Neuroscience Letters 464 (2009) 15

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Neuroscience Letters
journal homepage: www.elsevier.com/locate/neulet

An fMRI study of neuronal specicity of an acupoint: Electroacupuncture

stimulation of Yanglingquan (GB34) and its sham point
Byung-jo Na a, , Geon-Ho Jahng b , Seong-uk Park c , Woo-sang Jung d ,
Sang-kwan Moon d , Jung-mi Park c , Hyung-sup Bae c
a
Department of Internal Medicine, Kang-Nam Oriental Medicine Hospital, College of Oriental Medicine, Kyung-Hee University,
994-5 Dachil-dong, Gangnam-gu, Seoul, Republic of Korea
b
Department of Radiology, East-West Neo Medical Center, Kyung-Hee University, Seoul, Republic of Korea
c
Stoke and Neurologic Disorder Center, East-West Neo Medical Center, Kyung-Hee University, Seoul, Republic of Korea
d
Department of Cardiovascular and Neurologic Diseases (Stroke Center), College of Oriental Medicine, Kyung-Hee University, Seoul, Republic of Korea

a r t i c l e

i n f o

Article history:
Received 25 April 2009
Received in revised form 31 July 2009
Accepted 4 August 2009
Keywords:
fMRI
Electroacupuncture
Neuronal specicity
Acupoint
GB34 (Yanglingquan)

a b s t r a c t
The neuronal specicity of acupoints has not been entirely supported by the results of fMRI studies. The
objective of this study was to investigate the neuronal specicity of an acupoint with electroacupuncture
stimulation (EAS) using functional magnetic resonance imaging (fMRI). Functional MR imaging of the
entire brain was performed in 12 normal healthy subjects during EAS of GB34 (Yanglingquan) and its
sham point over the left leg in counter-balanced order. Anatomically, both GB34 and its sham point
belong to the L5 spinal segment. EAS at the left GB34 specically activated the right putamen, caudate
body, claustrum, thalamus, cerebellum, as well as the left caudate body, ventral lateral thalamus, and
cerebellum, all related to motor function. EAS at the sham point of the left GB34 specically activated the
right BA6, BA8, BA40, BA44, thalamus, as well as the left thalamus and cerebellum. Taken together, these
ndings suggest that EAS at an acupoint and its sham point, in the same spinal segment, induced specic
cerebral response patterns. These ndings support neuronal specicity of the acupoint studied. EAS at
GB34 appears to be more related to motor function than EAS at its sham point, suggesting specicity of the
GB34 acupoint. The results of this study provide neurobiological evidence for the existence of acupoint
specicity, although further studies are necessary to better understand this phenomenon.
2009 Elsevier Ireland Ltd. All rights reserved.

Acupuncture has been gaining popularity among practitioners of

modern medicine as an alternative and complementary treatment
[5]. According to the theory of Oriental Medicine, each acupoint has
functional specicity; the specic acupoints are carefully selected
when acupuncture is used to treat disorders [12,16,20]. However, the underlying mechanisms of acupoint specicity are still
not well understood. Since the 1990s, advances in noninvasive
brain imaging techniques such as positron emission tomography and functional magnetic resonance imaging (fMRI) have
enabled direct study of the human brain [2,4,6,7,9,10,11,1315,
18,2124].
Studies conducted using fMRI have provided evidence of acupoint specicity by demonstrating a correlation between acupoints
and brain activation [4,14,15,18]. These ndings have indicated
that acupuncture, at disease-implicated acupoints, can modulate
the activity of the disease-related neuromatrix. For example, it has

Corresponding author. Tel.: +82 2 3457 9024; fax: +82 2 3457 9100.
E-mail address: hani114@paran.com (B.-j. Na).
0304-3940/$ see front matter 2009 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.neulet.2009.08.009

been reported that specic cerebral sites are activated in response

to stimulation of vision-associated acupoints (BL67, BL66, BL65,
and BL60) [14,18], hearing-associated acupoints (GB43) [4] and
language-associated acupoints (SJ8 and Du15) [15]. However, the
specicity of acupuncture stimulation has not been entirely supported by the results of fMRI studies [3,7]. For example, Gareus et
al. reported that stimulation of the vision-related acupoint did not
induce a signicant blood oxygenation level dependent (BOLD)effect in the visual cortex [7].
Therefore, in this study, we chose the GB34 (Yanglingquan) acupoint and its sham point, not located in the meridian but close to
each other in the same segment, to evaluate acupoint specicity.
Anatomically, both GB34 and the sham point of GB34 belong to the
L5 spinal segment. We rstly hypothesized that electroacupuncture
stimulation (EAS) at the acupoint and its sham point, in the same
spinal segment, would induce specic central responses, based on
acupoint specicity.
In fact, the acupoint GB34 is used to treat hemiplegia, a variety of
muscle disorders, and knee pain [12,16,20]. We secondly hypothesized that EAS at GB34 was more likely related to motor function
than EAS at its sham point. To test these hypotheses, we used blood

B.-j. Na et al. / Neuroscience Letters 464 (2009) 15

Table 1
Denition of the two types of electroacupuncture (EA).
Real EA (Yanglinquan)

Sham EA (for Yanglinquan)

Location

GB34 lateral area of left leg

Needle depth
EA, current (mA)
EA (Hz)
Duration

About 2 cm
Subjectively optimal
2
30 s 3 blocks

2.0 cm lateral in the

nonmeridian, to GB34
About 2 cm
The same current as real EA
2
30 s 3 blocks

oxygenation level dependent (BOLD) fMRI during EAS of GB34 and

its sham point.
Twelve healthy right-handed male volunteers (mean and standard deviation = 33.6 6.2, range = 2643 years) participated in this
study. The study protocol was approved by the local institutional
review board. Informed consents were obtained from all subjects.
The subjects had some knowledge of acupuncture due to cultural
exposure, but had never received such treatment. None of the subjects had a history of psychiatric problems, neurological disorders
or head trauma.
Electroacupuncture stimulation (EAS) has been widely used as
a substitute for classical acupuncture [8,13,21]. We applied actual
electroacupuncture (EA) at acupoint GB34 and the sham EA of GB34
to the left leg of the subjects in counter-balanced order. The denition of the two types of electroacupuncture is provided in Table 1.
The acupoint GB34 is located at the bular aspect of the leg, in the
depression anterior and distal to the head of the bula [12,16,20].
The sham point was 2.0 cm lateral in the nonmeridian, to GB34. The
other needle at the negative electrode was placed 1 cm proximally
down along the gallbladder meridian for real EA, or along an imaginary line, for the sham EA. The other needle for the real EA and the
sham EA was located in the L5 spinal segment (Fig. 1).
Prior to the start of the fMRI experiments, all subjects were
informed that different models of EAS, at various points, might
be used for comparison. However, the precise locations of needle
placement, the expected acupuncture effects, and the stimulation
paradigm were not divulged. In addition, prior to the actual fMRI
experiments, an EAS practice session was performed to determine the intensity of the EAS at which the subject could feel
Deqi, which is the acupuncture effect of needle-manipulation characterized by sensations of numbness, heaviness, distention, and
soreness.
One experienced acupuncturist performed all electroacupuncture procedures using an EA device (ES-160, Ito Co. Ltd., Tokyo,

Japan). For all stimulations, a stainless steel acupuncture needle

with a diameter of 0.25 mm and a length of 30 mm was inserted
into the skin to a depth of approximately 2 cm at the acupoints or
sham points.
The needles were then adjusted to obtain Deqi. Of additional
importance here is that sharp pain remained a specic concern and
was avoided. Next, the needle, electrode, and electroacupuncture
device were connected to a wire lead modied for safe use in the
high magnetic eld environment of MRI.
For each subject, the specic stimulation intensity was determined by gradually increasing and adjusting the voltage applied
at each point, until the subject reported a mild to moderate sensation of Deqi. This was done at the beginning of each session, prior to
fMRI scanning. The intensity was adjusted to a reasonable, but comfortable level that ranged from 2.4 to 3.2 mA (average, 2.82 mA) at
which the subject could feel Deqi. The electroacupuncture stimulation was delivered using a continuous rectangular waveform with
a pulse width of 0.4 ms at a frequency of 2 Hz.
After each scan, subjects were asked to quantify their sensations
about both acute pain and anxiety. The subjects rated the intensity
of each sensation and their anxiety using a 5-point Likert scale:
none, mild, moderate, severe and unbearable.
No subjects reported experiences of sharp pain during the
experiment. All the participants rated the intensity of each sensation and their anxiety as mild or moderate. There were no
signicant differences in the intensity of each sensation and their
anxiety evoked by stimulating the acupoint or its sham point under
Fishers exact test (p > 0.05).
All fMRI experiments were conducted using a 3.0 T whole
body scanner (Philips Achieva, Best, the Netherlands) with an 8channel phase array head coil. During the experiment, subjects
were instructed to remain relaxed with their eyes closed.
First, T1-weighted spin-echo images were obtained to provide
an anatomic reference (repetition time [TR]/echo time [TE] =
9.335/5 ms, eld of view [FOV] = 240 240 mm, ip angle = 90 ,
imaging matrix = 128 128). The images covered the entire brain
and were parallel to the anterior commissureposterior commissure (ACPC) line. Next, functional images were obtained
using a gradient-echo echo planar imaging (EPI) sequence.
The parameters used were: TR = 3000 ms, TE = 35 ms, ip
angle = 90 , FOV = 230 230 mm, imaging matrix = 64 64, slice
thickness = 4.5 mm and gap between slices = 0 mm, and voxel
size = 3.43 mm 3.43 mm 4.5 mm. A three-dimensional anatomic
image was also acquired to reconstruct functional areas into brain

Fig. 1. Anatomical locations of the electroacupuncture stimulation points of GB34 (left) and its sham acupoint (right). The upper electrode is the positive pole and the lower
electrode is the negative pole.

B.-j. Na et al. / Neuroscience Letters 464 (2009) 15

Table 2
Foci of brain activation in the multisubject analysis of the real electroacupuncture (EA) at the left GB34 and sham EA at the left GB34.
Brain areas

Lentiform nucleus, putamen

Side

BA

Z-max

44, 4, 8
52, 14, 6

4.80
3.80

10, 14, 58
10, 22, 56
2, 20, 48

3.80
3.75
3.25

40

48, 32, 32

4.58

R
Caudate, caudate body
L
R

Precentral gyrus

Superior frontal gyrus

Inferior parietal lobule

Thalamus

R
L

Thalamus, Pulvinar

Thalamus, ventral lateral nucleus

Coordinates
x, y, z

Z-max

24, 4, 20
28, 0, 12

4.14
3.13

16, 10, 20
20, 14, 22
12, 10, 22
14, 2, 22

3.71
3.95
3.80
3.37

28, 18, 22

3.94

44
6

R
Cerebellum, inferior semi-lunar lobule
L

R
Cerebellum, cerebellar tonsil

Sham EA > rest

Coordinates
xyz

Claustrum

Real EA > rest

20, 16, 14

3.63

20, 10, 14

3.84

20, 70, 38
18, 62, 40
12, 66, 38
30, 64, 42
22, 68, 40

3.82
3.71
3.60
3.57
3.31

22, 50, 34

3.41

6, 24, 4

3.48

4, 30, 6

3.56

24, 64, 40

3.73

24, 48, 38
32, 58, 38

4.03
3.71

BA: Brodmann area.

regions (TR = 9.9 ms, TE = 4.6 ms, imaging matrix = 240 240,
FOV = 240 240 mm, ip angle = 7 , slice thickness = 1 mm, voxel
size = 1 mm 1 mm 1 mm).
Each subject was then subjected to two 3-min fMRI scans,
with a 10 min interval between scans. During each scanning session, the EAS was delivered on one of the pairs of acupoints
in the left leg. The block design for the two stimulations was
R30 A30 R30 A30 R30 A30 , in which three stimulation periods (A,
electrical manipulation stimulation for 30 s) were interposed with
three rest periods (R, rest period during which time there was no
stimulation for 30 s).
Post-processing of the fMRI data from all subjects was performed using Statistical Parametric Mapping software (SPM2,
www.l.ion.ud.ac.uk/spm/). To avoid the non-equilibrium effects
of magnetization, we removed the rst 2 scans from the data of
each subject, which left 240 scans for each subject to be analyzed. The images corresponding to each subject were realigned
to correct for head motion and registered to the rst scan. After
the realigned functional MR images were coregistered to the corresponding anatomical images, the three-dimensional anatomical
images and the coregistered functional images were normalized to
the Montreal Neurological Institute space and then spatially normalized functional images were smoothed using a 9-mm full-width
half-maximum Gaussian kernel.
The statistical mapping included two levels. First, the smoothed
images were used for the xed-effect analysis based on the general
linear model using a reference waveform adopted boxcar convolved with the canonical hemodynamic response function. The
cerebral areas activated during stimulation (relative to baselines)
were then identied (p < 0.001 uncorrected, spatial extent threshold, 100 voxels). Next, the group-level activation during stimulation

(relative to baselines) was determined using a random-effect analysis based on a one-sample t-test model using the results of the
rst-level analysis for within-group analysis (p < 0.001 uncorrected,
spatial extent threshold, 100 voxels). The resulting coordinates
were then transformed into Talairach space. The results of the multisubject analysis are summarized in Table 2 and Fig. 2.
The comparison of EAS, at the left GB34 versus the resting state,
showed that EAS specically activated the right putamen, caudate
body, claustrum, thalamus, cerebellum, as well as the left caudate
body, ventral lateral nucleus, and cerebellum (Table 2; Fig. 2). The
comparison of the EAS at the sham point of the left GB34 versus resting state showed that EAS specically activated the right BA6, BA8,
BA40, BA44, thalamus, as well as the left thalamus and cerebellum
(Table 2; Fig. 2).
The purpose of the present study was to determine whether
a different but close acupoint GB34 and its sham point, in the
same spinal segment, would cause different fMRI responses. If no
acupoint specicity exists, they should produce virtually similar
responses. Conversely, if signicantly different responses resulted
from these stimulations, this would provide evidence to support
the specicity of an acupoint [24].
The brain regions activated by EAS at GB34 were different
from those activated by EAS at its sham point (Table 2; Fig. 2).
In addition, the results demonstrated that real EAS at GB34 had
a greater effect and broad neuromatrix responses that involved
limbic-related brain structures including the putamen, caudate
body, and claustrum compared to the EAS at its sham point (Table 2;
Fig. 2). The regions of the brain activated by EAS at GB34 were
the basal ganglia, thalamus, and cerebellum, regarded as motor
structures. Damage to these brain regions produces well-described
alterations in motor function such as tremor, rigidity, akinesia, or

B.-j. Na et al. / Neuroscience Letters 464 (2009) 15

Fig. 2. Areas of activation in the multisubject analysis: (a) activation by electroacupuncture stimulation (EAS) at GB34 and (b) activation by EAS at the sham point of GB34.

dysmetria [1,17]. These activated brain regions suggest the indications for acupoint GB34 stimulation, such as hemiplegia and various
muscle disorders [12,16,20]. Therefore, these results support neuronal specicity associated with EAS of GB34 as indicated by the
activation of basal ganglia and cerebellar loops with motor areas
of the cerebral cortex, all related to movement. EAS at GB34 might
be helpful for stroke patients with motor disturbances caused by
damage to the basal ganglia and cerebellar components of circuits
associated with the motor areas of the cortex. However, additional
studies are needed to conrm these ndings.
These ndings support the results of previous fMRI studies on
acupuncture or electroacupuncture at GB34. Jeun et al. reported
that acupuncture stimulation at GB34 modulates the cortical activities of the somatomotor area in humans [11]. Zhang et al. reported
that EAS at GB34 and BL57 induced deactivation in MI/PMC, as well
as activation at the dorsal thalamus and putamen, known to be
involved in motor functions [24].
A common region of the brain activated by EAS at its sham point
as well as the GB34 acupoint was the cerebellum. This nding suggests that acupuncture performed at sites not located on meridians
can have varying degrees of physiological and clinical effects, and
that the cerebellum coordinates many functions of the brain such
as autonomic control, cognition and affect, as well as in sensorimotor control with its complicated afferent and efferent connections
with the cerebrum, brain stem and other regions [10,19,23].
Recent fMRI investigations of electroacupuncture and manual
acupuncture have demonstrated increased cerebellar activity in
response to treatment [10,22,23]. Yoo et al. found that cerebellar
activity occurred in response to acupuncture stimulation of acupoint PC6 [23]. In addition, Yan et al. found that one of the common
activation areas, in response to Liv3 or LI4 acupuncture, was the
cerebellum, which was related to motor function [22]. Recently
Hui et al. also suggested that modulation of the cerebro-cerebellar
and limbic system activity may constitute an important pathway
of acupuncture action [10].
One limitation of this study was the design of the controlled
experiments. It is known that acupuncture performed at sites that
are not located on meridians can have varying degrees of physiological and clinical effects [6]. In our study, the sham acupoint was

innervated by the same spinal nerve as the real acupoint, but was
located 2 cm away from the meridian. In addition, we applied the
sham EA, at nonmeridian points, using the same needle depth, stimulation intensity, frequency and pulse wave as those used for the
real EA, because we were interested in the effects of EA at different locations. Furthermore, the sham EA used in our study elicited
similar Deqi as the real EA; this was different from previous studies that used a placebo or minimal acupuncture devised to elicit
no Deqi in the controls [2,9]. Therefore, there is the possibility that
different results of this study compared to other studies occurred
due to the different types of sham EA used.
We thought it was more reasonable to base the detection of
functional activity on the comparison of an activation task such
as EAS with the baseline (without stimulation) as in our study.
Therefore, we used the comparison of an electrical stimulation
with the baseline (without stimulation) to investigate the neuronal
specicity of an acupoint. Another limitation of this study was the
sample size and statistical power. Conrmation of our ndings is
needed with a larger sample size with greater statistical power. In
addition, only the acupoint GB34 and its sham point were investigated; further study at other acupoints in other meridians will be
needed to conrm our ndings.
In conclusion, we have shown that EAS at an acupoint and its
sham point, in the same spinal segment, induced specic cerebral
response patterns, which provides evidence for neuronal specicity of an acupoint. We also have shown that EAS at GB34 may
be more related to motor function than EAS at its sham point, and
this is correlated with the clinical indications for acupoint stimulation of GB34. The results of this study may offer some primary
neurobiological evidence for the existence of acupoint specicity,
although further studies are necessary to better understand this
phenomenon.

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