Neural Biomarkers for Identifying Atopic Dermatitis and Assessing Acupuncture Treatment Response Using Resting-State fMRI.

Purpose: Only a few studies have focused on the brain mechanisms underlying the itch processing in AD patients, and a neural biomarker has never been studied in AD patients. We aimed to develop a deep learning model-based neural signature which can extract the relevant temporal dynamics, discriminate between AD and healthy control (HC), and between AD patients who responded well to acupuncture treatment and those who did not. Patients and Methods: We recruited 41 AD patients (22 male, age mean ± SD: 24.34 ± 5.29) and 40 HCs (20 male, age mean ± SD: 26.4 ± 5.32), and measured resting-state functional MRI signals. After preprocessing, 38 functional regions of interest were applied to the functional MRI signals. A long short-term memory (LSTM) was used to extract the relevant temporal dynamics for classification and train the prediction model. Bootstrapping and 4-fold cross-validation were used to examine the significance of the models. Results: For the identification of AD patients and HC, we found that the supplementary motor area (SMA), posterior cingulate cortex (PCC), temporal pole, precuneus, and dorsolateral prefrontal cortex showed significantly greater prediction accuracy than the chance level. For the identification of high and low responder to acupuncture treatment, we found that the lingual-parahippocampal-fusiform gyrus, SMA, frontal gyrus, PCC and precuneus, paracentral lobule, and primary motor and somatosensory cortex showed significantly greater prediction accuracy than the chance level. Conclusion: We developed and evaluated a deep learning model-based neural biomarker that can distinguish between AD and HC as well as between AD patients who respond well and those who respond less to acupuncture. Using the intrinsic neurological abnormalities, it is possible to diagnose AD patients and provide personalized treatment regimens.

Using the right design controls for acupuncture trials: Methodological rigor and validity in research.

Acupuncture treatment can be defined as a medical procedure with an acupuncture needle at acupoints. Establishing suitable control settings is essential, based on the target elements of the acupuncture therapy. In order to properly design a clinical trial or an experiment, a control group must be established. Here, we overview the significance of the control group and its limitations in acupuncture research. Clinical trials have employed a variety of study designs and controls for acupuncture treatment in order to compare the effects of actual treatments with control groups that include no treatment or treatment as usual, sham acupuncture at true acupoints, real acupuncture at non-acupoints, and sham acupuncture at non-acupoints. In order to determine the point-specificity of acupuncture, real acupuncture at non-acupoints should be taken into consideration, whereas sham acupuncture at the same true acupoints should be used to determine the needling-specific effect of acupuncture. It is crucial to choose the optimum control for acupuncture treatments depending on the study's main goal and to interpret the results in accordance with the research design.

Graded brain fMRI response to somatic and visual acupuncture stimulation.

Increased stimulation can enhance acupuncture clinical response; however, the impact of acupuncture stimulation as "dosage" has rarely been studied. Furthermore, acupuncture can include both somatic and visual components. We assessed both somatic and visual acupuncture dosage effects on sensory ratings and brain response. Twenty-four healthy participants received somatic (needle inserted, manually stimulated) and visual (needle video, no manual stimulation) acupuncture over the leg at three different dosage levels (control, low-dose, and high-dose) during functional magnetic resonance imaging (fMRI). Participants reported the perceived deqi sensation for each acupuncture dose level. Blood-oxygen-level dependent imaging data were analyzed by general linear model and multivariate pattern analysis. For both somatic and visual acupuncture, reported deqi sensation increased with increased dosage of acupuncture stimulation. Brain fMRI analysis demonstrated that higher dosage of somatic acupuncture produced greater brain responses in sensorimotor processing areas, including anterior and posterior insula and secondary somatosensory cortex. For visual acupuncture, higher dosage of stimulation produced greater brain responses in visual-processing areas, including the middle temporal visual areas (V5/MT+) and occipital cortex. Psychophysical and psychophysiological responses to both somatic and visual acupuncture were graded in response to higher doses. Our findings suggest that acupuncture response may be enhanced by the dosage of needling-specific and nonspecific components, represented by different neural mechanisms.

Acupuncture treatment for functional gastrointestinal disorders: Identification of major acupoints using network analysis.

Background: Using network analysis, we sought to determine the acupoints most commonly used to treat functional gastrointestinal disorders (FGIDs), particularly functional dyspepsia (FD) and irritable bowel syndrome (IBS). Methods: To explore the acupoint patterns used for FGID, data on acupoint combinations for FD and IBS were gathered from systematic reviews. Network analysis was used to determine the degree, closeness centrality, betweenness centrality, and eigenvector centrality of each acupoint. The most common acupoint combinations for FD and IBS were examined based on the eigenvector centrality. Results: Network analysis revealed that CV12, ST25, ST36, CV10, and LR3, which had the highest eigenvector centrality values, were the main acupoints for treating FGID. CV12 was the main acupoint for treating FD, while ST25 was the hub acupoint for treating IBS in the abdomen. ST36, LR3, and PC6 were the key peripheral acupoints for FD and IBS. Conclusions: Using network analysis, we provided data that will aid the selection of both general and specific acupoints for FD and IBS, along with spatial information (i.e., the positions of acupoints on a body map). These findings could be applied in future acupuncture research on therapy for gastrointestinal system dysfunction. They may also help bridge the gap between the traditional meridian theory, which assumes that there is a link between diseases/symptoms and the specific body region being treated, and real-world clinical evidence.

Sensory and emotional responses to deep pressure stimulation at myofascial trigger points: a pilot study.

Objective: Although manual pressure, such as that used during a massage, is often associated with pain, it can simultaneously be perceived as pleasant when applied to certain body areas. We hypothesized that stimulation of myofascial trigger points (TPs) leads to simultaneous pain and pleasure. TPs are hyperirritable points located in the taut band of the skeletal muscle. Method: In this study, we measured the muscle tone, muscle stiffness, and pressure pain threshold of TPs and control points in the left brachioradialis muscle of 48 healthy participants. We also applied deep compression to the two points and collected subjective data on pain, pleasantness, unpleasantness, and relief. Result: Greater muscle stiffness was observed in the TPs versus control points (t = 6.55, p < 0.001), and the pain threshold was significantly lower in the TPs (t = -6.21, p < 0.001). Unpleasantness ratings after deep compression were significantly lower in the TPs compared with control points (t = -2.68, p < 0.05). Participants experienced greater relief at the TPs compared with control points (t = 2.01, p < 0.05), although the perceived pain did not differ between the two types of points. Conclusion: We compared the properties of TPs and control points, and found that deep compression at TPs was associated with higher muscle tone and stiffness, lower unpleasantness ratings, and higher relief ratings compared with the control points. These findings suggest that, at least for some TPs, pain and pleasantness are simultaneously elicited by deep pressure stimulation.

Central Regulation of Eating Behaviors in Humans: Evidence from Functional Neuroimaging Studies.

Neuroimaging has great potential to provide insight into the neural response to food stimuli. Remarkable advances have been made in understanding the neural activity underlying food perception, not only in normal eating but also in obesity, eating disorders, and disorders of gut-brain interaction in recent decades. In addition to the abnormal brain function in patients with eating disorders compared to healthy controls, new therapies, such as neurofeedback and neurostimulation techniques, have been developed that target the malfunctioning brain regions in patients with eating disorders based on the results of neuroimaging studies. In this review, we present an overview of early and more recent research on the central processing and regulation of eating behavior in healthy and patient populations. In order to better understand the relationship between the gut and the brain as well as the neural mechanisms underlying abnormal ingestive behaviors, we also provide suggestions for future directions to enhance our current methods used in food-related neuroimaging studies.

A prospective observational study of optimal acupoint selection on patients with functional gastrointestinal disorders.

INTRODUCTION: Functional gastrointestinal disorders (FGIDs), which include irritable bowel syndrome (IBS) and functional dyspepsia (FD), are common gastrointestinal (GI) diseases that have a large financial impact on patients' quality of life (QoL). Traditional Korean medicine has a particular diagnostic pattern for treating FGIDs. However, FGIDs have not been thoroughly explored because of their complexity. In this proposed study, we will investigate the acupoint selection pattern for FGID patients with various disease patterns, and further determine the best acupoints for treating FGID patients using a machine-learning algorithm. METHODS: We will collect clinical data from 15 multi-center Korean medical clinics that treat FGID as part of an observational study registry. Patients who meet the criteria will be added to the registry after screening. They will receive a maximum 4-week treatment, and they will respond 3 times to a series of questions. We will investigate how doctors of FGID patients with diverse disease patterns choose the acupoints, and we will use a machine learning technique to identify the best acupoints for treating FGID patients. DISCUSSION: This will be the first multi-center observational registry study to assess how traditional Korean medical practitioners diagnose and treat patients in the real world. The findings will shed light on how traditional Korean medicine treats FGIDs and demonstrate the rationale for the diagnostic and acupuncture treatment flow.

ACURATE: a Guide for Reporting Sham Controls in Trials Using Acupuncture.

This paper presents the Acupuncture Controls gUideline for Reporting humAn Trials and Experiments (ACURATE) checklist, an extension of The Consolidated Standards for Reporting of Trials (CONSORT), which is to be used with STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) when real and sham acupuncture needles are used in a study. This checklist focuses on a clear depiction of sham needling procedures to enhance replicability and enable a precise appraisal. We encourage researchers to use ACURATE in trials and reviews involving sham acupuncture to assist in the reporting of sham acupuncture procedures and related components.

ACURATE: A guide for reporting sham controls in trials using acupuncture.

This paper presents the Acupuncture Controls gUideline for Reporting humAn Trials and Experiments (ACURATE) checklist, an extension of The Consolidated Standards for Reporting of Trials (CONSORT) and to be used along with STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) when both real and sham acupuncture needles are used in the study. This checklist focuses on a clear depiction of sham needling procedures to enhance replicability and enable a precise appraisal. We encourage researchers to use ACURATE in trials and reviews involving sham acupuncture to assist reporting of sham acupuncture procedures and the related components.

ACURATE: A guide for reporting sham controls in trials using acupuncture.

OBJECTIVE: To promote better reporting quality regarding sham acupuncture in clinical trials for a precise appraisal of the adequacy of the sham acupuncture procedure. METHODS: A three-stage online Delphi survey was conducted to a group of experts. Items with higher than 80% consensus from the initial checklist were selected as the final candidates. Further discussion among the working group was convened to preclude potential redundancy among the items. RESULTS: A total of 23 experts out of 35 (66%) responded to the Delphi process. The final checklist consists of 23 items in six categories: type of sham acupuncture, details of sham acupuncture manipulation, location of sham acupuncture, treatment regimen, practitioner, and protocol and settings. CONCLUSION: This paper presents the Acupuncture Controls gUideline for Reporting humAn Trials and Experiments (ACURATE) checklist, an extension of The Consolidated Standards for Reporting of Trials (CONSORT) and to be used along with STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) when sham acupuncture needles are used in the study. This checklist focuses on a clear depiction of sham needling procedures to enhance replicability and enable a precise appraisal. We encourage researchers to use ACURATE in trials and reviews involving sham acupuncture to assist reporting sham acupuncture procedures and the related components.

Acupuncture and Acupoints for Low Back Pain: Systematic Review and Meta-Analysis.

Acupuncture has been used as a therapeutic intervention for the treatment of numerous diseases and symptoms for thousands of years, and low back pain has been studied and treated the most in acupuncture clinics. Traditional theory strongly suggests that the selection of acupoints will influence their clinical effects and combinations (e.g., the clinical effects of a particular acupoint or combination on reducing pain), but this idea was not considered in earlier systematic reviews and meta-analyses. We performed a systematic review, meta-analysis, and network analysis to evaluate the magnitude of the effects of acupoints used to treat low back pain in randomized controlled clinical trials. We found that acupuncture significantly reduced pain in patients with low back pain compared with the control group. The most frequently prescribed acupoints were BL23, GV3, BL20, BL40, and BL25, whereas the acupoints with the highest average effect size scores were BL20, GV3, GB30, GB34, and BL25. Further, the combinations of BL23-BL40, BL23-B25, and BL23-BL60 were the most frequently prescribed, while BL23-GV3, BL40-GV4, and BL23-BL25 showed the largest average effect size. By calculating clinical outcomes based on average effect sizes, we found that the most popular acupoints might not always be associated with the best results. Although a more thorough investigation is necessary to determine the clinical effects of each acupoint and combination on patients, we suggest that our approach may offer a fresh perspective that will be useful for future research.

Enhanced Empathic Pain by Facial Feedback.

The facial feedback hypothesis states that feedback from cutaneous and muscular afferents affects our emotion. Based on the facial feedback hypothesis, the purpose of this study was to determine whether enhancing negative emotion by activating a facial muscle (corrugator supercilii) increases the intensity of cognitive and emotional components of empathic pain. We also assessed whether the muscle contraction changed the pupil size, which would indicate a higher level of arousal. Forty-eight individuals completed 40 muscular contraction and relaxation trials while looking at images of five male and five female patients with neutral and painful facial expressions, respectively. Participants were asked to rate (1) how much pain the patient was in, and (2) how unpleasant their own feelings were. We also examined their facial muscle activities and changes in pupil size. No significant differences in pain or unpleasantness ratings were detected for the neutral face between the two conditions; however, the pain and unpleasantness ratings for the painful face were considerably higher in the contraction than relaxation condition. The pupils were considerably larger in the contraction than relaxation condition for both the painful and neutral faces. Our findings indicate that, by strengthening the corrugator supercilii, facial feedback can affect both the cognitive evaluative and affective sharing aspects of empathic pain.

Comparison of the acupuncture manipulation properties of traditional East Asian medicine and Western medical acupuncture.

Background: Acupuncture treatments frequently use manipulation techniques. The therapeutic advantages of acupuncture differ depending on the acupuncture manipulation. The purpose of this article was to compare manipulation techniques in traditional East Asian medicine (TEAM) and Western medical acupuncture (WMA). Methods: Manipulation techniques in TEAM and WMA were compared according to purpose, modulating parameters, and indications. The practical understanding of manipulation in terms of acupuncture stimulation intensity was also explored. The TEAM manipulation techniques of twirling and lifting and thrusting are discussed in terms of the objectives of tonification and sedation. Results: The main therapeutic effect of WMA is mediated through activation of the nervous system, which is achieved with adequate intensity of needling. The TEAM tonification and sedation techniques were designed to produce mild or intense stimulation, respectively, to elicit varying degrees of deqi sensation. Conclusions: Further research is needed to clarify the differences between the TEAM and WMA practices, and to determine whether different needling manipulations affect treatment outcomes.

Similarities between Ashi acupoints and myofascial trigger points: Exploring the relationship between body surface treatment points.

Although acupuncture points and myofascial trigger points (TPs) are based in different medical fields, the two points share important attributes. We explored the relationship between acupuncture points and TPs based on their characteristics and the results of previous studies. We outlined the relationship between acupuncture points and TPs by examining their similarities and differences. Among the acupuncture point subgroups, TPs mostly corresponded to Ashi points. Based on the common features of TPs and Ashi points, we suggest that TPs are more closely related to Ashi points than to other acupoints. However, TPs also share some features, such as pain indication and location, with classical acupuncture points (CA) and extra acupuncture points (EA), which makes it difficult to elucidate their relationship with other subgroups. Therefore, we suggest to understand the relationship of CAs, EAs, Ashi points, and TPs. In this report, we concluded that concerning muscular pain symptoms Ashi points and TPs are indistinguishable.

The role of visual expectations in acupuncture analgesia: A quantitative electroencephalography study.

Acupuncture is a complex treatment comprising multisensory stimulation, including visual and tactile sensations and experiences of body ownership. The purpose of this study was to investigate the role of these three components of acupuncture stimulation in acupuncture analgesia. 40 healthy volunteers participated in the study and received acupuncture treatment under three different conditions (real-hand, rubber-hand synchronous, and rubber-hand asynchronous). The tolerance for heat pain stimuli was measured before and after treatment. Brain oscillation changes were also measured using electroencephalography (EEG). The pain tolerance was significantly increased after acupuncture treatment under all three conditions. Noticeable deqi (needle) sensations in response to acupuncture stimulation of the rubber hand were found under both rubber-hand synchronous and rubber-hand asynchronous conditions. Deqi sensations were significantly correlated with acupuncture analgesia only under the rubber-hand synchronous condition. Increased delta and decreased theta, alpha, beta, and gamma waves were observed after acupuncture treatment under all three conditions. Our findings clarified the role of cognitive components of acupuncture treatment in acupuncture analgesia through the rubber-hand illusion. This study is a first step toward separating various components of acupuncture analgesia, i.e. visual, tactile, and body ownership, and utilizing those components to maximize analgesic effects.

Pain modalities in the body and brain: Current knowledge and future perspectives.

Development and validation of pain biomarkers has become a major issue in pain research. Recent advances in multimodal data acquisition have allowed researchers to gather multivariate and multilevel whole-body measurements in patients with pain conditions, and data analysis techniques such as machine learning have led to novel findings in neural biomarkers for pain. Most studies have focused on the development of a biomarker to predict the severity of pain with high precision and high specificity, however, a similar approach to discriminate different modalities of pain is lacking. Identification of more accurate and specific pain biomarkers will require an in-depth understanding of the modality specificity of pain. In this review, we summarize early and recent findings on the modality specificity of pain in the brain, with a focus on distinct neural activity patterns between chronic clinical and acute experimental pain, direct, social, and vicarious pain, and somatic and visceral pain. We also suggest future directions to improve our current strategy of pain management using our knowledge of modality-specific aspects of pain.

Exploring Acupuncture Actions in the Body and Brain.

Acupuncture's actions have been explained by biomedical research. However, the meridian system used in acupuncture needs further clarification. This review describes how acupuncture affects the body and brain. From the perspective of traditional East Asian medicine, the meridian system is closely connected with acupuncture's treatment effects. In the body, the indications of acupoints, primarily established based on the meridian system, have spatial symptom patterns. Spatial patterns of acupoint indications are distant from the stimulated sites and strongly associated with the corresponding meridian's route. Understanding how acupuncture works based on the original meridian system is important. From a neuroscience perspective, an acupuncture-induced sensation originates from the bottom-up action of simple needling in the peripheral receptor and the reciprocal interaction with top-down brain modulation. In the brain, enhanced bodily attention triggered by acupuncture stimulation can activate the salience network and deactivate the default mode network regardless of the actual stimulation. The application of data science technology to acupuncture research may provide new tools to uncover the principles of acupoint selection and enhance the clinical efficacy of acupuncture treatment in various diseases.

Reporting quality of sham needles used as controls in acupuncture trials: a methodological evaluation.

OBJECTIVE: The description of controls is important in acupuncture clinical trials to interpret its effectiveness without fallacy. This paper aims to evaluate the reporting quality of acupuncture studies on the characteristics of sham needles. STUDY DESIGN AND SETTING: Using a checklist developed from previously published reporting guidelines, the distribution of reported items and changes of reporting rates over time were investigated. Two-way ANOVA and linear regression were conducted. RESULTS: Original articles of RCTs of any design involving sham needles as controls were eligible for assessment. 117 trials from three 2-year time periods between 2009 and 2018 were included. Seven items out of 25 were reported in more than 50% of the studies. While significant differences of reporting scores among categories were observed, there were no significant differences among time periods; no significant improvement was observed over time. CONCLUSIONS: Low reporting qualities of sham needles used in acupuncture studies may influence how researchers understand the effectiveness of acupuncture. This study evaluated previous publications from 2009 to 2018 and found that reporting qualities on sham needles did not improve over time. Further studies are required to validate the items used in this study to endorse better reporting of controls in acupuncture trials.