전신수 교수 논문

“침의 신비”

Acupuncture Stimulation for Motor Cortex

Activities: A 3T fMRI Study

Sin-Soo Jeun,* Jeong-Seok Kim,† Bum-Soo Kim,‡ Sang-Dong Park,§

Eun-Chul Lim,§ Gi-Soon Choi§ and Bo-Young Choe†

Departments of *Neurosurgery, †Biomedical Engineering and ‡Radiology, College of Medicine

The Catholic University of Korea, Seoul, Korea

§Dong-Seo Hospital of Oriental Medicines, Seoul, Korea

Abstract: The acupoint, GB34, located in the back of the knee, is known to be effective in

recovering motor function after a stroke. This study uses a functional magnetic resonance

imaging (fMRI) study with 3T scanner to investigate whether or not acupuncture of GB34

produces a significant response of the modulation of somatomotor areas. A fMRI of the whole

brain was performed in ten normal healthy subjects during two task stimulations of acupuncture

manipulation on GB34 and sham points, inserting and twisting the needle for 25 seconds at a

rate of approximately 120 times per minute; the needle manipulation was paused for a duration

of 25 seconds as a control state. The process was repeated four times to have four epochs

of stimulation. Bilateral sensorimotor areas (BA 3, 4, 6 and 7) showed approximately 6% of

stimulation-related BOLD signal contrast, whereas very few areas were activated when sham

stimulation was given. Acupuncture stimulation in GB34 modulates the cortical activities of the

somatomotor area in humans. The present findings may shed light on the CNS mechanism of

motor function by acupuncture, and form a basis for future investigations of motor modulation

circuits in stroke patients.

Keywords: Acupuncture; Functional Magnetic Resonance Imaging.

Introduction

Acupuncture is an ancient therapeutic modality originating in ancient China; it has been

used extensively in Oriental medicine. Acupuncture techniques are based on the theory

of meridians and energy flow, which evolved after painstaking observation against a

background of Chinese philosophy. However, acupuncture was not widely introduced as

an alternative medicine in the West until the scientific basis of acupuncture analgesia began

to be explored in the early 1980s (Han and Terenius, 1982; Melzack, 1994; Pomeranz,

The American Journal of Chinese Medicine, Vol. 33, No. 4, 573–78

© 2005 World Scientific Publishing Company

Institute for Advanced Research in Asian Science and Medicine

573

Correspondence to: Dr. Sin-Soo Jeun, Department of Neurosurgery, Kangnam St. Mary’s Hospital, College of

Medicine, The Catholic University of Korea, #505 Banpo-Dong, Seocho-Gu, Seoul 137-040, Korea. Tel: (+82)

2-590-2734, Fax: (+82) 2-594-4248, E-mail: ssjeun@catholic.ac.kr

574 S.-S. JEUN et al.

1995; Filshie and White, 1998). In recent years, acupuncture has gained increasing

popularity in modern healthcare and increasing support among scientific investigators

(Eisenberg et al., 1993; Fisher and Ward, 1994). Acupuncture is emerging as an important

complementary and alternative medicine in the Western scientific and medical community

(Diehl et al., 1997; Eisenberg et al., 1993 and 1998). Although the exact mechanism of

acupuncture is still unknown and in need of further investigation, various animal-based

data and clinical observations suggest that acupuncture modulates activities in the central

nervous system (CNS), and influences the designated treatment area (Wu et al., 1999;

Cho et al., 1998). We postulate that widely connected neural networks that integrate

multiple physiological and mental functions are modulated with acupuncture stimulation.

Therefore, a demonstration of a regionally specific characterization of activation in the

CNS by acupuncture would provide further knowledge and possible explanation for this

hypothesized modulation.

We used functional magnetic resonance imaging (fMRI) to investigate the effect of

acupuncture on the CNS by measuring changes in the local blood oxygenation level as

associated with neuronal activities (i.e. BOLD effect), upon acupuncture on extremities

(Kwong et al., 1992). For this report, we studied the neural substrates targeting somatomotor

areas that are modulated by the stimulation of acupoint GB34 (Yang-ling-quan). GB34 is

located in the lateral aspect of the posterior knee, and is often targeted for the treatment

of hemiplegia and rehabilitation for motor functional deficit/impairment after stroke

(Wiseman et al., 1991). Our experimental hypothesis is that acupuncture in GB34 directly

modulates the activities in somatomotor areas, and assists in the functional reorganization

of the neural circuitry in motor areas to regain partial mobility after stroke-related CNS

damage. Before we determine its efficacy on the damaged brain, we performed fMRI on

normal volunteers.

Materials and Methods

Subjects

The study was performed with informed consent on 12 right-handed, normal, healthy

volunteer adults (ten males and two females, all aged 27–3 years). None of them had a

history of psychiatric or neurological disorders, head trauma with loss of consciousness,

or intake of tranquilizing drugs within the last three days. Ten had no previous exposure to

or knowledge of acupuncture; two had some knowledge of acupuncture by way of cultural

exposure or learning, but had never received such a treatment. No subject was in pain

or distress at the time of the study. All subjects were briefed about the range of possible

acupuncture sensations they might experience during needle manipulation before entering

the magnet. There were no differences in the degree of acupuncture sensation experienced,

or in the fMRI results obtained due to differences in past acupuncture experience; thus the

data were combined for analysis. Kangnam St. Mary’s Hospital Subcommittee on Human

Studies in College of Medicine, the Catholic University of Korea, approved the study.

3T fMRI OF ACUPUNCTURE ON MOTOR CORTEX ACTIVITIES 575

Functional MRI

The study was conducted using a 3 Tesla whole body MRI (Medinus Co. Ltd, Korea)

system with a standard quadrature head coil for RF transmission and detection. In each

functional experiment, a Gradient Echo EPI sequence with TR/TE = 2500/35 msec

was used for imaging 20 contiguous axial slices of 6 mm thickness, covering the

whole brain volume (240 mm field-of-view, 64 × 64 in-plane resolution 3.75 × 3.75 mm)

(Kwong et al., 1992). Prior to functional scan, high-resolution T1-weighted anatomical

data were acquired to provide an anatomical reference.

Stainless steel needle used in the acupuncture did not raise any safety-related issues

under the 3T environment. Two sets of conditions were used in the experiment: one with

actual left GB34 stimulation, the other with a “sham” stimulation adjacent to the designated

acupuncture point (without known clinical effects). The sham condition was applied in

order to examine the desired region-specific effects of acupuncture. The location of this

sham point and of the real acupoint was not discernable by the subjects. After the five sets

of dummy data were acquired to account for the T1 equilibration, each functional scan

session was initiated without the needle insertion. At the 11th scan, the needle was inserted

and twisted for 25 seconds at a rate of approximately 120 times per minute. The needle

manipulation was paused for 25 seconds as a control state. The process was repeated four

times to have four epochs of stimulation interleaved by five epochs of control states, with

equal lengths of time. Since the sensation of “Deqi” (a tingling sensation near the site of

acupuncture, which differs from pain or tactile sensation) is known to be an important

criteria in determining the efficacy of the acupuncture manipulation (Hui et al., 2000),

subjects were interviewed about the possible pain and existence of “Deqi” after each

functional session. Subjects were also questioned about the existence of motor imagery

during the scan, since imagery is known to elicit activations in motor-related areas.

A CCD camera and an observer confirmed the absence of actual movement during the

session.

Data Analysis

After the off-line reconstruction, data were processed using SPM99 based on the Matlab

computing environment. Data were realigned with respect to the first set of images,

smoothed with a 6 mm FWHM Gaussian kernel to reduce the spatial noise, and normalized

to Talairach-Tournoux space. The analysis was performed in two steps. Individual

contrasts with acupuncture manipulation were analyzed using a fixed-effects model (Friston

et al., 1994) and group data used a random-effects model (Holmes and Friston, 1998).

Effects were modeled using a boxcar convolved with a canonical hemodynamic response

function. For group analysis, the data were analyzed with paired-samples t-tests, where

p < 0.05 was considered significant to account for multiple comparisons to create a

series of SPM maps depicting differences in brain activation between and within

acupuncture manipulation.

576 S.-S. JEUN et al.

Results

All subjects successfully underwent the designated acupuncture stimulation without

any undesirable peripheral sensations that are known to be associated with high-field

environments. Two subjects with significant motion (i.e. more than 2 mm from the first

image set) were excluded from further data analysis. All the remaining ten subjects

reported that the “Deqi” phenomenon was present during the acupuncture stimulation but

absent during the sham stimulation. Neither imagery nor pain was reported by any of the

subjects.

The activation map from group analysis across the ten individuals (Random Effect

Analysis, thresholded at p < 0.01 d.f. = 4) from Fig. 1B shows that there were several

motor-related regions that showed BOLD signal change during GB34 stimulation. The

areas include bilateral premotor [Brodmann’s Area (BA 6)], superior parietal lobule

(BA 7) and left primary motor areas (BA 4). During the sham stimulation near GB34, the

majority of these areas [except premotor areas (BA 6)] did not show eloquent activation,

suggesting the spatially dependent selective efficacy of the acupuncture. A small activation

locus of the right middle frontal lobe (BA 8) was observed during the sham stimulation.

In the examination of the time course of signal changes during the primary motor area

from subjects, a signal contrast of ~6% (compared to 2%–% in the 1.5T environment)

with respect to the baseline signal level was observed. The Talairach coordinate of the

activation in BA 4 was x-y-z = −37; −22; 62; this was very close to the hand motor

area observed from brain mapping via electrocortical stimulation and PET study

(x-y-z = −37; −23; 57) (Boling et al., 1999).

Figure 1. (A) An illustration of GB34 in the left leg. (B) Averaged group activation map (threshold in p < 0.01)

from ten subjects using random-effect analysis employing two stages of hierarchical process. Axial slices at three

different Talairach coordinate levels in superior-inferior directions (z = 62, 50 and 42) were shown for both GB34

stimulation (upper row) and for sham stimulation (lower row).

GB34

A

Z=

BA 6 BA 6 BA 8

L Z=62 R Z=42

Sham

Z=50

BA 6

BA 4 BA 7

BA 6

BA 3

GB34

Z=62 Z=50 Z=42

B

3T fMRI OF ACUPUNCTURE ON MOTOR CORTEX ACTIVITIES 577

Discussion

The imagery of hand movement is known to elicit activations in the somatomotor areas,

even in the absence of overt hand movement; however, the possibility of occurrences

of motor imagery during the stimulation was unlikely, since the subjects did not report

any imagery events during the acupuncture manipulation. Hypothesized activation in

the somatosensory areas (BA 3, 1, 2 and 5) was not evident in our group analysis. The

sensation of “Deqi” may not elicit significant activation in somatosensory areas to pass

the p-threshold condition for display. It is interesting to find that both right and left motor

areas were activated, but more dominantly in the left hemisphere where it is ipsilateral to

the site of the acupuncture application. In Oriental medicine, when acupuncture is applied,

acupuncture stimulation is usually treated at the contralateral part of the lesion. This

acupuncture treatment is based on the theory that, when patients complain of hemiplegia,

acupuncture is applied at the contralateral part of hemiplegic lesion (i.e. when patients

complain of right hemiplegia, acupuncture is applied at the acupoint of left GB34). Our

result may correspond with the theory of Oriental medicine. The stimulation of acupuncture

evoked an ipsilateral activation of brain, and this activation signal might be transduced to a

hemiplegic lesion through a crossed corticospinal tract. Further study is required.

All fMRI sessions were safely administered to all volunteers in the absence of pain, or

without engaging motor imagery during acupuncture in the 3T environment. Before the

present study, our preliminary results demonstrated that no muscle activity was observed

in GB34 stimulation on EMG recording. Thus, we focused on the neuro-functional activity

of the brain using fMRI and have demonstrated that several cortical areas, especially

motor functional areas, manifested quantifiable BOLD signal changes associated with

acupuncture stimulation. To compare with fMRI data from the sham stimulation, the

modulation of neural substrates was spatially specific to the acupoints. It is possible, as

hypothesized (Han and Terenius 1982; Melzack, 1994; Pomeranz, 1995), that the activation

in these somatomotor areas were mediated by activations in subcortical areas, including

limbic and paralimbic systems. An investigation of fMRI targeting subcortical areas is,

therefore, urgently needed. Since the consistency and reproducibility of acupuncture vary

significantly depending on subjects, the choice of acupoints and imaging parameters used,

further studies are needed to examine the reproducibility among subjects for the stimulation

of GB34 and other relevant acupoints to a wider subject population, including both normal

subjects and patients.

Acknowledgments

We express our gratitude to Mr. Hee-Keun Jee (Kangnam St. Mary’s Hospital, Seoul,

Korea) for providing technical support and patient treatment. We are grateful to the

Catholic Medical Center (CMC) staff, residents, interns, and graduate students for their

voluntary participation. This study was supported by a grant of the Korea Health 21 R&D

Project, Ministry of Health & Welfare, Republic of Korea (02-PJ1-PG1-CH06-0001).

578 S.-S. JEUN et al.

References

Boling, W., A. Olivier, R.G. Bittar and D. Reutens. Localization of hand motor activation is localized

in Broca’s pli de passage moyen. J. Neurosurg. 91(6): 903–10, 1999.

Cho, Z.H., S.C. Chung, J.P. Jones, J.B. Park, H.J. Park, H.J. Lee, E.K. Wong and B.I. Min. New findings

of the correlation between acupoints and corresponding brain cortices using functional MRI.

Proc. Natl. Acad. Sci. USA 95: 2670–673, 1998.

Diehl, D.L., G. Kaplan, I. Coulter, D. Glik and E.L. Hurwitz. Use of acupuncture by American

physicians. J. Altern. Complement. Med. 3(2): 119–26, 1997.

Eisenberg, D.M., R.B. Davis, S.L. Ettner, S. Appel, S. Wilkey, M. Van Rompay and R.C. Kessler.

Trends in alternative medicine use in the United Sates, 1990–997. JAMA 280: 1569–575,

1998.

Eisenberg, D.M., R.C. Kessler and C. Foster. Unconventional medicine in the United Sates. N. Engl.

J. Med. 328: 246–52, 1993.

Filshie, J. and A. White. Medical Acupuncture: A Western Scientific Approach. Churchill Livingstone,

London, England, 1998.

Fisher, P. and A. Ward. Complementary medicine in Europe. Br. Med. J. 309: 107–11, 1994.

Friston, K.J., P. Jezzard and R. Turner. Analysis of functional MRI time-series. Hum. Brain Mapp.

1: 153–71, 1994.

Han, J.S. and L. Terenius. Neurochemical basis of acupuncture analgesia. Annu. Rev. Pharmacol.

Toxicol. 22: 193–20, 1982.

Holmes, A.P. and K.J. Friston. Generalisability, random effects and population inference. NeuroImage

7: S754, 1998.

Hui, K.K.S., J. Liu, N. Makris, R.L. Gollub, A.J.W. Chen, C.I. Moore, D.N. Kennedy, B.R. Rosen

and K.K. Kwong. Acupuncture modulates the limbic system and subcortical gray structures

of the human brain: evidence from fMRI studies in normal subjects. Hum. Brain Mapp. 9:

13–5, 2000.

Kwong, K.K., J.W. Belliveau, D.A. Chesler, I.E. Goldberg, R.M. Weisskoff, B.P. Poncelet, D.N.

Kennedy, B.E. Hoppel, M.S. Cohen, R. Turner and H.M. Cheng. Dynamic magnetic resonance

imaging of human brain activity during primary sensory stimulation. Proc. Natl. Acad. Sci.

USA 89: 5675–679, 1992.

Melzack, R. Folk medicine and the sensory modulation of pain. In: P. D. Wall and R. Melzack (eds.) The

Textbook of Pain, 3rd ed., Churchill Livingstone, London, England, 1994, pp. 1209–218.

Pomeranz, B. Scientific basis of acupuncture. In: G. Stux and B. Pomeranz (eds.) Basics of Acupuncture,

3rd ed. Springer-Verlag, New York, NY, 1995, pp. 4–0.

Wiseman, N., K. Boss, A.W. Ellis and R. Feit. Fundamentals of Chinese Acupuncture. Redwing Books

Co., Brookline, MA, USA, 1991.

Wu, M.T., J.C. Hiesh, J. Xiong, C.F. Yang, H.B. Pan, Y.C. Chen, G. Tsai, B.R. Rosen and K.K. Kwong.

Central nervous pathway for acupuncture stimulation: localization of processing with functional

MRI of the brain —Preliminary experience. Radiology 212: 133–41, 1999.