Identifying Scalp Acupuncture For Chronic Pain

Brain Behavior and Immunity Integrative 5 (2024) 100050
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Brain Behavior and Immunity Integrative

journal homepage: www.editorialmanager.com/bbii
Identifying potential scalp acupuncture targets for chronic pain and

comorbid disorders using functional and anatomical connectivity of critical
deep brain structures
Qiao Kong , Sierra Hodges , Amy Katherine Ursitti , Sveta Reddy , Meixuan Zhu , Jian Kong *
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, USA
A R T I C L E I N F O A B S T R A C T
Keywords: Scalp acupuncture is an innovative approach that integrates acupuncture needling stimulation with the modern
Scalp acupuncture understanding of brain function. In recent decades, scalp acupuncture has been applied to treat chronic pain and
Chronic pain has achieved promising results. This study aimed to identify potential brain surface targets for scalp acupuncture
Resting state functional connectivity
based on the functional and anatomical connectivity of the hippocampus, amygdala, and nucleus accumbens,
Tractography
Hippocampus
three deep brain structures that are believed to play an important role in the pathophysiology of chronic pain, as
Amygdala well as multiple comorbid psychiatric and neurological disorders. Resting-state functional magnetic resonance
Nucleus accumbens imaging (fMRI) and diffusion tensor imaging (DTI) datasets from 119 healthy participants were included in our
Mental disorders analysis. We found that the medial prefrontal cortex (mPFC), corresponding to the acupoints EX-HN3 (Yintang) /
Neurological disorders BL2 (Cuanzhu), is functionally and anatomically connected to all three subcortical regions, while the precuneus,
corresponding to the acupoints GV19 (Houding) / GV20 (Baihui) and the MS12 scalp acupuncture line, is
connected to the hippocampus and amygdala. Our results suggest that the mPFC and precuneus, two key hubs of
the default mode network (DMN), and other cortical areas distributed at the prefrontal, parietal, and temporal
cortices may hold potential as novel targets for scalp acupuncture in the treatment of chronic pain and its
comorbidities. These identified locations may also be used for the treatment of psychiatric and neurological
disorders, such as anxiety, depression, insomnia, and cognitive decline, in which the three corresponding deep
brain structures play a crucial role.
1. Introduction anatomy and function to determine stimulation locations, modern

neuroscientific discoveries provide a solid foundation for the ongoing
Chronic pain affects over 30% of the global population and imposes development of scalp acupuncture (W. Liu et al., 2020; S. Wang et al.,
significant personal and economic burdens (Cohen et al., 2021). It is also 2017a). In recent decades, scalp acupuncture has exhibited positive
commonly accompanied by emotional and cognitive symptoms, such as results in treating chronic pain conditions, including fibromyalgia,
depression, anxiety, cognitive impairment, and sleep disturbances osteoarthritis, migraines, and complex regional pain syndrome (Allam
(Bushnell et al., 2013). Existing treatments for chronic pain are far from and Mohammed, 2013; Hommer, 2012; Minakawa et al., 2022; Rezvani
satisfactory, particularly when pain is comorbid with psychiatric and/or et al., 2014). However, few studies have explored potential scalp
neurological disorders. Therefore, more effective treatment options for acupuncture targets for treating chronic pain, particularly when it is
chronic pain and its comorbid symptoms are urgently needed. comorbid with psychiatric and neurological disorders.
Scalp acupuncture is an innovative approach integrating Traditional Recent neuroimaging studies have indicated that the limbic circuitry
Chinese needling methods with the modern understanding of brain and reward motivation system, encompassing the hippocampus, amyg
function (Hao and Hao, 2012). Through the insertion of needles into dala, and nucleus accumbens (NAc), play an important role in the
specific layers of the scalp, scalp acupuncture can modulate the func neuropathology of chronic pain (Chang et al., 2017; Taylor, 2018; Eti
tions of corresponding brain areas to achieve treatment effects (Chung enne Vachon-Presseau et al., 2016b; E. Vachon-Presseau et al., 2016a) as
et al., 2019; Liu et al., 2021a). Because scalp acupuncture relies on brain well as psychiatric and neurological disorders, such as anxiety,
* Correspondence to: Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Building 120, 2nd Ave, Charlestown, MA 02129, USA,.
E-mail address: jkong2@mgh.harvard.edu (J. Kong).
https://doi.org/10.1016/j.bbii.2024.100050
Received 16 July 2023; Received in revised form 15 January 2024; Accepted 4 February 2024
Available online 8 February 2024
2949-8341/© 2024 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Q. Kong et al. Brain Behavior and Immunity Integrative 5 (2024) 100050
Fig. 1. International standard scalp acupuncture lines based on WHO scalp acupuncture diagram and traditional acupoints on head.
depression, insomnia, and cognitive decline (T. Chen et al., 2022; Toda 2.2. Seed-based functional connectivity analysis
et al., 2019; Zheng et al., 2021). Thus, modulating the activity and/or
connectivity of these specific brain regions through scalp acupuncture Similar to our previous study (Kong et al., 2023), resting-state fMRI
could facilitate the development of new treatment targets for both data were preprocessed using the CONN toolbox version 21a (http:
chronic pain and comorbid psychiatric and neurological symptoms. //www.nitrc.org/projects/conn), following standard pipelines,
However, due to the deep locations of the hippocampus, amygdala, and including removal of the first five volumes, slice-timing correction,
NAc, it is challenging for scalp acupuncture to directly influence their realignment, outlier detection, alignment with the structural MRI,
function. normalization to MNI 152 space, smoothing with a 6-mm FWHM
Recent studies have highlighted the promising integration of struc Gaussian kernel, regression of nuisance covariates and head motion
tural and functional connectivity analyses for determining scalp stimu scrubbing (Behzadi et al., 2007), linear detrending, and bandpass
lation targets (Luber et al., 2022; Weigand et al., 2018; Zhu et al., 2021). filtering with a frequency window of 0.008 to 0.09 Hz.
We proposed an approach to identify brain surface regions that may For the resting-state functional connectivity (rsFC) analysis, we
influence the function of these deep brain structures by combining chose the left and right hippocampus, amygdala, and NAc as seeds from
functional connectivity analysis and tractography (Kong et al., 2023). the Harvard-Oxford subcortical atlas (maxprob-thr25–2 mm). To
This study aims to identify brain surface regions that exhibit func investigate functional connectivity patterns, we computed the correla
tional and structural connectivity with the hippocampus, amygdala, and tion between each seed and all other voxels within the brain. In the first-
NAc for the treatment of chronic pain and its comorbid symptoms level analysis, a correlation map for each subject was extracted by the
through scalp acupuncture. blood oxygen level-dependent (BOLD) time course from each seed,
respectively. Then, Pearson correlation was performed between the time
2. Materials and methods course of the seeds and all other voxels across the entire brain. Corre
lation coefficients were transformed into Fisher’s z scores to improve
The data and methodology have been applied in a recent study to normality. To obtain a group-level correlation map for each seed, a one-
identify surface targets for brain stimulation (Kong et al., 2023). This sample t-test was applied (positive and negative correlation separately).
study aims to incorporate our previous findings into the scalp For the whole-brain analysis, a voxel-wise p < 0.001 and a cluster-level
acupuncture system for the treatment of chronic pain and its comor false discovery rate (FDR) p < 0.05 was implemented.
bidities using scalp acupuncture, an approach according to the current To identify cortically-accessible scalp acupuncture targets, we
literature (Please see detailed information on data analysis methods in employed a brain surface mask based on established methods to opti
Supplementary Material and previous publication). mize the targets derived from rsFC findings(Liu et al., 2023; Zhang et al.,
2023). We used DPABI version 7.0 (http://rfmri.org/dpabi) to refine the
2.1. Participants surface clusters and enhance statistical significance. The results were
mapped onto the MNI standard template using SurfIce (https://www.
In brief, a total of 119 healthy participants (age range: 18–60 years; nitrc.org/projects/surfice/) and MRIcroGL (https://www.nitrc.org/pr
60 female) with no presently reported major neurological or psychiatric ojects/mricrogl), aligning them with the international standard scalp
conditions were recruited for this study, and their MRI data were ac acupuncture lines and acupoints(“A standard international acupuncture
quired (see Supplementary Material for the details of the MRI data nomenclature: memorandum from a WHO meeting, 1990). The mapped
acquisition). The study protocol was approved by the Partners Institu scalp acupuncture locations were further checked visually by the study
tional Review Board (IRB) of Massachusetts General Hospital, and all investigators (see Supplementary Material for details).
participants were provided with written informed consent prior to their
involvement in the research study.
2
Table 1
Potential scalp acupuncture targets derived from the left hippocampus resting-state functional and structural connectivity analysis.
rsFC SA Cluster Peak Peak coordinate Identified brain regions Needle localization and
targets size T recommended procedures✦
x y z
Brain regions from resting-state functional connectivity analysis*

Positive LHIP-1 66 14.60 − 27 30 − 15 L Orbitofrontal cortex ~ 1 cun anterior and inferior to the left GB6, insert needle forward
and downward
LHIP-2 181 13.66 − 39 − 69 33 L Angular ~ 1 cun posterior and superior to the left GB9, insert needle
backward and upward
LHIP-3 44 10.69 − 18 30 45 L Superior frontal gyrus ~ 0.5 cun right anterior to the left GB17, insert needle forward
and downward
LHIP-4 194 13.07 45 − 66 30 R Angular ~ 0.5 cun posterior and superior to the right GB9, insert needle
backward and upward
LHIP-5 280 16.39 63 − 6 − 24 R Middle/Superior temporal gyrus ~ 0.5 cun anterior and inferior to the right GB7, insert needle
backward and upward
LHIP-6 571 20.42 − 3 42 − 12 Bil Medial prefrontal cortex ~ near EX-HN3, insert needle diagonally upward
Negative LHIP-7 213 − 7.38 − 36 42 30 L Middle frontal gyrus ~ 1 cun anterior and inferior to the left GB4, insert needle forward
and downward
LHIP-8 76 − 5.98 − 54 12 6 L Inferior frontal gyrus ~ 0.5 cun anterior to the left GB6, insert needle forward and
downward
LHIP-9 237 − 9.63 − 57 − 36 33 L Supramarginal gyrus ~ 1 cun superior to the left GB8, insert needle backward and
upward
LHIP-10 221 − 8.80 15 9 69 R Superior frontal gyrus/ ~ near the right BL6, inset needle left forward
Supplementary motor area
LHIP-11 435 − 9.77 63 − 36 36 R Supramarginal gyrus ~ 0.5 cun superior to the right GB8, insert needle backward and
upward
LHIP-12 78 − 6.85 45 6 51 R Middle frontal gyrus ~ 0.5 cun posterior and anterior to the right GB4, insert needle
backward and upward
LHIP-13 176 − 7.99 57 15 9 R Inferior frontal gyrus ~ 0.5 cun anterior to the right GB6, insert needle forward and
downward
LHIP-14 354 − 9.06 30 54 27 R Middle/superior frontal gyrus ~ 0.5 cun superior to the right GB14, insert needle backward and
upward
LHIP-15 431 − 6.47 0 − 90 27 L Cuneus/R Precuneus ~ near GV19, insert needle right upward
Overlapping brain regions from functional and structural connectivity analysis†
Positive LHIP-a 46 10.22 − 30 − 75 42 L Inferior parietal gyrus ~ 0.5 cun posterior and inferior to the left BL8, insert needle
diagonally downward
LHIP-b 30 16.55 − 9 42 − 12 L Medial prefrontal cortex ~ 0.5 cun left inferior to the right BL2, insert needle directly,
penetrating 0.5 cun, avoid the eyeball
Negative LHIP-c 289 − 6.47 0 − 90 27 Bil Cuneus ~ near GV19, insert needle diagonally downward
LHIP-d 56 − 5.70 9 − 60 57 R Precuneus ~ 0.5 cun left to BL8, insert needle diagonally upward
✦
Acupoints Localization Principle: For SA targets near the scalp acupoints, the distance ranges from approximately 0–0.2 cun. ~ 0.5 cun, the distance ranges from
approximately 0.3–0.7 cun. ~ 1 cun, the distance ranges from approximately 0.3–0.7 cun. Keep the needles parallel to the scalp skin surface.
Notes: A “cun” is a traditional Chinese unit of measurement used to locate acupuncture points on the body. 1 cun = the width of the thumb at the knuckle.
Reference acupoints on head: GB6 (Xuanli), GB9 (Tianchong), GB17 (Zhengying), GB7 (Qubin), EX-HN3 (Yintang), GB4 (Hanyan), GB8 (Shuaigu), BL6 (Chengguang),
GB14 (Yangbai), GV19 (Houding), BL8 (Luoque), BL2 (Cuanzhu).
Abbreviations: SA: scalp acupuncture; L: Left, R: Right; Bil: Bilateral; HIP: hippocampus.
* The threshold for positive rsFC is T > 8, and for negative rsFC is T < − 4. † The threshold for positive rsFC is T > 4.5, and for negative rsFC is T < − 3.
2.3. Probabilistic tractography rsFC map. These overlaps were then constrained to the brain surface
mask. The final scalp acupuncture protocols were obtained following the
The diffusion-weighted images were preprocessed on FMRIB Soft procedures described in Section 2.2.
ware Library (FSL) version 6.0.3 (https://fsl.fmrib.ox.ac) using FMRIB’s To facilitate clinical application, we utilized the World Health Or
Diffusion Toolbox (FDT). The preprocessing pipelines included head ganization (WHO) standard (ISBN 92 4 15441 7 1) and national stan
motion and eddy current correction, alignment with the b0 reference dard acupoint localization and scalp acupuncture lines of the People’s
image, and registration to a structural reference image. Republic of China (GB/T 21709.2–2021) to provide localization sug
Briefly, to perform tractography, BEDPOSTX by FSL modeled gestions for scalp acupuncture targets (see Fig. 1). For clinical scalp
crossing fibers within each voxel of the brain using default parameters acupuncture procedures, the figures indicated the marked edges of each
(number of samples: 5000, curvature threshold: 0.2, step length: 0.5 cluster and the longest axis passing through the peak MNI coordinate.
mm, number of steps: 2000) (Woolrich et al., 2009). Then, probtrackx2 The proposed approach suggested inserting needles at the peak point,
produced sample streamlines by starting from each seed to the brain aligning their direction with the longest axis of the respective cluster,
surface. We set the brain surface mask in Section 2.2 as a waypoint mask, aiming to effectively regulate the corresponding brain area during the
allowing only streamlines passing through this mask to be considered acupuncture process(Liu et al., 2023; Zhang et al., 2023).
valid. Streamline density maps were binarized and set at a threshold of
1% for each subject (Lambert et al., 2012; Vasques et al., 2015). Indi 3. Results
vidual maps were combined into group-level maps, with a 15%
threshold applied to remove sparse connections (Robinson et al., 2015). 3.1. The Hippocampus
3.1.1. resting-state functional connectivity results

2.4. Overlap of functional and structural connectivity results Based on the rsFC results, we identified a total of 15 brain surface
areas (6 positive and 9 negative) of the left hippocampus. Similarly, for
To identify the overlapping brain regions, we binarized the group the right hippocampus, we found 15 brain surface areas (7 positive and 8
streamline density map of each ROI and applied it to the corresponding
3
Table 2
Potential scalp acupuncture targets derived from the right hippocampus resting state functional and anatomical connectivity analysis.
rsFC SA Cluster Peak T Peak coordinate Identified brain regions Needle localization and
targets size recommended procedures✦
x y z
Brain regions from resting state functional connectivity analysis*

Positive RHIP-1 131 11.90 − 60 − 9 − 18 L Middle/Superior temporal gyrus ~ 0.5 cun anterior and inferior to the left GB7, insert needle
forward
RHIP-2 100 12.21 − 42 − 69 33 L Angular ~ 0.5 cun posterior and superior to the left GB9, insert needle
forward and upward
RHIP-3 68 12.62 21 27 48 R Superior frontal gyrus ~ 0.5 cun right to GV22, insert needle diagonally forward
RHIP-4 224 14.01 48 − 63 36 R Angular ~ 0.5 cun posterior and superior to the right GB9, insert
needle backward and upward
RHIP-5 694 20.39 63 − 6 − 21 R Middle/Superior temporal gyrus ~ 0.5 cun anterior and inferior to the right GB7, insert needle
backward and upward
RHIP-6 56 13.76 30 33 − 15 R Orbitofrontal cortex ~ 1 cun posterior and superior to the right GB6, insert needle
forward and downward
RHIP-7 512 20.52 3 33 − 15 Bil Medial prefrontal cortex ~ near EX-HN3, insert needle diagonally forward
Negative RHIP-8 215 − 7.88 − 36 48 24 L Middle frontal gyrus ~ 0.5 cun right superior to the left GB14, insert needle
backward and upward
RHIP-9 134 − 7.70 − 45 18 3 L Inferior frontal gyrus ~ 0.5 cun anterior to the left GB6, insert needle backward and
upward
RHIP-10 260 − 10.64 − 54 − 42 36 L Supramarginal gyrus ~ 0.5 cun superior to the left GB8, insert needle backward and
upward
RHIP-11 174 − 9.34 15 9 69 R Superior frontal gyrus/ ~ near the right BL6, insert needle diagonally forward
Supplementary motor area
RHIP-12 275 − 9.03 63 − 39 36 R Supramarginal gyrus ~ 0.5 cun superior to the right GB8, insert needle backward
and upward
RHIP-13 90 − 7.63 54 15 3 R Inferior frontal gyrus ~ 0.5 cun anterior and inferior to the right GB6, insert needle
backward and upward
RHIP-14 212 − 8.87 33 54 27 R Middle frontal gyrus ~ 0.5 cun superior to the right GB14, insert needle backward
and upward
RHIP-15 262 − 6.92 3 − 87 30 Bil Cuneus ~ near GV19, insert needle diagonally downward
Overlapping brain regions from functional and anatomical connectivity analysis†
Positive RHIP-a 38 6.58 45 − 45 − 15 R Inferior temporal gyrus ~ 0.5 cun anterior and inferior to the right GB10, insert needle
backward and upward
RHIP-b 482 19.17 60 − 12 − 21 R Middle temporal gyrus ~ 0.5 cun anterior and inferior to the right GB7, insert needle
backward and upward
RHIP-c 51 12.61 36 33 − 12 R Orbitofrontal cortex ~ 1 cun anterior and inferior to the right GB6, insert needle
forward and upward
RHIP-d 33 14.64 9 42 − 15 R Medial prefrontal cortex ~ near the right BL2, insert needle inward and upward
Negative RHIP-e 30 − 4.90 − 15 − 57 57 L Precuneus ~ 0.5 cun left to GV20, insert needle backward and downward
RHIP-f 407 − 5.96 15 − 93 33 R Superior occipital gyrus ~ 0.5 cun right to GV19, insert needle diagonally upward
✦
Acupoints Localization Principle: For SA targets near the scalp acupoints, the distance ranges from approximately 0–0.2 cun. ~ 0.5 cun, the distance ranges from
Reference acupoints on head: GB7 (Qubin), GB9 (Tianchong), GV22 (Xinhui), GB6 (Xuanli), EX-HN3 (Yintang), GB14 (Yangbai), GB8 (Shuaigu), BL6 (Chengguang),
GV19 (Houding), GB10 (Fubai), BL2 (Cuanzhu), GV20 (Baihui).
Abbreviations: SA: scalp acupuncture; L: Left, R: Right; Bil: Bilateral; HIP: hippocampus.
* The threshold for positive rsFC is T > 8.5, and for negative rsFC is T < − 4.5. † The threshold for positive rsFC is T > 3, and for negative rsFC is T < − 3.
negative) based on the rsFC findings. These identified scalp acupuncture 3.1.3. Overlap between rsFC and PTG results
targets are located in close proximity to acupoints GB4 (Hanyan), GB6 For the left hippocampus, we identified 4 overlapping brain surface
(Xuanli), GB7 (Qubin), GB8 (Shuaigu), GB9 (Tianchong), GB10 (Fubai), areas based on the combined rsFC and PTG results (2 positive and 2
GB14 (Yangbai), GB17 (Zhengying), GV19 (Houding), GV20 (Baihui), negative). These findings indicate potential scalp acupuncture targets in
GV22 (Xinhui), EX-HN3 (Yintang), BL2 (Cuanzhu), BL6 (Chengguang), close proximity to acupoints BL2 (Cuanzhu), BL8 (Luoque), GV19
BL8 (Luoque), as well as along scalp acupuncture lines MS5, MS6, MS7, (Houding), as well as along the scalp acupuncture lines MS12 and MS13.
MS10, MS11, and GV18. Detailed information regarding the identified Similarly, for the right hippocampus, we identified 6 overlapping
brain regions, peak MNI coordinates, needle localization, and recom brain surface areas from the rsFC and PTG results (4 positive and 2
mended procedures can be found in Tables 1 and 2 and Fig. 2-A/B. The negative). These identified scalp acupuncture targets are located
probabilistic tractography results can be found in our previous study approximately to acupoints GB6 (Xuanli), GB7 (Qubin), GB10 (Fubai),
(Kong et al., 2023). BL2 (Cuanzhu), GV19 (Houding), GV20 (Baihui), as well as along the
scalp acupuncture lines MS11, MS12, and MS13. The identified brain
3.1.2. Probabilistic tractography results regions, peak MNI coordinates, needle localization, and recommended
The PTG results showed that the white matter fibers from the left procedures can be found in Tables 1 and 2 and Fig. 2-C.
hippocampus are mainly connected to brain surface regions in the left
frontal and temporal lobes as well as the bilateral parietal and occipital
lobes. Similarly, white matter fibers from the right hippocampus 3.2. The amygdala
exhibited connections with brain surface areas primarily located in the
right frontal and temporal lobes, as well as bilateral parietal and oc 3.2.1. resting-state functional connectivity results
cipital lobes. Based on the rsFC results, we identified a total of 11 brain surface
areas (4 positive and 7 negative) of the left amygdala. Similarly, for the
right amygdala, we found 10 brain surface areas (3 positive and 7
negative). These identified scalp acupuncture targets are located in close
4
Fig. 2. Potential scalp acupuncture targets based on hippocampus functional and structural connectivity. (A) potential scalp acupuncture targets based on the
positive rsFC of the left and right hippocampus. (B) potential scalp acupuncture targets based on the negative rsFC of the left and right hippocampus. (C) potential
scalp acupuncture targets based on overlapping of rsFC and PTG. Abbreviations: L: Left, R: Right, HIP: Hippocampus; rsFC: resting-state Functional Connectivity;
PTG: Probabilistic Tractography; Reference acupoints on head: GB4 (Hanyan), GB6 (Xuanli), GB7 (Qubin), GB8 (Shuaigu), GB9 (Tianchong), GB10 (Fubai), GB14
(Yangbai), GB17 (Zhengying), GV19 (Houding), GV20 (Baihui), GV22 (Xinhui), EX-HN3 (Yintang), BL2 (Cuanzhu), BL6 (Chengguang), BL8 (Luoque).
proximity to acupoints GB4 (Hanyan), GB6 (Xuanli), GB7 (Qubin), GB8 acupoints EX-HN3 (Yintang), BL2 (Cuanzhu), GV19 (Houding), as well
(Shuaigu), GB14 (Yangbai), GB15 (Toulinqi), GB17 (Zhengying), GV19 as close to the scalp acupuncture line MS12. The identified brain re
(Houding), GV22 (Xinhui), EX-HN3 (Yintang), BL6 (Chengguang), as gions, peak MNI coordinates, needle localization, and recommended
well as along the scalp acupuncture lines MS2, MS3, MS5, and MS12. procedures can be found in Tables 3 and 4 and Fig. 3-C.
Detailed information regarding the identified brain regions, peak MNI
coordinates, needle localization, and recommended procedures can be
3.3. The NAc
found in Tables 3 and 4 and Fig. 3-A/B.
3.3.1. resting-state functional connectivity results
3.2.2. Probabilistic tractography results
Based on the rsFC results, we identified a total of 9 brain surface
The PTG results showed that the white matter fibers from the left
areas (5 positive and 4 negative) of the left NAc. Similarly, for the right
amygdala are predominantly connected to brain surface areas distrib
NAc, we found 10 brain surface areas (5 positive and 5 negative). These
uted in the left frontal, temporal, parietal, and occipital lobes. Likewise,
identified scalp acupuncture targets are located in close proximity to
the white matter fibers from the right amygdala exhibited connections
acupoints GB5 (Xuanlu), GB6 (Xuanli), GB7 (Qubin), GB8 (Shuaigu),
with brain surface regions mainly distributed in the right frontal, tem
GB16 (Muchuang), GB18 (Chengling), TE20 (Jiaosun), BL2 (Cuanzhu),
poral, parietal, and occipital lobes.
GV19 (Houding), GV22 (Xinhui), EX-HN3 (Yintang), as well as along the
scalp acupuncture lines MS1, MS2, MS3, MS4, MS10, MS11 and MS12.
3.2.3. Overlap between rsFC and PTG results
Detailed information regarding the identified brain regions, peak MNI
For the left amygdala, we identified 2 overlapping brain surface re
coordinates, needle localization, and recommended procedures can be
gions based on the combined rsFC and PTG results (1 positive and 1
found in Tables 5 and 6 and Fig. 4-A/B.
negative). These findings indicate potential scalp acupuncture targets in
close proximity to acupoints EX-HN3 (Yintang) and GV19 (Houding), as
3.3.2. Probabilistic tractography results
well as close to the scalp acupuncture line MS12.
The PTG results showed that the white matter fibers from the left
Similarly, for the right amygdala, we identified 3 overlapping brain
NAc are predominantly connected to brain surface areas distributed at
surface areas from the rsFC and PTG results (1 positive and 2 negative).
the bilateral frontal lobe and left temporal lobe. Likewise, the white
These identified scalp acupuncture targets are located approximately to
matter fibers from the right NAc exhibited connections with brain
5
Table 3
Potential scalp acupuncture targets derived from the left amygdala resting state functional and anatomical connectivity analysis.
rsFC SA Cluster size Peak T Peak Identified brain regions Needle localization and
targets coordinate recommended procedures✦
x y z

Positive LAMYG1 144 12.05 − 3 42 − 15 Bil Medial prefrontal cortex ~ near EX-HN3, insert needle diagonally upward
LAMYG2 717 25.43 − 27 3 − 21 L Superior/Middle temporal gyrus ~ 0.5 cun inferior and anterior to the left GB7, insert needle
backward and upward
LAMYG3 414 15.67 27 6 − 21 R Superior temporal gyrus ~ 0.5 cun inferior and anterior to the right GB7, insert needle
backward and upward
LAMYG4 36 11.49 33 33 − 15 R Orbitofrontal cortex ~ 1 cun anterior and inferior to the right GB6, insert needle
backward and upward
Negative LAMYG5 158 − 6.02 − 33 54 12 L Middle/Superior frontal gyrus ~ near the left GB14, insert needle forward and downward
LAMYG6 46 − 5.17 − 39 39 30 L Middle frontal gyrus ~ 0.5 cun anterior and inferior to the left GB4, insert needle
diagonally upward
LAMYG7 54 − 7.19 3 33 36 Bil Medial superior frontal gyrus ~ near GV22, insert the needle forward
LAMYG8 156 − 7.39 21 15 63 R Superior frontal gyrus ~ near the right BL6, insert needle diagonally backward
LAMYG9 249 − 8.18 48 − 45 36 R Supramarginal gyrus ~ 0.5 cun superior to GB8, insert needle upward
LAMYG10 658 − 8.78 33 57 21 R Middle frontal gyrus ~ near the right GB14, insert needle diagonally forward and
upward
LAMYG11 732 − 7.92 12 − 69 45 R Precuneus ~ right superior to GV19, inset needle right upward
Positive LAMYG-a 66 11.29 − 3 45 − 15 Bil Medial prefrontal cortex ~ near EX-HN3, insert needle outward and downward
Negative LAMYG-b 211 − 7.44 − 3 − 75 48 Bil Precuneus ~ 0.5 cun left superior to GV19, insert needle downward
✦
Acupoint Localization Principle: For SA targets near the scalp acupoints, the distance ranges from approximately 0–0.2 cun. ~ 0.5 cun, the distance ranges from
Reference acupoints on head: GB6 (Xuanli), EX-HN3 (Yintang), GB7 (Qubin), GB4 (Hanyan), GV22 (Xinhui), BL6 (Chengguang), GB8 (Shuaigu), GB14 (Yangbai),
GV19 (Houding).
Abbreviations: SA: scalp acupuncture; L: Left, R: Right; Bil: Bilateral; AMYG: amygdala.
The threshold for positive rsFC is T > 8, and for negative rsFC is T < − 4. † The threshold for positive rsFC is T > 3, and for negative rsFC is T < − 3.
Table 4
Potential scalp acupuncture targets derived from the right amygdala resting state functional and anatomical connectivity analysis.
rsFC SA Cluster Peak Peak Identified brain regions Needle localization and
targets size T coordinate recommended procedures✦
x y z

Positive RAMYG1 414 18.78 − 24 3 − 21 L Superior/Middle temporal gyrus/ ~ 0.5 cun anterior and inferior to the left GB7, insert needle
Postcentral gyrus backward and upward
RAMYG2 783 31.06 27 3 − 24 R Superior/Middle temporal gyrus/ ~ 0.5 cun anterior and inferior to the right GB7, insert needle
Postcentral gyrus backward and upward
RAMYG3 148 13.34 3 48 − 12 Bil Medial prefrontal cortex ~ near EX-HN3, insert needle outward and upward
Negative RAMYG4 508 − 7.72 − 33 57 21 L Middle/Superior frontal gyrus ~ 0.5 cun superior to the right GB14, insert forward and
downward
RAMYG5 52 − 5.18 − 33 3 63 L Middle/Superior frontal gyrus ~ 0.5 cun left posterior to the left GB17, insert needle
diagonally forward
RAMYG6 187 − 6.15 − 51 − 48 39 L Inferior parietal gyrus ~ 0.5 cun posterior and superior to the left GB8, insert needle
backward and upward
RAMYG7 142 − 7.75 3 24 45 Bil Supplementary motor area ~ near GV22, insert needle diagonally backward
RAMYG8 237 − 8.34 45 − 48 42 R Inferior parietal gyrus ~ 0.5 cun posterior and superior to the right GB8, insert
needle upward
RAMYG9 787 − 8.83 39 36 39 R Middle/Superior frontal gyrus ~ 0.5 cun anterior and inferior to the right GB15, insert
needle forward and downward
RAMYG10 469 − 8.81 − 3 − 75 54 Bil Precuneus ~ 0.5 cun superior to GV19, insert needle backward and
downward
Positive RAMYG-a 37 12.53 6 48 − 12 R Medial prefrontal cortex ~ near EX-HN3, insert needle inward and upward
Negative RAMYG-b 36 − 4.66 21 57 − 3 R Orbitofrontal cortex ~ near right BL2, insert needle diagonally downward
RAMYG-c 216 − 7.78 12 − 72 45 R Precuneus ~ 0.5 cun right to GV19, insert needle inward and downward
✦
approximately 0.3–0.7 cun. ~ 1 cun, the distance ranges from approximately 0.3–0.7 cun. Keep the needles parallel to the skin surface.
Reference acupoints on head: GB7 (Qubin), EX-HN3 (Yintang), GB14 (Yangbai), GB17 (Zhengying), GB8 (Shuaigu), GV22 (Xinhui), GB15 (Toulinqi), GV19 (Houding),
BL2 (Cuanzhu).
Abbreviations: SA: scalp acupuncture; L: Left, R: Right; Bil: Bilateral; AMYG: amygdala.
* The threshold for positive FC is T > 7.5, and for negative rsFC is T < − 4. † The threshold for positive rsFC is T > 3, and for negative rsFC is T < − 3.
surface regions mainly distributed at the bilateral frontal lobe and right 3.3.3. Overlap between rsFC and PTG results
temporal lobe. For the left NAc, we identified one overlapping brain surface region
based on the combined positive rsFC and PTG results. This brain region
is located in close proximity to acupoints BL2 (Cuanzhu) and EX-HN3
6
Fig. 3. Potential scalp acupuncture targets based on amygdala functional and structural connectivity. (A) potential scalp acupuncture targets based on the positive
rsFC of the left and right amygdala. (B) potential scalp acupuncture targets based on the negative rsFC of the left and right amygdala. (C) potential scalp acupuncture
targets based on overlapping of rsFC and PTG. Abbreviations: L: Left, R: Right, AMYG: amygdala. Reference acupoints on head: GB4 (Hanyan), GB6 (Xuanli), GB7
(Qubin), GB8 (Shuaigu), GB14 (Yangbai), GB15 (Toulinqi), GV22 (Xinhui), EX-HN3 (Yintang), BL6 (Chengguang), GB17 (Zhengying), GV19 (Houding),
BL2 (Cuanzhu).
Table 5
Potential scalp acupuncture targets derived from the left NAc resting state functional and anatomical connectivity analysis.
rsFC SA Cluster Peak T Peak Identified brain regions Needle localization and
targets size coordinate recommended procedures✦
x y z

Positive LNAc1 108 8.54 − 48 − 21 6 L Superior temporal gyrus ~ 0.5 cun posterior to the left GB6, insert needle forward and
downward
LNAc2 60 7.28 60 − 33 15 R Superior temporal gyrus ~ near the right GB8, insert needle diagonally upward
LNAc3 79 7.48 54 3 − 12 R Middle temporal gyrus ~ 0.5 cun anterior and inferior to the right GB7, insert needle
diagonally downward
LNAc4 771 16.50 − 9 42 − 6 L Medial prefrontal cortex ~ near the left BL2, insert needle inward and upward
LNAc5 297 8.16 9 − 60 30 R Precuneus ~ near GV19, insert needle inward and upward
Negative LNAc6 768 − 7.21 − 48 42 3 L Inferior/Middle frontal gyrus/ ~ 1 cun anterior and inferior to the left GB5, insert needle
Precentral gyrus backward and upward
LNAc7 273 − 6.07 − 48 − 45 51 L Inferior parietal gyrus ~ 1 cun inferior and posterior to the left GB18, insert needle
backward and downward
LNAc8 31 − 4.43 − 57 − 51 − 6 L Inferior temporal gyrus ~ 0.5 cun posterior and inferior to the left TE20, insert needle
backward and downward
LNAc9 273 − 5.83 45 57 − 9 R Inferior frontal gyrus ~ 1 cun left to the right BL2, insert needle outward along the
brow arch
Positive LNAc- 524 16.50 − 9 42 − 6 Bil Medial prefrontal cortex ~ near the left BL2, insert needle inward horizontally
a
Negative − − − − − − − −
✦
Reference acupoints on head: GB6 (Xuanli), GB8 (Shuaigu), GB7 (Qubin), BL2 (Cuanzhu), GV19 (Houding), GB5 (Xuanlu), GB18 (Chengling), TE20 (Jiaosun).
Abbreviations: SA: scalp acupuncture; L: Left, R: Right; Bil: Bilateral; NAc: nucleus accumbens.
* The threshold for positive rsFC is T > 5, and for negative rsFC is T < 0. † The threshold for positive rsFC is T > 3, with no overlap between negative rsFC and PTG.
(Yintang). Similarly, for the right NAc, we identified one overlapping localization, and recommended procedures can be found in Tables 3 and
brain surface area from the combined positive rsFC and PTG results, 4 and Fig. 4-C.
approximately located near the acupoints BL2 (Cuanzhu) and EX-HN3
(Yintang). The identified brain regions, peak MNI coordinates, needle
7
Table 6
Potential scalp acupuncture targets derived from the right NAc resting state functional and anatomical connectivity analysis.
rsFC SA Cluster Peak T Peak Identified brain regions Needle localization and
targets size coordinate recommended procedures✦
x y z

Positive RNAc1 34 7.10 − 24 42 39 L Superior frontal gyrus ~ near the left GB16, insert needle diagonally forward
RNAc2 147 8.77 − 60 − 21 9 L Superior temporal gyrus ~ 0.5 cun anterior to the left GB8, insert needle backward and upward
RNAc3 383 7.59 57 − 15 6 R Superior temporal gyrus ~ 0.5 cun superior to the right GB7, insert needle forward and downward
RNAc4 56 8.18 24 33 − 15 R Orbitofrontal cortex ~ 0.5 cun left inferior to the right BL2, insert the needle directly, penetrating
0.5 cun, avoid the eyeball
RNAc5 713 18.17 − 3 45 − 6 Bil Medial prefrontal ~ near EX-HN3, insert needle upward
cortex
Negative RNAc6 409 − 6.20 − 48 51 − 3 L Middle/Inferior frontal ~ 0.5 cun anterior and inferior to the left GB5, insert needle backward and
gyrus upward
RNAc7 147 − 4.69 − 48 − 48 51 L Inferior parietal gyrus ~ 0.5 cun posterior and inferior to GB18, insert needle downward and
backward
RNAc8 40 − 5.41 − 6 36 45 L Medial superior frontal ~ near GV22, insert needle diagonally forward
gyrus
RNAc9 31 − 4.66 33 15 60 R Middle frontal gyrus ~ near the right GB17, insert needle diagonally forward
RNAc10 38 − 4.63 57 18 30 R Inferior frontal gyrus ~ near the right GB5, insert needle backward and upward
Positive RNAc-a 586 18.17 − 3 45 − 6 Bil Medial prefrontal ~ near EX-HN3, insert needle diagonally upward
cortex
Negative − − − − − − − −
✦
Reference acupoints on head: GB16 (Muchuang), GB8 (Shuaigu), GB7 (Qubin), BL2 (Cuanzhu), EX-HN3 (Yintang), GB5 (Xuanlu), GB18 (Chengling), GV22 (Xinhui),
GB17 (Zhengying), GB5 (Xuanlu).
Abbreviations: SA: scalp acupuncture; L: Left, R: Right; Bil: Bilateral; NAc: nucleus accumbens.
* The threshold for positive rsFC is T > 5.5, and for negative rsFC is T < 0. † The threshold for positive rsFC is T > 3, with no overlap between negative rsFC and PTG.
Fig. 4. Potential scalp acupoints based on nucleus accumbens functional and structural connectivity. (A) potential scalp acupuncture targets based on the positive
rsFC of the left and right NAc. (B) potential scalp acupuncture targets based on the negative rsFC of the left and right NAc. (C) potential scalp acupuncture targets
based on overlapping of rsFC and PTG. Abbreviations: L: Left, R: Right, NAc: nucleus accumbens. Reference acupoints on head: GB5 (Xuanlu), GB6 (Xuanli), GB8
(Shuaigu), GB7 (Qubin), GB16 (Muchuang), GB17 (Zhengying), GB18 (Chengling), BL2 (Cuanzhu), GV19 (Houding), GV22 (Xinhui), TE20 (Jiaosun), EX-
HN3 (Yintang).
8
3.4. Overlap of rsFC and PTG among three subcortical structures et al., 2012b; Löffler et al., 2022). Furthermore, the NAc plays a pivotal
role in regulating chronic pain and comorbid anxiety/depression (T.
We investigated overlapping brain regions of the rsFC/PTG results Chen et al., 2022).
across six ROIs. The results showed an overlap in the mPFC (close to Taken together, the above findings shed light on the complex
acupoints EX-HN3 [Yintang] and BL2 [Cuanzhu]) in all seed regions, engagement of limbic and reward circuitry, particularly the hippocam
while the precuneus (close to acupoints GV19 [Houding] / GV20 [Bai pus, amygdala, and NAc, in chronic pain and its comorbidities such as
hui], and the scalp acupuncture line MS12) was involved in the left and depression, anxiety, and cognitive decline. These relationships offer
right amygdala as well as the left and right hippocampus. insight into underlying mechanisms of chronic pain and potential scalp
stimulation targets through these neural pathways.
4. Discussion
4.2. Current scalp acupuncture protocols for chronic pain
This study aimed to identify potential brain surface targets for scalp
acupuncture based on the functional and structural connectivity of the The WHO (“A standard international acupuncture nomenclature:
hippocampus, amygdala, and NAc, three deep brain structures that play memorandum from a WHO meeting, 1990) and the national standard of
an important role in the pathophysiology of chronic pain and multiple the People’s Republic of China titled “Standardized manipulations of
psychiatric and neurological disorders. We found that the mPFC (cor acupuncture and moxibustion Part 2: Scalp Acupuncture” (GB/T
responding to the acupoints EX-HN3 [Yintang] and BL2 [Cuanzhu]) has 21709.2–2021) recommend using distinct acupuncture strategies to
both functional and structural connections with all three subcortical target specific pain locations. For instance, the middle line of the fore
regions. The precuneus (corresponding to acupoints GV19 [Houding] / head (MS1) is recommended for treating headaches, while line I lateral
GV20 [Baihui] and the MS12 scalp acupuncture line) is connected to the to the forehead (MS2) is recommended for treating angina; the middle
hippocampus and amygdala. The mPFC, precuneus, and other brain line of vertex (MS5) and line I lateral to vertex (MS8) are recommended
surface regions identified in connectivity analysis could potentially for treating low back, leg, and foot pain; line II lateral to vertex (MS9) is
modulate the function of these three subcortical structures indirectly recommended for treating shoulder, arm, and hand pain; the anterior
and thereby be used as scalp acupuncture targets for chronic pain and its temporal line (MS10) and posterior temporal line (MS11) are recom
comorbidities. mended for treating migraines; the upper-middle line of the occiput
(MS13) is recommended for treating red and swollen eyes; the
4.1. The role of the hippocampus, amygdala, and NAc in chronic pain lower-lateral line of the occiput (MS14) is suggested for treating poste
and its comorbidities rior headache and back pain.
Several studies have investigated the effectiveness of Yamamoto
As a key region of the limbic system, the hippocampus contributes to New Scalp Acupuncture (YNSA) in treating various chronic pain con
learning, memory, and high-level cognition (Zeidman and Maguire, ditions, including chronic low back pain, migraine, and osteoarthritis-
2016). In recent years, emerging evidence has indicated the involvement related pain (Allam and Mohammed, 2013; Rezvani et al., 2014).
of the hippocampus in chronic pain (Grilli, 2017; Mutso et al., 2012; Yu YNSA operates on the principle of a somatotope located on the scalp,
et al., 2020). For example, literature suggests that the hippocampus akin to the projection of the entire organism onto a specifically defined
plays a key role in the development and maintenance of both chronic area of the scalp (Schockert and Schockert, 2011).
pain and depression through cytokines, particularly tumor necrosis Current scalp acupuncture protocols for chronic pain often rely on
factor-α (TNFα), within the hippocampus (Fasick et al., 2015). In addi general scalp acupuncture lines and rough brain region delineations for
tion, studies also suggest that the hippocampus and amygdala – two key the selection of stimulation targets. However, given that chronic pain is
regions for encoding and consolidating memory – are implicated in a complex disorder that frequently coexists with emotional and cogni
experiential aspects of pain. Common neurotransmitters and mecha tive comorbidities, it is crucial to identify more precise targets. The scalp
nisms of neural plasticity (e.g., central sensitization, long-term poten acupuncture targets identified in this study hold promise for alleviating
tiation) suggest a mechanistic overlap between chronic pain and not only chronic pain symptoms, but also those of their complex
memory. Therefore, some investigators have proposed that chronic pain comorbidities. By selecting specific targets based on distinct complica
can be regarded as a persisting memory of pain and/or the inability to tions, we can broaden the range of options for the clinical application of
extinguish painful memories. Theoretically, pharmacologic, physical, scalp acupuncture in treating chronic pain.
and/or neuromodulation, as well as other approaches targeting the
hippocampus, should reverse the reorganization accompanying chronic 4.3. Potential mechanisms underlying scalp acupuncture
pain (Apkarian et al., 2009; McCarberg and Peppin, 2019).
The amygdala, another key region of the limbic system, is associated Scalp acupuncture operates on the foundational belief that stimu
with emotional processing, motivation, fear, and the influence of lating specific scalp areas can influence the activity of corresponding
negative emotion on pain (Janak and Tye, 2015; Wiech and Tracey, brain regions, leading to clinical improvements (S. Wang et al., 2017b).
2009). It is also part of the descending pain modulatory system, directly Both national bodies and international organizations, including the
projecting to the periaqueductal grey (PAG) (Fields, 2004; Yu et al., WHO, have established standards based on this belief. Furthermore, a
2014). An altered medial prefrontal cortex (mPFC)-amygdala-NAc cir wealth of clinical studies and extensive clinical practice over several
cuit, characterized by increased white matter and functional connec decades have consistently demonstrated the efficacy of scalp acupunc
tions, has been identified as a risk factor for the persistence of pain (E. ture. Nevertheless, the precise mechanisms of scalp acupuncture are still
Vachon-Presseau et al., 2016b). being studied.
The nucleus accumbens (NAc) is a key node of the brain reward Recent research proposes a potential neural pathway for scalp
system and plays a critical role in reward processing, emotional acupuncture in modulating brain function and treating cerebral dis
response, and motivation (Salgado and Kaplitt, 2015). Accumulating eases, termed as trigeminal nerve – meninges – cerebrospinal fluid –
evidence supports the involvement of the NAc in chronic pain, as indi contacting neurons – brain (S. Wang et al., 2017c). An animal study
cated by its volumetric decrease and altered connectivity with other using a migraine rat model demonstrated that scalp acupuncture con
limbic brain regions in chronic low back pain (CLBP) (Baliki et al., tributes to analgesic effects through the convergence of inputs from
2012a). Studies also suggest that the functional connectivity between facial territories and the dura mater in wide dynamic range neurons
the NAc, ventromedial prefrontal cortex, and reward learning inde (Wang et al., 2020). The connection between scalp acupoints and
pendently predict the transition from acute to chronic back pain (Baliki intracranial structures might occur through the presynaptic dorsal root
9
reflex, postsynaptic neurogenic responses, and convergent neural path modulation (Kong et al., 2010). Previous studies have shown that the
ways (Y. Chen et al., 2022). mPFC and ACC play an important role in the expectancy effect during
Recent investigations on healthy subjects and stroke patients have the treatment of chronic pain (Kong et al., 2018). The mPFC / ACC –
provided insights into scalp acupuncture’s impact on functional con PAG circuit is involved in the acupuncture treatment of migraine (Li
nectivity within specific brain regions. In a previous study, investigators et al., 2016). The critical role of mPFC-hippocampus circuits in memory
found that scalp acupuncture along specific scalp acupuncture lines – the formation and retrieval has been extensively studied (Bonnici et al.,
MS5, left anterior/posterior oblique lines of vertex-temporal (MS6 and 2012; Rolls, 2022). The mPFC is also recognized as a target for regu
MS7) – could enhance connectivity among brain regions associated with lating mood and anxiety, as it inhibits brain regions involved in pro
cognition and implementation and their adjacent areas in healthy cessing negative emotions, particularly the amygdala (Motzkin et al.,
elderly participants (Chung et al., 2019). Furthermore, studies have 2015).
shown that scalp acupuncture can enhance functional connectivity of In this study, we have identified mPFC targets adjacent to the acu
visual and cognitive-motor function networks in patients with acute points EX-HN3 (Yintang) and BL2 (Cuanzhu). This identification was
ischemic stroke (H. Liu et al., 2020), as well as the functional activities based on the overlapping functional and structural connectivity of the
related to sensory integration, language processing, and motor coordi bilateral hippocampus, amygdala, and NAc. Consistent with our finding,
nation within the dominant cerebral hemisphere and the bilateral a previous study has shown that combining transcutaneous auricular
frontal lobe responsible for motor control (Liu et al., 2021b). These vagus nerve stimulation (taVNS) with electroacupuncture at EX-HN3
studies typically employed needle placement along the scalp acupunc (Yintang) and GV20 (Baihui) acupoints produced comparable positive
ture line MS5/MS6/MS7. effects on chronic pain and depressive symptoms in patients, with sus
More recently, a literature review has indicated that the efficacy of tained effectiveness lasting at least 8 weeks when compared to cit
scalp acupuncture in treating brain diseases may be achieved by stim alopram (Li et al., 2022). These findings suggest that stimulating these
ulating specific areas or scalp nerves, including the trigeminal, facial, mPFC targets with scalp acupuncture may hold promise for alleviating
and the cervical nerves to improve cerebral blood flow (Jin et al., 2023). chronic pain symptoms and associated emotional and cognitive
DTI studies have further supported the benefits of scalp acupuncture disorders.
treatment on the motor brain areas, improving conditions such as ce
rebral palsy and stroke, potentially through the repair and regeneration 4.4.2. Precuneus
of white matter tracts related to motor functions (Xu and Tong, 2023; Our findings revealed functional (negative) and anatomical con
Zhao et al., 2018, 2017). A study on rats has suggested that scalp nectivity between the precuneus and both the bilateral hippocampus
acupuncture protects cognitive functions of vascular dementia by and amygdala. The precuneus, as another crucial hub within the DMN,
improving white matter perfusion and integrity (Ma et al., 2020). has been implicated in the processing of salient sensory experiences
Collectively, these studies suggest that scalp acupuncture can rather than specific nociceptive processing (Cavanna and Trimble, 2006;
modulate multiple brain functional and anatomical connectivities, Legrain et al., 2011).
demonstrating its potential in treating brain diseases. The effects extend The identified scalp acupuncture targets in the precuneus are in close
beyond the target area to the surrounding area and connected distal proximity to the acupoints GV19 (Houding), GV20 (Baihui), and the
regions, validating our methodology in identifying scalp acupuncture MS12 scalp acupuncture line. Previous research on rats has demon
targets for chronic pain and comorbid disorders. strated the efficacy of electroacupuncture at GV20 (Baihui) in allevi
Notably, electroacupuncture on the scalp can be regarded as a new ating complete Freund’s adjuvant (CFA)-induced inflammatory pain (Ji
form of transcranial electrical stimulation (tES), and is very similar to et al., 2020). Another study highlighted the effectiveness and safety of
alternating current (tACS). Rich literature has shown that tES (including electroacupuncture when combining GV20 (Baihui) with other body
tACS) can exert neuromodulation effects beyond the targeted cortical acupoints compared to fentanyl transdermal patches in managing cancer
area. For instance, studies have suggested that local brain activation pain (Xu et al., 2018). Furthermore, electroacupuncture at GV20 (Bai
induced by stimulation can trigger a transsynaptic spread of action po hui) has shown antidepressant and anxiolytic effects in rats with
tentials, engaging interconnected subcortical brain regions and entire neuropathic pain by potentially restoring the phosphorylation of
brain networks, modulating endogenous neuronal oscillation and con N-methyl-D-aspartate (NMDA) receptor type I in the hippocampus (Li
nectivity between brain regions (Cummiford et al., 2016; Lin et al., et al., 2014).
2017; Reed and Cohen Kadosh, 2018; Sacca et al., 2023; Tu et al., 2021). Previous research has shown that hub nodes in the brain that exhibit
high average controllability within the DMN may have significant im
4.4. Promising scalp acupuncture targets within the default mode network pacts on brain system functioning (Gu et al., 2015). Consistent with this
concept, our findings support that the mPFC and precuneus (in close
Disrupted connectivity within the default mode network (DMN) has proximity to acupoints EX-HN3 / GV20, and the MS12 scalp acupunc
been observed in many chronic pain disorders, including chronic low ture line), two vital nodes within the DMN, can be targeted by scalp
back pain, fibromyalgia, episodic migraines, and abdominal pain, which acupuncture to concurrently modulate the activity / connectivity in the
may lead to behavioral dysfunctions (Čeko et al., 2020; Cunningham hippocampus, amygdala, and NA, offering a potential approach for
et al., 2022; Hunt et al., 2022; Jones et al., 2020; Kregel et al., 2015; managing chronic pain disorders.
Zhang et al., 2014). We have identified two key brain regions within the
DMN, the mPFC and the precuneus, as potential targets for the treatment 4.5. Other potential scalp acupuncture targets
of chronic pain through scalp acupuncture.
We found that the hippocampus, amygdala, and NAc also exhibited
4.4.1. Medial prefrontal cortex intrinsic FC with cortical brain regions distributed at the frontal cortices
The mPFC has recently been recognized as a central hub for neuro (dorsolateral/ventrolateral prefrontal cortex, orbitofrontal frontal cor
logical and psychiatric comorbidities associated with chronic pain, tex) and the lateral temporal and parietal lobes, suggesting the potential
exerting top-down control of the pain sensation (Kummer et al., 2020). for scalp acupuncture to simultaneously modulate these three deep brain
Our findings revealed functional (positive) and structural connections structures.
between the mPFC and the hippocampus, amygdala, and NAc. Specifically, the DLPFC, a vital node of the cognitive circuit involved
As a key node of the descending pain modulation system, the mPFC in executive control and other critical cognitive processes, is a widely-
and its surrounding areas, such as the anterior cingulate cortex (ACC), used target for non-invasive brain stimulation (NIBS) techniques in
play an important role in chronic pain (Tu et al., 2019) and pain treating various chronic pain conditions and accompanying pain-related
10
Fig. 5. Recommended Scalp Needling Techniques – using medial prefrontal cortex (mPFC) and Precuneus Areas as Examples. The upper figures showed overlap in
the mPFC and precuneus using three left seed regions. Each overlapping mPFC area was selected based on the positive rsFC and PTG results of the left hippocampus,
amygdala, and NAcc, respectively. The mPFC region from positive rsFC results is indicated by yellow color; the overlapping mPFC region is indicated by red color.
Each overlapping precuneus area was selected based on the negative rsFC and PTG results of the left hippocampus and amygdala, respectively. The precuneus area
from negative rsFC results is indicated by yellow color; the overlapping precuneus region isindicated by blue color. We suggest combining the centro-square needling
technique (Yang Ci) with electroacupuncture to enhance the effects of scalp acupuncture. Illustrated in Figs. A and B, the centro-square needling involves placing four
needles about 1 cun away from the central points on the scalp identified in our study. To improve both effectiveness and safety, we recommend alternating between
horizontal and vertical orientations during the application of electroacupuncture stimulation. Fig. 5A: Scalp Acupuncture Needling Techniques Targeting the mPFC
Area; Fig. 5B: Scalp Acupuncture Needling Techniques Targeting the Precuneus Area.
depression (Che et al., 2021; Zhu et al., 2022). Moreover, the VLPFC, of sensorimotor integration (Gombaut and Holmes, 2022). Thus, it is
associated with memory and emotional functioning (Li et al., 2019), worthwhile to consider targeting the M1 and SMA regions, given their
may be a suitable target for treating chronic pain that is comorbid with significant roles in modulating chronic pain.
cognitive and emotional disorders. In line with these findings, we also The OFC is associated with various brain functions including mem
identified scalp acupuncture targets at the DLPFC/VLPFC, located near ory and memory-related emotions, cognitive regulation, and reward
the acupoints GB14 (Yangbai), GB15 (Toulinqi), as well as along the (Takahashi et al., 2019; Wang et al., 2019). In addition, the OFC is
scalp acupuncture lines MS3, and MS4, which may serve as targets for known to be involved in regulating negative affect and fear responses
chronic pain and associated depressive symptoms. (Mao et al., 2020). Stimulating this area (located near the acupoints GB6
Furthermore, motor control dysfunction is common across many [Xuanli] and BL2 [Cuanzhu]) with scalp acupuncture may help improve
chronic pain conditions, making the motor cortex – particularly the symptoms of cognitive decline and mood disorders by simultaneously
primary motor cortex (M1) – a crucial target for chronic pain treatment modulating the function of the hippocampus, amygdala, and NAc
with NIBS techniques (Chang et al., 2018; Corti et al., 2022). Although (Colasanti et al., 2016; Guo et al., 2014; Kim et al., 2011; Yan et al.,
our functional connectivity analysis findings did not directly identify the 2019).
M1 region, we did identify the supplementary motor area (SMA), which The scalp acupuncture targets in the lateral parietal cortex (IPG/
is adjacent to M1. Increased activity within the SMA suggests that the ANG/SMG) are located at the temporoparietal junction (TPJ), which
motor system plays a prominent role in responding to pain in the context plays a crucial role in multisensory integration and processing
11
(Donaldson et al., 2015). Recently, one fMRI study demonstrated that findings may provide valuable stimulation guidance. Finally, clinical
functional connectivity within the IPG may serve as a neural substrate in trials and additional studies are needed to validate our findings.
the association between anxiety, depression, and sleep quality, sug
gesting it as a potential target for the treatment of sleep disturbance (Lai 5. Conclusions
et al., 2023). Previous work has demonstrated that NIBS of the lateral
parietal cortex could alter hippocampal neural activity to improve We found that the mPFC (located slightly inferior to the acupoint EX-
memory function (Hebscher and Voss, 2020; Hermiller et al., 2020). HN3), precuneus (located in close proximity to acupoints GV19/20 and
Additionally, we found FC between the hippocampus and the temporal above the scalp acupuncture line MS12), and other surface brain regions
cortices (STG/MTG/ITG). The temporal lobe is involved in processing may be used as potential scalp acupuncture locations for the treatment
sensory input into derived meanings for the retention of visual memory of chronic pain and its comorbidities. These identified locations may
as well as emotion association (Smith and Kosslyn, 2007). Thus, stim also be used for the treatment of psychiatric and neurological disorders,
ulating the above areas (located near acupoints GB8 [Shuaigu], GB18 such as anxiety, depression, insomnia, and cognitive decline, in which
[Chengling], BL8 [Luoque], and scalp acupuncture lines MS7/MS9) with these regions play crucial roles.
scalp acupuncture holds promise for treating emotional and memory
impairments as well as sleep disturbances associated with chronic pain. CRediT authorship contribution statement
4.6. Needling maneuver for identified scalp acupuncture targets Kong Jian: Conceptualization, Formal analysis, Writing – review &
editing. Zhu Meixuan: Writing – review & editing. Reddy Sveta:
To enhance scalp acupuncture treatment efficacy and target deep Writing – review & editing. Ursitti Amy Katherine: Writing – review &
brain structures, researchers may consider adopting specific needling editing. Hodges Sierra: Writing – review & editing. Kong Qiao:
techniques, such as centro-square needling (Yang Ci) or triple needling Conceptualization, Data curation, Formal analysis, Writing – original
(Qi Ci). Centro-square needling employs four extra needles surrounding draft, Writing – review & editing.
the main acupoint, while triple needling entail one needle in the center
and one on each side. These additional needles enhance stimulation,
Declaration of Competing Interest
promoting blood circulation, lymph flow, and tissue regeneration,
thereby contributing to pain relief, and have been widely used in
The authors declare that they have no known competing financial
treating musculoskeletal and brain diseases (HUO and ZHAO, 2021;
interests or personal relationships that could have appeared to influence
SHENG et al., 2017; B. Wang et al., 2017; Yang et al., 2017).
the work reported in this paper.
The incorporation of electrical stimulation into scalp acupuncture
presents an alternative to manual maneuvers. Electro- scalp acupuncture
Acknowledgements
ensures precise stimulation intensity and frequency, potentially
reducing treatment duration while enhancing therapeutic efficacy.
Jian Kong is supported by R33AT009341, R34DA046635 (through
Recent clinical trials and literature review consistently indicate that
the NIH HEAL Initiative), R01AG063975, and R01NS129059 from NIH.
compared to manual acupuncture, electroacupuncture demonstrate su
The content is solely the responsibility of the authors and does not
perior outcomes in chronic pain conditions such as chronic neck pain
necessarily represent the official views of the National Institutes of
(Seo et al., 2017), knee osteoarthritis (Chen et al., 2017), and chronic
Health or its NIH HEAL Initiative.
low back pain (Kong et al., 2020).
Furthermore, the refinement of electroacupuncture parameters for
chronic pain treatment, including frequency, intensity, and duration, Appendix A. Supporting information
remains an ongoing challenge. Previous research suggests that specific
frequencies applied during electroacupuncture can induce the release of Supplementary data associated with this article can be found in the
site-specific neuropeptides to produce analgesia (Han, 2003). However, online version at doi:10.1016/j.bbii.2024.100050.
determining the optimal frequency poses challenges, as distinct fre
quencies may engage different neural pathways in the mediation of References
analgesia (Lao et al., 2004; Zhang et al., 2005). In addition to frequency,
A standard international acupuncture nomenclature: memorandum from a WHO
electrical current intensity of electroacupuncture typically ranges from 1 meeting, 1990. Bull World Health Organ 68, 165–169.
to 10 mA, lasting 20 to 30 min per session, adjusted based on individual Allam, H., Mohammed, N.H., 2013. The role of scalp acupuncture for relieving the
tolerances (Comachio et al., 2020; Lv et al., 2019; Mao et al., 2021). chronic pain of degenerative osteoarthritis: a pilot study of Egyptian Women. Med
Acupunct. 25, 216–220. https://doi.org/10.1089/ACU.2012.0892.
Future studies are needed to refine these parameters for optimized Apkarian, A.V., Baliki, M.N., Geha, P.Y., 2009. Towards a theory of chronic pain. Prog.
electro- scalp acupuncture efficacy in various chronic pain management. Neurobiol. 87, 81–97. https://doi.org/10.1016/J.PNEUROBIO.2008.09.018.
The recommended scalp needing techniques for the identified scalp Baliki, M.N., Petre, B., Torbey, S., Herrmann, K.M., Huang, L., Schnitzer, T.J., Fields, H.
L., Apkarian, A.V., 2012a. Corticostriatal functional connectivity predicts transition
acupuncture targets can be found in Fig. 5. to chronic back pain. Nat. Neurosci. 15, 1117–1119. https://doi.org/10.1038/
NN.3153.
4.7. Limitations Baliki, M.N., Petre, B., Torbey, S., Herrmann, K.M., Huang, L., Schnitzer, T.J., Fields, H.
L., Apkarian, A.V., 2012b. Corticostriatal functional connectivity predicts transition
to chronic back pain. Nat. Neurosci. 15, 1117–1119. https://doi.org/10.1038/
Our study has several limitations. The connectivity analysis was NN.3153.
performed on healthy subjects, and chronic pain patients may exhibit Behzadi, Y., Restom, K., Liau, J., Liu, T.T., 2007. A component based noise correction
method (CompCor) for BOLD and perfusion based fMRI. Neuroimage 37, 90–101.
altered functional and anatomical connectivity. Nevertheless, the con https://doi.org/10.1016/J.NEUROIMAGE.2007.04.042.
nectivity alteration associated with chronic pain should be mild, and it Bonnici, H.M., Chadwick, M.J., Lutti, A., Hassabis, D., Weiskopf, N., Maguire, E.A., 2012.
may be different depending on the specific pain condition and severity Detecting representations of recent and remote autobiographical memories in
vmPFC and hippocampus. J. Neurosci. 32, 16982–16991. https://doi.org/10.1523/
level. We thus have decided to choose healthy participants with a
JNEUROSCI.2475-12.2012.
relatively large sample size in this study. Furthermore, our findings are Bushnell, M.C., Čeko, M., Low, L.A., 2013. Cognitive and emotional control of pain and
based on group analysis. Individualized rsFC and PTG analysis may its disruption in chronic pain. Nat. Rev. Neurosci. 14, 502. https://doi.org/10.1038/
provide more accurate locations. Nevertheless, for clinics that do not NRN3516.
Cavanna, A.E., Trimble, M.R., 2006. The precuneus: a review of its functional anatomy
have MRI data available, or clinicians who do not have the expertise / and behavioural correlates. Brain 129, 564–583. https://doi.org/10.1093/BRAIN/
resources to perform complicated brain imaging data analysis, our AWL004.
12
Čeko, M., Frangos, E., Gracely, J., Richards, E., Wang, B., Schweinhardt, P., Catherine Hebscher, M., Voss, J.L., 2020. Testing network properties of episodic memory using
Bushnell, M., 2020. Default mode network changes in fibromyalgia patients are non-invasive brain stimulation. Curr. Opin. Behav. Sci. 32, 35–42. https://doi.org/
largely dependent on current clinical pain. Neuroimage 216. https://doi.org/ 10.1016/J.COBEHA.2020.01.012.
10.1016/J.NEUROIMAGE.2020.116877. Hermiller, M.S., Chen, Y.F., Parrish, T.B., Voss, J.L., 2020. Evidence for immediate
Chang, P.C., Centeno, M.V., Procissi, D., Baria, A., Apkarian, A.V., 2017. Brain activity enhancement of hippocampal memory encoding by network-targeted theta-burst
for tactile allodynia: a longitudinal awake rat functional magnetic resonance stimulation during concurrent fMRI. J. Neurosci. 40, 7155–7168. https://doi.org/
imaging study tracking emergence of neuropathic pain. Pain 158, 488–497. https:// 10.1523/JNEUROSCI.0486-20.2020.
doi.org/10.1097/J.PAIN.0000000000000788. Hommer, D.H., 2012. Chinese scalp acupuncture relieves pain and restores function in
Chang, W.J., O’Connell, N.E., Beckenkamp, P.R., Alhassani, G., Liston, M.B., Schabrun, S. complex regional pain syndrome. Mil. Med 177, 1231–1234. https://doi.org/
M., 2018. Altered primary motor cortex structure, organization, and function in 10.7205/MILMED-D-12-00193.
chronic pain: a systematic review and meta-analysis. J. Pain. 19, 341–359. https:// Hunt, C.A., Letzen, J.E., Krimmel, S.R., Burrowes, S.A.B., Haythornthwaite, J.A.,
doi.org/10.1016/J.JPAIN.2017.10.007. Finan, P.H., Vetter, M., Seminowicz, D.A., 2022. Is mindfulness associated with
Che, X., Cash, R.F.H., Luo, X., Luo, H., Lu, X., Xu, F., Zang, Y.F., Fitzgerald, P.B., lower pain reactivity and connectivity of the default mode network? A replication
Fitzgibbon, B.M., 2021. High-frequency rTMS over the dorsolateral prefrontal cortex and extension study in healthy and episodic migraine participants. J. Pain. 23,
on chronic and provoked pain: a systematic review and meta-analysis. Brain Stimul. 2110–2120. https://doi.org/10.1016/J.JPAIN.2022.07.011.
14, 1135–1146. https://doi.org/10.1016/J.BRS.2021.07.004. HUO, J., ZHAO, J.-Q., 2021. Triple needling combined with thermo-electroacupuncture
Chen, N., Wang, J., Mucelli, A., Zhang, X., Wang, C., 2017. Electro-acupuncture is at Huantiao (GB 30) for trunk-sciatica. Chin. Acupunct. Moxibustion 41, 275–278.
beneficial for knee osteoarthritis: the evidence from meta-analysis of randomized https://doi.org/10.13703/J.0255-2930.20200210-K0003.
controlled trials. Am. J. Chin. Med (Gard. City N. Y) 45, 965–985. https://doi.org/ Janak, P.H., Tye, K.M., 2015. From circuits to behaviour in the amygdala. Nature 517,
10.1142/S0192415X17500513. 284. https://doi.org/10.1038/NATURE14188.
Chen, T., Wang, J., Wang, Y.Q., Chu, Y.X., 2022. Current understanding of the neural Ji, B.Bin, Chen, L.B., Zhuang, X.X., Han, K.Y., Dai, Q.X., Mo, Y.C., Wang, J.L., 2020.
circuitry in the comorbidity of chronic pain and anxiety. Neural Plast. 2022 https:// Study on efficacy specificity of electroacupuncture at "Zusanli "(ST36) and “Baihui”
doi.org/10.1155/2022/4217593. (GV20) in cerebral ischemia and inflammatory pain rats. Zhen Ci Yan Jiu 45,
Chen, Y., Liu, Y., Song, Y., Zhao, S., Li, B., Sun, J., Liu, L., 2022. Therapeutic applications 823–828. https://doi.org/10.13702/J.1000-0607.190738.
and potential mechanisms of acupuncture in migraine: a literature review and Jin, G.Y., Jin, L.L., Jin, B.X., Zheng, J., He, B.J., Li, S.J., 2023. Neural control of cerebral
perspectives. Front Neurosci. 16, 1022455 https://doi.org/10.3389/ blood flow: scientific basis of scalp acupuncture in treating brain diseases. Front.
FNINS.2022.1022455/BIBTEX. Neurosci. 17, 1210537 https://doi.org/10.3389/FNINS.2023.1210537/BIBTEX.
Chung, W.Y., Liu, S.Y., Gao, J.C., Jiang, Y.J., Zhang, J., Qu, S.S., Zhang, J.P., Tan, X.L., Jones, S.A., Morales, A.M., Holley, A.L., Wilson, A.C., Nagel, B.J., 2020. Default mode
Chen, J.Q., Wang, S.X., 2019. Modulatory effect of International Standard Scalp network connectivity is related to pain frequency and intensity in adolescents.
Acupuncture on brain activation in the elderly as revealed by resting-state fMRI. Neuroimage Clin. 27, 102326 https://doi.org/10.1016/J.NICL.2020.102326.
Neural Regen. Res. 14, 2126. https://doi.org/10.4103/1673-5374.262590. Kim, M.J., Loucks, R.A., Palmer, A.L., Brown, A.C., Solomon, K.M., Marchante, A.N.,
Cohen, S.P., Vase, L., Hooten, W.M., 2021. Chronic pain: an update on burden, best Whalen, P.J., 2011. The structural and functional connectivity of the amygdala: from
practices, and new advances. Lancet 397, 2082–2097. https://doi.org/10.1016/ normal emotion to pathological anxiety. Behav. Brain Res. 223, 403–410. https://
S0140-6736(21)00393-7. doi.org/10.1016/J.BBR.2011.04.025.
Colasanti, A., Guo, Q., Giannetti, P., Wall, M.B., Newbould, R.D., Bishop, C., Onega, M., Kong, J., Tu, P.C., Zyloney, C., Su, T.P., 2010. Intrinsic functional connectivity of the
Nicholas, R., Ciccarelli, O., Muraro, P.A., Malik, O., Owen, D.R., Young, A.H., periaqueductal gray, a resting fMRI study. Behav. Brain Res. 211, 215. https://doi.
Gunn, R.N., Piccini, P., Matthews, P.M., Rabiner, E.A., 2016. Hippocampal org/10.1016/J.BBR.2010.03.042.
neuroinflammation, functional connectivity, and depressive symptoms in multiple Kong, J., Wang, Z., Leiser, J., Minicucci, D., Edwards, R., Kirsch, I., Wasan, A.D., Lang, C.,
sclerosis. Biol. Psychiatry 80, 62–72. https://doi.org/10.1016/J. Gerber, J., Yu, S., Napadow, V., Kaptchuk, T.J., Gollub, R.L., 2018. Enhancing
BIOPSYCH.2015.11.022. treatment of osteoarthritis knee pain by boosting expectancy: a functional
Comachio, J., Oliveira, C.C., Silva, I.F.R., Magalhães, M.O., Marques, A.P., 2020. neuroimaging study. Neuroimage Clin. 18, 325–334. https://doi.org/10.1016/J.
Effectiveness of manual and electrical acupuncture for chronic non-specific low back NICL.2018.01.021.
pain: a randomized controlled trial. J. Acupunct. Meridian Stud. 13, 87–93. https:// Kong, J.T., Puetz, C., Tian, L., Haynes, I., Lee, E., Stafford, R.S., Manber, R., MacKey, S.,
doi.org/10.1016/J.JAMS.2020.03.064. 2020. Effect of electroacupuncture vs sham treatment on change in pain severity
Corti, E.J., Marinovic, W., Nguyen, A.T., Gasson, N., Loftus, A.M., 2022. Motor cortex among adults with chronic low back pain: a randomized clinical Trial. JAMA Netw.
excitability in chronic low back pain. Exp. Brain Res 240, 3249. https://doi.org/ Open 3. https://doi.org/10.1001/JAMANETWORKOPEN.2020.22787.
10.1007/S00221-022-06492-7. Kong, Q., Sacca, V., Zhu, M., Ursitti, A.K., Kong, J., 2023. Anatomical and functional
Cummiford, C.M., Nascimento, T.D., Foerster, B.R., Clauw, D.J., Zubieta, J.K., Harris, R. connectivity of critical deep brain structures and their potential clinical application
E., DaSilva, A.F., 2016. Changes in resting state functional connectivity after in brain stimulation. J. Clin. Med. 2023 12 (4426 12), 4426. https://doi.org/
repetitive transcranial direct current stimulation applied to motor cortex in 10.3390/JCM12134426.
fibromyalgia patients. Arthritis Res Ther. 18 https://doi.org/10.1186/S13075-016- Kregel, J., Meeus, M., Malfliet, A., Dolphens, M., Danneels, L., Nijs, J., Cagnie, B., 2015.
0934-0. Structural and functional brain abnormalities in chronic low back pain: a systematic
Cunningham, N.R., Nahman-Averbuch, H., Lee, G.R., King, C.D., Coghill, R.C., 2022. review. Semin Arthritis Rheum. 45, 229–237. https://doi.org/10.1016/J.
Amygdalar functional connectivity during resting and evoked pain in youth with SEMARTHRIT.2015.05.002.
functional abdominal pain disorders. Pain 163, 2031–2043. https://doi.org/ Kummer, K.K., Mitrić, M., Kalpachidou, T., Kress, M., 2020. The medial prefrontal cortex
10.1097/J.PAIN.0000000000002601. as a central hub for mental comorbidities associated with chronic pain. Int J. Mol.
Donaldson, P.H., Rinehart, N.J., Enticott, P.G., 2015. Noninvasive stimulation of the Sci. 21 https://doi.org/10.3390/IJMS21103440.
temporoparietal junction: a systematic review. Neurosci. Biobehav. Rev. 55, Lai, M., Gao, Y., Lu, L., Huang, X., Gong, Q., Li, J., Jiang, P., 2023. Functional
547–572. https://doi.org/10.1016/J.NEUBIOREV.2015.05.017. connectivity of the left inferior parietal lobule mediates the impact of anxiety and
Fasick, V., Spengler, R.N., Samankan, S., Nader, N.D., Ignatowski, T.A., 2015. The depression symptoms on sleep quality in healthy adults. Cereb. Cortex. https://doi.
hippocampus and TNF: common links between chronic pain and depression. org/10.1093/CERCOR/BHAD253.
Neurosci. Biobehav Rev. 53, 139–159. https://doi.org/10.1016/J. Lambert, C., Zrinzo, L., Nagy, Z., Lutti, A., Hariz, M., Foltynie, T., Draganski, B.,
NEUBIOREV.2015.03.014. Ashburner, J., Frackowiak, R., 2012. Confirmation of functional zones within the
Fields, H., 2004. State-dependent opioid control of pain. Nat. Rev. Neurosci. 5, 565–575. human subthalamic nucleus: patterns of connectivity and sub-parcellation using
https://doi.org/10.1038/NRN1431. diffusion weighted imaging. Neuroimage 60, 83–94. https://doi.org/10.1016/J.
Gombaut, C., Holmes, S.A., 2022. Sensorimotor integration and pain perception: NEUROIMAGE.2011.11.082.
mechanisms integrating nociceptive processing. a systematic review and ALE-meta Lao, L., Zhang, R.X., Zhang, G., Wang, X., Berman, B.M., Ren, K., 2004. A parametric
analysis. Front Integr. Neurosci. 16. https://doi.org/10.3389/FNINT.2022.931292/ study of electroacupuncture on persistent hyperalgesia and Fos protein expression in
PDF. rats. Brain Res 1020, 18–29. https://doi.org/10.1016/j.brainres.2004.01.092.
Grilli, M., 2017. Chronic pain and adult hippocampal neurogenesis: translational Legrain, V., Iannetti, G.D., Plaghki, L., Mouraux, A., 2011. The pain matrix reloaded: a
implications from preclinical studies. J. Pain. Res 10, 2281. https://doi.org/ salience detection system for the body. Prog. Neurobiol. 93, 111–124. https://doi.
10.2147/JPR.S146399. org/10.1016/J.PNEUROBIO.2010.10.005.
Gu, S., Pasqualetti, F., Cieslak, M., Telesford, Q.K., Yu, A.B., Kahn, A.E., Medaglia, J.D., Li, M., Liu, Y., Chen, H., Hu, G., Yu, S., Ruan, X., Luo, Z., Wei, X., Xie, Y., 2019. Altered
Vettel, J.M., Miller, M.B., Grafton, S.T., Bassett, D.S., 2015. Controllability of global synchronizations in patients with parkinson’s disease: a resting-state fMRI
structural brain networks. Nat. Commun. 6 https://doi.org/10.1038/NCOMMS9414. study. Front Aging Neurosci. 11 https://doi.org/10.3389/FNAGI.2019.00139.
Guo, X., Li, J., Wang, J., Fan, X., Hu, M., Shen, Y., Chen, H., Zhao, J., 2014. Hippocampal Li, Q., Yue, N., Liu, S.Bin, Wang, Z.F., Mi, W.L., Jiang, J.W., Wu, G.C., Yu, J., Wang, Y.Q.,
and orbital inferior frontal gray matter volume abnormalities and cognitive deficit in 2014. Effects of chronic electroacupuncture on depression- and anxiety-like
treatment-naive, first-episode patients with schizophrenia. Schizophr. Res 152, behaviors in rats with chronic neuropathic pain. Evid. -Based Complement. Altern.
339–343. https://doi.org/10.1016/J.SCHRES.2013.12.015. Med. 2014 https://doi.org/10.1155/2014/158987.
Han, J.S., 2003. Acupuncture: neuropeptide release produced by electrical stimulation of Li, S., Zhang, Zixuan, Jiao, Y., Jin, G., Wu, Y., Xu, F., Zhao, Y., Jia, H., Qin, Z.,
different frequencies. Trends Neurosci. 26, 17–22. https://doi.org/10.1016/S0166- Zhang, Zhangjin, Rong, P., 2022. An assessor-blinded, randomized comparative trial
2236(02)00006-1. of transcutaneous auricular vagus nerve stimulation (taVNS) combined with cranial
Hao, J.J., Hao, L.L., 2012. Review of clinical applications of scalp acupuncture for electroacupuncture vs. citalopram for depression with chronic pain. Front Psychiatry
paralysis: an excerpt from chinese scalp acupuncture. Glob. Adv. Health Med 1, 102. 13. https://doi.org/10.3389/FPSYT.2022.902450/PDF.
https://doi.org/10.7453/GAHMJ.2012.1.1.017. Li, Z., Liu, M., Lan, L., Zeng, F., Makris, N., Liang, Y., Guo, T., Wu, F., Gao, Y., Dong, M.,
Yang, J., Li, Y., Gong, Q., Liang, F., Kong, J., 2016. Altered periaqueductal gray
13
resting state functional connectivity in migraine and the modulation effect of Seo, S.Y., Lee, K.B., Shin, J.S., Lee, J., Kim, M.R., Ha, I.H., Ko, Y., Lee, Y.J., 2017.
treatment. Sci. Rep. 6 https://doi.org/10.1038/SREP20298. Effectiveness of acupuncture and electroacupuncture for chronic neck pain: a
Lin, R.L., Douaud, G., Filippini, N., Okell, T.W., Stagg, C.J., Tracey, I., 2017. Structural systematic review and meta-analysis. Am. J. Chin. Med (Gard. City N. Y) 45,
connectivity variances underlie functional and behavioral changes during pain relief 1573–1595. https://doi.org/10.1142/S0192415X17500859.
induced by neuromodulation. Sci. Rep. https://doi.org/10.1038/srep41603. SHENG, G., LI, J., TANG, Y., 2017. Clinical observation of centro-square needling at
Liu, H., Chen, L., Zhang, G., Jiang, Y., Qu, S., Liu, S., Huang, Y., Chen, J., 2020. Scalp shangxing (GV23) for anxiety after cerebral stroke. Shanghai J. Acupunct.
acupuncture enhances the functional connectivity of visual and cognitive-motor Moxibustion 142–145. https://doi.org/10.13460/J.ISSN.1005-0957.2017.02.0142.
function network of patients with acute ischemic stroke. Evid. Based Complement Smith, E.E., Kosslyn, S.M., 2007. Cognitive psychology: mind and brain 610.
Altern. Med 2020. https://doi.org/10.1155/2020/8836794. Takahashi, T., Nakamura, M., Nishikawa, Y., Komori, Y., Nishiyama, S., Takayanagi, Y.,
Liu, H., Jiang, Y., Wang, N., Yan, H., Chen, L., Gao, J., Zhang, J., Qu, S., Liu, S., Liu, G., Furuichi, A., Kido, M., Sasabayashi, D., Higuchi, Y., Noguchi, K., Suzuki, M., 2019.
Huang, Y., Chen, J., 2021a. Scalp acupuncture enhances local brain regions Potential role of orbitofrontal surface morphology on social and cognitive functions
functional activities and functional connections between cerebral hemispheres in in high-risk subjects for psychosis and schizophrenia patients. Psychiatry Res
acute ischemic stroke patients. Anat. Rec. (Hoboken) 304, 2538. https://doi.org/ Neuroimaging 283, 92–95. https://doi.org/10.1016/J.PSCYCHRESNS.2018.12.002.
10.1002/AR.24746. Taylor, A.M.W., 2018. Corticolimbic circuitry in the modulation of chronic pain and
Liu, H., Jiang, Y., Wang, N., Yan, H., Chen, L., Gao, J., Zhang, J., Qu, S., Liu, S., Liu, G., substance abuse. Prog. Neuropsychopharmacol. Biol. Psychiatry 87, 263. https://
Huang, Y., Chen, J., 2021b. Scalp acupuncture enhances local brain regions doi.org/10.1016/J.PNPBP.2017.05.009.
functional activities and functional connections between cerebral hemispheres in Toda, T., Parylak, S.L., Linker, S.B., Gage, F.H., 2019. The role of adult hippocampal
acute ischemic stroke patients. Anat. Rec. (Hoboken) 304, 2538. https://doi.org/ neurogenesis in brain health and disease. Mol. Psychiatry 24, 67. https://doi.org/
10.1002/AR.24746. 10.1038/S41380-018-0036-2.
Liu, J., Zhang, B., Cui, F., Cao, J., Yu, S., Kong, Q., Kong, J., 2023. Scalp acupuncture Tu, Y., Jung, M., Gollub, R.L., Napadow, V., Gerber, J., Ortiz, A., Lang, C., Mawla, I.,
targets for neurological disorders: evidence from neuroimaging studies (part 2). Shen, W., Chan, S.T., Wasan, A.D., Edwards, R.R., Kaptchuk, T.J., Rosen, B., Kong, J.,
acupuncture. Research 1–18. https://doi.org/10.13702/j.1000-0607.20230016. 2019. Abnormal medial prefrontal cortex functional connectivity and its association
Liu, W., Chen, C., Wang, F., Guo, S., Hao, Y., Li, S., 2020. Development trend and current with clinical symptoms in chronic low back pain. Pain 160, 1308–1318. https://doi.
situation of acupuncture-moxibustion indications. World J. Acupunct. Moxibustion org/10.1097/J.PAIN.0000000000001507.
30, 245–250. https://doi.org/10.1016/J.WJAM.2020.07.014. Tu, Y., Cao, J., Guler, S., Chai-Zhang, T., Camprodon, J.A., Vangel, M., Gollub, R.L.,
Löffler, M., Levine, S.M., Usai, K., Desch, S., Kandić, M., Nees, F., Flor, H., 2022. Dougherty, D.D., Kong, J., 2021. Perturbing fMRI brain dynamics using transcranial
Corticostriatal circuits in the transition to chronic back pain: The predictive role of direct current stimulation. Neuroimage 237, 118100. https://doi.org/10.1016/J.
reward learning. Cell Rep. Med 3. https://doi.org/10.1016/J.XCRM.2022.100677. NEUROIMAGE.2021.118100.
Luber, B., Davis, S.W., Deng, Z.De, Murphy, D., Martella, A., Peterchev, A.V., Lisanby, S. Vachon-Presseau, E., Centeno, M.V., Ren, W., Berger, S.E., Tétreault, P., Ghantous, M.,
H., 2022. Using diffusion tensor imaging to effectively target TMS to deep brain Baria, A., Farmer, M., Baliki, M.N., Schnitzer, T.J., Apkarian, A.V., 2016. The
structures. Neuroimage 249, 118863. https://doi.org/10.1016/J. emotional brain as a predictor and amplifier of chronic pain. J. Dent. Res 95,
NEUROIMAGE.2021.118863. 605–612. https://doi.org/10.1177/0022034516638027.
Lv, Z.T., Shen, L.L., Zhu, B., Zhang, Z.Q., Ma, C.Y., Huang, G.F., Yin, J., Yu, L.L., Yu, S.Y., Vachon-Presseau, E., Tétreault, P., Petre, B., Huang, L., Berger, S.E., Torbey, S., Baria, A.
Ding, M.Q., Li, J., Yuan, X.C., He, W., Jing, X.H., Li, M., 2019. Effects of intensity of T., Mansour, A.R., Hashmi, J.A., Griffith, J.W., Comasco, E., Schnitzer, T.J.,
electroacupuncture on chronic pain in patients with knee osteoarthritis: a Baliki, M.N., Apkarian, A.V., 2016. Corticolimbic anatomical characteristics
randomized controlled trial. Arthritis Res Ther. 21 https://doi.org/10.1186/S13075- predetermine risk for chronic pain. Brain 139, 1958–1970. https://doi.org/10.1093/
019-1899-6. BRAIN/AWW100.
Ma, S.M., Wang, L., Su, X.T., Yang, N.N., Huang, J., Lin, L.L., Shao, J.K., Yang, J.W., Vasques, X., Richardet, R., Hill, S.L., Slater, D., Chappelier, J.C., Pralong, E., Bloch, J.,
Liu, C.Z., 2020. Acupuncture improves white matter perfusion and integrity in rat Draganski, B., Cif, L., 2015. Automatic target validation based on neuroscientific
model of vascular dementia: an MRI-based imaging study. Front Aging Neurosci. 12, literature mining for tractography. Front Neuroanat. 9, 66. https://doi.org/10.3389/
582904 https://doi.org/10.3389/FNAGI.2020.582904/BIBTEX. FNANA.2015.00066/ABSTRACT.
Mao, J.J., Liou, K.T., Baser, R.E., Bao, T., Panageas, K.S., Romero, S.A.D., Li, Q.S., Wang, B., Hu, J., Zhang, N., Wang, J., Chen, Z., Wu, Z., 2017. Clinical study of fire
Gallagher, R.M., Kantoff, P.W., 2021. Effectiveness of electroacupuncture or acupuncture with centro-square needles for knee osteoarthritis. Zhongguo Zhen Jiu
auricular acupuncture vs usual care for chronic musculoskeletal pain among cancer 37, 463–466. https://doi.org/10.13703/J.0255-2930.2017.05.003.
survivors: The PEACE randomized clinical trial. JAMA Oncol. 7, 1. https://doi.org/ Wang, Q., Poh, J.S., Wen, D.J., Broekman, B.F.P., Chong, Y.S., Yap, F., Shek, L.P.,
10.1001/JAMAONCOL.2021.0310. Gluckman, P.D., Fortier, M. v, Qiu, A., 2019. Functional and structural networks of
Mao, Y., Zuo, X., Ding, C., Qiu, J., 2020. OFC and its connectivity with amygdala as lateral and medial orbitofrontal cortex as potential neural pathways for depression in
predictors for future social anxiety in adolescents. Dev. Cogn. Neurosci. 44, 100804 childhood. Depress Anxiety 36, 365–374. https://doi.org/10.1002/DA.22874.
https://doi.org/10.1016/J.DCN.2020.100804. Wang, S., Liu, K., Wang, Y., Wang, Shuyou, He, X., Cui, X., Gao, X., Zhu, B., 2017a.
McCarberg, B., Peppin, J., 2019. Pain pathways and nervous system plasticity: learning A proposed neurologic pathway for scalp acupuncture: trigeminal
and memory in pain. Pain. Med 20, 2421–2437. https://doi.org/10.1093/PM/ nerve–meninges–cerebrospinal fluid–contacting neurons–brain. Med. Acupunct. 29,
PNZ017. 322. https://doi.org/10.1089/ACU.2017.1231.
Minakawa, Y., Saito, S., Matsumoto, Y., Oka, H., Miki, K., Yukioka, M., Itoh, K., 2022. Wang, S., Liu, K., Wang, Y., Wang, Shuyou, He, X., Cui, X., Gao, X., Zhu, B., 2017b.
Effects of acupuncture therapy on drug-resistant fibromyalgia: an exploratory single- A proposed neurologic pathway for scalp acupuncture: trigeminal nerve-meninges-
arm nonrandomized trial. Med Acupunct. 34, 193–200. https://doi.org/10.1089/ cerebrospinal fluid-contacting neurons-brain. Med. Acupunct. 29, 322–326. https://
ACU.2022.0005. doi.org/10.1089/ACU.2017.1231.
Motzkin, J.C., Philippi, C.L., Wolf, R.C., Baskaya, M.K., Koenigs, M., 2015. Ventromedial Wang, S., Liu, K., Wang, Y., Wang, Shuyou, He, X., Cui, X., Gao, X., Zhu, B., 2017c. A
prefrontal cortex is critical for the regulation of amygdala activity in humans. Biol. Proposed Neurologic Pathway for Scalp Acupuncture: Trigeminal
Psychiatry 77, 276–284. https://doi.org/10.1016/J.BIOPSYCH.2014.02.014. Nerve–Meninges–Cerebrospinal Fluid–Contacting Neurons–Brain. https://home.
Mutso, A.A., Radzicki, D., Baliki, M.N., Huang, L., Banisadr, G., Centeno, M.V., liebertpub.com/acu 29, 322–326. https://doi.org/10.1089/ACU.2017.1231.
Radulovic, J., Martina, M., Miller, R.J., Apkarian, A, Vania, 2012. Abnormalities in Wang, S., Wang, J., Liu, K., Bai, W., Cui, X., Han, S., Gao, X., Zhu, B., 2020. Signaling
hippocampal functioning with persistent pain. J. Neurosci. 32, 5747–5756. https:// Interaction between facial and meningeal inputs of the trigeminal system mediates
doi.org/10.1523/JNEUROSCI.0587-12.2012. peripheral neurostimulation analgesia in a rat model of migraine. Neuroscience 433,
Reed, T., Cohen Kadosh, R., 2018. Transcranial electrical stimulation (tES) mechanisms 184–199. https://doi.org/10.1016/J.NEUROSCIENCE.2020.03.004.
and its effects on cortical excitability and connectivity. J. Inherit. Metab. Dis. 41, Weigand, A., Horn, A., Caballero, R., Cooke, D., Stern, A.P., Taylor, S.F., Press, D.,
1123. https://doi.org/10.1007/S10545-018-0181-4. Pascual-Leone, A., Fox, M.D., 2018. Prospective validation that subgenual
Rezvani, M., Yaraghi, A., Mohseni, M., Fathimoghadam, F., 2014. Efficacy of Yamamoto connectivity predicts antidepressant efficacy of transcranial magnetic stimulation
new scalp acupuncture versus Traditional Chinese acupuncture for migraine sites. Biol. Psychiatry 84, 28–37. https://doi.org/10.1016/J.
treatment. J. Alter. Complement Med 20, 371–374. https://doi.org/10.1089/ BIOPSYCH.2017.10.028.
ACM.2013.0120. Wiech, K., Tracey, I., 2009. The influence of negative emotions on pain: behavioral
Robinson, J.L., Barron, D.S., Kirby, L.A.J., Bottenhorn, K.L., Hill, A.C., Murphy, J.E., effects and neural mechanisms. Neuroimage 47, 987–994. https://doi.org/10.1016/
Katz, J.S., Salibi, N., Eickhoff, S.B., Fox, P.T., 2015. Neurofunctional topography of J.NEUROIMAGE.2009.05.059.
the human hippocampus. Hum. Brain Mapp. 36, 5018–5037. https://doi.org/ Woolrich, M.W., Jbabdi, S., Patenaude, B., Chappell, M., Makni, S., Behrens, T.,
10.1002/HBM.22987. Beckmann, C., Jenkinson, M., Smith, S.M., 2009. Bayesian analysis of neuroimaging
Rolls, E.T., 2022. The hippocampus, ventromedial prefrontal cortex, and episodic and data in FSL. Neuroimage 45. https://doi.org/10.1016/J.
semantic memory. Prog. Neurobiol. 217 https://doi.org/10.1016/J. NEUROIMAGE.2008.10.055.
PNEUROBIO.2022.102334. Xu, J.-B., Tong, G.-L., 2023. Efficacy and mechanism of scalp acupuncture for spastic
Sacca, V., Maleki, N., Wen, Y., Hodges, S., Kong, J., 2023. Modulation effects of repeated cerebral palsy. Zhongguo Zhen Jiu 43, 163–169. https://doi.org/10.13703/J.0255-
transcranial direct current stimulation at the dorsolateral prefrontal cortex: a pulsed 2930.20220408-0001.
continuous arterial spin labeling study. Brain Sci. 2023 Vol. 13. https://doi.org/ Xu, L., Wan, Y., Huang, J., Xu, F., 2018. Clinical analysis of electroacupuncture and
10.3390/BRAINSCI13030395. multiple acupoint stimulation in relieving cancer pain in patients with advanced
Salgado, S., Kaplitt, M.G., 2015. The nucleus accumbens: a comprehensive review. Stereo hepatocellular carcinoma. J. Cancer Res Ther. 14, 99–102. https://doi.org/10.4103/
Funct. Neurosurg. 93, 75–93. https://doi.org/10.1159/000368279. JCRT.JCRT_736_17.
Schockert, T., Schockert, T., 2011. Yamamoto new scalp acupuncture (YNSA): Yan, R., Tao, S.W., Liu, H.Y., Chen, Y., Shi, J.B., Yang, Y.Y., Zhu, R.X., Yao, Z.J., Lu, Q.,
development, principles, safety, effectiveness and clinical applications. Acupunct. 2019. Abnormal alterations of regional spontaneous neuronal activity in inferior
Clin. Pract. Part. Tech. Spec. Issues. https://doi.org/10.5772/23422. frontal orbital gyrus and corresponding brain circuit alterations: a resting-state fMRI
14
study in somatic depression. Front Psychiatry 10. https://doi.org/10.3389/ experimental low back pain. Neural Regen. Res 9, 135–142. https://doi.org/
FPSYT.2019.00267/PDF. 10.4103/1673-5374.125341.
Yang, Y., Qi, S., Liu, M., Zhao, Y., Li, N., 2017. [Therapeutic effect observation of chronic Zhao, N., Zhang, J., Qiu, M., Wang, C., Xiang, Y., Wang, H., Xie, J., Liu, S., Wu, J., 2018.
knee joint pain assisted with the central-square needling technique of the thumb- Scalp acupuncture plus low-frequency rTMS promotes repair of brain white matter
tack needles]. Zhongguo Zhen Jiu 37, 1052–1056. https://doi.org/10.13703/ tracts in stroke patients: A DTI study. J. Integr. Neurosci. 17, 61–69. https://doi.org/
J.0255-2930.2017.10.007. 10.31083/JIN-170043.
Yu, R., Gollub, R.L., Spaeth, R., Napadow, V., Wasan, A., Kong, J., 2014. Disrupted Zhao, W. jian, Liu, Z. huan, Li, N., Zhao, Y., Fu, W. jie, Jin, B. xu, 2017. Clinical
functional connectivity of the periaqueductal gray in chronic low back pain. observation on scalp acupuncture for diffusion tensor imaging in cerebral palsy
Neuroimage Clin. 6, 100–108. https://doi.org/10.1016/J.NICL.2014.08.019. children with periventricular leukomalacia. J. Acupunct. Tuina Sci. 15, 36–41.
Yu, S., Li, W., Shen, W., Edwards, R.R., Gollub, R.L., Wilson, G., Park, J., Ortiz, A., https://doi.org/10.1007/S11726-017-0972-4/METRICS.
Cao, J., Gerber, J., Mawla, I., Chan, S.T., Lee, J., Wasan, A.D., Napadow, V., Zheng, Z.H., Tu, J.L., Li, X.H., Hua, Q., Liu, W.Z., Liu, Y., Pan, B.X., Hu, P., Zhang, W.H.,
Kaptchuk, T.J., Rosen, B., Kong, J., 2020. Impaired mesocorticolimbic connectivity 2021. Neuroinflammation induces anxiety- and depressive-like behavior by
underlies increased pain sensitivity in chronic low back pain. Neuroimage 218. modulating neuronal plasticity in the basolateral amygdala. Brain Behav. Immun.
https://doi.org/10.1016/J.NEUROIMAGE.2020.116969. 91, 505–518. https://doi.org/10.1016/J.BBI.2020.11.007.
Zeidman, P., Maguire, E.A., 2016. Anterior hippocampus: the anatomy of perception, Zhu, Y., Li, D., Zhou, Y., Hu, Y., Xu, Z., Lei, L., Xu, F., Wang, J., 2022. Systematic review
imagination and episodic memory. Nat. Rev. Neurosci. 17, 173–182. https://doi. and meta-analysis of high-frequency rTMS over the dorsolateral prefrontal cortex.on
org/10.1038/NRN.2015.24. chronic pain and chronic-pain-accompanied depression. ACS Chem. Neurosci. 13,
Zhang, B., Liu, J., Cui, F., Cao, J., Yu, S., Kong, Q., Kong, J., 2023. Scalp acupuncture 2547–2556. https://doi.org/10.1021/ACSCHEMNEURO.2C00395.
targets for neurological disorders: evidence from neuroimaging studies (part 1). Zhu, Z., Hubbard, E., Guo, X., Barbosa, D.A.N., Popal, A.M., Cai, C., Jiang, H., Zheng, Z.,
acupuncture. Research 1–14. https://doi.org/10.13702/j.1000-0607.20230020. Lin, J., Gao, W., Zhang, J., Bartas, K., Macchia, D., Derdeyn, P., Halpern, C.H.,
Zhang, R.X., Lao, L., Wang, X., Fan, A., Wang, L., Ren, K., Berman, B.M., 2005. Mayberg, H.S., Beier, K.T., Zhu, J., Wu, H., 2021. A connectomic analysis of deep
Electroacupuncture attenuates inflammation in a rat model. J. Alter. Complement brain stimulation for treatment-resistant depression. Brain Stimul. 14, 1226–1233.
Med 11, 135–142. https://doi.org/10.1089/ACM.2005.11.135. https://doi.org/10.1016/J.BRS.2021.08.010.
Zhang, S.S., Wu, W., Huang, G.Z., Liu, Z.P., Guo, S.G., Yang, J.M., Wang, K.L., 2014.
Resting-state connectivity in the default mode network and insula during
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Identifying Scalp Acupuncture For Chronic Pain

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Brain Behavior and Immunity Integrative 5 (2024) 100050

Contents lists available at ScienceDirect

Brain Behavior and Immunity Integrative

Identifying potential scalp acupuncture targets for chronic pain and

1. Introduction anatomy and function to determine stimulation locations, modern

Brain regions from resting-state functional connectivity analysis*

3.1.1. resting-state functional connectivity results

Brain regions from resting state functional connectivity analysis*

Brain regions from resting state functional connectivity analysis*

Brain regions from resting state functional connectivity analysis*

Brain regions from resting state functional connectivity analysis*

Brain regions from resting state functional connectivity analysis*

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