A parallel-group study of near-infrared spectroscopy-neurofeedback in children with attention deficit hyperactivity disorder.

The present study aimed to assess the efficacy of Near-infrared spectroscopy (NIRS) real-time neurofeedback (NF) vs. atomoxetine (AT) in children with attention deficit hyperactivity disorder (ADHD). A parallel-group study was conducted to enroll children with ADHD between 8 and 12 years of age. Participants were assigned into the NIRS group and AT group as their wish. Subjects in the NIRS group received 12 sessions of NF training within 6 weeks, and subjects in the AT group were given oral medication. Changes in Swanson, Nolan, and Pelham-V rating scales (SNAP-IV), and performance of Go/No-Go and N-back working memory tasks at week 3, 6 and 8 were evaluated. Forty-nine patients completed the study, including 18 ADHD in the NIRS group and 31 in the AT group. Total scores of SNAP-IV significantly decreased from baseline to week 3, week 6, and week 8 in both groups. Patients in the NIRS group showed significant lower scores on the inattention subscale of SNAP-IV at week 3 and week 6, compared to the AT group. NIRS group had a shorter reaction time during the Go/No-Go task at week 6 and fewer errors during 2-back than the AT group at week 3. The findings revealed that NIRS real-time NF is more efficacious relative to AT in improving behavioral performance, highlighting its potential role and advantages in treating patients with ADHD.

Electroacupuncture enhances resting-state functional connectivity between dorsal caudate and precuneus and decreases associated leptin levels in overweight/obese subjects.

Electroacupuncture (EA) is a safe and effective method for treating obesity. However, how it modulates reward-related brain activity/functional connectivity and gut hormones remains unclear. We employed resting-state functional magnetic resonance imaging (RS-fMRI) and resting-state functional connectivity (RSFC) to investigate EA induced changes in resting-state activity and RSFC in reward-related regions and its association with gut hormones in overweight/obese subjects who received real (n = 20) and Sham (n = 15) stimulation. Results showed reduced leptin levels was positively correlated with reduced body mass index (BMI) and negatively correlated with increased cognitive-control as measured with Three-Factor-Eating-Questionnaire (TFEQ). Significant time effects on RSFC between dorsal caudate (DC) and precuneus were due to significant increased RSFC strength in both EA and Sham groups. In addition, increased RSFC of DC-precuneus was negatively correlated with reduced BMI and leptin levels in the EA group. Mediation analysis showed that the relationship between increased DC-precuneus RSFC strength and reduced BMI was mediated by reduced leptin levels. These findings reflect the association between EA-induced brain reward-related RSFC and leptin levels, and decreased leptin levels mediated altered DC-precuneus RSFC strength and consequent weight-loss, suggesting the potential role of EA in reducing weight and appetite.

Distinct Basal Brain Functional Activity and Connectivity in the Emotional-Arousal Network and Thalamus in Patients With Functional Constipation Associated With Anxiety and/or Depressive Disorders.

OBJECTIVE: Functional constipation (FC) is a common gastrointestinal disorder. Anxiety and/or depressive disorders are common in patients with FC (FCAD). Brain dysfunction may play a role in FC, but the contribution of comorbid anxiety and/or depression in patients with FC is poorly understood. METHODS: Sixty-five FC patients and 42 healthy controls (HCs) were recruited, and a hierarchical clustering algorithm was used to classify FC patients into FCAD and patients without anxiety/depressive status (FCNAD) based on neuropsychological assessment. Resting-state functional magnetic resonance imaging measures including fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity were used to investigate brain functional differences. RESULTS: Thirty-seven patients were classified as FCAD, and 28 patients were classified as FCNAD; as compared with HC, both groups showed decreased activity (fALFF) in the perigenual anterior cingulate cortex (pACC), dorsomedial prefrontal cortex (DMPFC), and precuneus; enhanced precentral gyrus-thalamus connectivity and attenuated precuneus-thalamus connectivity in FCAD/FCNAD highlighted the thalamus as a critical connectivity node in the brain network (pFWE < .05). In comparison with FCNAD/HC, the FCAD group also had decreased fALFF in the orbitofrontal cortex (OFC) and thalamus, and increased OFC-hippocampus connectivity. In the FCNAD group, brain activities (pACC/DMPFC) and connection (precuneus-thalamus) had correlations only with symptoms; in the FCAD group, brain activities (OFC, pACC/DMPFC) and connectivities (OFC-hippocampus/precentral gyrus-thalamus) showed correlations with both constipation symptoms and anxiety/depressive status ratings. Mediation analysis indicated that the relationship between abdominal distension and OFC activity was completely mediated by anxiety in FCAD. CONCLUSIONS: These findings provide evidence of differences in brain activity and functional connectivity between FCAD and FCNAD, potentially providing important clues for improving treatment strategies.

Functional constipation is associated with alterations in thalamo-limbic/parietal structural connectivity.

BACKGROUND: Functional constipation (FCon) is a common functional gastrointestinal disorder (FGID) with a high prevalence in clinical practice. Previous studies have identified that FCon is associated with functional and structural alterations in the primary brain regions involved in emotional arousal processing, sensory processing, somatic/motor-control, and self-referential processing. However, whether FCon is associated with abnormal structural connectivity (SC) among these brain regions remains unclear. METHODS: We selected the brain regions with functional and structural abnormalities as seed regions and employed diffusion tensor imaging (DTI) with probabilistic tractography to investigate SC changes in 29 patients with FCon and 31 healthy controls (HC). KEY RESULTS: Results showed lower fractional anisotropy (FA) in the fibers connecting the thalamus, a region involved in sensory processing, with the amygdala (AMY), hippocampal gyrus (HIPP), precentral (PreCen) and postcentral gyrus (PostCen), supplementary motor area (SMA) and precuneus in patients with FCon compared with HC. FCon had higher mean diffusivity (MD) and radial diffusivity (RD) in the thalamus connected to the AMY and HIPP. In addition, FCon had significantly increased RD of the thalamus-SMA tract. Sensation of incomplete evacuation was negatively correlated with FA of the thalamus-PostCen and thalamus-HIPP tracts, and there was a negative correlation between difficulty of defecation and FA of the thalamus-SMA tract. CONCLUSIONS AND INFERENCES: These findings reflected that FCon is associated with alterations in SC between the thalamus and limbic/parietal cortex, highlighting the integrative role of the thalamus in brain structural network.

Abnormalities in the thalamo-cortical network in patients with functional constipation.

Functional constipation (FCon) is a common functional gastrointestinal disorder (FGID); neuroimaging studies have shown brain functional abnormalities in thalamo-cortical regions in patients with FGID. However, association between FCon and topological characteristics of brain networks remains largely unknown. We employed resting-state functional magnetic resonance imaging (RS-fMRI) and graph theory approach to investigate functional brain topological organization in 42 patients with FCon and 41 healthy controls (HC) from perspectives of global, regional and modular levels. Results showed patients with FCon had a significantly lower normalized clustering coefficient and small-worldness, implying decreased brain functional connectivity. Regions showed altered nodal degree and efficiency mainly located in the thalamus, rostral anterior cingulate cortex (rACC), and supplementary motor area (SMA), which are involved in somatic/sensory, emotional processing and motor-control. For the modular analysis, thalamus, rACC and SMA had an aberrant within-module nodal degree and nodal efficiency, and thalamus-related network exhibited abnormal interaction with the limbic network (amygdala and hippocampal gyrus). Nodal degree in the thalamus was negatively correlated with difficulty of defecation, and nodal degree in the rACC was negatively correlated with sensation of incomplete evacuation. These findings indicated that FCon was associated with abnormalities in the thalamo-cortical network.

Acute and long-term effects of electroacupuncture alter frontal and insular cortex activity and functional connectivity during resting state.

Electroacupuncture (EA) is a safe method for treating obesity; however, its underlying neural mechanisms remain unclear. We employed resting-state-functional-magnetic-resonance-imaging (RS-fMRI) and amplitude-of-low-frequency-fluctuation (ALFF) to investigate acute/long-term effects of EA on brain activity and resting-state-functional-connectivity (RSFC) in overweight/obesity subjects who received real/Sham stimulation. For acute effects, 26 and 19 overweight/obesity subjects were included in EA and Sham groups respectively. There were significant time effects on ALFF in the right insula (INS) and left dorsolateral-prefrontal-cortex (DLPFC) due to decreases/increases in INS/DLPFC in both groups. There were weaker positive RSFC between INS and supplementary-motor-area (SMA)/right DLPFC and weaker negative RSFC between INS and precuneus (PCUN); stronger negative RSFC between DLPFC and dorsomedial-prefrontal-cortex (DMPFC) in both groups. For long-term study, body-mass-index (BMI) had significant reduction in EA (n = 17) and Sham (15) groups; EA had higher BMI reduction than in Sham. There were significant time effects on ALFF in right ventrolateral-prefrontal-cortex (VLPFC) due to significant increases in EA group, and stronger positive RSFC between VLPFC and orbitofrontal-cortex and negative RSFC between VLPFC and left thalamus (THA) in both groups after long-term treatment. These findings suggest that changes in resting-activity and RSFC implicated in inhibitory-control, gastric-motility and satiety-control are associated with EA-induced weight-loss.

Altered thalamo-cortical resting state functional connectivity in smokers.

The thalamus has widespread connections with the prefrontal cortex (PFC) and modulates communication between the striatum and PFC, which is crucial to the neural mechanisms of smoking. However, relatively few studies focused on the thalamic resting state functional connectivity (RSFC) patterns and their association with smoking behaviors in smokers. 24 young male smokers and 24 non-smokers were enrolled in our study. Fagerström Test for Nicotine Dependence (FTND) was used to assess the nicotine dependence level. The bilateral thalamic RSFC patterns were compared between smokers and non-smokers. The relationship between neuroimaging findings and smoking behaviors (FTND and pack-years) were also investigated in smokers. Relative to nonsmokers, smokers showed reduced RSFC strength between the left thalamus and several brain regions, i.e. the right dorsolateral prefrontal cortex (dlPFC), the anterior cingulate cortex (ACC) and the bilateral caudate. In addition, the right thalamus showed reduced RSFC with the right dlPFC as well as the bilateral insula in smokers. Therefore, the findings in the current study revealed the reduced RSFC of the thalamus with the dlPFC, the ACC, the insula and the caudate in smokers, which provided new insights into the roles of the thalamus in nicotine addiction from a function integration perspective.

Connectivity Study of the Neuromechanism of Acute Acupuncture Needling during fMRI in "Overweight" Subjects.

This functional connectivity study depicts how acupoints ST 36 and SP 9 and their sham acupoints acutely act on blood glucose (GLU), core body temperature (CBT), hunger, and sensations pertaining to needling (De-qi) via the limbic system and dopamine (DA) to affect various brain areas in fasting, adult, and "overweight" Chinese males using functional magnetic resonance imaging. Functional connectivity (FC) analysis utilized the amygdala (AMY) and hypothalamus (HYP) as regions of interest (ROIs) in the discrete cosine transform and seed correlation analysis methods. There was a significant difference in the spatial patterns of the distinct brain regions between groups. Correlation results showed that increased HYP-hippocampus FC after ACU was positively correlated with ACU-induced change in CBT; increased HYP-putamen-insula FC after ACU was positively correlated with ACU-induced change in GLU; and increased HYP-anterior cingulate cortex FC after ACU was positively correlated with ACU-induced change in HUNGER suggesting that increased DA modulation during ACU was probably associated with increased poststimulation limbic system and spinothalamic tract connectivity. Decreased HYP-thalamus FC after ACU was negatively correlated or anticorrelated with ACU-induced change in HUNGER suggesting that increased DA modulation during ACU was possibly associated with decreased poststimulation limbic system and spinothalamic tract connectivity. No correlation was found for min SHAM. This was an important study in addressing acute acupuncture effects and neural pathways involving physiology and appetite regulation in overweight individuals.

Changes in thalamic connectivity in the early and late stages of amnestic mild cognitive impairment: a resting-state functional magnetic resonance study from ADNI.

We used resting-state functional magnetic resonance imaging (fMRI) to investigate changes in the thalamus functional connectivity in early and late stages of amnestic mild cognitive impairment. Data of 25 late stages of amnestic mild cognitive impairment (LMCI) patients, 30 early stages of amnestic mild cognitive impairment (EMCI) patients and 30 well-matched healthy controls (HC) were analyzed from the Alzheimer's disease Neuroimaging Initiative (ADNI). We focused on the correlation between low frequency fMRI signal fluctuations in the thalamus and those in all other brain regions. Compared to healthy controls, we found functional connectivity between the left/right thalamus and a set of brain areas was decreased in LMCI and/or EMCI including right fusiform gyrus (FG), left and right superior temporal gyrus, left medial frontal gyrus extending into supplementary motor area, right insula, left middle temporal gyrus (MTG) extending into middle occipital gyrus (MOG). We also observed increased functional connectivity between the left/right thalamus and several regions in LMCI and/or EMCI including left FG, right MOG, left and right precuneus, right MTG and left inferior temporal gyrus. In the direct comparison between the LMCI and EMCI groups, we obtained several brain regions showed thalamus-seeded functional connectivity differences such as the precentral gyrus, hippocampus, FG and MTG. Briefly, these brain regions mentioned above were mainly located in the thalamo-related networks including thalamo-hippocampus, thalamo-temporal, thalamo-visual, and thalamo-default mode network. The decreased functional connectivity of the thalamus might suggest reduced functional integrity of thalamo-related networks and increased functional connectivity indicated that aMCI patients could use additional brain resources to compensate for the loss of cognitive function. Our study provided a new sight to understand the two important states of aMCI and revealed resting-state fMRI is an appropriate method for exploring pathophysiological changes in aMCI.

Effects of long-term acupuncture treatment on resting-state brain activity in migraine patients: a randomized controlled trial on active acupoints and inactive acupoints.

BACKGROUND: Acupuncture has been commonly used for preventing migraine attacks and relieving pain during a migraine, although there is limited knowledge on the physiological mechanism behind this method. The objectives of this study were to compare the differences in brain activities evoked by active acupoints and inactive acupoints and to investigate the possible correlation between clinical variables and brain responses. METHODS AND RESULTS: A randomized controlled trial and resting-state functional magnetic resonance imaging (fMRI) were conducted. A total of eighty migraineurs without aura were enrolled to receive either active acupoint acupuncture or inactive acupoint acupuncture treatment for 8 weeks, and twenty patients in each group were randomly selected for the fMRI scan at the end of baseline and at the end of treatment. The neuroimaging data indicated that long-term active acupoint therapy elicited a more extensive and remarkable cerebral response compared with acupuncture at inactive acupoints. Most of the regions were involved in the pain matrix, lateral pain system, medial pain system, default mode network, and cognitive components of pain processing. Correlation analysis showed that the decrease in the visual analogue scale (VAS) was significantly related to the increased average Regional homogeneity (ReHo) values in the anterior cingulate cortex in the two groups. Moreover, the decrease in the VAS was associated with increased average ReHo values in the insula which could be detected in the active acupoint group. CONCLUSIONS: Long-term active acupoint therapy and inactive acupoint therapy have different brain activities. We postulate that acupuncture at the active acupoint might have the potential effect of regulating some disease-affected key regions and the pain circuitry for migraine, and promote establishing psychophysical pain homeostasis. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-13003635.

Two sets of acupoint combination of similar functions engage shared neural representation: a functional magnetic resonance imaging study.

OBJECTIVE: To investigate whether the neural representations underlying alternating two acupoint combinations (ACs) are the same or not. METHODS: In this functional magnetic resonance imaging study, two sets of analgesia ACs were utilized, including Waiguan (TE5) and Qiuxu (GB40) for Group A, and Neiguan (PC6) and Taichong (LR3) for Group B, which are the most commonly adopted in clinical treatment. Each group had 20 healthy subjects. An experimental design was proposed, which consisted of a pre-needling resting phase, a needling phase and a post-needling resting phase. This paradigm optimally mimics the clinical protocol as well as focuses on both the stimulation and the resting periods. The results were subjected to general linear model analysis, conjunction analysis and the functional connectivity analysis. RESULTS: The rostral anterior cingulated cortex was engaged in the initiative period of the acupuncture effect in both groups, and it was chosen as the seed region for the functional connectivity analysis for the following resting period. The results showed that several shared brain regions were involved in both groups, in particular the insula, amygdala and hypothalamus. Moreover, significant differences were located at the posterior cingulated cortex as revealed by a two sample -test (P<0.05, corrected). Other regions showed no significant differences. This finding was further supported by the spatial correlation analysis that the two groups were significantly correlated (r =0.51, P<0.01). CONCLUSION: This preliminary research helps us understand the neurophysiological mechanisms of acupuncture when following clinical guidelines on ACs, as well as provides an important opportunity to develop better treatment strategies for reducing, or even preventing pain.

Expertise modulates local regional homogeneity of spontaneous brain activity in the resting brain: an fMRI study using the model of skilled acupuncturists.

Studies on training/expertise-related effects on human brain in context of neuroplasticity have revealed that plastic changes modulate not only task activations but also patterns and strength of internetworks and intranetworks functional connectivity in the resting state. Much has known about plastic changes in resting state on global level; however, how training/expertise-related effect affects patterns of local spontaneous activity in resting brain remains elusive. We investigated the homogeneity of local blood oxygen level-dependent fluctuations in the resting state using a regional homogeneity (ReHo) analysis among 16 acupuncturists and 16 matched nonacupuncturists (NA). To prove acupuncturists' expertise, we used a series of psychophysical tests. Our results demonstrated that, acupuncturists significantly outperformed NA in tactile-motor and emotional regulation domain and the acupuncturist group showed increased coherence in local BOLD signal fluctuations in the left primary motor cortex (MI), the left primary somatosensory cortex (SI) and the left ventral medial prefrontal cortex/orbitofrontal cortex (VMPFC/OFC). Regression analysis displayed that, in the acupuncturists group, ReHo of VMPFC/OFC could predict behavioral outcomes, evidenced by negative correlation between unpleasantness ratings and ReHo of VMPFC/OFC and ReHo of SI and MI positively correlated with the duration of acupuncture practice. We suggest that expertise could modulate patterns of local resting state activity by increasing regional clustering strength, which is likely to contribute to advanced local information processing efficiency. Our study completes the understanding of neuroplasticity changes by adding the evidence of local resting state activity alterations, which is helpful for elucidating in what manner training effect extends beyond resting state.

Length of Acupuncture Training and Structural Plastic Brain Changes in Professional Acupuncturists.

BACKGROUND: The research on brain plasticity has fascinated researchers for decades. Use/training serves as an instrumental factor to influence brain neuroplasticity. Parallel to acquisition of behavioral expertise, extensive use/training is concomitant with substantial changes of cortical structure. Acupuncturists, serving as a model par excellence to study tactile-motor and emotional regulation plasticity, receive intensive training in national medical schools following standardized training protocol. Moreover, their behavioral expertise is corroborated during long-term clinical practice. Although our previous study reported functional plastic brain changes in the acupuncturists, whether or not structural plastic changes occurred in acupuncturists is yet elusive. METHODOLOGY/PRINCIPAL FINDINGS: Cohorts of acupuncturists (N = 22) and non-acupuncturists (N = 22) were recruited. Behavioral tests were delivered to assess the acupuncturists' behavioral expertise. The results confirmed acupuncturists' tactile-motor skills and emotion regulation proficiency compared to non-acupuncturists. Using the voxel-based morphometry technique, we revealed larger grey matter volumes in acupuncturists in the hand representation of the contralateral primary somatosensory cortex (SI), the right lobule V/VI and the bilateral ventral anterior cingulate cortex/ventral medial prefrontal cortex. Grey matter volumes of the SI and Lobule V/VI positively correlated with the duration of acupuncture practice. CONCLUSIONS: To our best knowledge, this study provides first evidence for the anatomical alterations in acupuncturists, which would possibly be the neural correlates underlying acupuncturists' exceptional skills. On one hand, we suggest our findings may have ramifications for tactile-motor rehabilitation. On the other hand, our results in emotion regulation domain may serve as a target for our future studies, from which we can understand how modulations of aversive emotions elicited by empathic pain develop in the context of expertise. Future longitudinal study is necessary to establish the presence and direction of a causal link between practice/use and brain anatomy.

What Is the de-qi-Related Pattern of BOLD Responses? A Review of Acupuncture Studies in fMRI.

de-qi, comprising mostly subjective sensations during acupuncture, is traditionally considered as a very important component for the possible therapeutic effects of acupuncture. However, the neural correlates of de-qi are still unclear. In this paper, we reviewed previous fMRI studies from the viewpoint of the neural responses of de-qi. We searched on Pubmed and identified 111 papers. Fourteen studies distinguishing de-qi and sharp pain and eight studies with the mixed sensations were included in further discussions. We found that the blood oxygenation level-dependent (BOLD) responses associated with de-qi were activation dominated, mainly around cortical areas relevant to the processing of somatosensory or pain signals. More intense and extensive activations were shown for the mixed sensations. Specific activations of sharp pain were also shown. Similar BOLD response patterns between de-qi evoked by acupuncture stimulation and de-qi-like sensations evoked by deep pain stimulation were shown. We reckon that a standardized method of qualification and quantification of de-qi, deeper understanding of grouping strategy of de-qi and sharp pain, and making deep pain stimulation as a control, as well as a series of improvements in the statistical method, are crucial factors for revealing the neural correlates of de-qi and neural mechanisms of acupuncture.

Partly Separated Activations in the Spatial Distribution between de-qi and Sharp Pain during Acupuncture Stimulation: An fMRI-Based Study.

Nowadays, functional magnetic resonance imaging (fMRI) has become one of the most important ways to explore the central mechanism of acupuncture. Among these studies, activations around the somatosensory-related brain network had the most robust blood oxygen level-dependent (BOLD) responses. However, due to the insufficient control of the subjective sensations during acupuncture stimulation, whether these robust activations reflected the pattern of de-qi, sharp pain, or mixed (de-qi + sharp pain) sensations was largely unknown. The current study recruited 50 subjects and grouped them into two groups according to whether he/she experienced sharp pain during acupuncture stimulation to give a definite answer to the aforesaid question. Our results indicated that BOLD responses associated with de-qi during acupuncture stimulation at ST36 were activation dominated. Furthermore, both the quantitative and qualitative differences of BOLD responses between de-qi and mixed sensations evoked by acupuncture stimulation were significant. The pattern of BOLD responses of sharp pain might be partly separated from that of de-qi in the spatial distribution. Therefore, we proposed that in order to explore the specific central mechanism of acupuncture, subjects with sharp pain should be excluded from those with only de-qi.

Impact of global normalization in FMRI acupuncture studies.

Global normalization is often used as a preprocessing step for dispelling the "nuisance effects." However, it has been shown in cognitive and emotion tasks that this preprocessing step might greatly distort statistical results when the orthogonality assumption of global normalization is violated. The present study examines this issue in fMRI acupuncture studies. Thirty healthy subjects were recruited to evaluate the impacts of the global normalization on the BOLD responses evoked by acupuncture stimulation during De-qi sensation and tactile stimulation during nonpainful sensations. To this end, we compared results by conducting global normalization (PSGS) and not conducting global normalization (NO PSGS) based on a proportional scaling model. The orthogonality assumption of global normalization was violated, and significant changes between BOLD responses for NO PSGS and PSGS were shown in most subjects. Extensive deactivations of acupuncture in fMRI were the non-specifically pernicious consequences of global normalization. The central responses of acupuncture during De-qi are non-specifically activation-dominant at the somatosensory-related brain network, whose statistical power is specifically enhanced by PSGS. In conclusion, PSGS should be unjustified for acupuncture studies in fMRI. The differences including the global normalization or not may partly contribute to conflicting results and interpretations in previous fMRI acupuncture studies.

Tempo-spatial analysis of vision-related acupoint specificity in the occipital lobe using fMRI: an ICA study.

Functional acupoint specificity is one of the most debated topics in acupuncture neuroimaging research. Conventional studies investigating vision-related acupoint specificity empirically assume that acupuncture-induced hemodynamic response can be defined a priori and thus concentrate on distinguishing the spatial variations of response patterns across acupoints in the occipital lobe. However, evidence suggests that acupuncture-invoked BOLD signal changes are independent of a priori time shape. Additionally, temporal profiles reflect how a stimulus corresponds with the brain, implying the hemodynamic coherence induced by stimulation. Therefore, temporal information carried in acupuncture-related neural activity may be more crucial to specificity issues. This paper initiates the detection into tempo-spatial dimension and the goal of this study is to detect functional acupoint specificity by uniquely comparing the temporal activities of the occipital lobe among vision-related acupoints (VRA) and a non-acupoint (NAP). We utilized the independent component analysis (ICA) to extract temporal patterns of occipital response by stimulating a VRA, i.e. GB37, and a NAP. As an improvement over previous ones, another VRA, i.e., BL60 was employed to consolidate our findings. Results showed that although all groups showed V1 activity in the occipital lobe, dissociable temporal activities in this region categorized GB37 and NAP (r=0.05, p=0.64). This finding was replicable with regard to BL60 and NAP (r=-0.03, p=0.77). Intriguingly, stimulation at two VRAs induced highly correlated temporal activities (p<0.0001). This study adds positive evidence to the issue of vision-related acupoint specificity. The utilization of ICA and consideration of temporal dynamics may shed light on future studies.

Divergent neural processes specific to the acute and sustained phases of verum and SHAM acupuncture.

PURPOSE: To discuss which brain region potentially functioned and switched between the immediate and delayed response of acupuncture. MATERIALS AND METHODS: A nonrepeated event-related functional MRI (fMRI) design was used to investigate the spatial and temporal patterns of acupuncture effects induced by needling an acupoint ST36 (ACU) and a nonmeridian point (SHAM). The standard general linear model was used to detect the immediate neural responses of acupuncture. Graph theory analysis was used to characterize the functional integrated network of the acupuncture delayed effect. RESULTS: Acupuncture induced significant signal changes in the limbic/paralimbic areas, neocortical regions, brainstem, and cerebellum for immediate effect both in ACU and SHAM. Some of these brain regions showed strong functional connectivity for a delayed effect in ACU. Conjunction analysis showed that the insula played a critical role during the overall process of ACU. No overlapping brain regions were found in SHAM. CONCLUSION: The findings of this study suggested that the delayed effects may reflect a more significant characteristic underlying acupuncture. Given that the insula as a relay station switched between the immediate and delayed response, it suggested that divergent functional connectivity patterns may mediate the acupuncture-related effects for ACU and SHAM.

Evaluation of group homogeneity during acupuncture stimulation in fMRI studies.

PURPOSE: To evaluate the extent of individual differences of functional MRI (fMRI) signal changes induced by acupuncture stimulation. MATERIALS AND METHODS: Acupuncture at ST36 and checkerboard stimulation was applied to 16 subjects. We calculated the mean distance using beta values in a generalized linear model (GLM) analysis and employed it to study the group homogeneity by detecting the outliers. RESULTS: A more significant individual difference was presented in acupuncture stimulation compared with visual stimulation through evaluation of the mean distance. From the group results, we found that the activations were more significant in the homogeneous group results. Combining the behavior and fMRI results, there was no direct correlation between deqi index and mean distance in acupuncture stimulation. The deqi index of the outlier was in the normal range and did not differ significantly from others. CONCLUSION: Traditional group results without removing outliers were not sensitive enough to detect the real acupuncture effect. We suggest that individual difference should be taken into consideration for future acupuncture studies. Also, group analysis paralleled with individual analysis is critical for a full understanding of acupuncture effects.

The hybrid GLM-ICA investigation on the neural mechanism of acupoint ST36: an fMRI study.

Ample clinical reports and neuroimaging studies have demonstrated that the acupuncture has sustained effects after manipulation. However, most previous fMRI studies of acupuncture have paid little attention to this issue, only investigating on the manipulation effects. In the current study, we attempted to explore both acupuncture effects, which have positive influence to therapeutic efficiency, to reveal the neural mechanism of acupuncture. This paper combined the conventional general linear model (GLM) and independent component analysis (ICA) to study the topography and the temporal feature of brain activity to detect the brain responses to stimulation at ST36 (Zusanli) and a sham acupoint. The results showed that the manipulation-related effects and the sustained acupuncture effects separately induced statistically significant increases/decreases in the cortical-subcortical areas, including the anterior cingulate cortex (ACC), ventrolateral prefrontal cortex (VLPFC), supplementary motor area (SMA) primary/secondary somatosensory cortex (SI/SII), occipital cortices and midbrain. Our findings suggested that the analgesia effects of ST36 integrated sophisticated physiological and psychological procedures. In addition, our results have shed light on methodology in acupuncture research.