us to discriminate empirically.
▸ From My Experience
In my practice at the Pain Center of HC-FMUSP, ST-36 is one of the three or four points I most use in multipoint protocols for chronic pain and functional gastrointestinal disorders. What strikes me about this meta-analysis is the correspondence between what we observe clinically and the neural substrate identified: patients with pain of predominantly affective character — that profile with high catastrophizing scores — respond to ST-36 in a particularly consistent way, which makes sense given the involvement of the cingulate. In terms of response speed, I typically perceive the first changes between the third and fifth session; for maintenance in chronic pain, we usually work with 10 to 12 initial sessions, with subsequent reassessment. We routinely combine ST-36 with local and distal points according to the diagnostic pattern, and we frequently incorporate electroacupuncture precisely in cases where we seek greater central modulation — which this meta-analysis now justifies with neuroimaging data. Patients with comorbid anxiety and irritable bowel syndrome form the group that, in my experience, presents the best response-per-session ratio with this point.
Full original article
Read the full scientific study
Frontiers in Neurology · 2022
DOI: 10.3389/fneur.2022.930753
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.
Related articles
Based on this article’s categories