Article

Acupuncture mobilizes the brain's default mode and its anti-correlated network in healthy subjects

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Abstract

Previous work has shown that acupuncture stimulation evokes deactivation of a limbic-paralimbic-neocortical network (LPNN) as well as activation of somatosensory brain regions. This study explores the activity and functional connectivity of these regions during acupuncture vs. tactile stimulation and vs. acupuncture associated with inadvertent sharp pain. Acupuncture during 201 scans and tactile stimulation during 74 scans for comparison at acupoints LI4, ST36 and LV3 was monitored with fMRI and psychophysical response in 48 healthy subjects. Clusters of deactivated regions in the medial prefrontal, medial parietal and medial temporal lobes as well as activated regions in the sensorimotor and a few paralimbic structures can be identified during acupuncture by general linear model analysis and seed-based cross correlation analysis. Importantly, these clusters showed virtual identity with the default mode network and the anti-correlated task-positive network in response to stimulation. In addition, the amygdala and hypothalamus, structures not routinely reported in the default mode literature, were frequently involved in acupuncture. When acupuncture induced sharp pain, the deactivation was attenuated or became activated instead. Tactile stimulation induced greater activation of the somatosensory regions but less extensive deactivation of the LPNN. These results indicate that the deactivation of the LPNN during acupuncture cannot be completely explained by the demand of attention that is commonly proposed in the default mode literature. Our results suggest that acupuncture mobilizes the anti-correlated functional networks of the brain to mediate its actions, and that the effect is dependent on the psychophysical response.

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... The 3 research studies that met the criteria involved acupoints located on the mid-back to the sacrum. There were both clinical and experimental studies; BL 20 and BL 32 were a part of the same study by Minagawa et 15 Autonomic functions X Hui, 2005 29 fMRI (cerebral function) X Liu, 2011 30 fMRI (cerebral function) X Mori, 2010 16 Pupillary response X Zhou, 2014 31 Neural electrical signals X Claunch, 2012 32 fMRI (acu mechanism) X Cho, 2010 33 fMRI (cerebral function) X Karatay, 2011 10 Immune function X Wang, 2014 34 Cerebral blood flow X Park, 2010 35 Hypertension X Hui, 2009 36 fMRI (acu mechanism) X Hui, 2010 37 fMRI (acu mechanism) X Ozerkan, 2007 38 Knee-extension ability X Huang, 2012 39 Dyspepsia X ST 38 Lin, 2005 40 Frozen shoulder X ST 43 Wang, 2000 41 Pulse spectrum X ST 44 Lietz, 2008 42 CAEP X Usichenko, 2011 43 BAEP X Light gray shading indicates experimental studies; dark gray shading indicates that the same studies reported on more than 1 acupoint. X indicates no relationship to the ZJJYJ; X indicates a relationship with the ZJJYJ. ...
... The LRchannel studies had a special interest in fMRI (n = 8) and in the areas of the brain that are activated by acupuncture stimulation at LR 2 and LR 3. No studies reflected the ZJJYJ RP indications. See Table 9. 32,36,37,[52][53][54][55][56][57][58][59][60] ...
... The Hui et al. study concluded that manual acupuncture at those acupoints modulates the limbic system, which is an important intrinsic regulatory system of the human brain. 36 Another notable fMRI study was by Yan et al., in 2005, 59 in which LR 3 and LI 4 were explored for deactivation patterns of the frontal area in analgesia and activation of the visual cortex to correlate with eye disorders. Yan et al. concluded that manual acupuncture at different acupoints elicits different fMRI activation patterns in the brain. ...
Article
Objective: Huang Fu Mi's Zhen Jiu Jia Yi Jing (ZJJYJ) is regarded as the earliest text (282 ce) on differential diagnosis and clinical acumoxa therapy in Chinese Medicine. Are contemporary manual acupuncture practices consistent with those reported in the ZJJYJ? The aim of this research was to investigate if modern manual acupuncture uses reported in research are consistent with classical practices reported in the ZJJYJ. Materials and Methods: A database search of human research studies from 1995 to 2016 was performed for all 270 acupoints for all 8 leg/body channels. The clinical foci of these modern publications were compared with acupoint clinical indications documented in the Song Dynasty Chinese edition (1077) of the ZJJYJ and the sole English translation (translated and compiled by Yang and Chace in 1994) of The Systematic Classic of Acupuncture and Moxibustion. Results: Of 2149 articles in English, 63 met the search criteria. These articles predominately reported acupoints on the lower leg, back, chest, and head. Correlations between the acupoints used in modern research and those used in the ZJJYJ were minimal. Clinical indications from the ZJJYJ typically involved symptoms relating to pain, swelling, fever, seizures, hallucinatory states, dysentery, malaria, and tuberculosis, which are now treated pharmacologically. However, one-third of modern studies were functional magnetic resonance imaging (fMRI) investigations of neurophysiologic effects of manual acupuncture on the human brain. Conclusions: While, superficially, the ZJJYJ might seem irrelevant in modern manual acupuncture practices, well-documented physical effects (e.g., pain relief) of manual acupuncture do provide measurable outcomes for use in fMRI research. Therefore, the classical text does provide a guide for future research on influential acupoints on the leg and body channels.
... Hui et al. further demonstrated acupuncture stimulation produces deactivation of the medial prefrontal, medial parietal and medial temporal lobes and activation of regions in the sensorimotor and paralimbic structures, in a pattern consistent with acupuncture modulating the default mode network and the anti-correlated task-positive network to produce its analgesic effects (91). ...
... As previously discussed, the work of Cheng and Pomerantz demonstrated acupuncture stimulation causes release of endorphins and enkephalins from the pituitary, which are experimentally proven to be fundamentally involved in acupuncture analgesia, including the bilateral analgesia produced by unilateral acupuncture (78,(80)(81)(82)(83)(84)(85). Acupuncture also activates descending spinal cord and brain pain pathways (including the DNIC system) and brain antinociceptive networks as described in the previous section (56,75,77,(89)(90)(91). ...
... Hui et al. further demonstrated acupuncture stimulation produces deactivation of the medial prefrontal, medial parietal and medial temporal lobes and activation of regions in the sensorimotor and paralimbic structures, in a pattern consistent with acupuncture modulating the default mode network and the anti-correlated task-positive network to produce its analgesic effects (91). ...
... As previously discussed, the work of Cheng and Pomerantz demonstrated acupuncture stimulation causes release of endorphins and enkephalins from the pituitary, which are experimentally proven to be fundamentally involved in acupuncture analgesia, including the bilateral analgesia produced by unilateral acupuncture (78,(80)(81)(82)(83)(84)(85). Acupuncture also activates descending spinal cord and brain pain pathways (including the DNIC system) and brain antinociceptive networks as described in the previous section (56,75,77,(89)(90)(91). ...
Article
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Abstract: Ever since acupuncture’s tenets were first delineated in the Huangdi Neijing (Neijing) treatise ~200 BCE, theorists and researchers have sought to define the anatomic and physiologic bases for acupuncture’s beneficial clinical effects in treating pain and non-pain medical conditions. In the last century, technical advances in both the basic biomedical sciences (including anatomy, biochemistry, pharmacology, electrophysiology, and radiology) and also clinical research methodologies have led to publication of an extensive body of basic science and clinical research publications on the topics of acupuncture anatomy, physiology, and clinical effects. This body of literature demonstrates that the beneficial clinical effects of acupuncture derive from the activation of peripheral nerves by needling, with resulting secondary modulatory effects on the peripheral nervous system, the central nervous system (CNS) (including the limbic system), the autonomic nervous system, and the immunologic and endocrinologic systems. A neuroanatomic and neurophysiologic model of acupuncture’s mechanisms and effects is the only theory that can be reconciled with research findings of the efficacy of laser acupuncture and the positive randomized clinical trial results in studies that used non-penetrating or minimally penetrating “sham” needle control interventions, and this model is also consistent with anatomic and physiologic descriptions contained in the Neijing. This review article summarizes the anatomic, basic science, and clinical evidence that demonstrates acupuncture signaling and its myriad clinical benefits can be understood as arising from and transduced by neural mechanisms. Keywords: Acupuncture; anatomy; meridians; nerves; neurophysiology Received: 14 August 2021; Accepted: 24 November 2021; Published: 30 March 2022. doi: 10.21037/lcm-21-48 View this article at: https://dx.doi.org/10.21037/lcm-21-48
... Many reliable studies, including systematic reviews and randomized controlled trials, have indicated that acupuncture is safe and effective in treating a wide range of diseases [1][2][3][4][5][6]. A number of neuroimaging studies have examined the neural correlates of acupuncture as well as its other biological mechanisms [7][8][9][10][11]. Recently, the doubtful effects of acupuncture with respect to acupoints and nonacupoints have been investigated in clinical research [12][13][14], and neuroimaging results have also raised questions regarding the existence of acupoint specificity [15,16]. ...
... Studies on acupoint specificity, especially those conducted overseas using neuroimaging, have been carried out on healthy participants [11,15,[68][69][70]. Studies on the correlation between the status and specificity of acupoints have demonstrated the following: acupoints are relatively "silent" under normal physiological conditions, yet they are relatively "sensitive" under pathological conditions [71]. ...
Article
The theory of acupoint specificity is the basis for elucidating the actions of acupoints as employed in clinical practice. Acupoint specificity has become a focus of attention in international research efforts by scholars in the areas of acupuncture and moxibustion. In 2006, the Chinese Ministry of Science approved and initiated the National Basic Research Program (973 Program), one area of which was entitled Basic Research on Acupoint Specificity Based on Clinical Efficacy. Using such approaches as data mining, evidence-based medicine, clinical epidemiology, neuroimaging, molecular biology, neurophysiology, and metabolomics, fruitful research has been conducted in the form of literature research, clinical assessments, and biological studies. Acupoint specificity has been proved to exist, and it features meridian-propagated, relative, persistent, and conditional effects. Preliminarily investigations have been made into the biological basis for acupoint specificity.
... But till now there is still no consistency being reached towards it as a result of the discrepancy for a publicly acknowledged standardized measurement. Furthermore, the main controversy is concentrated on the characterization of acupuncture Deqi with visualized approaches [19][20][21][22][23][24][25][26] along with behavioral manners [11,18,[27][28][29][30], while most of these studies were performed on healthy subjects. ...
... Because the deactivation of LPNN caused by attention is less extensive than that of Deqi, then the demand of attention might be incomplete to explain the comprehensive signal attenuation of the entire brain. Their further study demonstrated that acupuncture may modulate the anticorrelated functional cerebral network to mediate its actions, and that the effect is relying on the psychophysical response [20,24]. In another study carried out by Fang et al., similar salient response pattern was identified for Deqi produced by other points (Taichong (LV3), Xingjian (LV2), and Neiting (ST44)) other than Hui's points. ...
Article
Acupuncture as an oriental natural healing therapy with prolonged history has been extensively utilized in the management of great numbers of disorders. Deqi, a renowned acupuncture needling sensation, is profoundly regarded as the predictor and also the prerequisite of a preferable acupuncture treatment efficacy. Till now, there is still no consistency being reached towards the mechanism of acupuncture Deqi as a result of the discrepancy for publicly acknowledged evidence. Recent visualized research on Deqi using modern technologies has demonstrated possible central mechanism towards it. However, there is a conspicuous paradox underway in the research of cerebral response to acupuncture Deqi. This paper provided a view of up-to-date studies using visualized tools to characterize the brain response to acupuncture Deqi, such as functional magnetic resonance imaging (fMRI) and positron emission tomography/computed tomography (PET/CT). The paradox was extruded to highlight certain reasons from a TCM view. It is hypothesized that acupoints located at different dermal sites, state of participant, and needling manipulation can all contribute to the current paradox. Hence, further studies on acupuncture Deqi should pay more attention to the strategy of experiment design with generalized measurement, valid sham control methods, and more to subjects in diseased condition.
... Another study showed that acupuncture impacted selective attention networks, enhancing the efficiency of the alerting and executive control networks, and that acupuncture had a significantly greater effect on the alerting network compared to painful stimulation (Liu et al., 2013). Therefore, the subjective quality and the intensity of the stimulation seem to have an impact on the brain activity changes observed (Hui et al., 2005(Hui et al., , 2009Huang et al., 2012). ...
... Other studies have also shown that acupuncture can affect functional connectivity of brain networks such as the default mode network (DMN) or sensorimotor network in pain, stroke, or mental conditions (Dhond et al., 2008;Bai et al., 2009;Hui et al., 2009;Chae et al., 2013;Napadow et al., 2013;Liang et al., 2014;Zhao et al., 2014;Deng et al., 2016). Numerous studies could show that the precuneus (as part of the DMN) is frequently affected by acupuncture (Chae et al., 2013;Nierhaus et al., 2015b). ...
Article
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Xingnao Kaiqiao (XNKQ) acupuncture is an acupuncture technique used for stroke patients. In 24 healthy volunteers, we applied this complex acupuncture intervention, which consists of a manual needle-stimulation on five acupuncture points (DU26 unilaterally, PC6, and SP6 bilaterally). XNKQ was compared to three control conditions: (1) insertion of needles on the XNKQ acupuncture points without stimulation, (2) manual needle-stimulation on five nearby non-acupuncture points, and (3) insertion of needles on the non-acupuncture points without stimulation. In a within-subject design, we investigated functional connectivity changes in resting-state functional magnetic resonance imaging (fMRI) by means of the data-driven eigenvector centrality (EC) approach. With a 2 × 2 factorial within-subjects design with two-factor stimulation (stimulation vs. non-stimulation) and location (acupuncture points vs. non-acupuncture points), we found decreased EC in the precuneus after needle-stimulation (stimulation<non-stimulation), whereas the factor location showed no statistically significant EC differences. XNKQ acupuncture compared with needle-stimulation on non-acupuncture points showed decreased EC primarily in subcortical structures such as the caudate nucleus, subthalamic nucleus, and red nucleus. Post-hoc seed-based analysis revealed that the decrease in EC was mainly driven by reduced temporal correlation to primary sensorimotor cortices. The comparison of XNKQ acupuncture with the other two (non-stimulation) interventions showed no significant differences in EC. Our findings support the importance of the stimulation component of the acupuncture intervention and hint toward the modulation of functional connectivity by XNKQ acupuncture, especially in areas involved in motor function. As a next step, similar mechanisms should be validated in stroke patients suffering from motor deficits. ClinicalTrials.gov ID: NCT02453906
... 15 The limbic structures are considered to play a central role in the regulation and integration of sensorimotor, autonomic, cognition 16 as well as affect and emotion. 16,17 In Chinese medical texts such as the Huang Di Neijing (The Yellow Emperor's Classic of Internal Medicine) and the Zhen Jiu Da Cheng (Great Compendium of Acupuncture and Moxibustion), the patients' psychological state is considered an important factor associated with De Qi [ ]. 18 However in Traditional Chinese Medicine (TCM) there is no such term that corresponds exactly to anxiety, several early Chinese disease entities closely resemble the symptoms related to anxiety such as; 'Jing Kong (fright and fear)', 19,20 'Jing Ji (fear and palpitation)', [19][20][21] 'Zheng Chong (panic throbbing)' [19][20][21] as defined in the Jing Yue Quan Shu, 21 'Zang Zao (agitation)' in the Jin Gui Yao Lue, 21 and 'Li Ji (Rebellious Qi of the Chong Mai)'. 21 The importance given to De Qi stems often from its purported clinical significance, [22][23][24][25][26][27] needling is effective when one obtains De Qi (Ling Shu, chapter3), 28 a belief held by practitioners' traditional and conservative viewpoints throughout the many dynasties of ancient China, and which still influence today's clinical practice. ...
... 41,42 These complex psychophysical responses are suggested to be particularly important in modulating Central Nervous System (CNS) activity, 43 involving a broad spectrum of afferents nerve fibers 26,29,35,44,45 without reaching the threshold of overt noxious simulation. 26 Neuroimaging studies have also shown that the hypothalamus 46,47 and the limbic system are important networks in mediating acupuncture's diverse effects and the perception of De Qi. 16,17,26,46,48 It is also noteworthy to point out that the therapeutic effects of acupuncture on various psycho-behavioral disorders may also be attributed to the inhibitory effects of acupuncture manipulation with De Qi on Dorsomedial Prefrontal Cortex (DMPFC) activity. 3 There are different pharmacological and non-pharmacological approaches in the management of anxiety 49 including selective serotonin reuptake inhibitors, 50 administration of benzodiazepine, 49 cognitive behavioral therapy and various self-help measures. ...
Article
Acupuncture has been broadly applied in the management of many diseases and conditions; however, its mechanism of action has been partially elucidated. Additionally, assessment of psychophysical responses in the acupuncture therapy is not common regarding anxiety disorder studies. Taken together, the therapeutic effect of acupuncture appears when De Qi psychophysical response is experienced following stimulation of the afferent sensory nerves. The present study investigates the level of anxiety perceived at different occasions in acupuncture and mock laser group. Furthermore, it examines the relationship between perceived De Qi psychophysical response and the level of anxiety experienced during administration of each intervention. The study was embedded in a two-arm parallel design multi-center, randomized clinical trial, the Tennis Elbow Acupuncture-International Study-China, Hong Kong, Australia, Italy. Participants’ level of anxiety was measured using a validated instrument, the Massachusetts General Hospital Acupuncture Sensation Mood Scale. Ninety-six participants with Lateral Elbow Pain were randomly allocated into two groups; the acupuncture treatment group (n = 47) and the inactive mock laser control group (n = 49). Data were collected immediately following the interventions at the first and the ninth session within the clinical trial. Acupuncture with De Qi did not induce higher level of anxiety compared to prior administration of acupuncture. In fact, participants were more relaxed after receiving acupuncture than those who received mock laser. There was also a weak association between participants’ perception of anxiety during acupuncture and the MASS De Qi Index in session nine only (p < 0.01). Further investigation of the result revealed weak positive correlation between anxiety perceived during administration of acupuncture and the following De Qi characteristics; ‘soreness’ (p < 0.01), ‘Deep pressure’ (p < 0.05), ‘Heaviness’ (p < 0.05), and ‘Fullness/distension’ (p < 0.05). Acupuncture can be regarded as a potential therapy for preoperative anxiety through its possible regulatory function of emotion. While culture may not alter the expectation of the individual regarding anxiety, symptomology associated with anxiety should be understood within the context of the cultural background.
... The precuneus and inferior parietal lobule are included in the main distribution of DMN. The results were consistent with previous studies that DMN activity was diminished during needling [37,41]. Previous studies had con- firmed that acupuncture treatment could help to establish psychophysical pain homeostasis by enhancing the FC of the DMN in MWoA patients [23,25]. ...
... Conversely, the DMN is inhibited during the task state [30]. Furthermore, a previous study showed the genuine acupuncture led to the decreased DMN deactivation in comparison with the sham acupuncture, which indicated that attentional processes could not fully explain the DMN deactivation evoked by acupuncture [41]. Thus, we speculated that the DMN deactivation elicited by acupuncture probably reflected the central neural mechanism of acupuncture analgesia. ...
Article
To study the modulatory effects of acupuncture on the amplitude of low frequency fluctuations (ALFF) in migraine without aura (MWoA) patients. 16 MWoA patients and 16 healthy controls were recruited to undergo resting-state fMRI scanning before and after needling at GB41. Voxel-based analysis to characterize the difference of amplitude of low frequency fluctuations was employed. Before needling, compared with healthy controls, the MWoA patients showed decreased ALFF values in the left calcarine, cuneus, parietal gyrus, and increased ALFF values in the right hippocampus, parahippocampal gyrus, insula, middle temporal gyrus and superior temporal gyrus. After acupuncture at GB41, decreased ALFF values in the bilateral precuneus, right middle frontal gyrus and right inferior parietal lobule, and increased ALFF values in the right precentral and postcentral gyri were observed in MWoA patients. Compared with healthy controls, the MWoA patients after needling showed mainly decreased ALFF values in the left precuneus, calcarine, cuneus, parietal gyrus, and increased ALFF values in the right precentral, postcentral gyri, hippocampus, middle temporal gyrus and superior temporal gyrus. Our findings provided further insight into possible mechanisms of the modulatory effects of acupuncture, which could be interpreted in terms of pain processing.
... Acupuncture thereby has been increasingly and widely accepted by western countries (Lee et al., 2014). Neuroimaging technologies have been used to investigating neural mechanisms of acupuncture, and it has been found that acupuncture stimulation may modulate the DMN in healthy subjects and patients with certain psychiatric disorders, such as stroke, migraine and Alzheimer's disease (AD; Dhond et al., 2008;Fang et al., 2009;Hui et al., 2009;Liu et al., 2009b;Wang et al., 2014;Zhang et al., 2014). ...
... Results showed that the significantly decreased FC between the PC/PCC and the left middle prefrontal cortex, left angular gyrus and bilateral HIPP/paraHIPP in MDD patients after EAS at GV20. The present findings were similar to the ones from several previous studies, which reported that acupuncture stimulation induced signal attenuation in the middle prefrontal cortex, HIPP/paraHIPP and IPC (Wu et al., 1999;Yoo et al., 2004;Hui et al., 2009). HIPP/paraHIPP is implicated in cognitivebehavioral functions and emotional memory (LaBar and Cabeza, 2006;Savitz and Drevets, 2009). ...
Article
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Background: Previous neuroimaging studies have revealed that acupuncture modulates the default mode network (DMN) in healthy subjects and patients with certain disorder. However, few studies have been performed to investigate whether or not acupuncture might modulate the DMN in patients with major depressive disorder (MDD). Thereby, the aim of the present study was to assess alterations of the DMN induced by acupuncture stimulation in patients with first-episode, drug-naïve MDD. Materials and methods: Twenty nine patients with first-episode, drug-naïve MDD and 29 healthy subjects were enrolled in this study. All the healthy subjects underwent 6-min resting-state functional magnetic resonance imaging (R-fMRI) scan. While patients underwent acupuncture stimulation for 20-min electro-acupuncture stimulation (EAS) at Baihui acupoint (GV20) and two 6-min R-fMRI scans before and after EAS. Based on the precuneus/posterior cingulate cortex (PC/PCC) as the seed region, functional connectivity (FC) method was adopted to examine abnormal DMN in patients by comparing with healthy subjects and to evaluate the influence of EAS on intrinsic connectivity within the DMN in patients with MDD. Results: Compared to healthy subjects, MDD patients had abnormal DMN. Moreover, results showed that EAS at GV20 induced increased FC between the PC/PCC and bilateral anterior cingulate cortex (ACC), and decreased FC between the PC/PCC and left middle prefrontal cortex, left angualr gyrus and bilateral hippocampus/parahippocampus (HIPP/paraHIPP) in patients with MDD, which were the main brain regions showing significant differences between the patients and healthy subjects. Conclusion: Our findings provide imaging evidence to support that GV20-related acupuncture stimulation may modulate the DMN in patients with first-episode, drug-naïve MDD. This study may partly interpret the neural mechanisms of acupuncture at GV20 which is used to treat patients with MDD in clinical.
... These studies, brought together in a meta-analysis of brain activities associated with acupuncture stimulation, reveal activation in the sensorimotor cortical network (insula, thalamus, ACC and primary / secondary somatosensory cortex) and deactivation of the limbic-paralimbic-neocortical network (LPNN) composed of mPCF, caudate, amygdala, PCC and parahippocampus. This "LPNN" terminology was given by the authors for the network of brain regions involved in the acupuncture response (Hui et al., 2009). The LPNN is composed of the main nodes of the DMN, amygdala and hypothalamus. ...
Article
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Anxiety disorders are among the most common mental disturbances around the world, and they can negatively impact a patient's quality of life and disrupt important activities of daily living. Recent studies have shown that the psychopathology of anxiety involves altered neural circuits and the normalization of these circuits would be the key factor for therapeutic effects. Acupuncture has an anxiolytic effect recognized in the treatment of anxiety. However, neural mechanism underlying the anxiolytic acupuncture effect is unknown. Some studies have shown that brain circuits related to the control of the autonomic nervous system, emotional, memory and cognitive processing are modulated by acupuncture. These circuits overlap the circuits related to psychopathology of anxiety. Thus, in this paper, we presented a hypothesis about how the acupuncture can reduces anxiety through modulation of brain circuits. In conclusion, the consulted literature showed that acupuncture has the potential to modulate the brain regions implicated in the anxious behaviors. Nonetheless, future studies should be done to elucidate the neuroendocrine mechanisms of acupuncture in the anxiety disorders.
... However, previous findings in HC are inconsistent. Some studies provided showed evidence that acupoints may have their functional specificity (He et al., 2015), whereas other findings Hui et al., 2009) showed that no statistical difference was found between acupoints and sham acupoints. This may be explained by similar segmental innervations in HC. ...
Article
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The neural mechanisms of acupuncture are not well-understood. Over the past decades, an increasing number of studies have used MRI to investigate the response of the brain to acupuncture. The current review aims to provide an update on acupuncture therapy in disease. The PubMed, Embase, Web of Science, and Cochrane Library databases were searched from inception to January 31, 2021. Article selection and data extraction were conducted by two review authors. A total of 107 publications about MRI in acupuncture were included, the collective findings of which were as follows: (1) stroke and GB34 (Yanglingquan) are the most studied disease and acupoint. Related studies suggested that the mechanism of acupuncture treatment for stroke may associate with structural and functional plasticity, left and right hemispheres balance, and activation of brain areas related to movement and cognition. GB34 is mainly used in stroke and Parkinson's disease, which mainly activates brain response in the premotor cortex, the supplementary motor area, and the supramarginal gyrus; (2) resting-state functional MRI (rs-fMRI) and functional connectivity (FC) analysis are the most frequently used approaches; (3) estimates of efficacy and brain response to acupuncture depend on the type of sham acupuncture (SA) used for comparison. Brain processing after acupuncture differs between patients and health controls (HC) and occurs mainly in disorder-related areas. Factors that influence the effect of acupuncture include depth of needling, number and locations of acupoints, and deqi and expectation effect, each contributing to the brain response. While studies using MRI have increased understanding of the mechanism underlying the effects of acupuncture, there is scope for development in this field. Due to the small sample sizes, heterogeneous study designs, and analytical methods, the results were inconsistent. Further studies with larger sample sizes, careful experimental design, multimodal neuroimaging techniques, and standardized methods should be conducted to better explain the efficacy and specificity of acupuncture, and to prepare for accurate efficacy prediction in the future.
... For instance, numbness is related to the conduction of A / fibers, whereas swelling sensation is related to A fibers, and soreness is related to C fibers. 30 Nociceptive sensory nerve endings express different receptors, for instance ion-channel receptors such as TRPV1 receptors, excitatory amino acids, TLR, as well as TNFs, IL-6, and prostaglandin receptors, among others. Various receptors would sense acupuncture stimulus and be activated to a certain or lower excitation threshold. ...
Article
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Acupuncture is a centuried and unfading treatment of traditional Chinese medicine, which has been proved to exert curative effects on various disorders. Numerous works have been put in to uncover the effective mechanisms of acupuncture. And the interdependent interaction between acupuncture and acupoint microenvironment is a crucial topic. As a benign minimally invasive stimulation, the insertion and manipulation of needle at acupoint could cause deformation of local connective tissue and secretion of various molecules, such as high mobility group box 1 and ATP. The molecules are secreted into extracellular space and bind to the corresponding receptors thus active NF-B, MAPK, ERK pathways on mast cells, fibroblasts, keratinocytes, and monocytes/macrophages, among others. This is supposed to trigger following transcription and translation of immune factors and neural active substance, as well as promote the free ion movement (such as Ca 2+ influx) and the expansion of blood vessels to recruit more immune cells to acupoint. Finally, acupuncture could enhance network connectivity of local microenvironment at acupoints. The earlier mentioned substances further act on a variety of receptors in local nerve endings, transmitting electrical and biochemical signals to the CNS, and giving full play to the acupuncture action. In conclusion, we portrayed a neuro-immune microenvironment network of acupoints that medicates the acupuncture action, and would lay a foundation for the systematic study of the complex network relationship of acupoints in the future.
... There is a close physiologic and pathologic relationship between the cardiovascular and nervous systems, as evidenced by the observation that myocardial injury, can lead to inactivation of neurons in speci c brain regions [2]. Electroacupuncture( EA ) regulates interactions within neural networks [3,4] and has been used in the treatment of various diseases, including cardiovascular disorders [5]. There is substantial evidence for the e cacy of EA in the treatment of AMI [6][7][8]. ...
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Background: Electroacupuncture (EA) alleviates acute myocardial ischemia (AMI) by regulating some brain areas, including hippocampus. The locus coeruleus (LC) is the main source of norepinephrine (NE) in the brain, including the hippocampus, and regulates cardiovascular function. The aim of the present work was to assess whether LC mediates the positive effects of EA in AMI by altering gene expression levels in the hippocampus. We addressed this in the present study by hippocampus transcriptome profiling in a rat model of AMI following EA treatment. Results: Myocardial injury markers (ischemia-modified albumin, homocysteine and lipoprotein- associated phospholipase A2) in the serum were downregulated in EA (P<0.05) compared to the M group and upregulated in E+L group (P<0.05) compared to E group. RNA sequencing analysis of the hippocampus revealed that the downregulation of 27 genes in M vs S as well as upregulation of 40 genes in M vs S were reversed by EA. These differentially expressed genes, which were validated by quantitative real-time PCR, were enriched in 20 Kyoto Encyclopedia of Genes and Genomes pathways related to glycerolipid, glycerophospholipid, and arachidonic acid metabolism as well asnervous system function (glutamatergic, cholinergic, serotonergic, GABAergic synapses). Conclusions: LC mediates the beneficial effects of EA on AMI-induced injury may be related to the observed transcriptional regulations in the hippocampus. These results provide molecular-level evidence for the therapeutic efficacy of EA in the treatment of AMI.
... Acupuncture has increasingly been integrated into health care systems, and its effectiveness in treating different conditions has been investigated. Prolonged acupuncture can modulate the interrelationships of the internal functions of the wholebrain network [29,30]. ...
Article
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The locus coeruleus (LC) is closely linked with cardiovascular disease. However, whether it mediates the alleviating effect of electroacupuncture (EA) on acute myocardial ischemia (AMI) remains unclear. A rat model of myocardial ischemia was established through occlusion of the left anterior descending coronary artery. Multichannel in vivo recording and other techniques were used to assess neurons in the LC, norepinephrine (NE) and dopamine (DA) levels in central and myocardial tissue, serum levels of inflammatory factors, and cardiac function. After induction of AMI, LC neuron activity increased and the central NE concentrations increased, while those of DA decreased. Moreover, the serum levels of high-sensitivity C-reactive protein (hs-CRP) increased, whereas those of interleukin-10 (IL-10) decreased. However, these effects were reversed by EA. Additionally, LC lesioning affected NE and DA levels in myocardial tissue and weakened the antimyocardial ischemic effect of EA. Collectively, our results indicated that LC is closely related to AMI and plays an important role in the antimyocardial ischemic effect of EA. This mechanism may be related to inhibition of LC neuron activity by EA, which inhibits the release of large amounts of hs-CRP and promotes that of IL-10 in the serum. Besides, after LC lesioning, EA may improve cardiac function by inhibiting the release of large amounts of NE and promoting the release of DA in myocardial tissue.
... Other preclinical studies highlight specific brain regions such as paraventricular nucleus for cardiovascular modulation by acupuncture (Cheng et al.) and cuneate nucleus in drug dependence (Chang et al.). Human research studies explore the role of the brain's default mode network, previously implicated in acupunctureevoked brain response and analgesia (Hui et al., 2009;Napadow et al., 2012), in acupuncture clinical response more broadly (Zhang et al.). Human neuroimaging studies in this issue also evaluate potential brain-based mechanisms of acupuncture for motor outcomes (Nierhaus et al.) and itch (Min et al.). ...
... However, acupuncture-treated patients demonstrated global deactivation in the DMN and activation of its anticorrelation (Figure 3b), which is consistent with the results from a task fMRI study demonstrating that acupuncture may mobilize the brain's default mode and its anticorrelated network in healthy controls (Hui et al., 2009). ...
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Aims: To investigate the functional connectivity (FC) in nonacute sciatica and the neuronal correlation of acupuncture analgesia. Methods: A prospective study employing resting-state functional magnetic resonance imaging was conducted. Twelve sciatica patients were enrolled to receive six or 18 acupoints of acupuncture treatment twice a week for 4 weeks. Regional homogeneity (ReHo) and seed-based FC were performed. Results: Regional homogeneity analysis demonstrated a greater alteration in the right posterior cingulate cortex (PCC) during the pre-acupuncture phase than during the postacupuncture phase. Compared to that of healthy controls, the PCC-seeded FC (default mode network, DMN) of sciatica patients exhibited hyperconnectivity of PCC-FC with the PCC-bilateral insula, cerebellum, inferior parietal lobule, right medial prefrontal cortex, and dorsal anterior cingulate cortex during the pre-acupuncture phase as well as hypoconnectivity of PCC-FC with the right cerebellum, left precuneus, and left dorsal medial prefrontal cortex during the postacupuncture phase. Correlation analysis between PCC-seeded FC and behavior measurements revealed a positive association with the duration of sciatica in the right inferior parietal lobule prior to acupuncture treatment. Conclusions: Acupuncture in chronic sciatica patients is associated with normalized DMN activity and modulation of descending pain processing. The changes in the subclinical endophenotype of brain FC after acupuncture treatment may provide clues for understanding the mechanism of acupuncture-mediated analgesia in chronic pain.
... As already elucidated, current evidence suggests that any kind of needling procedure constitutes a nociceptive and/or pain signal (Biella et al., 2001;Pariente et al., 2005;Beissner et al., 2012;Theysohn et al., 2014); for overview and discussion see Wang et al. (2008), Zhao (2008), Beissner et al. (2012), and that acupuncture needling (a meta-analysis across 28 fMRI studies) induces an activation of the pain matrix (sensorimotor cortical network, including the insula, thalamus, anterior cingulate cortex, and both primary and secondary somatosensory cortices) (Chae et al., 2013). Moreover, data from healthy humans subjects in response to needling of commonly used acupuncture points for the treatment of pain syndromes (manual acupuncture at LI4, ST36) revealed a partial overlap with the pain matrix as well as a deactivation of a limbic-paralimbic-neocortical network (Hui et al., 2009;Claunch et al., 2012). This limbic deactivation is correlated to the psychophysical response modulating the bottom-up nociceptive signal. ...
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Several control conditions, such as penetrating sham acupuncture and non-penetrating placebo needles, have been used in clinical trials on acupuncture effects in chronic pain syndromes. All these control conditions are surprisingly effective with regard to their analgesic properties. These findings have fostered a discussion as to whether acupuncture is merely a placebo. Meta-analyses on the clinical effectiveness of placebo revealed that placebo interventions in general have minor, clinically important effects. Only in trials on pain and nausea, including acupuncture studies, did placebo effects vary from negligible to clinically important. At the same time, individual patient meta-analyses confirm that acupuncture is effective for the treatment of chronic pain, including small but statistically significant differences between acupuncture and sham acupuncture. All acupuncture control conditions induce de qi, a distinct stimulation associated with pain and needling which has been shown to be a nociceptive/pain stimulus. Acupuncture therefore probably activates the pain matrix in the brain in a bottom-up fashion via the spino-thalamic tract. Central nervous system effects of acupuncture can be modulated through expectations, which are believed to be a central component of the placebo response. However, further investigation is required to determine how strong the influence of placebo on the attenuation of activity in the pain matrix really is. A meta-analysis of individual participant functional magnetic imaging data reveals only weak effects of placebo on the activity of the pain network. The clinical acupuncture setting is comprised of a combination of a distinct neurophysiological stimulus, the needling stimulus/experience, and a complex treatment situation. A broader definition of placebo, such as that proposed by Howick (2017) acknowledges a role for expectation, treatment context, emotions, learning, and other contextual variables of a treatment situation. The inclusion of particular treatment feature as a definitional element permits a contextual definition of placebo, which in turn can be helpful in constructing future clinical trials on acupuncture.
... On the contrary, aromatic herbs, such as Bo He (Peppermint) and Mu Xiang (Radix Auklandiae Lappae), are used in clinic to moves Qi, relieve Pain, and regulate the Middle Jiao with the property of spicy, so they should be cooked for periods shorter than 20 minutes. For the purpose keeping aroma, cook the rest of the herbs first and finally add these aromatic herbs to keep volatile oils from quick evaporation.DiscussionDeqi, which is believed to be an important variable in the studies of the mechanism and efficacy of acupuncture treatment, has attracted much more attention in recent years and great efforts like to qualify and quantify deqi sensations with questionnaires, neuroimaging studies of deqi and acupuncture, physiological mechanisms of deqi, and the relation between deqi and clinical efficacy have been made to learn more about deqi and explore if deqi sensation can be achieved through manipulation and the needle retaining to strengthen deqi sensation[11]. Hyperuricemia in TCM is viewed as the result of dampness, which is classified as Yin, in the body on the base of Spleen qi deficiency. ...
... This elevation in temperature may be related to an increase in blood flow induced by deqi [45,46]. Several studies have suggested that deqi involves extensive deactivation of blood oxygen-level dependent signals in multiple regions of the brain, such as mesial prefrontal cortex, medial temporal lobe, middle temporal gyrus, fusiform gyrus, and lingual gyrus [47][48][49][50] these regions are related to the limbic-paralimbic-neocortical network which has been implicated by multiple studies as potentially involved in acupuncture analgesia via serotonin and dopamine release [51]. In our prior work, while an alleviation of pain occurred in patients who did not self-report deqi, this effect was greater in those who did [40]. ...
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Although deqi, the phenomenon whereby excitation of Qi in the meridians occurs with needling, is critical to the practice of acupuncture and its efficacy, it is poorly understood. So we investigate the influence of the deqi sensation on the analgesic effects of acupuncture in patients who were enrolled in a randomised controlled trial for the treatment of patients with primary dysmenorrhea, a painful and common condition, and cold and dampness stagnation . Two groups were assessed: a deqi group (undergoing deep needling with thick needles and manipulation, n=17) and a non-deqi group (undergoing shallow needling with thin needles and no manipulation, n=51). The Sanyinjiao (SP6) was needled for 30 min in both groups. Pain scores at baseline, upon needle removal, and at 10, 20, and 30 min after needle removal were evaluated by the Visual Analogue Scale for pain. The deqi sensation was evaluated by the Acupuncture Deqi Clinical Assessment Scale. Patients who experienced a genuine deqi sensation (n=39) were selected for further analysis. Compared with patients in the non-deqi group who experienced deqi (n=25), patients who self-reported deqi in the deqi group (n=14) felt a stronger deqi sensation, experienced soreness and fullness more frequently, felt a greater intensity of soreness, fullness, electric sensation, spreading, and radiating, and experienced larger spreading distances. In those who experienced the deqi sensation in the deqi group, the intensity of the sensation, as well as their degree of soreness and fullness, was negatively correlated with pain reduction. In patients who experienced the deqi sensation in the non-deqi group, deqi intensity was positively correlated with pain reduction, while soreness was negatively correlated with pain reduction. The distance of spreading was not correlated with pain reduction in either group. We found, in SP6 needling of patients with primary dysmenorrhea with cold and dampness stagnation , that a moderate deqi response predicted a prolonged analgesic effect better than a strong deqi response.
... [19,20] However, recent studies suggest that neural responses to event-related tasks also rely on the integrity of the resting-state networks. [21,22] fMRI allows evaluation of changes in neural responses following removal of an acupuncture needle, and studies have demonstrated that the resting-state network may be altered after acupuncture stimulation and removal of the needle. [21,23,24] A method called regional homogeneity (ReHo) has been used to investigate functional modulations during the resting-state in patients with PD. [25] ReHo reflects the temporal homogeneity of the regional blood-oxygen-level-dependent (BOLD) signal. ...
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Background: Parkinson's disease (PD) is a degenerative brain disorder, resulting in decreased neural responses in the supplementary motor area, putamen, and thalamus. Previous research showed that acupuncture was able to improve the motor dysfunction. The primary aim of this study is to assess the efficacy of longer acupuncture treatment for preventing brain degeneration in patients with PD. Methods: Ten outpatients with PD were recruited from Kyung Hee Medical Hospital. Behavioral and neural responses were examined before and after 8 weeks of acupuncture treatment. A semi-individualized treatment approach was used; patients were treated for 15 minutes with 120-Hz electro-acupuncture at the right GB34 and Taechung (LR3), followed by manual acupuncture based on the individual symptoms of the patient. Results: Immediately after 8 weeks of acupuncture treatment, the Unified Parkinson's Disease Rating Scale (UPDRS) sub-scores and the depression scores for the patients had statistically decreased compared to the scores before acupuncture treatment; moreover, 8 weeks later, these scores remained stable. Compared to the neural responses before the acupuncture stimulation, those after the acupuncture treatment were significantly higher in the thalamus, cingulate gyrus, anterior cingulate, lingual gyrus, parahippocampal gyrus, lateral globus pallidus, mammillary body, middle temporal gyrus, cuneus, and fusiform gyrus. Finally, a positive correlation was found between the UPDRS and the mean magnetic resonance signal change for the thalamus. Conclusion: This study found beneficial clinical effects of 8-week acupuncture treatment in the brains of patients with PD.
... These studies mapped the brain regions involving in acupuncture effect. For example, Hui. and her co-investigators found that acupuncture with deqi can elicit extensive negative BOLD signal changes (deactivation) in the limbic-paralimbic-neocortical network (LPNN) and positive BOLD signal changes in somatosensory regions of the brain [53]. This study provided functional brain imaging evidence of the influence of deqi on cerebral activity. ...
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Background: The mechanism of the long-lasting effect and the relationship between the long-lasting effect and the deqi sensation, which is the key of achieving the acupuncture effect, has not been well investigated. This trial focuses on investigating the possible central mechanism of the long-lasting effect influenced by the deqi sensation. Methods: A randomized controlled functional brain imaging trial is currently being conducted in Sichuan, China. In total 105 functional dyspepsia (FD) patients will be allocated into three groups: an acupuncture with deqi group, an acupuncture without deqi group, and a wait-list group. This trial will include a 2-week baseline period, a 4-week treatment period, and a 4-week follow-up period. During the 4-week treatment, patients in two acupuncture groups will receive 20 sessions of acupuncture treatment with or without deqi. The Nepean Dyspepsia Index (NDI) and the short form Leeds Dyspepsia Questionnaire (SF-LDQ) will be used to evaluate the clinical efficacy of acupuncture treatment at baseline, the end of treatment, and the end of the follow-up. Functional magnetic resonance imaging (fMRI) scans will be performed to detect cerebral functional changes in 25 patients in each group at three time points mentioned above. The clinical data and fMRI data will be analyzed, respectively. Correlation analysis will be conducted to investigate the relationship between cerebral functional changes and symptom improvement. Discussion: The results of this trial will allow us to compare the changes of acupuncture therapeutic effect at three time points (the baseline vs. the end of treatment vs. the end of follow-up), and investigate the potential central mechanism of the long-lasting effect influenced by acupuncture with deqi. This trial aims to re-identify the long-lasting effect of acupuncture and investigate its central mechanism, and to further explore the central influence of deqi sensation on the long-lasting effect. Trial registration: Chinese Clinical Trial Registry, IDF: ChiCTR-IOR-15006523 . Registered on 5 June 2015.
... Furthermore, through electroacupuncture stimulation, it has been shown that the limbic/paralimbic regions, such as the amygdala, hippocampus, and anterior cingulate cortex, form a neural network center [20]. During the process of acupuncture, these brain regions play an important role in the regulation of the specific functions of the whole-brain network [21]. PVN is the central integrated area and the most important central site, which directly regulates sympathetic efferent activity. ...
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We investigated the hippocampus-paraventricular nucleus- (PVN-) sympathetic nerve pathway in electroacupuncture (EA) at the heart meridian for the treatment of myocardial ischemia by observing PVN neuronal discharge, sympathetic nerve discharge, and hemodynamics parameters. Sprague Dawley (SD) rats were equally divided into four groups: Sham, Model, Model + EA, and Model + EA + Lesion. The model rat was established by ligating the left anterior descending branch of the coronary artery. Changes in the sympathetic nerve discharge and hemodynamic parameters were observed. The Model + EA exhibited a significantly lower discharge frequency of PVN neurons compared with the Model. The Model + EA + Lesion had a significantly higher discharge frequency compared with the Model + EA. The total discharge frequency of PVN neurons and interneurons were positively correlated with the sympathetic nerve discharge. The total discharge frequency of PVN neurons was positively correlated with heart rate (HR) and negatively correlated with mean arterial pressure (MAP) and rate pressure product (RPP). The discharge frequency of interneurons was positively correlated with HR and negatively correlated with MAP and RPP. The hippocampus-PVN-sympathetic nerve pathway is involved in electroacupuncture at the heart meridian and interneurons are the key neurons in PVNs.
... [1][2][3] Over the past 20 years, functional magnetic resonance imaging (fMRI) has been widely used to image the brain in acupuncture studies. Many fMRI studies [4][5][6][7][8] have examined acupuncture specificity by comparing different acupoints, real and sham acupoints, or true and sham acupuncture. The technique with twirling manipulation was commonly used. ...
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Objective: To investigate the effects on the brain using three needling manipulations (twirling, lifting-thrusting, and twirling plus lifting-thrusting) when the right-side Zusanli (ST 36) acupoint was stimulated with needles. Methods: Seventeen healthy subjects accepted three needling manipulations stimulating the right Zusanli (ST 36) over separate days. Functional magnetic resonance imaging was used to detect changes in the brain during the manipulations, and then the needling sensations were recorded using the MGH acupuncture sensation scale (MASS) after each scan. fMRI data were processed using Statistical Parametric Mapping 8 to analyze the positive and negative activation in the brain induced by different acupuncture manipulations. Results: The individual needling sensations showed no statistically significant differences among the three manipulations. However, the MASS index showed that lifting-thrusting > twirling plus lifting-thrusting > twirling. Lifting-thrusting activated left premotor cortex, left postcentral, right middle frontal gyrus, left inferior frontal gyrus, right lingual gyrus, left insula, right putamen, bilateral cingulate gyrus and right cerebellum; and deactivated bilateral hippocampus and left caudate. Twirling activated bilateral orbital middle frontal gyrus, left opercular and triangular inferior frontal gyrus, and right middle occipital gyrus; and deactivated bilateral precuneus, right amygdala, left anterior cingulate gyrus, right inferior temporal gyrus, right middle frontal gyrus, right supplementary motor gyrus, and left postcentral. Twirling plus lifting-thrusting activated bilateral postcentral, left inferior occipital gyrus, left insula, left thalamus, left cingulate gyrus, and right putamen; and deactivated right superior frontal gyrus, right superior parietal gyrus, right temporal gyrus, right middle occipital gyrus, right insula, and left lingual gyrus. Pairwise comparisons of the three manipulations showed that signals induced by lifting-thrusting were the strongest, especially in the limbic system, followed by twirling plus lifting-thrusting; twirling alone was the weakest. Conclusion: Three methods of needling manipulations similarly activated areas associated with the somatosensory system, vision, cognition, and emotional regulation. This may have significant implications for acupuncture in clinical practice.
... Furthermore, Asghar et al. [31] reported a synergistic signal attenuation in the middle temporal gyrus, the fusiform gyrus, and the lingual gyrus when the subjects sensed De Qi sensations. These regions are all related to the limbic-paralimbic-neocortical network (LPNN) [32]. Bai et al. [33] and Wu et al. [34] obtained similar results. ...
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Background De Qi is a special sensational response upon acupuncture needling. According to traditional acupuncture theory, the treatment is “effective only after Qi arrival”; that is, De Qi is an important indicator of therapeutic efficacy and good prognosis. However, it is still disputable whether De Qi improves the efficacy of acupuncture therapy. This prospective, randomized controlled trial aims to explore the influence of De Qi induced by acupuncture on immediate and accumulated analgesic effects in patients with knee osteoarthritis (KOA). Methods/design Eighty-eight patients with KOA will be recruited and randomly assigned to the De Qi group (enhanced stimulation to evoke De Qi) and the control group (weak stimulation to avoid De Qi) in the Department of Acupuncture and Physical Therapy, Beijing Luhe Hospital Affiliated to Capital Medical University. Each patient will receive three 30-minute sessions per week for 4 consecutive weeks and undergo a 1 month follow-up. The severity of knee pain, as measured on a 100-mm visual analog scale (where 0 indicates no pain and 100 indicates intolerable pain) will be used as the primary outcome, and the Knee injury and Osteoarthritis Outcome Score will be used as the secondary outcome. Both indexes will be measured before and after the 1st (for evaluating the immediate analgesic effects), 3rd, 6th, 9th, and 12th (for evaluating the accumulated analgesic effects) treatments and at the end of the follow-up. The intensity of the De Qi sensation will be assessed by the Chinese-Modified Massachusetts General Hospital Acupuncture Sensation Scale at the end of each treatment. Side effects during the treatments will be recorded and analyzed as well. The comparisons between the De Qi group and the control group will be done by using both an intention-to-treat analysis and a per-protocol analysis. Discussion This prospective randomized controlled study will be helpful in enhancing our understanding of the analgesic effect of De Qi on patients with KOA and may provide a clinical basis for further investigation of the relationship between De Qi and the therapeutic efficacy of acupuncture, thereby offering some evidence for the role of De Qi in an efficacious acupuncture therapy. Trial registration Chinese Clinical Trial Registry, ChiCTR-IIR-16008972. Registered on 4 August 2016 Additional file 2. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-1975-7) contains supplementary material, which is available to authorized users.
... Moreover, researches have demonstrated that the aging brain can still morph, reorganize and change (Kuo et al., 2013;Gutchess, 2014). Hence, it is possible that neuro-stimulation like this produced by tDCS could influence ameliorate-specific parts of the brain, as well as the anticorrelated functional networks of the brain in order to control ameliorate effects (Li et al., 2003;Hui et al., 2009). Studies have shown significant changes in brain activity in the medial temporal lobes and temporoparietal cortex (TPC) during a memory task in AD patients (Rémy et al., 2005). ...
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Transcranial direct current stimulation (tDCS) is a widely-used tool to induce neuroplasticity and modulate cortical function by applying weak direct current over the scalp. In this review, we first introduce the underlying mechanism of action, the brief history from discovery to clinical scientific research, electrode positioning and montages, and parameter setup of tDCS. Then, we review tDCS application in clinical samples including people with drug addiction, major depression disorder, Alzheimer's disease, as well as in children. This review covers the typical characteristics and the underlying neural mechanisms of tDCS treatment in such studies. This is followed by a discussion of safety, especially when the current intensity is increased or the stimulation duration is prolonged. Given such concerns, we provide detailed suggestions regarding safety procedures for tDCS operation. Lastly, future research directions are discussed. They include foci on the development of multi-tech combination with tDCS such as with TMS and fMRI; long-term behavioral and morphological changes; possible applications in other research domains, and more animal research to deepen the understanding of the biological and physiological mechanisms of tDCS stimulation.
... This parameter is a classical behavioral indicator of open space-induced anxiety (Pellow et al. 1985). Activity in the open arms reflects a conflict between the rodent's preference for protected areas (such as the ones presented by the walls of the closed arms) and their innate drive toin the central nervous system depends on the kind of tissue in the accupoint region, usually muscular and conjunctive tissues (Hui et al. 2005, Fang et al. 2007), the presence of nervous fibers (Hui et al. 2007Hui et al. , 2009) and the stimulus type (Claunch et al. 2012) The unexpected effect of EEA applied in the rat tail, at first considered as a " non-point " , raises a discussion about the acupuncture specificity. It is important to mention that the designation of a " real acupuncture point " is empirical (Fang et al. 2009). ...
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The aim of this work was to investigate if eletroacupuncture at PC6 would modulate the stress-induced anxiety-like behavior and the level of activation of several brain areas. Rats were distributed in groups: control; submitted to immobilization; submitted to immobilization and eletroacupuncture at PC6 or at the tail. Immobilization increased grooming and decreased stretched attend postures and the time spent in the open arms of the ele-vated plus-maze. Eletroacupuncture at PC6 or tail canceled the effect of immobilization on grooming and attenuated the stretched attend posture. Immobilization increased Fos-immunoreactivity in the prefrontal cortex, medial and central amygdala, paraventricular and dorsomedial nuclei of the hypothalamus, lateral hypothalamus, dentate gyrus, CA1, CA2 and CA3 hippocampal areas. The activation of paraventricular, dorsomedial nuclei and prefrontal cortex by immobilization was canceled by electroacupuncture at PC6 and attenuated by electroacupuncture in the tail. The activation of the other areas was canceled by electroacupuncture in PC6 or the tail. It is concluded that immobilization induced anxiety-like behavior that was moderately attenuated by eletroacupuncture with difference between the stimulation in PC6 or the rat tail. Eletroacupuncture showed specificity concerning to the attenuation of the effects of immobilization in the CNS areas related to the stress response, anxiety and cardiovascular system.
... This method has been used in investigating CFS patients and has revealed differences between CFS patients and healthy people 20 . Acupuncture has been shown to influence the central nervous system 21 and the functional status of the ANS in humans 22,23 and laboratory animals 24 . Acupuncture has also been shown to be effective in modulating HRV, although there was not sufficient evidence to determine if HRV could be an indicator of the therapeutic effect of acupuncture 25 . ...
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In order to investigate the different effects of acupuncture and moxibustion on chronic fatigue syndrome (CFS) and alterations in the autonomic nervous system by measuring heart rate variability (HRV). Forty-five participants were recruited and randomly divided into 3 groups using a randomization schedule. The control group (CG, n = 15) and the acupuncture group (AG, n = 15) were treated by manipulation acupuncture, and the moxibustion group (MG, n = 15) was treated by indirect moxibustion. Primary outcomes were the scores of the Fatigue Assessment Instrument (FAI). Secondary outcomes were the HRV parameters which can reflect activity of the autonomic nervous system. This trial considered both instantaneous changes and long-term effectiveness. FAI scores decreased after the 4th and 10th treatments in the 3 groups. The decrease in FAI in the MG was greater than that in the AG. Acupuncture was more effective in instantaneous changes of HRV and moxibustion in long-term aspects. Both acupuncture and moxibustion improved fatigue in CFS patients, but moxibustion was more effective. The possible mechanism of the intervention may be through activation of the vagus nerve. Moxibustion was more effective than acupuncture in long-term treatment of CFS.
... Studies with functional magnetic resonance imaging and acupuncture points have shown the possibility that these points increase or decrease activation of the brain areas rather than changing the motor behavior [4]. We have found studies of activation of the brainstem, basal ganglia, cerebellum [18e22], thalamus and insula [23], and motor area [24]. ...
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We previously showed that a yin meridian of the upper limb decreased electromyographic activity (root mean square) and muscle strength ipsilateral and contralateral to the side of stimulation. Here, we tested the upper trapezius (UT) muscle response after stimulation of a yang meridian of the upper limb, the small intestine (SI). Thirty-eight healthy volunteers were randomized into the following groups: UT muscle (SI14), distant of the UT muscle (SI8), without stimulation (CG), and sham (R3). An acupuncturist certificated by the Brazilian Society of Physical Therapists and Acupuncturists performed the needle insertion. Each volunteer received only one stimulation to the right upper limb. The evaluation occurred before, 5 minutes after, and 20 minutes after needle withdrawal. The root mean square activity increased on the right side in the UT muscle for the SI8 and SI14 groups (F3,37 = 4.67; p < 0.025) at the 20-minute evaluation. The most vigorous response occurred on the contralateral side because the effects were maintained for 5 minutes after withdrawal (F3,37 = 4.52; p < 0.025). Both groups showed an increase in the UT muscle strength at the 20-minute evaluation (F3,37 = 3.41; p < 0.025). The CG and R3 groups did not show any changes. Our data indicate that SI a yang meridian increases the UT muscle response.
... Dhond et al. (2008) showed increased DMN connectivity with limbic antinociceptive (anterior cingulated cortex, periaqueductal gray), affective (amygdala, anterior cingulated cortex), and memory (hippocampal formation, middle temporal gyrus) related brain regions following acupuncture, but not sham. The DMN was deactivated during acupuncture stimulation (Bai et al., 2009;Napadow et al., 2013), but not when acupuncture was associated with sharp pain (Hui et al., 2009). For chronic pain conditions, such as chronic lower back pain and migraine, the pain relief was correlated with DMN alteration after acupuncture treatments Zhao et al., 2014). ...
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Acupuncture can have instant and sustained effects, however, its mechanisms of action are still unclear. Here, we investigated the sustained effect of acupuncture by evaluating centrality changes in resting-state functional magnetic resonance imaging after manually stimulating the acupuncture point ST36 at the lower leg or two control point locations (CP1 same dermatome, CP2 different dermatome). Data from a previously published experiment evaluating instant BOLD effects and S2-seed-based resting state connectivity was re-analyzed using eigenvector centrality mapping and degree centrality mapping. These data-driven methods might add new insights into sustained acupuncture effects on both global and local inter-region connectivity (centrality) by evaluating the summary of connections of every voxel. We found higher centrality in parahippocampal gyrus and middle temporal gyrus after ST36 stimulation in comparison to the two control points. These regions are positively correlated to major hubs of the default mode network, which might be the primary network affected by chronic pain. The stronger integration of both regions within the whole-brain connectome after stimulation of ST36 might be a potential contributor to pain modulation by acupuncture. These findings highlight centrality mapping as a valuable analysis for future imaging studies investigating clinically relevant outcomes associated with physiological response to acupuncture stimulation. Clinical trial registration: NCT01079689, ClinicalTrials.gov.
... Recently, rsFC has been used to investigate the underlying mechanism of acupuncture in healthy subjects (Bai et al., 2009;Dhond et al., 2008;Hui et al., 2009;Liu et al., 2009;Qin et al., 2008;Zhong et al., 2012) and patient populations, such as patients with MDD (Deng et al., 2016;Yi et al., 2012), knee osteoarthritis Egorova et al., 2015), migraines and Alzheimer's disease . For instance, investigators found that peripheral nerve stimulation and acupuncture can significantly modulate the rsFC of the default mode network (Deng et al., 2016;Fang et al., 2016), amygdala , and anterior cingulate cortex (Yi et al., 2012) in MDD patients. ...
... Previous research has demonstrated that acupuncture modulates activity within specific brain areas related to pain, including the somatosensory cortex and the limbic system, 20 and deactivates the LPNN. 21 Patterns of activation and deactivation following acupuncture suggest that the haemodynamic responses in the brain simultaneously reflect the sensory, cognitive, and affective dimensions of pain. 22 However, further research is needed to determine whether the mechanism of deactivation of key brain areas involved in pain differs between males and females following needling at GB34, and whether this influences its efficacy in terms of pain or other clinical outcomes. ...
Article
Objective To examine gender differences and similarities in the psychophysical and brain responses to acupuncture at GB34, a point that is frequently used to treat motor function issues in Traditional Chinese Medicine. Methods Functional MRI (fMRI) was used to measure brain activation in response to acupuncture at GB34 (on the right) in 19 healthy participants (9 male, 10 female). De qi sensations were rated to measure their psychophysical responses. Results Overall de qi scores did not differ by gender, although females reported greater intensity of aching (p=0.04). Acupuncture activated the hippocampus, thalamus, globus pallidus, caudate body, claustrum, cingulate gyrus, and culmen in males, and the middle and inferior frontal gyrus, precuneus, postcentral gyrus, inferior parietal lobule, superior temporal gyrus, caudate body, insula, fusiform gyrus, cingulate gyrus, amygdala, and parahippocampal gyrus in females. The middle/medial frontal gyrus, middle temporal gyrus, thalamus, globus pallidus, caudate body, uvula, and cerebellar tonsil were activated when data from all subjects were combined. Relative to males, females exhibited greater brain activation in the right-sided postcentral gyrus, precentral gyrus, precuneus, postcentral gyrus, inferior parietal lobule, declive, middle occipital gyrus and parahippocampal gyrus. Conclusions The neural effects of GB34 acupuncture might differ between males and females because different brain structures were modulated in response to acupuncture. This potential gender effect should be taken into account in future clinical research. We also revealed that the caudate body was activated by GB34 acupuncture in both males and females and may represent a major target of GB34 acupuncture. Trial registration number KMC IRB 0861-06.
... Since the 1990s, advances in non-invasive brain imaging techniques such as positron emission tomography and functional magnetic resonance imaging (fMRI) have enabled direct study of the human brain [12][13][14][15][16][17][18][19][20][21][22][23][24] . Studies conducted using fMRI have provided evidence of acupoint specificity by demonstrating a correlation between acupoints and brain activation [25][26][27][28][29] . These findings have indicated that acupuncture, at disease-implicated acupoints, can modulate the activity of the disease-related neuromatrix. ...
Article
Positive activation and negative activation of glucose metabolism can be detected in different brain regions under acupuncture conditions using functional magnetic resonance imaging (fMRI) which reveals acupoint function and location-acupoint specificity. This study observed the regional cerebral activation of the Waiguan (SJ 5) acupoint following true needling at the true Waiguan acupoint, sham needling at the true Waiguan acupoint and true needling at a sham point using fMRI. The fMRI results demonstrated that compared with sham needling, true needling at Waiguan activated the BA8 area and left cerebellum. Compared with needling at the sham point, needling at Waiguan activated the BA2 area, the left cerebellum and the right inferior semilunar lobule. Thus the activated brain areas caused by needling Waiguan may be the basis for treatment of certain diseases.
Article
Background: There is a relationship between low back pain (LBP) and central nervous system dysfunction. Needling therapies (e.g. acupuncture, dry needling) are proposed to impact the nervous system, however their specific influence is unclear. Purpose: Determine how needling therapies alter functional connectivity and LBP as measured by functional magnetic resonance imaging (fMRI). Methods: Databases were searched following PRISMA guidelines. Studies using fMRI on individuals with LBP receiving dry needling or acupuncture compared to control or sham treatments were included. Results: Eight studies were included, all of which used acupuncture. The quality of studies ranged from good (n = 6) to excellent (n = 2). After acupuncture, individuals with LBP demonstrated significant functional connectivity changes across several networks, notably the salience, somatomotor, default mode network (DMN) and limbic networks. A meta-analysis demonstrated evidence of no effect to potential small effect of acupuncture in reducing LBP (SMD -0.28; 95% CI: -0.70, 0.13). Conclusion: Needling therapies, like acupuncture, may have a central effect on patients beyond the local tissue effects, reducing patients' pain and disability due to alterations in neural processing, including the DMN, and potentially other central nervous system effects. The meta-analysis should be interpreted with caution due to the narrow focus and confined sample used.
Article
Objective To conduct an inductive analysis of neuroimaging studies following the global popularity surrounding the effects of acupuncture. Methods The 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. Results Neuroimaging research on the effects of acupuncture began in the 1960s 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. Conclusions This 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.
Article
There is significant overlap in the cerebral pain matrix within the brain networks associated with both normal pain stimulation and acupuncture needle stimulation. In recent years, significant efforts have been made to scientifically support the longtime effects of acupuncture treatment. The extent to which functional magnetic resonance imaging (fMRI) was able to expand the knowledge of the central mode of action of acupuncture is the subject of this review.The hemodynamic-metabolic reactions of the brain to acupuncture stimulation reflect sensory discriminatory as well as cognitive and affective pain dimensions. Disruptive factors such as pain, emotions, and sensory influences during acupuncture contribute at least partially to the pattern of brain activity. The increasing number of fMRI studies shows a complex mechanism of action of acupuncture in the sense of a modulation of the functional network connectivity of central brain networks: activation patterns in the cortical sensorimotor network and the default mode network, with its anticorrelated network, deactivation patterns in the limbic-paralimbic neocortical network, and partial modulations in the brain stem, cerebellum, subcortical, and hippocampal brain areas.Acupuncture has a modulating effect on the central functional network connectivity in various forms, and central integration plays a decisive role in the acupuncture mechanism. The activation and deactivation patterns, which are only relevant for acupuncture stimulation, are far from being sufficiently specified.
Article
Using neuroimaging techniques to explore the central mechanism of acupuncture gains increasing attention, but the quality control of acupuncture-neuroimaging study remains to be improved. We searched the PubMed Database during 1995 to 2014. The original English articles with neuroimaging scan performed on human beings were included. The data involved quality control including the author, sample size, characteristics of the participant, neuroimaging technology, and acupuncture intervention were extracted and analyzed. The rigorous inclusion and exclusion criteria are important guaranty for the participants' homogeneity. The standard operation process of acupuncture and the stricter requirement for acupuncturist play significant role in quality control. More attention should be paid to the quality control in future studies to improve the reproducibility and reliability of the acupuncture-neuroimaging studies.
Article
Drug addiction is a chronically relapsing disorder, affecting people from all walks of life. Studies of acupuncture effects on drug addiction are intriguing in light of the fact that acupuncture can be used as a convenient therapeutic intervention for treating drug addiction by direct activation of brain pathway. The current review aims to discuss the neurobiological mechanisms underlying acupuncture’s effectiveness in the treatment of drug addiction, on the basis of two different theories (the incentive sensitization theory and the opponent process theory) that have seemingly opposite view on the role of the mesolimbic reward pathways in mediating compulsive drug-seeking behavior. This review provides evidence that acupuncture may reduce relapse to drug-seeking behavior by regulating neurotransmitters involved in drug craving modulation via somatosensory afferent mechanisms. Also, acupuncture normalizes hyper-reactivity or hypoactivity of the mesolimbic dopamine system in these opposed processes in drug addiction, suggesting bidirectional role of acupuncture in regulation of drug addiction. This proposes that acupuncture may reduce drug craving by correcting both dysfunctions of the mesolimbic dopamine pathway.
Article
Resumen Existen diferentes interpretaciones sobre el deqi descrito en los textos de la Medicina Tradicional China, lo que ha generado controversia en cuanto a lo que es o debería constituir el deqi. Con base en el estudio de los caracteres tradicionales y de las evidencias experimentales recientes, el presente artículo propone un concepto integrador del deqi, como la suma de las respuestas psiconeurofisiológicas desencadenadas durante la intervención acupuntural y que pueden ser percibidas por el paciente y el acupunturista. Tales respuestas tienen una base anatómica, funcional y emergente que se integran en un biocircuito conformado por receptores, vías aferentes, centros de procesamiento, vías eferentes y efectores, los cuales son retroalimentados entre el paciente y el acupunturista.
Chapter
Acupuncture, an ancient Chinese healing methodology, is becoming increasingly popular throughout the world. However, the mechanism by which acupuncture exerts its effects is not yet fully understood. Functional magnetic resonance imaging (fMRI) is a widely used technique to observe brain activity noninvasively. In this chapter, the authors first review the existing literature on the effects of acupuncture on brain activity and connectivity. The authors next discuss some basic issues in the study of acupuncture with fMRI, including deqi, baseline and control measures, acupuncture modalities, and experimental paradigms. At the end of the chapter, future research directions in the study of acupuncture with fMRI are suggested.
Article
Acupuncture is a centuried and unfading treatment of traditional Chinese medicine, which has been proved to exert curative effects on various disorders. Numerous works have been put in to uncover the effective mechanisms of acupuncture. And the interdependent interaction between acupuncture and acupoint microenvironment is a crucial topic. As a benign minimally invasive stimulation, the insertion and manipulation of needle at acupoint could cause deformation of local connective tissue and secretion of various molecules, such as high mobility group box 1 and ATP. The molecules are secreted into extracellular space and bind to the corresponding receptors thus active NF‐κB, MAPK, ERK pathways on mast cells, fibroblasts, keratinocytes, and monocytes/macrophages, among others. This is supposed to trigger following transcription and translation of immune factors and neural active substance, as well as promote the free ion movement (such as Ca2+ influx) and the expansion of blood vessels to recruit more immune cells to acupoint. Finally, acupuncture could enhance network connectivity of local microenvironment at acupoints. The earlier mentioned substances further act on a variety of receptors in local nerve endings, transmitting electrical and biochemical signals to the CNS, and giving full play to the acupuncture action. In conclusion, we portrayed a neuro‐immune microenvironment network of acupoints that medicates the acupuncture action, and would lay a foundation for the systematic study of the complex network relationship of acupoints in the future. Review of the constitution of the acupoint and how the complex network within it initiate acupuncture action.
Chapter
Thrombolytic therapy is of proven benefit in ischemic stroke but its associated risk of intracerebral hemorrhage has encouraged the search for alternative medicines, including acupuncture treatment. In clinical research, acupuncture has exhibited significant effects on motor dysfunction, shoulder-hand syndrome, balance impairment, cognitive impairment, and dysphagia in the subacute or chronic stage of stroke. During cerebral ischemia, pathological processes including inflammatory response, oxidative stress, and apoptosis are evoked, which exacerbate cerebral ischemia-reperfusion (I/R) injury. In animal models of cerebral ischemia, acupuncture (electroacupuncture [EA] or manual acupuncture) stimulation provides neuroprotective effects through the downregulation of inflammation-related molecules (including tumor necrosis factor-α [TNF-α], interleukin [IL] -1β, IL-6, matrix metalloproteinases [MMPs], chemokines, and aquaporins) and enzymes (cyclooxygenase-2 [COX-2] and myeloperoxidase [MPO]), and modulation of oxidative stress-related molecules (including malondialdehyde [MDA], superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], and gamma-glutamylcysteine synthetase [γ-GCS]) in the ischemic area. The anti-apoptotic effect of acupuncture can be attributed to the upregulation of anti-apoptotic proteins (Bcl-2 and Bcl-xL), and downregulation of pro-apoptotic proteins (Bad and Bax) and caspases (including caspase-3, 8, and 9) through various signaling pathways. Acupuncture stimulation also induces neurogenesis through modulation of BrdU/nestin, collapsin response mediator protein-4 (CRMP-4), microtubule-associated protein-2 (MAP-2), retinaldehyde dehydrogenases, dopamine D2 receptors, astrocytes, and glycogen synthase kinase-3β (GSK-3β) protein phosphatase 2A (PP2A) expression in the ischemic area.
Chapter
As an ancient therapeutic method, acupuncture has been clinically practiced in Eastern Asia for more than 2000 years. Though acupuncture is used worldwide in recent decades, the underlying biology mechanism is still confusing. Functional magnetic resonance imaging (fMRI), which is a noninvasive, safe, and effective imaging procedure, opens a new window to investigate human brain response to acupuncture stimulation. This chapter will induce the early-stage studies of acupuncture by using fMRI. In early acupuncture fMRI studies, most of the researchers focused on the characteristics of acupuncture like specificity of acupoints and deqi sensation and the comparison of brain responses among different needle parameters, such as the stimulation method, depth of the needle, and duration of the needle. However, there are a number of methodological problems in these studies which may directly result in inconsistent even conflict outcomes. So the reliability of the results is questioned. More suitable experimental design for acupuncture, stricter statistics, and high-quality acupuncture fMRI studies are needed.
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Background: Fibromyalgia and complex regional pain syndrome (CRPS) are both chronic pain syndromes with pathophysiologic mechanisms related to autonomic nervous system dysregulation and central sensitization. Both syndromes are considered difficult to treat with conventional pain therapies. Case presentations: Here we describe a female veteran with fibromyalgia and a male veteran with CRPS, both of whom failed multiple pharmacologic, physical and psychological therapies for pain, but responded to percutaneous electrical neural field stimulation (PENFS) targeted at the auricular branches of the cranial nerves. Discussion: While PENFS applied to the body has been previously described for treatment of localized pain, PENFS effects on cranial nerve branches of the ear is not well-known, particularly when used for regional and full-body pain syndromes such as those described here. PENFS of the ear is a minimally-invasive, non-pharmacologic therapy that could lead to improved quality of life and decreased reliance on medication. However, further research is needed to guide clinical application, particularly in complex pain patients.
Article
Acupuncture is a therapeutic treatment that is characterised by the insertion of a needle at a particular location on the body. Acupuncture stimulation includes sensory-discriminative and affective-social touch dimensions. In this review, we discuss the role of touch during acupuncture stimulation with an emphasis on the therapeutic, sensory-discriminative and affective-social aspects. In the discriminative dimension, de qi, which is associated with needling, includes a combination of various sensations, such as heaviness, numbness, soreness and distension. Achieving the appropriate de qi sensation appears to be fundamental to the therapeutic outcome following acupuncture treatment. In the affective dimension, the acupuncture procedure typically includes gentle manual touch stimulation, which induces feelings of calm and well-being, perhaps by activating C tactile fibres. Enhanced activity of C tactile afferents may induce a 'limbic touch' response, resulting in emotional and hormonal reactions. Because acupuncture is a 'therapist intensive' and complex intervention, it is necessary to understand the role of social touch between the practitioner and patient. Both sensory-discriminative and affective-social touch aspects play an important role in the therapeutic effect of acupuncture treatment in clinical practice.
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As a widely-applied alternative therapy, acupuncture is gaining popularity in Western society. One challenge that remains, however, is incorporating it into mainstream medicine. One solution is to combine acupuncture with other conventional, mainstream treatments. In this study, we investigated the combination effect of acupuncture and the antidepressant fluoxetine, as well as its underlying mechanism using resting state functional connectivity (rsFC) in patients with major depressive disorders. Forty-six female depressed patients were randomized into a verum acupuncture plus fluoxetine or a sham acupuncture plus fluoxetine group for eight weeks. Resting-state fMRI data was collected before the first and last treatments. Results showed that compared with those in the sham acupuncture treatment, verum acupuncture treatment patients showed 1) greater clinical improvement as indicated by Montgomery–Åsberg Depression Rating Scale (MADRS) and Self-Rating Depression Scale (SDS) scores; 2) increased rsFC between the left amygdala and subgenual anterior cingulate cortex (sgACC)/preguenual anterior cingulate cortex (pgACC); 3) increased rsFC between the right amygdala and left parahippocampus (Para)/putamen (Pu). The strength of the amygdala-sgACC/pgACC rsFC was positively associated with corresponding clinical improvement (as indicated by a negative correlation with MADRS and SDS scores). Our findings demonstrate the additive effect of acupuncture to antidepressant treatment and suggest that this effect may be achieved through the limbic system, especially the amygdala and the ACC.
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Using neuroimaging techniques to explore the central mechanism of acupuncture gains increasing attention, but the quality control of acupuncture-neuroimaging study remains to be improved. We searched the PubMed Database during 1995 to 2014. The original English articles with neuroimaging scan performed on human beings were included. The data involved quality control including the author, sample size, characteristics of the participant, neuroimaging technology, and acupuncture intervention were extracted and analyzed. The rigorous inclusion and exclusion criteria are important guaranty for the participants’ homogeneity. The standard operation process of acupuncture and the stricter requirement for acupuncturist play significant role in quality control. More attention should be paid to the quality control in future studies to improve the reproducibility and reliability of the acupuncture-neuroimaging studies.
Article
Objective: This study aimed to observe the cerebral activation effects of acupuncturing the Zusanli (ST36) plusYanglingquan (GB34) points in young healthy volunteers based on Regional Homogeneity (ReHo) indices. Methods: Ten healthy volunteers were enrolled, including 4 males and 6 females between the ages 20 and 34 years with a median age of 23 years. Magnetic resonance imaging (GE Signa HDxt 3.0T) was performed in four groups: Before acupuncture (Control Group), after acupuncture at Zusanli (ST36 Group), after acupuncture at Yanglingquan (GB34 Group) and after acupuncture at both Zusanli and Yanglingquan (Compatibility Group). Differences in the brain ReHo indices of the 4 groups were analyzed by statistical parametric mapping (SPM8) and ReHo data processing methods. The significantly different brain regions were obtained using a false discovery rate correction (FDR-Corrected). Results: The ReHo indices revealed that the main significant effect was in the Compatibility Group. Compared with the resting state of the Control Group, the ReHo values of the Compatibility Group increased in the right middle frontal gyrus (BA8, 9), left superior temporal areas (BA22), ventral anterior cingulate area (BA24) and right inferior parietal lobe (BA40); in contrast, the ReHo values decreased in the left thalamus, right insular cortex (BA13), left inferior frontal lobe (BA9) and right dorsal anterior cingulate area (BA32). Our analysis showed that the Compatibility Group had higher ReHo values than the left inferior parietal lobule (BA40) and right frontal cortex (BA6) of the ST36 Group and the posterior lobe of the right cerebellum, dorsal anterior cingulate (BA32), left and right middle frontal gyrus (BA46, BA9), left precuneus (BA7), right inferior parietal love (BA40) of the GB34 Group. Conclusion: The results of our neuroimaging study suggest that the combination of acupoints could more widely activate areas of the brain compared to a single acupoint. Additionally, the combination of acupoints can activate some new brain areas and generate new curative effects.
Article
Clusterin (CLU) is recognized as a secreted protein that is related to the processes of inflammation and immunity in the pathogenesis of Alzheimer's disease (AD). The effects of the risk variant of the C allele at the rs11136000 locus of the CLU gene are associated with variations in the brain structure and function. However, the relationship of the CLU-C allele to architectural disruptions in resting-state networks in amnestic mild cognitive impairment (aMCI) subjects (i.e., individuals with elevated risk of AD) remains relatively unknown. Using resting-state functional magnetic resonance imaging and an imaging genetic approach, this study investigated whether individual brain functional networks, i.e., the default mode network (DMN) and the task-positive network, were modulated by the CLU-C allele (rs11136000) in 50 elderly participants, including 26 aMCI subjects and 24 healthy controls. CLU-by-aMCI interactions were associated with the information-bridging regions between resting-state networks rather than with the DMN itself, especially in cortical midline regions. Interestingly, the complex communications between resting-state networks was enhanced in aMCI subjects with the CLU rs11136000 CC genotype and were modulated by the degree of memory impairment, suggesting a reconstructed balance of the resting-state networks in these individuals with an elevated risk of AD. The neuroimaging-genetic evidence indicates that immunity factors may contribute to alterations in brain functional networks in aMCI. These findings add to the evidence that the CLU gene may represent a potential therapeutic target for slowing disease progression in AD.
Article
Objective: Acupuncture is a therapeutic treatment defined as the insertion of needles into the body at specific points (i.e., acupoints). The acupuncture sensation of Deqi is an important component of acupuncture, but the functional brain responses of Deqi have not been entirely supported by the results of functional magnetic resonance imaging (fMRI) studies. The aims of this study were to test the conditions that would generate a Deqi sensation and to investigate the effect of Deqi and the response of acupuncture at different depths and intensities on brain fMRI blood oxygen level-dependent (BOLD) signals. Design/setting: Healthy subjects (n=16) completed two resting-state fMRI (rs-fMRI) scans, once during shallow needling (2 mm) and once during deep needling (10-20 mm) pseudorandomly, at the acupoint BL40. Results: When undergoing shallow needling, 16 subjects had a mild stabbing pain sensation, and no one had a composite Deqi sensation; when undergoing deep needling, 14 subjects had a composite Deqi sensation, and only 2 subjects had a sharp pain feeling. Composite deep needling of Deqi sensation modulated neural activity at multiple levels of the brain and cerebellum, decreased functional connectivity in the default mode networks (DMN) and the pain matrix networks, and increased connectivity in the right posterior cerebellar lobe, left parahippocampal gyrus, thalamus, and supplementary motor area (P<0.05, false discovery rate [FDR]<0.05). When subjects underwent shallow needling, the brain network increased functional connectivity in the right side (precentral gyrus, superior frontal gyrus, cerebellar tonsil) and both side thalami; moreover, the right side of the medial prefrontal cortex had a decreased functional connection (P<0.05, FDR<0.05). Conclusions: The hemodynamic response of deep needling of Deqi sensation hypothesis whereby deep needing could affect a variety of deep tissues and never fibers was supported as acupuncture modulates the limbic-paralimbic-neocortical network to produce its Deqi effects. The similarity of LPNN and DMN suggests that deep needing may mobilize an important intrinsic brain network for its multiple modulation effects.
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This book studies the organization of the white matter pathways of the brain. The book analyzes and synthesizes the corticocortical and corticosubcortical connections of the major areas of the cerebral cortex in the rhesus monkey. The result is a detailed understanding of the constituents of the cerebral white matter and the organization of the fiber tracts. The findings from the thirty-six cases studied are presented on a single template brain, facilitating comparison of the locations of the different fiber pathways. The summary diagrams provide a comprehensive atlas of the cerebral white matter. The text is enriched by close attention to functional aspects of anatomical observations. The clinical relevance of the pathways is addressed throughout the text and a chapter is devoted to human white matter diseases. The introductory account gives a detailed historical background. Translations of seminal original observations by early investigators are presented, and when these are considered in the light of the authors' new observations, many longstanding conflicts and debates are resolved.
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The function of the anterior-most portion of the temporal lobes, the temporal pole, is not well understood. Anatomists have long considered it part of an extended limbic system based on its location posterior to the orbital frontal cortex and lateral to the amygdala, along with its tight connectivity to limbic and paralimbic regions. Here we review the literature in both non-human primates and humans to assess the temporal pole's putative role in social and emotional processing. Reviewed findings indicate that it has some role in both social and emotional processes, including face recognition and theory of mind, that goes beyond semantic memory. We propose that the temporal pole binds complex, highly processed perceptual inputs to visceral emotional responses. Because perceptual inputs remain segregated into dorsal (auditory), medial (olfactory) and ventral (visual) streams, the integration of emotion with perception is channel specific.
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In the cerebral cortex, the activity levels of neuronal populations are continuously fluctuating. When neuronal activity, as measured using functional MRI (fMRI), is temporally coherent across 2 populations, those populations are said to be functionally connected. Functional connectivity has previously been shown to correlate with structural (anatomical) connectivity patterns at an aggregate level. In the present study we investigate, with the aid of computational modeling, whether systems-level properties of functional networks--including their spatial statistics and their persistence across time--can be accounted for by properties of the underlying anatomical network. We measured resting state functional connectivity (using fMRI) and structural connectivity (using diffusion spectrum imaging tractography) in the same individuals at high resolution. Structural connectivity then provided the couplings for a model of macroscopic cortical dynamics. In both model and data, we observed (i) that strong functional connections commonly exist between regions with no direct structural connection, rendering the inference of structural connectivity from functional connectivity impractical; (ii) that indirect connections and interregional distance accounted for some of the variance in functional connectivity that was unexplained by direct structural connectivity; and (iii) that resting-state functional connectivity exhibits variability within and across both scanning sessions and model runs. These empirical and modeling results demonstrate that although resting state functional connectivity is variable and is frequently present between regions without direct structural linkage, its strength, persistence, and spatial statistics are nevertheless constrained by the large-scale anatomical structure of the human cerebral cortex.
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Data from nine previous studies of human visual information processing using positron emission tomography were reanalyzed to contrast blood flow responses during passive viewing and active discriminations of the same stimulus array. The analysis examined whether active visual processing (i) increases blood flow in medial visual regions early in the visual hierarchy and (ii) decreases blood flow in auditory and somatosensory cortex. Significant modulation of medial visual regions was observed in six of nine studies, indicating that top-down processes can affect early visual cortex. Modulations showed several task dependencies, suggesting that in some cases the underlying mechanism was selective (e.g. analysis-or feature-specific) rather than non-selective. Replicable decreases at or near auditory Brodmann area (BA) left 41/42 were observed in two of five studies, but in different locations. Analyses that combined data across studies yielded modest but significant decreases. Replicable decreases were not found in primary somatosensory cortex but were observed in an insular region that may be a somatosensory association area. Decreases were also noted in the parietal operculum (perhaps SII) and BA 40. These results are inconsistent with a model in which the precortical input to task-irrelevant sensory cortical areas is broadly suppressed.
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Localized, task-induced decreases in cerebral blood flow are a frequent finding in functional brain imaging research but remain poorly understood. One account of these phenomena postulates processes ongoing during conscious, resting states that are interrupted or inhibited by task performance. Psychological evidence suggests that conscious humans are engaged almost continuously in adaptive processes involving semantic knowledge retrieval, representation in awareness, and directed manipulation of represented knowledge for organization, problem-solving, and planning. If interruption of such “conceptual” processes accounts for task-induced deactivation, tasks that also engage these conceptual processes should not cause deactivation. Furthermore, comparisons between conceptual and nonconceptual tasks should show activation during conceptual tasks of the same brain areas that are “deactivated” relative to rest. To test this model, functional magnetic resonance imaging data were acquired during a resting state, a perceptual task, and a semantic retrieval task. A network of left-hemisphere poly-modal cortical regions showed higher signal values during the resting state than during the perceptual task but equal values during the resting and semantic conditions. This result is consistent with the proposal that perceptual tasks interrupt processes ongoing during rest that involve many of the same brain areas engaged during semantic retrieval. As further evidence for this model, the same network of brain areas was activated in two direct comparisons between semantic and perceptual processing tasks. This same “conceptual processing” network was also identified in several previous studies that contrasted semantic and perceptual tasks or resting and active states. The model proposed here offers a unified account of these findings and may help to explain several unanticipated results from prior studies of semantic processing.
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To characterize the central nervous system (CNS) pathway for acupuncture stimulation in the human brain by using functional magnetic resonance (MR) imaging. Functional MR imaging of the whole brain was performed in two groups of nine healthy subjects during four stimulation paradigms: real acupuncture at acupoints ST.36 (on the leg) and LI.4 (on the hand) and control stimulations (minimal acupuncture and superficial pricking on the leg). Stimulations were performed in semirandomized, balanced order nested within two experiments. Psychophysical responses (pain, De-Qi effect [characteristic acupuncture effect of needle-manipulation sensation], anxiety, and unpleasantness) and autonomic responses were assessed. Talairach coordinates-transformed imaging data were averaged for a group analysis. Acupuncture at LI.4 and ST.36 resulted in significantly higher scores for De-Qi and in substantial bradycardia. Acupuncture at both acupoints resulted in activation of the hypothalamus and nucleus accumbens and deactivation of the rostral part of the anterior cingulate cortex, amygdala formation, and hippocampal complex; control stimulations did not result in such activations and deactivations. Functional MR imaging can demonstrate the CNS pathway for acupuncture stimulation. Acupuncture at ST.36 and LI.4 activates structures of descending antinociceptive pathway and deactivates multiple limbic areas subserving pain association. These findings may shed light on the CNS mechanism of acupuncture analgesia and form a basis for future investigations of endogenous pain modulation circuits in the human brain.
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Acupuncture, an ancient therapeutic technique, is emerging as an important modality of complementary medicine in the United States. The use and efficacy of acupuncture treatment are not yet widely accepted in Western scientific and medical communities. Demonstration of regionally specific, quantifiable acupuncture effects on relevant structures of the human brain would facilitate acceptance and integration of this therapeutic modality into the practice of modern medicine. Research with animal models of acupuncture indicates that many of the beneficial effects may be mediated at the subcortical level in the brain. We used functional magnetic resonance imaging (fMRI) to investigate the effects of acupuncture in normal subjects and to provide a foundation for future studies on mechanisms of acupuncture action in therapeutic interventions. Acupuncture needle manipulation was performed at Large Intestine 4 (LI 4, Hegu) on the hand in 13 subjects [Stux, 1997]. Needle manipulation on either hand produced prominent decreases of fMRI signals in the nucleus accumbens, amygdala, hippocampus, parahippocampus, hypothalamus, ventral tegmental area, anterior cingulate gyrus (BA 24), caudate, putamen, temporal pole, and insula in all 11 subjects who experienced acupuncture sensation. In marked contrast, signal increases were observed primarily in the somatosensory cortex. The two subjects who experienced pain instead of acupuncture sensation exhibited signal increases instead of decreases in the anterior cingulate gyrus (BA 24), caudate, putamen, anterior thalamus, and posterior insula. Superficial tactile stimulation to the same area elicited signal increases in the somatosensory cortex as expected, but no signal decreases in the deep structures. These preliminary results suggest that acupuncture needle manipulation modulates the activity of the limbic system and subcortical structures. We hypothesize that modulation of subcortical structures may be an important mechanism by which acupuncture exerts its complex multisystem effects.
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We review evidence for partially segregated networks of brain areas that carry out different attentional functions. One system, which includes parts of the intraparietal cortex and superior frontal cortex, is involved in preparing and applying goal-directed (top-down) selection for stimuli and responses. This system is also modulated by the detection of stimuli. The other system, which includes the temporoparietal cortex and inferior frontal cortex, and is largely lateralized to the right hemisphere, is not involved in top-down selection. Instead, this system is specialized for the detection of behaviourally relevant stimuli, particularly when they are salient or unexpected. This ventral frontoparietal network works as a 'circuit breaker' for the dorsal system, directing attention to salient events. Both attentional systems interact during normal vision, and both are disrupted in unilateral spatial neglect.
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To study the correlation of low-frequency blood oxygenation level-dependent (BOLD) fluctuations on magnetic resonance (MR) images obtained of the left- and right-hemisphere primary motor regions in healthy control subjects and patients with multiple sclerosis (MS). Sixteen healthy volunteers and 20 patients with MS underwent MR imaging with a 1.5-T imager by using a protocol designed to monitor low-frequency BOLD fluctuations. Data for low-frequency BOLD fluctuations were acquired with subjects at rest and during continuous performance of a bilateral finger-tapping task. These data were low-pass filtered (<0.08 Hz), and cross correlations of all acquired pixels to a region of interest in the left precentral gyrus were calculated. Confidence levels were calculated from the cross correlations. The fraction of pixels in the right precentral gyrus above a confidence level of 95% for correlation with the left precentral gyrus was calculated for each subject. A plot of the fraction of the right precentral gyrus with high correlation with the left precentral gyrus for the finger-tapping state versus the resting state showed a clear discrimination between patients with MS and control subjects. Compared with control subjects, patients with MS generally had a smaller fraction of the pixels in the right precentral gyrus above the confidence level. This finding indicates that our method results in greater than 60% sensitivity and 100% specificity for discriminating patients with MS from control subjects. No significant correlation was found between clinical measures of MS disease and correlations of low-frequency BOLD fluctuations between left and right precentral gyri. On the basis of the connectivity measure of low-frequency BOLD fluctuations, patients with MS exhibited lower functional connectivity between right- and left-hemisphere primary motor cortices when compared with that in control subjects.
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Recent neuroimaging studies have lead to the proposal that rest is characterized by an organized, baseline level of activity, a default mode of brain function that is suspended during specific goal-oriented mental activity. Previous studies have shown that the primary function subserved by the default mode is that of an introspectively oriented, self-referential mode of mental activity. The default mode of brain function hypothesis is readdressed from the perspective of the presence of low-frequency blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signal changes (0.012-0.1 Hz) in the resting brain. The results show that the brain during rest is not tonically active in a single mode of brain function. Rather, the findings presented here suggest that the brain recurrently toggles between an introspectively oriented mode (default mode) and a state-of-mind that tentatively might be interpreted as an extrospectively oriented mode that involves a readiness and alertness to changes in the external and internal environment.
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Activity and reactivity of the default mode network in the brain was studied using functional magnetic resonance imaging (fMRI) in 28 nondemented individuals with mild cognitive impairment (MCI), 18 patients with mild Alzheimer's disease (AD), and 41 healthy elderly controls (HC). The default mode network was interrogated by means of decreases in brain activity, termed deactivations, during a visual encoding task and during a nonspatial working memory task. Deactivation was found in the default mode network involving the anterior frontal, precuneus, and posterior cingulate cortex. MCI patients showed less deactivation than HC, but more than AD. The most pronounced differences between MCI, HC, and AD occurred in the very early phase of deactivation, reflecting the reactivity and adaptation of the network. The default mode network response in the anterior frontal cortex significantly distinguished MCI from both HC (in the medial frontal) and AD (in the anterior cingulate cortex). The response in the precuneus could only distinguish between patients and HC, not between MCI and AD. These findings may be consistent with the notion that MCI is a transitional state between healthy aging and dementia and with the proposed early changes in MCI in the posterior cingulate cortex and precuneus. These findings suggest that altered activity in the default mode network may act as an early marker for AD pathology.
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We review evidence for partially segregated networks of brain areas that carry out different attentional functions. One system, which includes parts of the intraparietal cortex and superior frontal cortex, is involved in preparing and applying goal-directed (top-down) selection for stimuli and responses. This system is also modulated by the detection of stimuli. The other system, which includes the temporoparietal cortex and inferior frontal cortex, and is largely lateralized to the right hemisphere, is not involved in top-down selection. Instead, this system is specialized for the detection of behaviourally relevant stimuli, particularly when they are salient or unexpected. This ventral frontoparietal network works as a 'circuit breaker' for the dorsal system, directing attention to salient events. Both attentional systems interact during normal vision, and both are disrupted in unilateral spatial neglect.
Chapter
This chapter emphasizes on the pain system, which is based primarily on experiments that used primates and on observations in human subjects. Although most of the studies described here refer to pathways that involve the spinal cord, there will be some reference to the comparable pain system that signals information conveyed by the trigeminal and other cranial nerves and their central connections. Pain signals are processed in humans and other mammals by the pain system, which is composed of primary afferent nociceptors, ascending spinal cord nociceptive pathways, descending modulatory pathways, and a number of brain structures that process information related to pain signals. There are a variety of reactions to painful stimuli, including not only sensory discrimination of pain but also motivational-affective responses to painful stimuli, as well as somatic and autonomic reflexes, endocrine changes, and memories of pain. Transmission of pain signals to the brain also activates feedback circuits that can inhibit the effects of sensory input at the spinal cord or brain stem level or, alternatively, accentuate pain responses.
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Abstract We describe a system of parcellation of the human neocortex, based upon magnetic resonance images, that conserves the topographic uniqueness of the individual brain. Subdivision of the neocortex, according to this system, is based entirely upon the configuration of a specified set of cerebral landmarks, principally neocortical fissures. These are present but unique in the details of their configurations in each individual brain. We introduce here a computer-assisted algorithm that ensures that a skilled investigator can execute the parcellation routine in a manageable period of time. Secondly, we outline a comprehensive set of conventions that specify how the boundaries of parcellation units are defined by anatomic landmarks. The average interobserver agreement in voxel assignment to parcellation units within the overall neocortex was 80.2%.
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Acupuncture, an ancient therapeutic technique, is emerging as an important modality of complementary medicine in the United States. The use and efficacy of acupuncture treatment are not yet widely accepted in Western scientific and medical communities. Demonstration of regionally specific, quantifiable acupuncture effects on relevant structures of the human brain would facilitate acceptance and integration of this therapeutic modality into the practice of modern medicine. Research with animal models of acupuncture indicates that many of the beneficial effects may be mediated at the subcortical level in the brain. We used functional magnetic resonance imaging (fMRI) to investigate the effects of acupuncture in normal subjects and to provide a foundation for future studies on mechanisms of acupuncture action in therapeutic interventions. Acupuncture needle manipulation was performed at Large Intestine 4 (LI 4, Hegu) on the hand in 13 subjects [Stux, 1997]. Needle manipulation on either hand produced prominent decreases of fMRI signals in the nucleus accumbens, amygdala, hippocampus, parahippocampus, hypothalamus, ventral tegmental area, anterior cingulate gyrus (BA 24), caudate, putamen, temporal pole, and insula in all 11 subjects who experienced acupuncture sensation. In marked contrast, signal increases were observed primarily in the somatosensory cortex. The two subjects who experienced pain instead of acupuncture sensation exhibited signal increases instead of decreases in the anterior cingulate gyrus (BA 24), caudate, putamen, anterior thalamus, and posterior insula. Superficial tactile stimulation to the same area elicited signal increases in the somatosensory cortex as expected, but no signal decreases in the deep structures. These preliminary results suggest that acupuncture needle manipulation modulates the activity of the limbic system and subcortical structures. We hypothesize that modulation of subcortical structures may be an important mechanism by which acupuncture exerts its complex multisystem effects. Hum Brain Mapp 9:13–25, 2000. © 2000 Wiley-Liss, Inc.
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An MRI time course of 512 echo-planar images (EPI) in resting human brain obtained every 250 ms reveals fluctuations in signal intensity in each pixel that have a physiologic origin. Regions of the sensorimotor cortex that were activated secondary to hand movement were identified using functional MRI methodology (FMRI). Time courses of low frequency (<0.1 Hz) fluctuations in resting brain were observed to have a high degree of temporal correlation (P < 10−3) within these regions and also with time courses in several other regions that can be associated with motor function. It is concluded that correlation of low frequency fluctuations, which may arise from fluctuations in blood oxygenation or flow, is a manifestation of functional connectivity of the brain.
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Resting-state functional connectivity magnetic resonance imaging (fcMRI) studies constitute a growing proportion of functional brain imaging publications. This approach detects temporal correlations in spontaneous blood oxygen level-dependent (BOLD) signal oscillations while subjects rest quietly in the scanner. Although distinct resting-state networks related to vision, language, executive processing, and other sensory and cognitive domains have been identified, considerable skepticism remains as to whether resting-state functional connectivity maps reflect neural connectivity or simply track BOLD signal correlations driven by nonneural artifact. Here we combine diffusion tensor imaging (DTI) tractography with resting-state fcMRI to test the hypothesis that resting-state functional connectivity reflects structural connectivity. These 2 modalities were used to investigate connectivity within the default mode network, a set of brain regions--including medial prefrontal cortex (MPFC), medial temporal lobes (MTLs), and posterior cingulate cortex (PCC)/retropslenial cortex (RSC)--implicated in episodic memory processing. Using seed regions from the functional connectivity maps, the DTI analysis revealed robust structural connections between the MTLs and the retrosplenial cortex whereas tracts from the MPFC contacted the PCC (just rostral to the RSC). The results demonstrate that resting-state functional connectivity reflects structural connectivity and that combining modalities can enrich our understanding of these canonical brain networks.
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The known regional abnormality of the dorsolateral prefrontal cortex (DLPFC) and its role in various neural circuits in schizophrenia has given prominence to its importance in studies on the dysconnection associated with schizophrenia. Abnormal functional connectivities of the DLPFC have been found during various goal-directed tasks; however, the occurrence of the abnormality during rest in patients with schizophrenia has rarely been reported. In the present study, we selected bilateral Brodmann's area 46 as region of interest and analyzed the differences in the DLPFC functional connectivity pattern between 17 patients with first-episode schizophrenia (FES) and 17 matched controls using resting-state fMRI. We found that the bilateral DLPFC showed reduced functional connectivities to the parietal lobe, posterior cingulate cortex, thalamus and striatum in FES patients. We also found enhanced functional connectivity between the left DLPFC and the left mid-posterior temporal lobe and the paralimbic regions in FES patients. Our results suggest that functional dysconnectivity associated with the DLPFC exists in schizophrenia during rest. This may be partially related to disturbance in the intrinsic brain activity.
Article
EEG-fMRI in epileptic patients is commonly analyzed using the general linear model (GLM), which assumes a known hemodynamic response function (HRF) to epileptic spikes in the EEG. In contrast, independent component analysis (ICA) can extract Blood-Oxygenation Level Dependent (BOLD) responses without imposing constraints on the HRF. This technique was evaluated on data generated by superimposing artificial responses on real background fMRI signals. Simulations were run using a wide range of EEG spiking rates, HRF amplitudes, and activation regions. The data were decomposed by spatial ICA into independent components. A deconvolution method then identified component time courses significantly related to the simulated spikes, without constraining the shape of the HRF. Components matching the simulated activation regions ("concordant components") were found in 84.4% of simulations, while components at discordant locations were found in 12.2% of simulations. These false activations were often related to large artifacts that coincidentally occurred simultaneously with some of the random simulated spikes. The performance of the method depended closely on the simulation parameters; when the number of spikes was low, concordant components could only be identified when HRF amplitudes were large. Although ICA did not depend on the shape of the HRF, data processed with the GLM did not reveal the appropriate activation region when the HRF varied slightly from the canonical shape used in the model. ICA may thus be able to extract BOLD responses from EEG-fMRI data in epileptic patients, in a way that is robust to uncertainty and variability in the shape of the HRF.