A functional magnetic resonance imaging study ... - Wiley Online Library

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A functional magnetic resonance imaging study of the neuronal specificity of an acupoint: acupuncture at Rangu (KI 2) and its sham point A. Li,1† X.-L. Li,2† F. Zhang,2 J.-H. Yue,3 C.-S. Yuan,2 K. Li1 and Q.-H. Zhang3,4 1

Department of Biostatistics, Public Health School, Harbin Medical University, 2Division of CT and MRI, First Affiliated Hospital of Heilongjiang University of Chinese Medicine, 4Department of Acupuncture and Moxibustion, Second Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, China, and 3Department of Anesthesia, Stanford University, Stanford, California, USA

Key words fMRI, acupuncture, Rangu acupoint, sham acupoint. Correspondence Kang Li, Department of Biostatistics, Public Health School, Harbin Medical University, Harbin 150086, China. Email: [email protected] and Qinhong Zhang, Department of Anesthesia, Stanford University, 300 Pasteur Drive, Stanford, CA 94305, USA. Email: [email protected]

Abstract The neuronal specificity of acupoints has not been entirely supported by the results of previous functional magnetic resource imaging studies. This study tested the specificity of an acupoint using right Rangu (KI 2) and its sham acupoint. The results showed specific cerebral response patterns and thus provided the evidence of the existence of acupoint neuronal specificity.

Received 25 November 2015; accepted 2 January 2016. doi:10.1111/imj.13154

Acupuncture involves the insertion of small needles in skin at different acupoints. It has been practised in China for 2000 years and is commonly used for treating various conditions, such as chronic knee pain1,2 and neck pain3,4 among others. According to the theory of acupuncture, each acupoint has its own functional specificity. When treating for disorders, specific acupoints are carefully selected.5 However, the mechanisms underlying its effects are still not well understood. Functional magnetic resource imaging (fMRI) is a non-invasive and safe functional neuroimaging procedure using MRI technology that measures and maps brain activity by detecting changes associated with blood

† X.-L. Li and A. Li contributed equally to this study. Funding: This work was supported in part by the National Foundation of Natural Science of China (grant no. 81373714; 81172741; 30972537), Natural Science of Heilongjiang Province (grant no. D201214), Outstanding Innovative Talents Supporting Project of Heilongjiang University of Chinese Medicine (grant no. 2012RCQ64) and Project of Young Innovative Talents of Heilongjiang Province Undergraduate College (UNPYSCT-2015119). Conflict of interest: None.

© 2016 Royal Australasian College of Physicians

flow. Previous studies have provided the evidence for the connections between acupuncture and the central nervous system,6 especially the correlation between acupoints stimulation and brain activation.7,8 For example, it has been reported that specific brain areas and systems are activated in response to acupuncture stimulation, such as the limbic system,9,10 visual cortex7 and areas processing language.11 However, the neuronal specificity of acupoints has not been entirely supported by the results of fMRI studies.12,13 Therefore, we chose the right Rangu (KI 2) acupoint and its sham point to evaluate acupoint specificity, which has not been reported earlier. Previous studies showed that the dominant (right) hand was controlled mainly by the contralateral (left) hemisphere during the fMRI study.14,15 In this study, we only examined right-handed volunteers to make sure that all subjects were controlled by the left hemisphere. Thus, 12 healthy right-handed male participants (range: 23–26 years; mean: 24.8 years) were recruited in this study. This study was approved by the Ethics Review Board of the First Affiliated Hospital of the Heilongjiang University of Chinese Medicine (Permission number: KY201400601). All subjects 973


provided informed consent. In addition, the inclusion criteria were as follows: (i) those with a regular diet; (ii) minimal consumption of alcohol, tobacco, tea and coffee; (iii) normal sleeping patterns (before 12 a.m.); and (iv) normal body mass index (18.5–23.9 for Chinese). The following were the exclusion criteria: (i) history of neurological or psychiatric disorders; (ii) history of head trauma; and (iii) no acupuncture intervention within 1 month before the test. Acupuncture was performed by a single experienced acupuncturist with sterilised, disposable, stainless steel needles (0.25 × 40 mm; Suzhou Medical Supplies Factory Co. Ltd, Suzhou, China). For both real and sham acupoints (30 oblique below the KI 2 in the direction of the heel and 2 cm from the heel, avoiding any of the meridians and blood vessels), the entire process lasted 8 minutes and consisted of two stages (manipulation and retention), the same as in our previous study.16 The person reading the fMRI was blinded to the treatment arm in this study. All subjects were conscious, placed in a supine position, with their eyes closed using eyeshades and wearing

earplugs. After the participants rested for 30 minutes, the scan began. The scan was conducted with a 3.0 T MRI system (Achieva 3.0 T TX; Philips, Eindhoven, The Netherlands), the same as in our previous study.16 All data were analysed with SPM 12 software (Statistical Parametric Mapping, http://www.fil.ion.ucl. ac.uk/spm/). Voxel-based individual task-related activation was evaluated. Significance was designated at P < 0.05, and a cluster size of >10 voxels was considered significantly different. Acupuncture at KI 2 caused an increase in fMRI signals at the left cerebellum anterior lobe, bilateral inferior frontal gyrus, bilateral insula, right inferior parietal lobule, bilateral postcentral gyrus, bilateral superior temporal gyrus, right precentral gyrus, left postcentral gyrus, bilateral middle frontal gyrus, bilateral middle temporal gyrus, left limbic lobe, left anterior cingulate gyrus, left paracentral lobule, right superior frontal gyrus and right parietal lobe (Fig. 1, Table 1). Meanwhile, the signals decreased at the left temporal lobe, bilateral limbic lobe, bilateral parahippocampal gyrus, left frontal lobe and left precentral gyrus (Fig. 1, Table 1).

Figure 1 Activated and deactivated brain areas by acupuncture stimulation at Rangu (KI 2) acupoint.

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Table 1 Montreal Neurologic Institute (MNI) coordinates of brain regions activated by acupuncture stimulation at right Rangu (KI 2) acupoint and its sham point Anatomical location

Activated brain areas at KI 2 Cerebellum anterior lobe Inferior frontal gyrus, insula Inferior parietal lobule, postcentral gyrus Superior temporal gyrus, precentral gyrus Inferior frontal gyrus, Insula Postcentral gyrus, superior temporal gyrus Middle frontal gyrus Middle temporal gyrus Middle temporal gyrus Limbic lobe Anterior cingulate gyrus Paracentral lobule Middle frontal gyrus, superior frontal gyrus Postcentral gyrus, paracentral lobule Parietal lobe Deactivated brain areas at KI 2 Temporal lobe Limbic lobe, parahippocampa gyrus Limbic lobe, parahippocampa gyrus Frontal lobe, precentral gyrus Activated brain areas at sham acupoint Cerebellum posterior lobe Cerebellum posterior lobe Cerebellum anterior lobe Cerebellum posterior lobe Occipital lobe Lingual gyrus, midbrain Insula Precentral gyrus Superior frontal gyrus Superior temporal gyrus Inferior frontal gyrus Precentral gyrus Middle temporal gyrus Inferior parietal lobule Parietal lobe, postcentral gyrus

Side (R/L)

BA

Number of voxels

T values

Z values

MNI coordinate system (mm) X

Y

Z

L R R R L L L R L L L L R L R

— 13 4 22 13 22 — 21 21 — 24 6 10 5 7

16 392, 310 258, 243 180, 129 364, 293 240, 188 120 36 45 459 376 42 33, 14 47, 33 43

4.45 9.16 8.29 7.93 11.85 9.37 9.08 7.93 5.09 7.55 5.95 5.90 4.98 7.60 4.42

3.30 4.78 4.58 4.49 5.24 4.82 4.76 4.49 3.56 4.39 3.90 3.88 3.53 4.40 3.28

−27 36 42 54 −57 −54 −60 54 −51 −3 0 6 33 −6 21

−39 9 −3 −18 −24 0 −27 −51 −51 27 45 24 42 −42 −48

−36 0 −9 30 24 0 33 −6 3 21 27 51 27 72 60

L R L L

— 27 27 4

24 17, 14 15, 15 22, 12

3.92 4.43 4.40 4.44

3.03 3.29 3.28 3.29

−42 15 −30 −30

0 −9 −30 −18

−30 −21 −15 45

R R R L L L R R R L L L R L R

— — — — — — 13 4 — 22 — — 22 23 23

229 229 203 243 59 49, 32 243 92 60 90 35 39 34 91 249, 143

Limbic lobe Medial frontal gyrus, anterior cingulate

R R

23 32

43 29, 22

Superior frontal gyrus, cingulate gyrus

R

6, 32

119, 86

4.70 4.70 5.43 6.38 5.74 5.58 9.38 9.27 8.14 5.54 4.84 4.56 4.00 7.22 6.98 4.20 4.52 7.79 3.36 5.28 5.09

3.41 3.41 3.71 4.05 3.83 3.77 4.82 4.80 4.54 3.75 3.47 3.35 3.08 4.30 4.23 3.18 3.33 4.46 2.73 3.65 3.57

18 18 21 −21 6 −9 39 60 51 −54 −60 −48 57 −57 63 63 0 12 0 6 3

−75 −75 −33 −66 −75 −72 6 9 3 12 0 12 −54 −30 −18 −39 −27 33 45 −9 15

−48 −48 −27 −18 −12 −18 −3 12 3 9 6 −9 −6 24 30 30 21 24 36 72 39

L L

10, 32 —

137, 48 34

6.96 3.74

4.22 2.94

−21 −15

42 30

0 36

Deactivated brain areas at sham acupoint Middle frontal gyrus, limbic lobe, anterior cingulate Frontal lobe

Voxels with P < 0.01(not corrected). t > 2.71 and clustered with 10 as threshold. BA, Brodmann area; L, left R, right;.

In contrast, acupuncture at sham KI 2 resulted in an fMRI signal increase at the bilateral cerebellum posterior lobe, right cerebellum anterior lobe, left occipital lobe, left


lingual gyrus, left midbrain, right insula, right precentral gyrus, right superior frontal gyrus, left superior temporal gyrus, left inferior frontal gyrus, left precentral gyrus, right 975


Figure 2 Activated and deactivated brain areas by acupuncture stimulation at the sham acupoint.

middle temporal gyrus, left inferior parietal lobule, right parietal lobe, right postcentral gyrus, right limbic lobe, right medial frontal gyrus, right anterior cingulate, right superior frontal gyrus and right cingulate gyrus (Fig. 2, Table 1). Meanwhile, the fMRI signals decreased at the left middle frontal gyrus, left limbic lobe, left anterior cingulate and left frontal lobe (Fig. 2, Table 1). When compared with sham KI 2, the fMRI signal of right KI 2 showed brain activation only at the following areas: left cerebellum anterior lobe, right inferior parietal lobule, right precentral gyrus, left postcentral gyrus, left limbic lobe, left anterior cingulate gyrus and left

References 1 Hinman RS, McCrory P, Pirotta M, Relf I, Forbes A, Crossley KM et al. Acupuncture for chronic knee pain: a randomized clinical trial. JAMA 2014; 312: 1313–22. 2 Zhang Q, Yue J, Lu Y. Acupuncture treatment for chronic knee pain: study by Hinman et al underestimates

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paracentral lobule; however, deactivation was observed at the left temporal lobe and left precentral gyrus. The results of this study indicate that the KI 2 acupoint may elicit specific activities in the human brain and provide neurobiological evidence for the existence of acupoint specificity. In conclusion, this study focused on the specificity of acupoints using right KI 2 and its sham acupoint, which induced specific cerebral response patterns and provided evidence for neuronal specificity of acupoints. However, further studies are still needed to understand this phenomenon better.

acupuncture efficacy. Acupunct Med 2015; 33: 170. 3 Sun ZR, Yue JH, Zhang QH. Electroacupuncture at Jing-jiaji points for neck pain caused by cervical spondylosis: a study protocol for a randomized controlled pilot trial. Trials 2013; 14: 360. 4 Sun ZR, Yue JH, Tian HZ, Zhang QH. Acupuncture at Houxi (SI 3) acupoint for

acute neck pain caused by stiff neck: study protocol for a pilot randomised controlled trial. BMJ Open 2014; 4: e006236. 5 World Health Organization. WHO standard acupuncture point locations in the Western Pacific Region. Geneva: World Health Organization; 2008. 6 Cho ZH, Oleson TD, Alimi D, Niemtzow RC. Acupuncture: the search for biologic evidence with



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normal subjects. Hum Brain Mapp 2000; 9: 13–25. Hui KK, Liu J, Marina O, Napadow V, Haselgrove C, Kwong KK et al. The integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 as evidenced by fMRI. Neuroimage 2005; 27: 479–96. Li G, Liu HL, Cheung RT, Hung YC, Wong KK, Shen GG et al. An fMRI study comparing brain activation between word generation and electrical stimulation of language-implicated acupoints. Hum Brain Mapp 2003; 18: 233–8. Campbell A. Point specificity of acupuncture in the light of recent clinical and imaging studies. Acupunct Med 2006; 24: 118–22. Gareus IK, Lacour M, Schulte AC, Hennig J. Is there a BOLD response of the visual cortex on stimulation

of the vision-related acupoint GB 37? J Magn Reson Imaging 2002; 15: 227–32. 14 Gut M, Urbanik A, Forsberg L, Binder M, Rymarczyk K, Sobiecka B et al. Brain correlates of right-handedness. Acta Neurobiol Exp (Wars) 2007; 67: 43–51. 15 Grabowska A, Gut M, Binder M, Forsberg L, Rymarczyk K, Urbanik A. Switching handedness: fMRI study of hand motor control in righthanders, left-handers and converted left-handers. Acta Neurobiol Exp (Wars) 2012; 72: 439–51. 16 Zhang QH, Li A, Yue JH, Zhang F, Sun ZR, Li XL. Using functional MRI to explore the possible mechanism of the action of acupuncture at Dazhong (KI 4) on the functional cerebral regions of healthy volunteers. Intern Med J 2015; 45: 669–71.

Evolving telehealth reimbursement in Australia S.-E. Bursell, S. Zang, A. C. Keech and A. J. Jenkins NHMRC Clinical Trials Centre, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia

Key words telehealth, remote consultation, mobile health, health insurance reimbursement, national health insurance. Correspondence Sven-Erik Bursell, NHMRC Clinical Trials Centre, Locked Bag 77, Camperdown, NSW 1450, Australia. Email: [email protected]

Abstract Video-based consultation is the only telehealth service reimbursed by the Medicare Benefits Schedule in Australia, but the uptake of telehealth is still low and inconsistent. There is a clear need for the development of appropriate medical evidence to support implementation of telehealth services. With the ubiquitous use of mobile phones, mobile health becomes important in facilitating health services and impacting clinical outcomes anywhere.

Received 12 October 2015; accepted 19 April 2016. doi:10.1111/imj.13150

Funding: NHMRC Partnership Project grant APP1016691, a grant from the Fred Hollows Foundation and an NHMRC/Fred Hollows Foundation CRE grant in Diabetic Retinopathy APP 1079864. Conflict of interest: S.-E. Bursell is a Consultant SocialEyes Corporation; he holds no stocks or shares. S. Zang: None. A. C. Keech has received speaker and/or advisor honoraria and/or research support from Abbott, Amgen, Astra-Zeneca, Bristol-Myers Squibb, Eli Lilly, Merck, Novartis, Pfizer, Roche Diagnostics and Solvay within the past 5 years; he is a named investigator on two patents related to the use of fenofibrate for diabetic retinopathy; he holds no pharmaceutical stocks or shares. A. J. Jenkins has received speaker and/or advisor honoraria and/or research support from Abbott, Eli Lilly, Merck, Medtronic, Roche and Sanofi-Aventis within the past 5 years; she is a named investigator on a patent related to the use of fenofibrate for diabetic retinopathy; she holds no pharmaceutical stocks or shares.


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