The role of insula-cerebellum connection underlying aversive regulation with acupuncture

Lijun Bai, Xuan Niu, Zhenyu Liu, Zhen Chen, Xiaocui Wang, Chuanzhu Sun, Zhuonan Wang, Shan Wang, Jieli Cao, Shuoqiu Gan, Geng Fan, Wenming Huang, Hui Xu, Shangjie Chen, Jie Tian, Lixing Lao, Ming Zhang, Lijun Bai, Xuan Niu, Zhenyu Liu, Zhen Chen, Xiaocui Wang, Chuanzhu Sun, Zhuonan Wang, Shan Wang, Jieli Cao, Shuoqiu Gan, Geng Fan, Wenming Huang, Hui Xu, Shangjie Chen, Jie Tian, Lixing Lao, Ming Zhang

Abstract

Acupuncture at pericardium 6 (PC6) shows a consistently positive efficacy in nausea response suggested by consensus expert guidelines. Nausea encompasses aversive symptom as well as strong emotional components. Disgust is a subjective emotion of uneasy commonly accompanying with a physiological response that is accompanied by strong visceral sensations (e.g., nausea). Understanding the brain circuitry by which acupuncture influences the disgust emotion may further elucidate the modulation effect of acupuncture on aversive experience. In the present study, a well-established aversive conditioning model on healthy subjects was combined with acupuncture intervention at PC6, as well as different acupoints (both local PC7 and distant GB37) as separate controls, to investigate the brain network involved aversive regulation with acupuncture; 48 healthy subjects were enrolled and randomized into four parallel groups: group 1 received disgust-induced (DI) stimuli only; groups 2, 3, and 4 received acupuncture at three single acupoints separately prior to the DI. Disgust sensations were rated at baseline and following disgust stimuli. Acupuncture PC6 can induce significant attenuations in disgust sensations than that of no intervention and acupuncture at other acupoints. Neuroimaging further showed that increased causal interaction strength between the cerebellum (nodulus) and insula can predict greater attenuations in aversive experiences. We also found evidence for radical reorganizations of local stronger casual interaction patterns to disgust-induced brain responses targeted by acupuncture at different acupoints. This study provided the brain substrate for acupuncture on aversion modulation. The coupling between the cerebellum (nodulus) and insula supported interoception system and vestibular control which provided the specific neural basis.

Keywords: Acupuncture; antiemetic effect; casual interaction; disgust regulation; insula-cerebellum; interoception system; vestibular control.

Figures

Figure 1.
Figure 1.
Experimental design. Run 1: A non-repeated event-related (NRER) fMRI acupuncture run for 4 min, including 2-min needling manipulations preceded by a 1-min rest, and followed by another 1 min rest scanning. Run 2: Disgust stimulus tasks were presented using a rapid event-related design; 20 trials for each type (disgust and neutral pictures) and 40 null trials (fixation cross) were presented in a random order. Group 1 conducted the disgust stimuli only and groups 2, 3, and 4 received acupuncture treatment first and then disgust stimuli. After each fMRI scanning, deqi sensations, disgust sensations, and anxiety degree were assessed using a 10-point visual analogue scale (VAS) across the four groups.
Figure 2.
Figure 2.
Illustration of anatomical locations of three acupoints: PC6 (Neiguan), PC7 (Daling), and GB37 (Guangming).
Figure 3.
Figure 3.
Averaged psychophysical response (N = 48). (a) The percentage of subjects who reported having experienced the given sensation (at least one subject experienced the seven sensations listed). (b) The intensity of reported sensations measured by an average score (with standard error bars) on a scale from 0 denoting no sensation to 10 denoting an unbearable sensation.
Figure 4.
Figure 4.
Comparison results from PC6 vs. DI, PC7 vs. DI, and GB37 vs. DI under the disgust stimuli task. Statistical significance was thresholded at P 

Figure 5.

Multivariate Granger causality relationships with…

Figure 5.

Multivariate Granger causality relationships with significant connections (P

Figure 5.
Multivariate Granger causality relationships with significant connections (P 
Similar articles
Cited by
References
    1. Pilkington K, Kirkwood G, Rampes H, Cummings M, Richardson J. Acupuncture for anxiety and anxiety disorders—a systematic literature review. Acupunct Med 2007; 25: 1–10. - PubMed
    1. Errington-Evans N. Acupuncture for anxiety. CNS Neurosci Ther 2012; 18: 277–284. - PMC - PubMed
    1. Dundee JW, Chestnutt WN, Ghaly RG, Lynas AG. Traditional Chinese acupuncture: a potentially useful antiemetic? Br Med J 1986; 293: 583–584. - PMC - PubMed
    1. Vickers AJ. Can acupuncture have specific effects on health? A systematic review of acupuncture antiemesis trials. J R Soc Med 1996; 89: 303–311. - PMC - PubMed
    1. NIH Consensus Conference. Acupuncture. JAMA 1998; 280: 1518–1524. - PubMed
Show all 53 references
MeSH terms
Related information
Full text links [x]
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM
Figure 5.
Figure 5.
Multivariate Granger causality relationships with significant connections (P 

References

    1. Pilkington K, Kirkwood G, Rampes H, Cummings M, Richardson J. Acupuncture for anxiety and anxiety disorders—a systematic literature review. Acupunct Med 2007; 25: 1–10.
    1. Errington-Evans N. Acupuncture for anxiety. CNS Neurosci Ther 2012; 18: 277–284.
    1. Dundee JW, Chestnutt WN, Ghaly RG, Lynas AG. Traditional Chinese acupuncture: a potentially useful antiemetic? Br Med J 1986; 293: 583–584.
    1. Vickers AJ. Can acupuncture have specific effects on health? A systematic review of acupuncture antiemesis trials. J R Soc Med 1996; 89: 303–311.
    1. NIH Consensus Conference. Acupuncture. JAMA 1998; 280: 1518–1524.
    1. Gan TJ, Diemunsch P, Habib AS, Kovac A, Kranke P, Meyer TA, Watcha M, Chung F, Angus S, Apfel CC, Bergese SD, Candiotti KA, Chan MTV, Davis PJ, Hooper VD, Lagoo-Deenadayalan S, Myles P, Nezat G, Philip BK, Tramèr MR. Consensus guidelines for the management of postoperative nausea and vomiting. Anesth Analg 2014; 118: 85–113.
    1. Wu X, Chung VCH, Hui EP, Ziea ETC, Ng BFL, Ho RST, Tsoi KKF, Wong SYS, Wu JCY. Effectiveness of acupuncture and related therapies for palliative care of cancer: overview of systematic reviews. Sci Rep 2015; 5: 16776.
    1. Miller AD, Rowley HA, Roberts TP, Kucharczyk J. Human cortical activity during vestibular- and drug-induced nausea detected using MSI. Ann NY Acad Sci 1996; 781: 670–672.
    1. Mukoyama N, Yoshimi A, Goto A, Kotani H, Ishikawa K, Miyazaki N, Miyazaki M, Yamada K, Kikkawa F, Hasegawa Y, Ozaki N, Noda Y. An analysis of behavioral and genetic risk factors for chemotherapy-induced nausea and vomiting in Japanese subjects. Biol Pharmaceut Bull 2016; 39: 1852–1858.
    1. Hui KK, Liu J, Marina O, Napadow V, Haselgrove C, Kwong KK, Kennedy DN, Makris N. The integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 as evidenced by fMRI. NeuroImage 2005; 27: 479–496.
    1. Hui KK, Liu J, Makris N, Gollub RL, Chen AJ, Moore CI, Kennedy DN, Rosen BR, Kwong KK. Acupuncture modulates the limbic system and subcortical gray structures of the human brain: evidence from fMRI studies in normal subjects. Hum Brain Mapp 2000; 9: 13–25.
    1. Avery JA, Gotts SJ, Kerr KL, Burrows K, Ingeholm JE, Bodurka J, Martin A, Kyle Simmons W. Convergent gustatory and viscerosensory processing in the human dorsal mid-insula. Hum Brain Mapp 2017; 38: 2150–2164.
    1. Verstaen A, Eckart JA, Muhtadie L, Otero MC, Sturm VE, Haase CM, Miller BL, Levenson RW. Insular atrophy and diminished disgust reactivity. Emotion 2016; 16: 903–912.
    1. Schmahmann JD. The cerebrocerebellar system: anatomic substrates of the cerebellar contribution to cognition and emotion. Int Rev Psychiatry 2001; 13: 247–260.
    1. Baumann O, Mattingley JB. Functional topography of primary emotion processing in the human cerebellum. NeuroImage 2012; 61: 805–811.
    1. Schienle A, Scharmuller W. Cerebellar activity and connectivity during the experience of disgust and happiness. Neuroscience 2013; 246: 375–381.
    1. Adamaszek M, D’Agata F, Ferrucci R, Habas C, Keulen S, Kirkby KC, Leggio M, Mariën P, Molinari M, Moulton E, Orsi L, Van Overwalle F, Papadelis C, Priori A, Sacchetti B, Schutter DJ, Styliadis C, Verhoeven J. Consensus paper: cerebellum and emotion. Cerebellum 2017; 16: 552–576.
    1. Schutter DJ, van Honk J. The cerebellum on the rise in human emotion. Cerebellum 2005; 4: 290–294.
    1. Zheng Y, Zhang J, Wang Y, Wang Y, Lan Y, Qu S, Tang C, Huang Y. Acupuncture decreases blood pressure related to hypothalamus functional connectivity with frontal lobe, cerebellum, and insula: a study of instantaneous and short-term acupuncture treatment in essential hypertension. Evid Based Complement Alternat Med 2016; 2016: 1–10.
    1. Li MK, Li YJ, Zhang GF, Chen JQ, Zhang JP, Qi J, Huang Y, Lai XS, Tang CZ. Acupuncture for ischemic stroke: cerebellar activation may be a central mechanism following Deqi. Neural Regen Res 2015; 10: 1997–2003.
    1. Chae Y, Chang DS, Lee SH, Jung WM, Lee IS, Jackson S, Kong J, Lee H, Park HJ, Lee H, Wallraven C. Inserting needles into the body: a meta-analysis of brain activity associated with acupuncture needle stimulation. J Pain 2013; 14: 215–222.
    1. Fang J, Jin Z, Wang Y, Li K, Kong J, Nixon EE, Zeng Y, Ren Y, Tong H, Wang Y, Wang P, Hui KK. The salient characteristics of the central effects of acupuncture needling: limbic-paralimbic-neocortical network modulation. Hum Brain Mapp 2009; 30: 1196–1206.
    1. Yoo SS, Teh EK, Blinder RA, Jolesz FA. Modulation of cerebellar activities by acupuncture stimulation: evidence from fMRI study. NeuroImage 2004; 22: 932–940.
    1. Streitberger K, Ezzo J, Schneider A. Acupuncture for nausea and vomiting: an update of clinical and experimental studies. Auton Neurosci 2006; 129: 107–117.
    1. Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 1971; 9: 97–113. 1971/03/01.
    1. Andrykowski MA, Gregg ME. The role of psychological variables in post-chemotherapy nausea: anxiety and expectation. Psychosom Med 1992; 54: 48–58.
    1. Schienle A, Walter B, Stark R, Vaitl D. A questionnaire for the assessment of disgust sensitivity. Z Klin Psychol Psychother 2002; 31: 110–120.
    1. Spielberger CD, Gorsuch RL, Lushene R, Vagg PR, Jacobs GA. Manual for the state-trait anxiety inventory. Palo Alto, CA: Consulting Psychologists Press, 1983.
    1. Beck AT, Steer RA, Carbin MG. Psychometric properties of the Beck Depression Inventory: twenty-five years of evaluation. Clin Psychol Rev 1988; 8: 77–100.
    1. De Pascalis V, Chiaradia C, Carotenuto E. The contribution of suggestibility and expectation to placebo analgesia phenomenon in an experimental setting. Pain 2002; 96: 393–402.
    1. Olatunji BO, Cisler J, McKay D, Phillips ML. Is disgust associated with psychopathology? Emerging research in the anxiety disorders. Psychiatry Res 2010; 175: 1–10.
    1. Goldstein JM, Jerram M, Poldrack R, Ahern T, Kennedy DN, Seidman LJ, Makris N. Hormonal cycle modulates arousal circuitry in women using functional magnetic resonance imaging. J Neurosci 2005; 25: 9309–9316.
    1. Sundstrom Poromaa I, Gingnell M. Menstrual cycle influence on cognitive function and emotion processing-from a reproductive perspective. Front Neurosci 2014; 8: 12–17.
    1. Bertron A, Petry M, Bruner R, Mcmanis M, Zabaldo D, Martinet S, Cuthbert S, Ray D, Koller K, Kolchakian M. International affective picture system (IAPS): technical manual and affective ratings. In: Lang PJ, Bradley MM & Cuthbert BN. International affective picture system (IAPS): Technical manual and affective ratings. Gainesville: The Center for Research in Psychophysiology, University of Florida 1997.
    1. Hamm AO, Vaitl D. Emotionsinduktion durch visuelle Reize: validierung einer Stimulations methode auf drei Reaktionsebenen. Psychologische Rundschau 1993; 44: 143–161.
    1. Bradley MM, Lang PJ. Measuring emotion: the self-assessment manikin and the semantic differential. J Behav Ther Exp Psychiatry 1994; 25: 49–59.
    1. Feng Y, Bai L, Zhang W, Xue T, Ren Y, Zhong C, Wang H, You Y, Liu Z, Dai J, Liu Y, Tian J. Investigation of acupoint specificity by multivariate granger causality analysis from functional MRI data. J Magn Reson Imag 2011; 34: 31–42.
    1. Ren Y, Bai L, Feng Y, Tian J, Li K. Investigation of acupoint specificity by functional connectivity analysis based on graph theory. Neurosci Lett 2010; 482: 95–100.
    1. Talairach J, TP. Co-planar stereotaxic atlas of the human brain: 3-dimensional proportional system: an approach to cerebral imaging. New York: Thieme Medical Publishers Inc, 1988.
    1. Blinowska KJ, Kuś R, Kamiński M. Granger causality and information flow in multivariate processes. Phys Rev E 2004; 70: 148–168.
    1. Ito M. Neurophysiology of the nodulofloccular system. Rev Neurol 1993; 149: 692–697.
    1. Shinder ME, Taube JS. Differentiating ascending vestibular pathways to the cortex involved in spatial cognition. J Vestib Res 2010; 20: 3–23.
    1. Wright P, He G, Shapira NA, Goodman WK, Liu Y. Disgust and the insula: fMRI responses to pictures of mutilation and contamination. Neuroreport 2004; 15: 2347–2351.
    1. Wicker B, Keysers C, Plailly J, Royet JP, Gallese V, Rizzolatti G. Both of us disgusted in My insula: the common neural basis of seeing and feeling disgust. Neuron 2003; 40: 655–664.
    1. Suzuki A. Insula and disgust. Rinsho Shinkeigaku 2010; 50: 1000–1002.
    1. Turner BM, Paradiso S, Marvel CL, Pierson R, Boles Ponto LL, Hichwa RD, Robinson RG. The cerebellum and emotional experience. Neuropsychologia 2007; 45: 1331–1341.
    1. Rotge JY, Lemogne C, Hinfray S, Huguet P, Grynszpan O, Tartour E, George N, Fossati P. A meta-analysis of the anterior cingulate contribution to social pain. Soc Cogn Affect Neurosci 2015; 10: 19–27.
    1. Murray RJ, Brosch T, Sander D. The functional profile of the human amygdala in affective processing: insights from intracranial recordings. Cortex 2014; 60: 10–33.
    1. Chen P, Zhao BX, Qin W, Chen HY, Tian J, Fan YP, Zhou B, Liu SS. Study on the mechanism of acupuncture at Daling (PC 7) for mental diseases by fMRI. Zhongguo Zhen Jiu 2008; 28: 429–432.
    1. Lade A. Point images and functions. Acupuncture points Images and Functions. Seattle: Eastland Press 1989, pp. 27-311.
    1. Kong J, Kaptchuk TJ, Webb JM, Kong JT, Sasaki Y, Polich GR, Vangel MG, Kwong K, Rosen B, Gollub RL. Functional neuroanatomical investigation of vision-related acupuncture point specificity—a multisession fMRI study. Hum Brain Mapp 2009; 30: 38–46.
    1. Cho ZH, Chung SC, Jones JP, Park JB, Park HJ, Lee HJ, Wong EK, Min BI. New findings of the correlation between acupoints and corresponding brain cortices using functional MRI. Proc Natl Acad Sci USA 1998; 95: 2670–2673.
    1. Lee A, Chan SK, Fan LT. Stimulation of the wrist acupuncture point PC6 for preventing postoperative nausea and vomiting. The Cochrane database of systematic reviews 2015; 11: Cd003281.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe