Download as pdf or txt
Download as pdf or txt
You are on page 1of 6

Available online at www.sciencedirect.

com

Neuroscience Letters 434 (2008) 144–149

Brain imaging of acupuncture: Comparing


superficial with deep needling
Hugh MacPherson a,∗ , Gary Green b , Angel Nevado b , Mark F. Lythgoe c ,
George Lewith d , Ross Devlin b , Robyn Haselfoot b , Aziz U.R. Asghar b,e
aDepartment of Health Sciences, University of York, YO10 5DD, United Kingdom
b York Neuroimaging Centre, University of York, Y10 5DG, United Kingdom
c RCS Unit of Biophysics, UCL Institute of Child Health, University College London, WC1N 3JH, United Kingdom
d Complementary Medicine Research Unit, University of Southampton, SO17 1BJ, United Kingdom
e Hull York Medical School and Department of Biological Sciences, University of Hull, Hull HU6 7RX , United Kingdom

Received 5 November 2007; received in revised form 16 January 2008; accepted 22 January 2008

Abstract
The difference between superficial and deep needling at acupuncture points has yet to be mapped with functional magnetic resonance imaging
(fMRI). Using a 3 T MRI, echo planar imaging data were acquired for 17 right-handed healthy volunteer participants. Two fMRI scans of acupuncture
needling were taken in random order in a block design, one for superficial and one for deep needling on the right hand at the acupuncture point
LI-4 (Hegu), with the participant blind to the order. For both scans needle stimulation was used. Brain image analysis tools were used to explore
within-group and between-group differences in the blood oxygen level dependent (BOLD) responses. The study demonstrated marked similarities
in BOLD signal responses between superficial and deep needling, with no significant differences in either activations (increases in BOLD signal) or
deactivations (decreases in BOLD signal) above the voxel Z score of 2.3 with corrected cluster significance of P = 0.05. For both types of needling,
deactivations predominated over activations. These fMRI data suggest that acupuncture needle stimulation at two different depths of needling,
superficial and deep, do not elicit significantly different BOLD responses. This data is consistent with the equivalent therapeutic outcomes that are
claimed by proponents of Japanese and Chinese styles of acupuncture that utilise superficial and deep needling, respectively.
© 2008 Elsevier Ireland Ltd. All rights reserved.

Keywords: Acupuncture; Neuroimaging; fMRI

Acupuncture is a treatment modality that is growing in pop- is integral to the putative therapeutic gain. A primary interest in
ularity [5,23] and is practised in many different ways, with this area therefore is whether these different depths of needling
one of the fundamental differences in approach being the depth elicit similar or different physiological responses.
that acupuncture needles are inserted. Practitioners trained in The primary aim of this investigation therefore was to utilize
Japanese styles of acupuncture commonly insert their nee- fMRI to measure the increases (activations) and decreases
dles superficially just below the skin to a depth of perhaps (deactivations) in the blood oxygen level dependent (BOLD)
1–2 mm [3]. In contrast, practitioners trained in Chinese styles response with acupuncture needling at LI-4, comparing the
of acupuncture, including what has become known as Tradi- impact of needling at two different depths: (1) superficial
tional Chinese Medicine (TCM), are of the view that therapeutic needling as commonly used in Japanese styles of acupuncture
responses are associated with needling depths that are often (3), and (2) deep needling to a depth commonly used in
called “deep”, usually 1–2 cm depending on the local mus- Chinese-based styles of acupuncture (4).
culature [4]. Practitioners of both acupuncture styles claim
therapeutic benefits while insisting that the depth of needling We recruited 17 healthy right-handed adult volunteer partic-
ipants who were naı̈ve to acupuncture: eight males (mean age
33 years, range 18–46, S.D. = 11.9) and nine females (mean age
∗ Corresponding author at: Department of Health Sciences, Area 3, Seebohm
39 years, range 20–54, S.D. = 10.2), with an average age of 36
Rowntree Building, University of York, Heslington, York YO10 5DD, United
Kingdom. Tel.: +44 1904 321394; fax: +44 1904 321388.
years. Participants were provided with an information leaflet
E-mail address: hm18@york.ac.uk (H. MacPherson). describing the study and a safety questionnaire that screened

0304-3940/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.neulet.2008.01.058
H. MacPherson et al. / Neuroscience Letters 434 (2008) 144–149 145

for contraindications for MRI scanning. When the York Neu- ratings of both pain and deqi [16]. Immediately after each 16 min
roimaging Centre received a completed safety questionnaire, scan, participants were asked questions about their experience
participants were screened for eligibility and informed consent of 25 individual needle sensations from the Park questionnaire
was obtained. Approval for the study was obtained from the York [18]. Participants rated the intensity of each sensation on an
Neuroimaging Centre’s Science and Ethics Committees, and all ordinal scale: “none” (zero), “slight” (one), “moderate” (two) or
ethical requirements were met. “strong” (three). In a previous study, these 25 sensations from
For all participants, and for all scans, acupuncture needling the Park scale were separated using a hierarchical cluster analy-
was performed at the acupuncture point Hegu (LI-4) on the sis into two categories: deqi being associated with aching, dull,
right hand by an experienced acupuncturist who is a member heavy, numb, radiating, spreading and tingling sensations and
of the British Acupuncture Council (HM). Needles were ster- acute pain being associated with burning, hot, hurting, pinch-
ile, disposable, non-magnetic stainless steel, 25 mm long, and ing, pricking, sharp, shocking, stinging and tender sensations
0.28 mm diameter, manufactured by Hwato, China. The inser- [16]. Deqi and acute pain sensation scores for each scan were
tion depth of the needle into the interosseus dorsalis muscle was determined from the participant’s 25 sensation scores (range 0–3
randomised to be either superficial (1–2 mm) or deep (8–12 mm). each sensation, divided by number of sensations reported). The
The depth for deep needling was adjusted by the acupuncturist to impact of prior expectation/anticipation was equalised across
take into account the variability of the participant’s interosseus superficial and deep needling as the participant was blind to the
dorsalis muscle, as would be judged appropriate in normal prac- intervention.
tice. The randomisation was computer generated with allocation Scanning was performed with a 3 T magnetic resonance
concealed in envelopes that were opened at the onset of the scans. imaging system (GE Signa HD Excite) with an eight chan-
fMRI scans were conducted over two 16 min periods; one nel head coil (GE Signa Excite 3.0T, High Resolution Brain
scan involved superficial needling only and another separate Array, MRI Devices Corp., Gainesville FL). Axial images were
scan involved deep needling only. Participants were informed acquired for functional and structural scans which covered the
that they would be receiving two types of acupuncture during whole brain. Localiser scans were used to align axial images
their time in the scanner. To minimise participants’ expectations along the anterior commissure-posterior commissure line, cov-
about which depth of needling they were about to receive, they ering both hemispheres.
were not informed of the order of the two scans. They were For functional imaging, Echo Planar Imaging (EPI) images
requested to lie still during scans with their eyes closed. were acquired using a T2* weighted gradient echo sequence
Each fMRI scan involved two identical active blocks of nee- (TR 4 s, TE 30 ms, flip angle 90◦ , acquisition matrix 128 × 128,
dle stimulation separated by a rest period (Fig. 1). Although FOV 240 mm, in-plane resolution 2 mm × 2 mm, contiguous
fMRI studies typically contain more stimulation blocks, previ- slice thickness 4.5 mm).
ous published research has shown that this experimental design High resolution T1-weighted structural images were acquired
paradigm using two long stimulation blocks is robust in detecting prior to the functional scans using an IR (Inversion Recovery)-
changes in the BOLD response (both activations and deacti- prepared 3D-FSPGR (Fast Spoiled Gradient Echo) pulse
vations) to acupuncture needling at LI-4 [11]. For the active sequence (TR 7.5 s, TE 3 ms, flip angle 20◦ , acquisition matrix
blocks, whether superficial or deep insertion, the needle was 256 × 224 interpolated to 512 × 512, FOV 260 mm, in plane
“stimulated” with a continuous alternating 180 degree rotation resolution 0.5 mm × 0.5 mm, slice thickness 2.6 mm with an
of the needle clockwise and anti-clockwise at approximately overlap of 1.3 mm).
two cycles per second. In acupuncture theory, this manipulation The primary outcomes evaluated were activations and
technique is also known as needle stimulation using the “bal- deactivations as represented by increases and decreases in
anced” or “even” method [4]. For the baseline, the needle was BOLD response. FSL software (FMRIB’s Software Library,
retained with no stimulation. www.fmrib.ox.ac.uk/fsl) based on generalised linear modelling
After each scan, participants reported experiential data on was used. The design matrix consisted of a single explanatory
needle sensation using the Park questionnaire [18], leading to variable which was “on” during the periods of stimulation and
otherwise “off” (see Fig. 1). Positive and negative parameter esti-
mates, referred to as activations and deactivations, respectively,
were calculated for each of the two conditions (superficial and
deep needling) in each participant.
For each participant, a first level analysis of individual scans
was carried out using FEAT (FMRI Expert Analysis Tool)
Version 5.4, part of FSL. The following pre-statistics process-
ing was applied; slice-timing correction using Fourier-space
time-series phase-shifting; motion correction using MCFLIRT
Fig. 1. Block design showing the two needle stimulation periods which were [13]; non-brain removal using BET [21]; spatial smoothing
provided consecutively within each scan, with both stimulation periods involving using a Gaussian kernel of FWHM 5mm; mean-based inten-
identical needling. For each participant two fMRI scans were performed using
this block design, one with two consecutive superficial needling stimulation
sity normalisation of all volumes by the same factor; highpass
periods and one with two consecutive deep needling stimulation periods. The temporal filtering (Gaussian-weighted LSF straight line fitting,
order of these two types of needling intervention was randomised. with sigma = 480 s). Time-series statistical analysis was car-
146 H. MacPherson et al. / Neuroscience Letters 434 (2008) 144–149

ried out using FILM (FMRIB’s Improved Linear Model) with needling did not reach statistical significance (paired t test) for
local autocorrelation correction [27]. Both positive (activations) deqi scores (P = 0.08) or for acute pain scores (P = 0.17).
and negative (deactivations) interactions were modelled. Reg- From the within-group analyses of deep needling scans
istration of EPI images to high resolution T1 images and then (considered as a single group), we observed a pattern of acti-
subsequently to the Montreal Neurological Institute standard vations above the Z = 4.3 threshold (with a corrected cluster
brain (MNI152) was carried out using FLIRT [13,14]. significance of P = 0.05) predominantly in the culmen of the
Motion correction was applied to the fMRI scans and cerebellum (Table 1B). Deactivations were observed in the
for each participant the mean (across voxels) voxel absolute occipital lobe (BA19), the frontal lobe and the medial frontal
(each time point with respect to the reference image) and gyrus (BA10) (Table 1E). From the within-group analyses of
relative (each time point with respect to the previous time superficial needling scans (considered as a single group), the
point) was calculated by the FSL software (Motion Correc- activations were similar to those of deep needling, predomi-
tion Report). Displacements across 34 separate scans from nantly in the culmen of the cerebellum (Table 1C). Superficial
17 participants were found to be small: mean ± S.D. of the needling deactivations were primarily located in the precuneus
absolute displacement = 0.48 ± 0.28 mm, and relative displace- (BA39), the precentral gyrus (BA4), and the inferior tempo-
ment = 0.09 ± 0.04 mm. ral gyrus (Table 1F). For both depths of needling, deactivations
Within-group analysis of scans were performed separately were predominantly in the left hemisphere (contralateral to
for each of the two depths of needling using FLAME (FMRIB’s the needling side). Despite these apparent within-group differ-
Local Analysis of Mixed Effects) [1,26]. Z (Gaussianised T/F) ences in patterns of deactivation, the statistical analysis based
statistic within-group images were identified using clusters on between-group subtraction of superficial from deep needling
determined by individual voxels above the threshold of Z > 4.3 scans (see above) showed no significant differences (i.e. no clus-
and a (corrected) voxel cluster significance threshold of P = 0.05 ters with Z > 2.3 and a corrected cluster significance of P = 0.05).
[28]. Based on the sizes of significant clusters, overall the deac-
Between-group differences were analysed by subtracting the tivations were substantially larger than activations for both
scans for superficial needling from those of deep needling in superficial and deep needling. For example with deep needling,
a two sample paired t-test using FSL software. We identified the largest area of deactivation involved a cluster with 1496 vox-
clusters with individual voxels having Z > 2.3, and (corrected) els, compared to a cluster of only 62 voxels for the largest area
voxel cluster significance threshold of P = 0.05 [28] For both of activation. For superficial needling, the largest deactivation
within-group and between-group analyses, significant clusters cluster contained 4209 voxels compared to 141 for activation.
(activations or deactivations) were registered and superimposed A region of interest analysis in the secondary somatosensory
onto the MNI152 standard brain template. Clusters sizes of area demonstrated bilateral activation with both types of
≤20 voxels were not considered further. needling (superficial needling:- right 60, −22, 16, Z = 3.17 and
left −68, −24, 20, Z = 3.26; deep needling:- right coordinates x =
The primary comparison in our study was between nee- 56, y = −26, z = 22, Z = 5.36 and left −68, −22,16, Z = 3.36, un-
dle stimulation at superficial compared to deep needling. This corrected P = 0.05) thus confirming the activations in this area
between-group analysis, in which superficial needling responses as reported previously in fMRI studies of acupuncture [11,31].
were subtracted from deep needling responses (paired t-tests),
showed no significant increases (activations) or decreases (deac- The main finding in this study is that, when subtracting the
tivations) in BOLD response above the threshold of Z = 2.3 BOLD responses between needle stimulation at superficial and
with a corrected cluster significance threshold of P = 0.05 deep needling, no significant differences are seen in activa-
(Table 1A and 1D, Fig. 1). tions (increase in BOLD response) or deactivations (decrease
The participant-reported sensory data showed levels of deqi in BOLD response) at the threshold of Z > 2.3 and corrected
and pain to be of the same order for both superficial and cluster significance level of P = 0.05. The data on needle sen-
deep needling. The mean deqi score was 0.50 (S.D. = 0.48) sation, whether associated with deqi or acute pain, indicated
per sensation for superficial needling and slightly higher at that sensation was not a confounder. The percentage BOLD
0.71 (S.D. = 0.49) for deep needling, while the acute pain response is of a similar order to that of other studies [11,12].
score was 0.44 (S.D. = 0.33) for superficial needling and again Previous research has primarily explored the impact of deep
slightly higher at 0.62 (S.D. = 0.57) for deep needling. There needling, and we know of no fMRI study directly comparing
were no significant differences between superficial and deep needle stimulation at superficial versus deep needling. Previ-
scans for deqi scores (P = 0.08) or for acute pain scores ous fMRI studies of deep needling have reported results similar
(P = 0.17). to our data for deep needling, with deactivations predominat-
The participant-reported sensory data showed levels of deqi ing, whether the same point at LI-4 has been used or at other
and pain to be of the same order for both superficial and acupuncture point locations [11,12,15,17,29,30]. Similar data on
deep needling. The mean ± standard error of the deqi score activations as a result of deep needling have also been reported
was 0.50 ± 0.12 per sensation for superficial needling and [31,12,15,17,29,30]. Taken together, our study replicates the
at 0.71 ± 0.12 for deep needling, while the acute pain score core findings of other studies on deep needling, which are useful
was 0.44 ± 0.08 for superficial needling and 0.62 ± 0.14 for in facilitating interpretations of the comparison between super-
deep needling. There differences between superficial and deep ficial and deep needling that we report here.
Table 1
Brain areas showing activation and deactivation with deep and superficial needling
Voxels with maximum effect Cluster

x y z P value (−log10 P) Z value % BOLD ± S.D. Number of voxels Mean Z value

H. MacPherson et al. / Neuroscience Letters 434 (2008) 144–149


Activation
A. Deep > Superficial (paired t test) (this comparison is No significant differences in activations between deep and superficial groups
equivalent to superficial > deep with respect to
deactivation)
B. Deep needling (N = 17)
Cerebellum (culmen) I 4 −48 −24 3.8 5.6 0.43 ± 0.07 62 4.9
C. Superficial needling (N = 17)
Cerebellum (culmen) I 10 −44 −28 7.5 6.8 0.36 ± 0.05 141 5.2
Cerebellum (culmen) I −30 −34 −26 3.2 6.6 0.49 ± 0.07 36 5.0
Deactivation
D. Deep > Superficial (paired t test) (this comparison is No significant differences in deactivations between deep and superficial groups
equivalent to superficial > deep with respect to activation)
E. Deep needling (N = 17)
Occipital lobe (BA19) I −44 −80 2 >20 7.6 −1.02 ± 0.13 1469 5.2
Frontal lobe I −28 0 44 5.6 6.2 −0.27 ± 0.03 113 5.0
Medial frontal gyrus (BA10) I −12 34 −10 4.1 6.1 −0.23 ± 0.04 69 4.9
F. Superficial needling (N = 17)
Precuneus (BA39) I −40 −68 34 >20 7.5 −0.52 ± 0.07 4209 5.2
Precentral gyrus (BA4) I −56 −14 30 5.8 6.7 −0.36 ± 0.05 93 5.3
Inferior temporal gyrus I −56 −56 −16 4.9 6.7 −0.48 ± 0.07 71 4.9

All Z value thresholding is >4.3 except for paired differences which are thresholded at Z > 2.3. The most significant clusters (maximum of three shown) with a (corrected) cluster significance threshold of P = 0.05
are presented along with the voxel having the highest Z score within each cluster, x, y, z are MNI152 brain coordinates (mm). L: left; R: right. BA: Brodmann area.

147
148 H. MacPherson et al. / Neuroscience Letters 434 (2008) 144–149

Fig. 2. Functional maps for cluster analysis showing significant clusters for activations and deactivations on (A) deep needling and (B) superficial needling of LI-4.
Functional data were thresholded at Z > 4.3 with a corrected cluster significance level of P = 0.05. Clusters have been overlaid onto a standard brain (MNI152) shown
in orthographic view. The crosshairs in each panel show the position of the voxel with the highest Z score in the cluster with the highest statistical significance. The
number at the bottom right corner of the axial images gives the z direction coordinate of the selected MNI152 standard brain slice. R: right brain hemisphere; L: left
brain hemisphere.

In this study, deactivations elicited by acupuncture were those related to acupuncture [12], observe white matter activa-
more marked than the activations, a finding that is consistent tions/deactivation.
with other neuroimaging studies of acupuncture [11,12]. The The current investigation only examined and analysed fMRI
predominance of deactivations has been speculatively linked responses to the needling at different depths, and these only
to acupuncture’s putative therapeutic role [11]. It is not clear within the relatively short-term time span of a block design. It
whether such deactivations might involve a reduction of exci- could be argued that possible differences between the two depths
tatory inputs or a reduction of inhibitory inputs or some of needling may be too subtle for detection in fMRI, or that
combination of both [7]. An argument has been made that neg- the differences might only emerge over time when the longer-
ative BOLD responses can be explained by the concept of a term impact of acupuncture is being investigated. Research into
“vascular steal” from nearby areas where there are activations endorphin release, for example, indicates that acupuncture’s
[20]. However, we do not observe any obvious pattern of BOLD physiological effects can continue for many hours [9] and clin-
responses which indicate that areas of activation are coupled ical benefits might be sustained over long periods [24]. More
with adjacent areas of deactivation. An alternative interpreta- accurate modelling of clinical effects may need to involve six
tion is that the brain can have a resting state that is a “default or more acupuncture sessions [6] Also, the participants in this
mode”, which involves a baseline level of sustained brain activ- study were healthy individuals and it is possible that superficial
ity that is inhibited during tasks [8,19]. Building on these studies, and deep acupuncture could potentially have different effects
further research is needed to establish the meaning and role of when used to treat people with pathology.
the extensive deactivations associated with acupuncture that we There is a question as to whether the BOLD responses that
observed in this study for both depths of needling. we have observed in this study were a response to the experience
In this study, it was noted that some of the activations and of pain rather than to the acupuncture. Painful stimuli are known
deactivations were located to the white matter of the brain to involve processing in the somatosensory cortex, the insula
(Fig. 2). One explanation for this is that large motion arte- and the anterior cingulate cortex [25]. In addition, experimental
facts may have been present in the fMRI scans. However, research has generally shown that pain is primarily associated
this is unlikely as movement displacements were well within with activations rather than deactivations [2,10]. Our results,
acceptable limits. Another possibility is that registration of the with patterns of BOLD response affecting different areas than
fMRI images from each participant onto a common standard commonly seen in pain research, is a finding supported by the
brain causes activations/deactivations to be shifted to the white data of Hui and colleagues [11,12]. Like these investigators, we
matter. It should be noted that many fMRI studies, including also observed a predominance of deactivations over activations.
H. MacPherson et al. / Neuroscience Letters 434 (2008) 144–149 149

These findings taken together suggest that the responses to [11] K.K. Hui, J. Liu, N. Makris, R.L. Gollub, A.J. Chen, C.I. Moore, D.N.
acupuncture are different from those to be expected from pain Kennedy, B.R. Rosen, K.K. Kwong, Acupuncture modulates the limbic
alone. system and subcortical gray structures of the human brain: evidence from
fMRI studies in normal subjects, Hum. Brain Mapp. 9 (1) (2000) 13–25.
This evidence is consistent with the equivalent therapeutic [12] K.K. Hui, J. Liu, O. Marina, V. Napadow, C. Haselgrove, K.K. Kwong,
outcomes that are claimed by proponents of both Japanese D.N. Kennedy, N. Makris, The integrated response of the human cerebro-
(superficial needling) and Chinese styles of acupuncture (deep cerebellar and limbic systems to acupuncture stimulation at ST 36 as
needling). Further research in the brain imaging of acupuncture evidenced by fMRI, Neuroimage 27 (3) (2005) 479–496.
is needed to explore the response to needle stimulation at other [13] M. Jenkinson, P. Bannister, M. Brady, S. Smith, Improved optimization for
the robust and accurate linear registration and motion correction of brain
acupuncture points as well as non-acupoints, to compare the images, Neuroimage 17 (2) (2002) 825–841.
stimulation of the needle versus no stimulation, to evaluate [14] M. Jenkinson, S. Smith, A global optimisation method for robust affine
responses of patients receiving acupuncture for specific condi- registration of brain images, Med. Image Anal. 5 (2) (2001) 143–156.
tions and identify the impact of non-penetrating sham needles [15] J. Kong, L. Ma, R.L. Gollub, J. Wei, X. Yang, D. Li, X. Weng, F. Jia,
[22]. To enhance clinical relevance, there is also a need to C. Wang, F. Li, R. Li, D. Zhuang, A pilot study of functional magnetic
resonance imaging of the brain during manual and electroacupuncture
correlate changes in brain images with changes in outcome for stimulation of acupuncture point (LI-4 Hegu) in normal subjects reveals
specific symptoms. differential brain activation between methods, J. Altern. Complement Med.
Our fMRI experimental results indicate that superficial and 8 (4) (2002) 411–419.
deep acupuncture needling are associated with imaging patterns [16] H. MacPherson, A. Asghar, Acupuncture needle sensations associated with
that have no significant differences. This evidence is consistent de qi: a classification based on experts’ ratings, J. Altern. Complement Med.
12 (7) (2006 Sep) 633–637.
with the equivalent therapeutic outcomes that are claimed by [17] V. Napadow, N. Makris, J. Liu, N.W. Kettner, K.K. Kwong, K.K. Hui,
proponents of Japanese and Chinese styles of acupuncture that Effects of electroacupuncture versus manual acupuncture on the human
utilise superficial and deep needling, respectively. brain as measured by fMRI, Hum. Brain Mapp. 24 (3) (2005) 193–
205.
Acknowledgements [18] J. Park, A. White, C. Stevinson, E. Ernst, M. James, Validating a new non-
penetrating sham acupuncture device: two randomised controlled trials,
Acupunct. Med. 20 (4) (2002) 168–174.
Acknowledgements are due to the 17 participants. The assis- [19] M.E. Raichle, A.M. MacLeod, A.Z. Snyder, W.J. Powers, D.A. Gusnard,
tance from Iain Lamb and the various support personnel at the G.L. Shulman, A default mode of brain function, Proc. Natl. Acad. Sci.
York Neuroimaging Centre is gratefully acknowledged. Others U.S.A. 98 (2) (2001 Jan 16) 676–682.
who have provided insight and support for this study include [20] A. Shmuel, E. Yacoub, J. Pfeuffer, P.F. Van de Moortele, G. Adriany, X. Hu,
Professor Trevor Sheldon, Professor David Torgerson and Anne K. Ugurbil, Sustained negative BOLD, blood flow and oxygen consumption
response and its coupling to the positive response in the human brain,
Burton, University of York, and Professor Robert Turner, Uni- Neuron 36 (6) (2002) 1195–1210.
versity College London. [21] S.M. Smith, Fast robust automated brain extraction, Hum. Brain Mapp. 17
(3) (2002) 143–155.
References [22] K. Streitberger, J. Kleinhenz, Introducing a placebo needle into acupuncture
research, Lancet 352 (9125) (1998) 364–365.
[1] C.F. Beckmann, M. Jenkinson, S.M. Smith, General multilevel linear mod- [23] K.J. Thomas, P. Coleman, J.P. Nicholl, Trends in access to complementary
eling for group analysis in FMRI, Neuroimage 20 (2) (2003) 1052–1063. or alternative medicines via primary care in England: 1995–2001 results
[2] U. Bingel, M. Quante, R. Knab, B. Bromm, C. Weiller, C. Buchel, Sub- from a follow-up national survey, Fam. Pract. 20 (5) (2003) 575–577.
cortical structures involved in pain processing: evidence from single-trial [24] K.J. Thomas, H. MacPherson, L. Thorpe, J. Brazier, M. Fitter, M.J. Camp-
fMRI, Pain 99 (1/2) (2002) 313–321. bell, M. Roman, S.J. Walters, J. Nicholl, Randomised controlled trial of
[3] S. Birch, R. Felt, Understanding Acupuncture, Churchill Livingstone, Edin- a short course of traditional acupuncture compared with usual care for
burgh, 1999. persistent non-specific low back pain, BMJ 333 (7569) (2006) 623–626.
[4] P. Deadman, M. Al-Khafaji, A manual of acupuncture, J. Chin. Med. Publ. [25] R.D. Treede, D.R. Kenshalo, R.H. Gracely, A.K. Jones, The cortical rep-
(1998). resentation of pain, Pain 79 (23) (1999) 105–111.
[5] D.M. Eisenberg, R.B. Davis, S.L. Ettner, S. Appel, S. Wilkey, M. Van [26] M.W. Woolrich, T.E. Behrens, S.M. Smith, Constrained linear basis sets
Rompay, R.C. Kessler, Trends in alternative medicine use in the United for HRF modelling using Variational Bayes, Neuroimage 21 (4) (2004)
States, 1990–1997: results of a follow-up national survey, JAMA 280 (18) 1748–1761.
(1998) 1569–1575. [27] M.W. Woolrich, B.D. Ripley, M. Brady, S.M. Smith, Temporal autocor-
[6] J. Ezzo, B. Berman, V.A. Hadhazy, A.R. Jadad, L. Lao, B.B. Singh, Is relation in univariate linear modeling of FMRI data, Neuroimage 14 (6)
acupuncture effective for the treatment of chronic pain? A systematic (2001) 1370–1386.
review, Pain 86 (3) (2000) 217–225. [28] K.J. Worsley, A.C. Evans, S. Marrett, P. Neelin, A three-dimensional sta-
[7] P.H. Ghatan, J.C. Hsieh, K.M. Petersson, S. Stone-Elander, M. Ingvar, tistical analysis for CBF activation studies in human brain, J. Cereb. Blood
Coexistence of attention-based facilitation and inhibition in the human Flow Metab. 12 (6) (1992) 900–918.
cortex, Neuroimage 7 (1) (1998) 23–29. [29] M.T. Wu, J.C. Hsieh, J. Xiong, C.F. Yang, H.B. Pan, Y.C. Chen, G. Tsai,
[8] D.A. Gusnard, M.E. Raichle, M.E. Raichle, Searching for a baseline: func- B.R. Rosen, K.K. Kwong, Central nervous pathway for acupuncture stim-
tional imaging and the resting human brain, Nat. Rev. Neurosci. 2 (10) ulation: localization of processing with functional MR imaging of the
(2001 Oct) 685–694. brain-preliminary experience, Radiology 212 (1) (1999) 133–141.
[9] J.S. Han, Acupuncture and endorphins, Neurosci. Lett. 361 (1–3) (2004) [30] B. Yan, K. Li, J. Xu, W. Wang, K. Li, H. Liu, B. Shan, X. Tang, Acupoint-
258–261. specific fMRI patterns in human brain, Neurosci. Lett. 383 (3) (2005)
[10] C. Helmchen, C. Mohr, C. Erdmann, D. Petersen, M.F. Nitschke, Differen- 236–240.
tial cerebellar activation related to perceived pain intensity during noxious [31] S.S. Yoo, E.K. Teh, R.A. Blinder, F.A. Jolesz, Modulation of cerebellar
thermal stimulation in humans: a functional magnetic resonance imaging activities by acupuncture stimulation: evidence from fMRI study, Neu-
study, Neurosci. Lett. 335 (3) (2003) 202–206. roimage 22 (2) (2004) 932–940.

You might also like