Neurobiological correlates of acupuncture: November 17-18, 2005

The "Neurobiological Correlates of Acupuncture" Conference was convened November 17-18, 2005 in Bethesda, Maryland. The conference was sponsored by the National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (NIH), U.S. Department of Health and Human Services (DHHS). Its goals were to encourage exchange of ideas regarding the direction of neuroimaging in acupuncture research as well as to discuss some of the challenges in this field. The use of neuroimaging, a relatively recent advance in the study of acupuncture, holds the promise of localizing and characterizing brain activity associated with acupuncture interventions in real time and in a minimally invasive way. Among the main challenges to research into the biological mechanisms of acupuncture are the multiple treatment variables and the difficulties of selecting appropriate experimental controls. Despite these challenges, numerous findings from acupuncture neuroimaging experiments were presented and discussed at the conference on topics related to possible signaling networks, sham acupuncture controls, acupoint specificity, acupuncture analgesia, acupuncture-associated brain response, and the potential for using neuroimaging in conjunction with translational and clinical acupuncture research. Future directions in acupuncture neuroimaging research, as recommended by conference participants, should focus on (1) continuing exploration of acupuncture signaling networks; (2) establishing standards and recommendations for performing and reporting acupuncture neuroimaging results; (3) enabling data sharing in the acupuncture neuroimaging community; (4) gaining a better understanding of placebo and control groups in acupuncture neuroimaging experiments; and (5) developing biomarkers that relate to physiologically and/or clinically relevant acupuncture responses to neuroimaging results.     

基于fMRI任务态与静息态对头针疗法的研究进展

头针疗法是针灸体系的重要组成部分且广泛应用于临床,但是有关其作用原理研究的文献却不足以完全阐明头针机理,并指导其发展方向.功能磁共振成像技术因其独特优势,成为穴位针刺脑部中枢效应机制研究的首选方法.通过阅读分析相关文献及该领域整体研究趋势,发现应用功能磁共振成像技术对头针疗法进行研究主要集中在特异性脑区激活、针刺作用机...     

Current status of neuroimaging research on the effects of acupuncture: a bibliometric and visual analyses

ObjectiveTo conduct an inductive analysis of neuroimaging studies following the global popularity surrounding the effects of acupuncture.MethodsThe relevant works of literature on acupuncture effects-related neuroimaging studies were retrieved from the web of science core collection database from the date of its establishment to 2022. Bibexcel software was used to extract information, such as article numbers, countries, journals, agencies, funding sources and keywords. The VOSviewer software’s co-occurrence and clustering module was used for the co-occurrence and cluster analysis of collaborative networks and high frequency keywords, such as authors, institutions and countries.ResultsNeuroimaging research on the effects of acupuncture began in the 1960 s and has since received the extensive attention of scholars. China, The United States and South Korea conduct more neuroimaging research on the effects of acupuncture than other countries. Academic journals such as Evidence-Based Complementary and Alternative Medicine, Journal of Alternative and Complementary Medicine, Neural Regeneration Research and Acupuncture in Medicine have published the highest number of acupuncture-related neuroimaging articles. Moreover, cluster analysis differentiates high-frequency keywords into six clusters. Furthermore, the use of the keyword ‘density atlas’ reveals that neuroimaging research on the effects of acupuncture surrounding pain and neurofunctional rehabilitation is currently the research focus.ConclusionsThis bibliometric study identifies six important research hot spots: Static brain functional connectivity analysis of acupuncture analgesic effects, key theories on the scientific problems of acupuncture, acupuncture analgesic effect of the placebo effect, the neuroimaging of acupoint ST-36, the value of acupuncture in regulating the autonomic nerves and acupuncture therapy as complementary medicine.     

Inserting Needles Into the Body: A Meta-Analysis of Brain Activity Associated With Acupuncture Needle Stimulation

Acupuncture is a therapeutic treatment that is defined as the insertion of needles into the body at specific points (ie, acupoints). Advances in functional neuroimaging have made it possible to study brain responses to acupuncture; however, previous studies have mainly concentrated on acupoint specificity. We wanted to focus on the functional brain responses that occur because of needle insertion into the body. An activation likelihood estimation meta-analysis was carried out to investigate common characteristics of brain responses to acupuncture needle stimulation compared to tactile stimulation. A total of 28 functional magnetic resonance imaging studies, which consisted of 51 acupuncture and 10 tactile stimulation experiments, were selected for the meta-analysis. Following acupuncture needle stimulation, activation in the sensorimotor cortical network, including the insula, thalamus, anterior cingulate cortex, and primary and secondary somatosensory cortices, and deactivation in the limbic-paralimbic neocortical network, including the medial prefrontal cortex, caudate, amygdala, posterior cingulate cortex, and parahippocampus, were detected and assessed. Following control tactile stimulation, weaker patterns of brain responses were detected in areas similar to those stated above. The activation and deactivation patterns following acupuncture stimulation suggest that the hemodynamic responses in the brain simultaneously reflect the sensory, cognitive, and affective dimensions of pain.PerspectiveThis article facilitates a better understanding of acupuncture needle stimulation and its effects on specific activity changes in different brain regions as well as its relationship to the multiple dimensions of pain. Future studies can build on this meta-analysis and will help to elucidate the clinically relevant therapeutic effects of acupuncture.     

Changes in FMRI in the human brain related to different durations of manual acupuncture needling

OBJECTIVES: The present study is aimed at evaluating the effects of manual acupuncture with different durations on the human brain using functional magnetic resonance imaging. MATERIALS AND METHODS: Eighteen healthy right-handed volunteers were divided into three groups randomly. Each group received only one kind of acupuncture on the right LI4 (Hegu) point, which lasted 30 sec, 60 sec, or 180 sec, respectively. Fix-effect and conjunction analysis were used to compare the effects of the three kinds of acupunctures. RESULTS: The results indicated that the stimulation of manual acupuncture with different durations could induce different effects in the central nervous system on the human brain. The longer duration of manual acupuncture might induce more significant areas. CONCLUSIONS: The present study provided not only neuroimaging evidence for manual acupuncture, but also a useful guide for clinical applications of acupuncture. In addition, the results might be helpful to understand the relationship between the central nervous system responses and the durations of acupuncture.     

Research on the neurophysiological mechanisms of acupuncture: review of selected studies and methodological issues

This presentation reviews studies that contribute to an understanding of the neurophysiological mechanisms of acupuncture. A 1973 study, using volunteer medical students, looked into acupuncture's analgesic effect on experimentally induced pain and suggests that humoral factors may mediate acupuncture-induced analgesia. In a study of the possible role of the cerebrospinal fluid transmission of pain suppression effects of acupuncture, cerebrospinal fluid from acupuncture-treated rabbits was infused into recipient rabbits. The analgesic effect was observed in the recipient rabbits, suggesting that acupuncture-induced analgesia may be mediated by substances released in the cerebrospinal fluid. Studies of electroacupuncture in rats revealed that both low-frequency and high-frequency stimulation could induce analgesia, but that there are differential effects of low- and high-frequency acupuncture on the types of endorphins released. In another study, low-frequency electroacupuncture, given as median nerve stimulation in cats, was shown to protect the myocardium by inhibiting sympathetic pressor response and increasing myocardial oxygen demand. The development of neuroimaging tools, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), make noninvasive studies of acupuncture's effects on human brain activity possible. Studies using PET have shown that thalamic asymmetry present among patients suffering from chronic pain was reduced after the patients underwent acupuncture treatment. Other studies, using fMRI, have pointed to relationships between particular acupoints and visual-cortex activation. These powerful new tools open the possibility to new scientific studies of this ancient therapy.     

康复治疗对脑卒中后脑网络运动功能重塑的磁共振研究进展

随着脑卒中后运动功能障碍研究的不断深入,功能磁共振成像(fMRI)受到广泛关注.脑卒中后皮质下病灶影响附近或远端相关脑区,导致运动功能障碍.镜像神经元疗法、重复性经颅磁、经颅电刺激可通过无创方式激活大脑皮质相关区域,恢复大脑半球之间的平衡,对全脑网络环路有调节作用,但经颅电刺激缺乏A级证据.针灸虽能广泛调节全脑功能网络...     

基于格兰杰因果分析的针刺不同效应阶段中枢神经传导通路研究

目的探讨针刺不同效应阶段是否会引发中枢神经信号不同的传导通路。材料与方法采用非重复事件相关的实验设计模式和多元格兰杰因果有效连接度分析方法。结果研究表明针刺即时效应仅引发大脑微弱、稀疏的因果有效连接,包括经丘脑的体感上行传导通路与由额叶皮层投射到疼痛反应区的自上而下的控制通路。持续性效应阶段,仅在针刺足三里穴后会引发广泛大脑区域的更为紧密的因果连接模式。结论针刺效应可能涉及大脑网络多水平层面信息流的整合与交互。     

Functional neuroimaging and cognitive rehabilitation for people with traumatic brain injury

Cognitive deficits are a common consequence of traumatic brain injury. Although such deficits are amenable to rehabilitation, methods for individualizing cognitive interventions are still unrefined. Functional neuroimaging methods such as positron emission tomography and functional magnetic resonance imaging are emerging as possible technologies for measuring and monitoring the cerebral consequences of plasticity associated with brain injury and for evaluating the effectiveness of rehabilitation interventions. Functional neuroimaging may even enable more customized and efficient selection, design, or adaptation of individual cognitive rehabilitation programs. We review the current literature on functional neuroimaging after traumatic brain injury, relating these findings to cognitive rehabilitation. Overall, functional neuroimaging after traumatic brain injury has shown reliable differences in brain activity within several regions of frontal cortex, partly but not uniformly consistent with neuropsychological and structural findings in traumatic brain injury. We also outline a number of promising research opportunities for applying functional neuroimaging in traumatic brain injury settings, along with associated challenges.     

近20年激光针灸脑效应研究进展

激光针灸作为社会科技进步的时代产物，是一种将低水平激光应用于经络系统的治疗方法，拓宽了传统针灸技术的应用及发展，其脑效应研究于近20年兴起，本文从当前应用较多的功能磁共振成像、脑电图和经颅多普勒超声3种技术层面对激光针灸脑效应的研究进展及未来展望加以论述。研究表明激光针灸在刺激不同穴位时产生的脑效应能够体现穴位的特异性且与其主治存在关联，同时有相似作用的穴位产生的脑效应存在一定的相关性。目前激光针灸作用机制仍未探查清楚，脑效应研究为探索其治疗以疼痛为代表的某些疾病的疗效机制提供了新的视角，虽然仍面临着许多挑战，但未来有着广阔的发展前景。      

基于fMRI技术探讨电针与手针中枢机制响应差异

目前功能磁共振技术在针刺（电针与手针）中枢机制研究取得了一定进展,但不同针刺参数及形式的刺激在大脑的响应不同。本文收集了“功能磁共振与针刺”相关的国内外文献,以针刺“刺激-响应”模式为切入点,对电针刺激量及电针与手针的的中枢响应差异作一初步的论述。结果表明,在功能磁共振技术观测中,不同电针参数存在不同的中枢响应机制,并应将多个参数联合研究;其次,电针与手针在传入途径、作用机制、靶点、临床疗效等方面存在差异,也有着各自的优势病种。      

Spatiotemporal mapping the neural correlates of acupuncture with MEG

Acupuncture is an ancient Eastern healing modality with putative therapeutic applications. Unfortunately, little is known about the central mechanisms by which acupuncture may exert its effects. In this study, 16 [corrected] healthy subjects were evaluated with magnetoencephalography (MEG) to map the location and timing of brain activity during low-frequency electroacupuncture (EA) and mechanical, noninsertive, sham acupuncture (SA) given at acupoint PC-6. Both EA and SA evoked brain responses that localized to contralateral primary somatosensory (SI) cortex. However, initial responses for EA peaked slightly earlier than those for SA and were located inferiorly within SI. Average equivalent current dipole strength was stronger (particularly at latencies >60 ms) for SA. These spatiotemporal differences between activations elicited by EA and SA are likely attributable to stimulus modality (electrical versus mechanical) and differences in the underlying somatosensory fibers transmitting these signals. The present data confirm that acupuncture modulates activity within somatosensory cortex, providing support for previous studies that suggest that the therapeutic effects of acupuncture are linked to SI modulation. Thus, MEG provides excellent spatiotemporal characterization of the somatosensory component of acupuncture, and future studies can contrast derived brain response parameters in healthy controls with those found in a diseased state.     

What Does It Mean to Call Chronic Pain a Brain Disease?

Multiple investigators have recently asked whether neuroimaging has shown that chronic pain is a brain disease. We review the clinical implications of seeing chronic pain as a brain disease. Abnormalities noted on imaging of peripheral structures have previously misled the clinical care of patients with chronic pain. We also cannot assume that the changes associated with chronic pain on neuroimaging are causal. When considering the significance of neuroimaging results, it is important to remember that “disease” is a concept that arises out of clinical medicine, not laboratory science. Following Canguilhem, we believe that disease is best defined as a structural or functional change that causes disvalue to the whole organism. It is important to be cautious in our assertions about chronic pain as a brain disease because these may have negative effects on 1) the therapeutic dialogue between clinicians and patients; 2) the social dialogue about reimbursement for pain treatments and disability due to pain; and 3) the chronic pain research agenda. Considered scientifically, we may be looking for the cause of chronic pain through neuroimaging, but considered clinically, we are in fact often looking to validate pain complaints. We should not yield to the temptation to validate pain with the magnetic resonance imaging scanner (structural or functional). We should not see pain as caused by the brain alone. Pain is not felt by the brain, but by the person.PerspectiveNeuroimaging investigators have argued that brain imaging may demonstrate that chronic pain is a brain disease. We argue that “disease” is a clinical concept and that conceiving of chronic pain as a brain disease can have negative consequences for research and clinical care of patients with chronic pain.     

Neuronal specificity of acupuncture response: a fMRI study with electroacupuncture

Recently, neuronal correlates of acupuncture stimulation in human brain have been investigated by functional neuroimaging. The preliminary findings suggest that acupuncture at analgesic points involves the pain-related neuromatrix and may have acupoint-brain correlation. Although multiple models of control stimulations have been applied to address the specificity of the needling effect clinically, their impacts have not been evaluated by functional neuroimaging. With the advantage of objective parameter setting, electroacupuncture (EA) was used in this study to devise three distinct controls for real EA, i.e., mock EA (no stimulation), minimal EA (superficial and light stimulation), and sham EA (same stimulation as real EA) applied at nonmeridian points. Fifteen healthy volunteers received real EA at analgesic point Gallbladder 34 (Yanglinquan), sham EA, and one of either mock EA or minimal EA over the left leg in counter-balanced orders. Multisubject analysis showed that sham EA and real EA both activated the reported distributed pain neuromatrix. However, real EA elicited significantly higher activation than sham EA over the hypothalamus and primary somatosensory-motor cortex and deactivation over the rostral segment of anterior cingulate cortex. In the comparison of minimal EA versus mock EA, minimal EA elicited significantly higher activation over the medial occipital cortex. Single-subject analysis showed that superior temporal gyrus (encompassing the auditory cortex) and medial occipital cortex (encompassing the visual cortex) frequently respond to minimal EA, sham EA, or real EA. We concluded that the hypothalamus-limbic system was significantly modulated by EA at acupoints rather than at nonmeridian points, while visual and auditory cortical activation was not a specific effect of treatment-relevant acupoints and required further investigation of the underlying neurophysiological mechanisms.     

When the brain is prepared to learn: enhancing human learning using real-time fMRI

The rate of learning or memory formation varies over time for any individual, partly due to moment-to-moment fluctuation of brain state. Functional neuroimaging has revealed the neural correlates of learning and memory, but here we asked if neuroimaging can causally enhance human learning by detection of brain states that reveal when a person is prepared or not prepared to learn. The parahippocampal cortex (PHC) is essential for memory formation for scenes. Here, activation in PHC was monitored in real-time, and scene presentations were triggered when participants entered “good” or “bad” brain states for learning of novel scenes. Subsequent recognition memory was more accurate for scenes presented in “good” than “bad” brain states. These findings show that neuroimaging can identify in real-time brain states that enhance or depress learning and memory formation, and knowledge about such brain states may be useful for accelerating education and training. Further, the use of functional neuroimaging as a causal, rather than correlative, tool to study the human brain may open new insights into the neural basis of human cognition.     

针刺对偏头痛大鼠脑内降钙素基因相关肽基因表达的影响

目的探讨偏头痛大鼠脑内降钙素基因相关肽(CGRP)的表达强度及针刺对CGRP基因表达的调控机制及针刺防治偏头痛的作用机制。方法参照Knyihar-Csillik方法复制大鼠偏头痛模型,将动物随机分成正常对照组、模型对照组、针刺预防组和针刺治疗组,每组10只,采用放射免疫分析法测定CGRP浓度;采用RT-PCR法测定CGRPmRNA表达。结果颈静脉血CGRP含量:正常大鼠保持低水平恒定量,模型对照组大鼠CGRP含量显著升高(P<0.01),针刺预防组及针刺治疗组与正常大鼠相近,但与模型对照组比较,显著降低(P<0.01);脑干及三叉神经节CGRPmRNA的表达变化:正常对照组表达在较低水平,模型对照组表达显著增强(P<0.01),针刺治疗组及针刺预防组与模型对照组比较,表达显著减弱(P<0.01)。结论实验性偏头痛大鼠脑内CGRP的过度表达,可能是偏头痛发作的分子机制之一;针刺调控CGRPmRNA表达可能是针刺防治偏头痛的机制之一。     

Role of neuroimaging in our understanding of the pathogenesis of primary headaches

This article reviews new advances in neuroimaging of primary headaches. Imaging of the brain is reaching a new stage of maturity as the basic neural systems that participate in the pathogenesis of headaches are identified. Given the rapid advances in functional neuroimaging, it is no surprise that recent studies have supported the neurovascular theory of migraine and cluster headache. It is clear that functional neuroimaging will continue to be of paramount importance and ultimately may serve as the bridge between molecular and clinical domains in the field of headache research.     

功能磁共振成像技术在针刺治疗中风偏瘫脑机制研究的现状及前景

随着功能磁共振成像分子影像技术的逐步成熟,针刺的脑效应机制研究也步入可视化阶段,且在中风病领域应用较多。功能磁共振成像研究范式主要分为任务态和静息态,分析方法主要包括脑区激活、功能连接、脑网络等。本文根据现有针刺-功能磁共振成像相关文献,归纳出针刺治疗中风偏瘫脑机制的研究进展,针对其试验设计、分析方法等方面分析目前研究可能存在的问题,并展望其应用前景。结果显示针刺可不同程度地激活大脑皮质运动区、感觉区以及小脑、基底节等部位,亦可提高脑区的功能连接,对运动、感觉、语言等脑功能网络发挥一定的调制作用。但仍存在诸多问题需要去改进,未来倡导以中医传统理论为纲,充分融合现代技术,多学科并举,构建针刺治疗中风的特异性脑效应网络。      

An infrared radiation study of the biophysical characteristics of traditional moxibustion

OBJECTIVES: Moxibustion has been a part of acupuncture practice for thousands of years. Traditionally, it includes direct moxibustion, in which moxa sticks are burned at acupuncture points on the skin, and indirect moxibustion, in which monkshood cakes or ginger or garlic slices are used to insulate the skin from burning moxa cones. Recently randomised clinical trials and clinical observations suggest that moxibustion can enhance physiological and immune functions, but there has been little investigation of the scientific basis of these traditional techniques. The present study compared the infrared radiation caused by these techniques to that of non-specific controls and to that of the human body surface at an acupuncture point. METHODS: A highly sensitive, infrared-spectrum detection device was used to compare the spectra of traditional moxibustion materials (n = 4/group) with those of control materials (n = 4/group) and to the spectrum at the surface of an acupuncture point LI 4 (Hegu) in healthy volunteers (n = 7). RESULTS: The infrared radiation intensity produced by a traditional moxa stick was 43300.41 mV, with a peak on the infrared spectrum of 3.5 microm, while the respective radiation intensities of two controls, a smokeless moxa stick and a 555 cigarette, were 31.15 mV and 37.03 mV with peaks of 7 microm and 3.5 microm. The infrared radiation intensities of the three traditional media of indirect moxibustion, monkshood cake, ginger slices and garlic slices, were 520.27 mV, 594.79 mV and 681.87 mV, respectively, all with peaks around 7.5 microm and similar spectra. In contrast, the infrared radiation intensities of slices of cucumber and carrot, used as control media for indirect moxibustion, were 274.47 mV and 50.53 mV, respectively, substantially different from those of the traditional media. Infrared radiation at LI 4 (Hegu) was 20.40 mV, and peaked on the infrared spectrum at about 7.5 microm. The experiment showed that the thermal action of the traditional moxa stick was more potent than that of indirect moxibustion and its radiation peak was different from that at the acupuncture point on the human body. In contrast, the thermal action of traditional indirect moxibustion was modest and its radiation peak matched that at the acupuncture point. CONCLUSION: Direct moxibustion with a traditional moxa stick may produce its potent therapeutic effects by thermal action, while traditional indirect moxibustion may act by producing modest thermal action and a sympathetic vibration at the skin surface. Non-traditional thermal materials and media may not be suitable substitutes for traditional materials. The data provide a scientific, biophysical rationale for traditional moxibustion.     

fMRI studies of eye movement control: investigating the interaction of cognitive and sensorimotor brain systems

Functional neuroimaging studies of eye movement control have been a useful approach for investigating the interaction of cognitive and sensorimotor brain systems. Building on unit recording studies of behaving nonhuman primates and clinical studies of patients with a focal brain lesion, functional neuroimaging studies have elucidated a pattern of hierarchical organization through which prefrontal and premotor systems interact with sensorimotor systems to support context-dependent adaptive behavior. Studies of antisaccades, memory-guided saccades, and predictive saccades have helped clarify how cognitive brain systems support contextually guided and internally generated action. The use of cognitive and sensorimotor eye movement paradigms is being used to develop a better understanding of life span changes in neurocognitive systems from childhood to late life, and about behavioral and systems-level brain abnormalities in neuropsychiatric disorders.