Research ReportThe effects of acupuncture on the brain networks for emotion and cognition: An observation of gender differences
Research Highlights
►Acupuncture modulates brain activity at the limbic–paralimbic–neocortical network (LPNN) and the default mode network (DMN). ►Deactivation at the LPNN/DMN during needle manipulation of acupuncture was more extensive in females than in males. ►However, needle manipulation during acupuncture induced greater activation at the secondary somatosensory cortex in males than in females. ►Soreness during acupuncture was correlated in intensity with deactivation of the angular gyrus in females; no such relationships were observed in males. ►Our study suggests that brains with sex dimorphism may process the acupuncture stimulation differently between women and men.
Introduction
Acupuncture, an ancient Chinese needle treatment, is used to relieve the clinical symptoms of pain, mood, and autonomic related disorders (Lundeberg et al., 2007). During the acupuncture procedure, needle is inserted at acupoints and then rotated manually. This manipulation of the needle after insertion induces deqi, a composite of unique sensations such as soreness, aching, pressure and heaviness, which is essential to the efficacy of acupuncture according to traditional Chinese medicine (Kong et al., 2007). It is proposed that pronounced action on the limbic system of the brain during the needle manipulation may underlie the beneficial effects of acupuncture on the clinical symptoms (Hui et al., 2007).
Using functional magnetic resonance imaging (fMRI), we and others have demonstrated that acupuncture produces deactivation of the limbic–paralimbic–neocortical network (LPNN) including the amygdala, hippocampus, septal nuclei, cingulate gyrus, precuneus and angular gyrus coupled with activation of the sensorimotor network (SMN) and a few paralimbic structures (Hui et al., 2005; Kong et al., 2007; Bai et al., 2007; Wang et al., 2007; Dhond et al., 2008, Fang et al., 2008; Qin et al., 2008). These limbic and limbic-associated structures have been shown to play a primary role in regulating emotion (Joseph, 1992; LeDoux, 1998). Furthermore, we have observed a marked similarity of the hemodynamic response to acupuncture with that of the default mode network (DMN) to attention tasks such as the cognitive examination (Buckner and Vincent, 2007; Raichle et al., 2001). The DMN structures modulated by acupuncture include 1) the frontal pole (FP) and the anterior cingulate in the medial prefrontal cortex (mPFC); 2) the hippocampus in the medial temporal lobe (MTL) and 3) the posterior cingulate (BA31), retrosplenial cortex (RSC) and precuneus (PCN) in the medial parietal cortex (MPC) (Bai et al., 2007, Dhond et al., 2008, Fang et al., 2008; Hui et al., 2005; Qin et al., 2008; Wang et al., 2007).
While sex is a biological term used to describe female vs. male, gender is a social term used to describe the identification of female vs. male. Although the majority of the studies do not measure sex hormones, except in some unusual situations, gender and sex are identical for the human subjects in the research studies. Studies have shown that the LPNN and DMN are sexually differentiated (Joseph, 2000), and sex dimorphisms exhibit significantly at the amygdala, hippocampus and neocortex (Juraska, 1991; Cahill, 2006). Functionally, gender differences in the brain are observed in the limbic system or the DMN when conducting emotional or cognitive tasks (Gur et al., 2000, Cahill et al., 2004, Goldstein et al., 2005). Though women seek complementary treatment modalities including acupuncture more frequently than men (Ben-Arye et al., 2009), the majority of studies evaluating acupuncture effects combine genders. Lund and Lundeberg (2008) have noticed that pain shows gender variations that might influence acupuncture treatment (Lund and Lundeberg, 2008)";. Brain fMRI shows the gender differences when experiencing calibrated pain (Kong et al., 2010a, Kong et al., 2010b) or during resting state (Kong et al., 2010a, Kong et al., 2010b). Because gender differences are shown in the LPNN and the DMN to mediate the tasks of emotion, cognition and pain and that these neural networks are also affected by acupuncture, we hypothesize that women and men may have different brain activation/deactivation patterns at the LPNN and the DMN in response to acupuncture procedure. In this study, using fMRI, we compared neural responses of the task-negative LPNN/DMN as well as the task-positive SMN in response to needle manipulation of acupuncture between two genders.
Section snippets
Subjects
Data on 38 subjects (19 females and 19 males) who had brain fMRI during acupuncture at matched acupoints were used for this study. All the subjects reported deqi sensations with a minimum total score of 3, and none reported sharp pain during needle manipulation. Females were comparable with males in age (Mean ± SE: 28.7 ± 1.8 vs. 29.4 ± 2.0) and ethnicity (percentage of Caucasian: 68% vs. 74%) (Table 1). There was no statistical difference in the total score of deqi between two genders (Table 1). The
Discussion
Female and male brains are similar in many aspects but different in others, which could lead to similar but also sex different neural responses depending on environmental stimuli (Witelson, 1991; Cahill, 2006). Pain shows gender variations that might influence acupuncture treatment (Lund and Lundeberg, 2008). This study revealed gender differences in the level of response and the preferential spatial distribution in each task-negative or task-positive network during needle manipulation of
Conclusion
To the best of our knowledge, this is the first report on the sex differences of the brain responding to the acupuncture stimulation as shown by fMRI. Significant gender differences were observed at both the LPNN/DMN networks and the sensation network in the brain. Since the modulation of these brain structures with acupuncture may be involved when used to treat clinical symptoms, our study suggests that the efficacy or action of acupuncture treatment might be different between women and men.
Subjects
The data from 38 subjects participating in a previous study were used (Hui et al., 2007) for this study analysis based on gender status. The subjects were right handed, generally healthy and screened to exclude those with neurological, psychiatric and medical disorders, and contraindications for exposure to high magnetic field. Experiments were conducted with the written consent of each subject and approved by the Massachusetts General Hospital Institutional Review Board.
Acupuncture
A single licensed
Acknowledgments
The manuscript is dedicated to Dr. Kathleen Kin-Sang Hui, who made a seminal contribution to link the acupuncture treatment with the modulation of brain function. We are saddened that she passed away while this manuscript was under review and consideration. This work was supported in part by a grant from the NIA, K23AG-022476 for W.Q.Q, and grants from the NIH/National Center for Complementary and Alternative Medicine (R21AT00978) (1-P01-002048-01) for K.K.H, (K01 AT003883) and (R21AT004497)
References (62)
- et al.
Complementary medicine in the primary care setting: Results of a survey of gender and cultural patterns in Israel
Gend. Med.
(2009) - et al.
Unrest at rest: default activity and spontaneous network correlations
Neuroimage
(2007) - et al.
Electrical stimulation modulates the amphetamine-induced hemodynamic changes: an fMRI study to compare the effect of stimulating locations and frequencies on rats
Neurosci. Lett.
(2008) - et al.
Evolving knowledge of sex differences in brain structure, function, and chemistry
Biol. Psychiatry
(2007) AFNI: software for analysis and visualization of functional magnetic resonance neuroimages
Comput. Biomed. Res.
(1996)- et al.
Acupuncture modulates resting state connectivity in default and sensorimotor brain networks
Pain
(2008) - et al.
A method for using blocked and event-related fMRI data to study "resting state" functional connectivity
Neuroimage
(2007) - et al.
Effects of gender on blood flow correlates of naming concrete entities
Neuroimage
(2003) - et al.
An fMRI study of sex differences in regional activation to a verbal and a spatial task
Brain Lang.
(2000) - et al.
The integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 as evidenced by fMRI
Neuroimage
(2005)
Acupuncture mobilizes the brain's default mode and its anti-correlated network in healthy subjects
Brain Res.
Exploring the brain in pain: activations, deactivations and their relation
Pain
Intrinsic functional connectivity of the periaqueductal gray, a resting fMRI study
Behav Brain Res
Gender and age effects in structural brain asymmetry as measured by MRI texture analysis
Neuroimage
Fear and the brain: where have we been, and where are we going?
Biol. Psychiatry
Functional connectivity in single and multislice echoplanar imaging using resting-state fluctuations
Neuroimage
Sex, stress and the hippocampus: allostasis, allostatic load and the aging process
Neurobiol. Aging
The impact of global signal regression on resting state correlations: are anti-correlated networks introduced?
Neuroimage
Hypothalamus and amygdala response to acupuncture stimuli in Carpal Tunnel Syndrome
Pain
Sex differences in the brain response to affective scenes with or without humans
Neuropsychologia
Brain abnormalities in murderers indicated by positron emission tomography
Biol. Psychiatry
Differential sex-independent amygdala response to infant crying and laughing in parents versus nonparents
Biol. Psychiatry
Stress and glucocorticoid footprints in the brain-the path from depression to Alzheimer's disease
Neurosci. Biobehav. Rev.
Neural sexual mosaicism: sexual differentiation of the human temporo-parietal region for functional asymmetry
Psychoneuroendocrinology
Exploratory analysis of functional connectivity network in acupuncture study by a graph theory mode
Conf. Proc. IEEE Eng. Med. Biol. Soc.
Functional connectivity in the motor cortex of resting human brain using echo-planar MRI
Magn. Reson. Med.
Why sex matters for neuroscience
Nat. Rev. Neurosci.
Sex-related hemispheric lateralization of amygdala function in emotionally influenced memory: an FMRI investigation
Learn. Mem.
Sex-specific responses to opiates: animal and human studies
Anesth. Analg.
The salient characteristics of the central effects of acupuncture needling: Limbic-paralimbic-neocortical network modulation
Hum. Brain Mapp.
The young adult human brain: an MRI-based morphometric analysis
Cereb. Cortex
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2018, Journal of Affective DisordersCitation Excerpt :For instance, Mineur et al. (2013) found that the increased activation of hippocampus is associated with anxiety and depression-related emotion regulation. Qiu et al. (2010) showed that functional connectivity between the precuneus/PCC and hippocampus was stronger in female when mediating negative emotion. Jeong et al. (2012) reported significantly increased GM volumes of hippocampus in premenstrual dysphoric disorder (PMDD), a severe form of PMS.
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2018, Journal of Integrative MedicineCitation Excerpt :A total of 44 studies with 1 191 participants were divided as follows: 19 studies [13–31] with 574 healthy subjects, 14 studies [32–45] with 289 subjects affected by nervous system diseases, 6 studies [4,46–50] with 189 subjects affected by motor system diseases and 5 studies [51–55] with 139 affected by various other diseases (Table 2). A total of 574 subjects were included in 19 studies [13–31] that only used healthy adult volunteers for fMRI studies. Acupuncture increased limbic-paralimbic-neocortical network/default-mode network (DMN)/sensorimotor network (SMN) connectivity of healthy subjects, and the correlations between limbic/paralimbic and subcortical regions, including the insula, amygdala, anterior cingulate cortex (ACC), precuneus and thalamus [13–31].
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2015, Medical HypothesesCitation Excerpt :The amygdala and hypothalamus that is not commonly associated with DMN show decreased activation during acupuncture stimulation. Acupuncture may mediate therefore its anti-pain, anti-anxiety, and other therapeutic effects via this intrinsic neural circuit that plays a central role in the affective and cognitive dimensions of pain as well as in the regulation and integration of emotion, memory processing, autonomic, endocrine, immunological, and sensorimotor functions [13,21,34]. 1.2.3 Acupuncture effects might also be related to the hypothalamus–pituitary–adrenal axis mechanism.
Neural mechanisms of acupuncture as revealed by fMRI studies
2015, Autonomic Neuroscience: Basic and ClinicalCitation Excerpt :Furthermore, different phenomena were observed in male and female on brain networks when mediating emotional and cognitive tasks (Dai et al., 2012; Qiu et al., 2010). Wei et al. discovered that deqi was correlated with deactivation of angular gyrus in females but not in males (Qiu et al., 2010). Finally, fMRI is an indirect reaction by MR signal measurement of blood oxygen saturation and the changes of blood flow, which could not directly display the function of nerve activity.
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2023, Chinese Journal of Integrative Medicine
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Deceased.