Imaging the functional connectivity of the Periaqueductal Gray during genuine and sham electroacupuncture treatment

Background Electroacupuncture (EA) is currently one of the most popular acupuncture modalities. However, the continuous stimulation characteristic of EA treatment presents challenges to the use of conventional functional Magnetic Resonance Imaging (fMRI) approaches for the investigation of neural mechanisms mediating treatment response because of the requirement for brief and intermittent stimuli in event related or block designed task paradigms. A relatively new analysis method, functional connectivity fMRI (fcMRI), has great potential for studying continuous treatment modalities such as EA. In a previous study, we found that, compared with sham acupuncture, EA can significantly reduce Periaqueductal Gray (PAG) activity when subsequently evoked by experimental pain. Given the PAG's important role in mediating acupuncture analgesia, in this study we investigated functional connectivity with the area of the PAG we previously identified and how that connectivity was affected by genuine and sham EA. Results Forty-eight subjects, who were randomly assigned to receive either genuine or sham EA paired with either a high or low expectancy manipulation, completed the study. Direct comparison of each treatment mode's functional connectivity revealed: significantly greater connectivity between the PAG, left posterior cingulate cortex (PCC), and precuneus for the contrast of genuine minus sham; significantly greater connectivity between the PAG and right anterior insula for the contrast of sham minus genuine; no significant differences in connectivity between different contrasts of the two expectancy levels. Conclusions Our findings indicate the intrinsic functional connectivity changes among key brain regions in the pain matrix and default mode network during genuine EA compared with sham EA. We speculate that continuous genuine EA stimulation can modify the coupling of spontaneous activity in brain regions that play a role in modulating pain perception.National Center for Complementary and Alternative Medicine (U.S.) (PO1-AT002048)National Center for Complementary and Alternative Medicine (U.S.) (R01AT005280)National Center for Complementary and Alternative Medicine (U.S.) (R21AT00949)National Center for Complementary and Alternative Medicine (U.S.) (KO1AT003883)National Center for Complementary and Alternative Medicine (U.S.) (R21AT004497)National Center for Complementary and Alternative Medicine (U.S.) (K24AT004095)National Center for Research Resources (U.S.) (Clinical Research Center Biomedical Imaging Core, M01-RR-01066)National Center for Research Resources (U.S.) (Clinical Research Center Biomedical Imaging Core, UL1 RR025758-01)National Center for Research Resources (U.S.) (Center for Functional Neuroimaging Technologies, P41RR14075

Imaging the Functional Connectivity of the Periaqueductal Gray During Genuine and Sham Electroacupuncture Treatment

Background: Electroacupuncture (EA) is currently one of the most popular acupuncture modalities. However, the continuous stimulation characteristic of EA treatment presents challenges to the use of conventional functional Magnetic Resonance Imaging (fMRI) approaches for the investigation of neural mechanisms mediating treatment response because of the requirement for brief and intermittent stimuli in event related or block designed task paradigms. A relatively new analysis method, functional connectivity fMRI (fcMRI), has great potential for studying continuous treatment modalities such as EA. In a previous study, we found that, compared with sham acupuncture, EA can significantly reduce Periaqueductal Gray (PAG) activity when subsequently evoked by experimental pain. Given the PAG's important role in mediating acupuncture analgesia, in this study we investigated functional connectivity with the area of the PAG we previously identified and how that connectivity was affected by genuine and sham EA. Results: Forty-eight subjects, who were randomly assigned to receive either genuine or sham EA paired with either a high or low expectancy manipulation, completed the study. Direct comparison of each treatment mode's functional connectivity revealed: significantly greater connectivity between the PAG, left posterior cingulate cortex (PCC), and precuneus for the contrast of genuine minus sham; significantly greater connectivity between the PAG and right anterior insula for the contrast of sham minus genuine; no significant differences in connectivity between different contrasts of the two expectancy levels. Conclusions: Our findings indicate the intrinsic functional connectivity changes among key brain regions in the pain matrix and default mode network during genuine EA compared with sham EA. We speculate that continuous genuine EA stimulation can modify the coupling of spontaneous activity in brain regions that play a role in modulating pain perception

Expectancy and Treatment Interactions: A Dissociation between Acupuncture Analgesia and Expectancy Evoked Placebo Analgesia

Recent advances in placebo research have demonstrated the mind's power to alter physiology. In this study, we combined an expectancy manipulation model with both verum and sham acupuncture treatments to address: 1) how and to what extent treatment and expectancy effects — including both subjective pain intensity levels (pain sensory ratings) and objective physiological activations (fMRI) — interact; and 2) if the underlying mechanism of expectancy remains the same whether placebo treatment is given alone or in conjunction with active treatment. The results indicate that although verum acupuncture + high expectation and sham acupuncture + high expectation induced subjective reports of analgesia of equal magnitude, fMRI analysis showed that verum acupuncture produced greater fMRI signal decrease in pain related brain regions during application of calibrated heat pain stimuli on the right arm. We believe our study provides brain imaging evidence for the existence of different mechanisms underlying acupuncture analgesia and expectancy evoked placebo analgesia. Our results also suggest that the brain network involved in expectancy may vary under different treatment situations (verum and sham acupuncture treatment).National Center for Complementary and Alternative Medicine (U.S.) (PO1-AT002048)National Center for Complementary and Alternative Medicine (U.S.) (R21AT00949

Brain connectivity Patterns Dissociate action of specific Acupressure Treatments in Fatigued Breast cancer survivors

Funding This work was supported by grants R01 CA151445 and 2UL1 TR000433-06 from the National Institutes of Health. The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. We thank the expert assistance by Dr. Bradley Foerster in acquisition of 1H-MRS and fMRI data.Peer reviewedPublisher PD

Methodological Problems in fMRI Studies on Acupuncture: A Critical Review with Special Emphasis on Visual and Auditory Cortex Activations

Functional magnetic resonance imaging (fMRI) has been used for more than a decade to investigate possible supraspinal mechanisms of acupuncture stimulation. More than 60 studies and several review articles have been published on the topic. However, till now some acupuncture-fMRI studies have not adopted all methodological standards applied to most other fMRI studies. In this critical review, we comment on some of the problems including the choice of baseline, interpretation of deactivations, attention control and implications of different group statistics. We illustrate the possible impact of these problems by focussing on some early findings, namely activations of visual and auditory cortical areas, when acupoints were stimulated that are believed to have a therapeutic effect on vision or hearing in traditional Chinese medicine. While we are far from questioning the validity of using fMRI for the study of acupuncture effects, we think that activations reported by some of these studies were probably not a direct result of acupuncture stimulation but rather attributable to one or more of the methodological problems covered here. Finally, we try to offer solutions for these problems where possible

The limbic-prefrontal network modulated by electroacupuncture at CV4 and CV12

fMRI studies showed that acupuncture could induce hemodynamic changes in brain networks. Many of these studies focused on whether specific acupoints could activate specific brain regions and were often limited to manual acupuncture at acupoints on the limbs. In this fMRI study, we investigated acupuncture\u27s modulation effects on brain functional networks by electroacupuncture (EA) at acupoints on the midline of abdomen. Acupoints Guanyuan (CV4) and Zhongwan (CV12) were stimulated in 21 healthy volunteers. The needling sensations, brain activation, and functional connectivity were studied. We found that the limbic-prefrontal functional network was deactivated by EA at CV4 and CV12. More importantly, the local functional connectivity was significantly changed during EA stimulation, and the change persisted during the period after the stimulation. Although minor differences existed, both acupoints similarly modulated the limbic-prefrontal functional network, which is overlapped with the functional circuits associated with emotional and cognitive regulation. Copyright © 2012 Jiliang Fang et al

Acupuncture modulates temporal neural responses in wide brain networks: evidence from fMRI study

<p>Abstract</p> <p>Background</p> <p>Accumulating neuroimaging studies in humans have shown that acupuncture can modulate a widely distributed brain network, large portions of which are overlapped with the pain-related areas. Recently, a striking feature of acupuncture-induced analgesia is found to be associated with its long-last effect, which has a delayed onset and gradually reaches a peak even after acupuncture needling being terminated. Identifying temporal neural responses in these areas that occur at particular time -- both acute and sustained effects during acupuncture processes -- may therefore shed lights on how such peripheral inputs are conducted and mediated through the CNS. In the present study, we adopted a non-repeated event-related (NRER) fMRI paradigm and control theory based approach namely change-point analysis in order to capture the detailed temporal profile of neural responses induced by acupuncture.</p> <p>Results</p> <p>Our findings demonstrated that neural activities at the different stages of acupuncture presented distinct temporal patterns, in which consistently positive neural responses were found during the period of acupuncture needling while much more complex and dynamic activities found during a post-acupuncture period. These brain responses had a significant time-dependent effect which showed different onset time and duration of neural activities. The amygdala and perigenual anterior cingulate cortex (pACC), exhibited increased activities during the needling phase while decreased gradually to reach a peak below the baseline. The periaqueductal gray (PAG) and hypothalamus presented saliently intermittent activations across the whole fMRI session. Apart from the time-dependent responses, relatively persistent activities were also identified in the anterior insula and prefrontal cortices. The overall findings indicate that acupuncture may engage differential temporal neural responses as a function of time in a wide range of brain networks.</p> <p>Conclusions</p> <p>Our study has provided evidence supporting a view that acupuncture intervention involves complex modulations of temporal neural response, and its effect can gradually resolve as a function of time. The functional specificity of acupuncture at ST36 may involve multiple levels of differential activities of a wide range of brain networks, which are gradually enhanced even after acupuncture needle being terminated.</p

The Limbic-Prefrontal Network Modulated by Electroacupuncture at CV4 and CV12

fMRI studies showed that acupuncture could induce hemodynamic changes in brain networks. Many of these studies focused on whether specific acupoints could activate specific brain regions and were often limited to manual acupuncture at acupoints on the limbs. In this fMRI study, we investigated acupuncture's modulation effects on brain functional networks by electroacupuncture (EA) at acupoints on the midline of abdomen. Acupoints Guanyuan (CV4) and Zhongwan (CV12) were stimulated in 21 healthy volunteers. The needling sensations, brain activation, and functional connectivity were studied. We found that the limbic-prefrontal functional network was deactivated by EA at CV4 and CV12. More importantly, the local functional connectivity was significantly changed during EA stimulation, and the change persisted during the period after the stimulation. Although minor differences existed, both acupoints similarly modulated the limbic-prefrontal functional network, which is overlapped with the functional circuits associated with emotional and cognitive regulation

Age Differences in Vestibular Processing: Neural and Behavioral Evidence

The vestibular system is well known for its role in balance, but its mechanisms of action in this role are not well understood. My dissertation aims to provide a better understanding of vestibular brain function, its correlation with postural control, and its alteration with advancing age. This is an important topic considering that falls are the current leading cause of injuries in older adults in the U.S., and they have negative consequences on wellbeing and independence. In this dissertation, I first review the conventional methods for studying vestibular function in the human brain, and I evaluate a novel MRI-compatible method, which relies on a pneumatic tapper. This approach successfully induces vestibular responses, while preventing the aversive effects of stimulation that are common in other approaches. Next, I assess age differences in brain responses to pneumatic vestibular stimulation, and find that older adults demonstrate less sensitivity to stimulation. Also, those with better postural control exhibit less deactivation of cross-modal sensory regions (e.g. visual and somatosensory cortices). This greater engagement of non-vestibular sensory regions in older adults with better balance could be a mechanism to compensate for inefficient vestibular processing. Consistent with this hypothesis, the relationship between postural control and deactivation of sensory regions was only evident in tasks of low difficulty (i.e. normal stance) in which compensatory neural recruitment might be most effective. After assessing the brain responses to vestibular stimulation in terms of activation and deactivation, I examine connectivity of the vestibular cortex with other regions. This last experiment demonstrates that vestibular cortex connectivity increases in response to vestibular stimulation, and young adults exhibit greater connectivity relative to older adults. Also, connectivity predicts postural stability in high difficulty tasks for young adults, and in low difficulty tasks for older adults. Better balance in young adults is associated with less vestibular connectivity (i.e. they engaged vestibular cortex more selectively), whereas better balance in older adults is associated with higher connectivity (i.e. more recruitment of other sensory regions). These findings reinforce the conclusions from the second experiment, and provide more evidence in support of the compensation related utilization of neural circuits hypothesis (CRUNCH) of neural processing in older adults.PHDKines & Psychology PhDUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/145857/1/fnoohi_1.pd