Levodopa improved different motor symptoms in patients with Parkinson's disease by reducing the functional connectivity of specific thalamic subregions.

BACKGROUND: The thalamus is an important relay station for the motor circuit of human. Levodopa can reverse the clinical manifestations by modulating the function of motor circuits, but its detailed mechanisms are still not fully understood. We aimed to explore (1) the mechanism by which levodopa modulates the functional connectivity (FC) in the subregions of the thalamus; (2) the relationship between the changed FC and the improvement of motor symptoms in Parkinson's disease (PD) patients. METHODS: Resting-state functional MRI was used to scan 36 PD patients and 37 healthy controls. The FC between the subregions in the thalamus and the whole brain was measured and compared under different medication states of PD patients. The correlation between the improvement of motor symptoms and changes in FC in the thalamus subregions was examined. RESULTS: The PD on state exhibited decreased FC between the right pre-motor thalamus and the right postcentral gyrus, as well as the right lateral pre-frontal thalamus and the right postcentral gyrus. These decreases were positively correlated with the improvement of resting tremor. The PD on state also exhibited decreased FC between the left lateral pre-frontal thalamus and right paracentral lobule, which was positively correlated with the improvement of bradykinesia. CONCLUSIONS: This study demonstrates that levodopa treats PD by decreasing the FC between the thalamus subregions and pre/post-central cortex. Our results provide a basis for further exploration of the functional activity of thalamic subregions and offer new insights into the precision treatment in PD patients.

Effect of acupuncture at the acupoints for Yizhi Tiaoshen on the functional connectivity between the hippocampus and the brain in the patients with Alzheimer's disease. / 针刺"益智调神"ç©´æ–¹å¯¹é˜¿å°”èŒ¨æµ·é»˜ç— æ‚£è€ æµ·é©¬ä¸Žå ¨è„‘åŠŸèƒ½è¿žæŽ¥çš„å½±å“.

OBJECTIVES: To analyze the effect of acupuncture at the acupoints for Yizhi Tiaoshen (benefiting the intelligence and regulating the spirit) on the functional connectivity between the hippocampus and the whole brain in the patients with Alzheimer's disease (AD), and reveal the brain function mechanism of acupuncture in treatment of AD using resting state functional magnetic resonance imaging (rs-fMRI). METHODS: Sixty patients with mild to moderate AD were randomly divided into an acupuncture + medication group (30 cases, 3 cases dropped out) and a western medication group (30 cases, 2 cases dropped out). In the western medication group, the donepezil hydrochloride tablets were administered orally, 2.5 mg to 5 mg each time, once daily; and adjusted to be 10 mg each time after 4 weeks of medication. Besides the therapy as the western medication group, in the acupuncture + medication group, acupuncture was supplemented at the acupoints for Yizhi Tiaoshen, i.e. Baihui (GV 20), Sishencong (EX-HN 1), and bilateral Shenmen (HT 7), Neiguan (PC 6), Zusanli (ST 36), Sanyinjiao (SP 6) and Xuanzhong (GB 39). The needles were retained for 30 min in one treatment, once daily; and 6 treatments were required weekly. The duration of treatment was 6 weeks in each group. The general cognitive function was assessed by the mini-mental state examination (MMSE) and Alzheimer's disease assessment scale-cognitive part (ADAS-Cog) before and after treatment in the two groups. Using the rs-fMRI, the changes in the functional connectivity (FC) of the left hippocampus and the whole brain before and after treatment were analyzed in the patients of the two groups (11 cases in the acupuncture + medication group and 12 cases in the western medication group). RESULTS: After treatment, compared with those before treatment, MMSE scores increased and ADAS-Cog scores decreased in the two groups (P<0.05); MMSE score was higher, while the ADAS-Cog score was lower in the acupuncture + medication group when compared with those in the western medication group (P≤0.05). After treatment, in the western medication group, FC of the left hippocampus was enhanced with the left fusiform gyrus, the inferior frontal gyrus of the left triangular region, the bilateral superior temporal gyrus and the right superior parietal gyrus (P<0.05), while FC was weakened with the left inferior temporal gyrus, the left middle frontal gyrus and the right dorsolateral superior frontal gyrus when compared with that before treatment (P<0.05). After treatment, in the acupuncture + medication group, FC of the left hippocampus was increased with the right gyrus rectus, the left inferior occipital gyrus, the right superior temporal gyrus and the left middle occipital gyrus (P<0.05), and it was declined with the left thalamus (P<0.05) when compared with those before treatment. After treatment, in the acupuncture + medication group, FC of the left hippocampus was strengthened with the bilateral inferior temporal gyrus, the bilateral middle temporal gyrus, the right gyrus rectus, the bilateral superior occipital gyrus, the left lenticular nucleus putamen, the left calcarine fissure and surrounding cortex, the inferior frontal gyrus of the left insulae operculum, the left medial superior frontal gyrus and the right posterior central gyrus (P<0.05) compared with that of the western medication group. CONCLUSIONS: Acupuncture at the acupoints for Yizhi Tiaoshen improves the cognitive function of AD patients, and its main brain functional mechanism is related to intensifying the functional connectivity of the left hippocampus with the default network (inferior temporal gyrus, middle temporal gyrus and superior frontal gyrus, gyrus rectus), as well as with the sensory (posterior central gyrus) and visual (calcarine fissure and surrounding cortex and superior occipital gyrus) brain regions.

The effects of laser acupuncture dosage at PC6 (Neiguan) on brain reactivity: a pilot resting-state fMRI study.

Previous studies indicated that laser acupuncture (LA) may effectively treat various medical conditions. However, brain responses associated with LA intervention have not been fully investigated. This study is focused on the effect of LA with different energy density (ED) in brain using resting-state functional magnetic resonance imaging (fMRI). We hypothesized that different ED would elicit various brain responses. We enrolled healthy adults participants and selected bilateral PC6 (Neiguan) as the intervention points. LA was applied, respectively, with ED of 0, 7.96, or 23.87 J/cm2. Two 500-s resting-state fMRI scans were acquired before and after intervention, respectively. The functional connectivity (FC) was calculated between autonomic nerve system-regulation associated brainstem structures and other brain regions. Compared to other dosages, the FC between rostral ventrolateral medulla and orbitofrontal cortex has more enhanced; the FC between caudal ventrolateral medulla, nucleus of the solitary tract/nucleus ambiguus, and dorsal motor nucleus of the vagus and somatosensory area has more weakened when ED was 23.87 J/cm2. Different dosages of LA have demonstrated varied regions of FC changes between regions of interest and other brain areas, which indicated that variations in EDs might influence the clinical efficacy and subsequent impacts through distinct neural pathways within the brain.

Scalp acupuncture regulates functional connectivity of cerebral hemispheres in patients with hemiplegia after stroke.

Background: Stroke is a common cause of acquired disability on a global scale. Patients with motor dysfunction after a stroke have a reduced quality of life and suffer from an economic burden. Scalp acupuncture has been proven to be an effective treatment for motor recovery after a stroke. However, the neural mechanism of scalp acupuncture for motor function recovery remains to be researched. This study aimed to investigate functional connectivity (FC) changes in region of interest (ROI) and other brain regions to interpret the neural mechanism of scalp acupuncture. Methods: Twenty-one patients were included and randomly divided into patient control (PCs) and scalp acupuncture (SAs) groups with left hemiplegia due to ischemic stroke, and we also selected 20 matched healthy controls (HCs). The PCs were treated with conventional Western medicine, while the SAs were treated with scalp acupuncture (acupuncture at the right anterior oblique line of vertex temporal). All subjects received whole-brain resting-state functional magnetic resonance imaging (rs-fMRI) scan before treatment, and the patients received a second scan after 14 days of treatment. We use the National Institutes of Health Stroke Scale (NIHSS) scores and the analyses of resting-state functional connectivity (RSFC) as the observational indicators. Results: The contralateral and ipsilateral cortex of hemiplegic patients with cerebral infarction were associated with an abnormal increase and decrease in basal internode function. An abnormal increase in functional connectivity mainly exists in the ipsilateral hemisphere between the cortex and basal ganglia and reduces the abnormal functional connectivity in the cortex and contralateral basal ganglia. Increased RSFC was observed in the bilateral BA6 area and bilateral basal ganglia and the connectivity between bilateral basal ganglia nuclei improved. However, the RSFC of the conventional treatment group only improved in the unilateral basal ganglia and contralateral BA6 area. The RSFC in the left middle frontal gyrus, superior temporal gyrus, precuneus, and other healthy brain regions were enhanced in SAs after treatment. Conclusion: The changes in functional connectivity between the cerebral cortex and basal ganglia in patients with cerebral infarction showed a weakening of the bilateral hemispheres and the enhancement of the connections between the hemispheres. Scalp acupuncture has the function of bidirectional regulation, which makes the unbalanced abnormal brain function state restore balance.

Electroacupuncture alleviates pain after total knee arthroplasty through regulating neuroplasticity: A resting-state functional magnetic resonance imaging study.

INTRODUCTION: We aimed to evaluate the efficacy of electroacupuncture in relieving acute pain after total knee arthroplasty (TKA) and related mechanism. METHODS: In this randomized, single-blind, and sham-acupuncture controlled study. Forty patients with postoperative acute pain were recruited and randomly divided electroacupuncture group (n = 20) and sham-acupuncture group (n = 20) from November 2020 to October 2021. All patients received electroacupuncture or sham-acupuncture for 5 days after TKA. Their brain regions were scanned with resting-state functional magnetic resonance imaging before and after intervention. Pain was scaled. Another 40 matched healthy controls underwent scanning once. The amplitude of low-frequency fluctuation (ALFF) values was compared. Pearson's correlation analysis was utilized to explore the correlation of ALFF with clinical variables in patients after intervention. RESULTS: Compared with the HCs, patients with acute pain following TKA had significantly decreased ALFF value in right middle frontal gyrus, right supplementary motor area, bilateral precuneus, right calcarine fissure and surrounding cortex, and left triangular part of inferior frontal gyrus (false discovery rate corrected p < .05). Patients had higher ALFF value in bilateral precuneus, right cuneus, right angular gyrus, bilateral middle occipital gyrus, and left middle temporal gyrus after electroacupuncture (AlphaSim corrected p < .01). Correlation analysis revealed that the change (postoperative day 7 to postoperative day 3) of ALFF in bilateral precuneus were negatively correlated with the change of NRS scores (r = -0.706; p = .002; 95% CI = -0.890 to -0.323) in EA group. CONCLUSIONS: The functional activities of related brain regions decreased in patients with acute pain after TKA. The enhancement of the functional activity of precuneus may be the neurobiological mechanism of electroacupuncture in treating pain following TKA.

Medio-dorsal thalamic dysconnectivity in chronic knee pain: A possible mechanism for negative affect and pain comorbidity.

The reciprocal interaction between pain and negative affect is acknowledged but pain-related alterations in brain circuits involved in this interaction, such as the mediodorsal thalamus (MDThal), still require a better understanding. We sought to investigate the relationship between MDThal circuitry, negative affect and pain severity in chronic musculoskeletal pain. For these analyses, participants with chronic knee pain (CKP, n = 74) and without (n = 36) completed magnetic resonance imaging scans and questionnaires. Seed-based MDThal functional connectivity (FC) was compared between groups. Within CKP group, we assessed the interdependence of MDThal FC with negative affect. Finally, post hoc moderation analysis explored whether burden of pain influences affect-related MDThal FC. The CKP group showed altered MDThal FC to hippocampus, ventromedial prefrontal cortex and subgenual anterior cingulate. Furthermore, in CKP group, MDThal connectivity correlated significantly with negative affect in several brain regions, most notably the medial prefrontal cortex, and this association was stronger with increasing pain burden and absent in pain-free controls. In conclusion, we demonstrate mediodorsal thalamo-cortical dysconnectivity in chronic pain with areas linked to mood disorders and associations of MDThal FC with negative affect. Moreover, burden of pain seems to enhance affect sensitivity of MDThal FC. These findings suggest mediodorsal thalamic network changes as possible drivers of the detrimental interplay between chronic pain and negative affect.

[Effect of acupuncture on hypothalamic functional connectivity in patients with premature ova-rian insufficiency based on resting-state functional magnetic resonance imaging].

OBJECTIVE: To compare the differences in functional connectivity(FC) between the hypothalamus and whole brain regions in patients with premature ovarian insufficiency (POI) and healthy volunteers based on resting-state functional magnetic resonance imaging (rs-fMRI) and investigate the mechanism of acupuncture on treatment of POI. METHODS: Twelve POI patients were recruited to the acupuncture group and 12 healthy volunteers to the control group. Patients in the acupuncture group received acupuncture at two groups of acupoints alternatively, including Baihui (GV20), Zhongwan (CV12), Shenting (GV24), Shenshu (BL23), Ciliao（BL32） and so on, 30 min once time, 3 times per week for 12 weeks. The state of patients was evaluated by modified Kupperman Index (KI) and self-rating anxiety scale (SAS). Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-mullerian hormone (AMH) were tested by microparticle-based chemiluminescence. B ultrasonography was used to detect the antral follicle count (AFC). Meanwhile, POI patients and healthy volunteers underwent the rs-fMRI examination before and after acupuncture treatment and after enrollment, respectively. With hypothalamus as the region of interest, the differences in FC between the hypothalamus and other brain regions in POI patients and healthy volunteers and the changes of FC between the hypothalamus and whole brain regions in POI patients before and after acupuncture were observed. RESULTS: The SAS and KI scores of pre-treatment POI patients were higher than those in the control group （P<0.01）.In compa-rison with those pre-treatment, FSH, LH, and SAS and KI scores of POI patients decreased after treatment, while AFC increased (P<0.05). Compared with the control group, the FC of the left hypothalamus with left central sulcus, right middle occipital gyrus, and left paracentral lobule increased, but decreased with left globus pallidus of the lenticular nucleus in POI patients. Furthermore, the FC of the right hypothalamus with the left hippocampus, the left para-central lobule, and the right central sulcus increased, while the FC between the right hypothalamus and the right superior frontal gyrus decreased (P<0.05). For the acupuncture group, compared with the conditions before treatment, the FC of the right hypothalamus with the left inferior frontal gyrus, the left insula, and right inferior frontal gyrus was strengthened, but weakened with the left gyrus rectus (P<0.05). CONCLUSION: The abnormal FC between the hypothalamus and whole brain regions may be one of the central pathological factors of POI. Acupuncture can improve the ovarian function and clinical symptoms of patients with POI, which may be related to its effect in regulating the FC between the hypothalamus and multiple brain regions.

Altered effective connectivity of thalamus with vigilance impairments after sleep deprivation.

The thalamus is an essential gating hub to relay brainstem ascending arousal signals to attention-related networks, including the frontal-parietal attention network and default mode network, which plays an important role in attentional maintenance. Research has proved that sleep loss leads to impairment of attentional performance by affecting neural connectivity between thalamic and attention-related cortical regions. However, the effective connectivity between thalamic and cortical areas in the resting state remains unclear after sleep deprivation. The present study aimed to investigate the effect of sleep deprivation on the effective connectivity between thalamic and cortical areas, and explored whether the alteration of the effective connectivity can predict vigilance impairment after sleep deprivation. We implemented resting-state functional magnetic resonance imaging with 31 participants under both normally-rested and sleep-deprivation conditions. The Granger causality analysis was used to investigate the alteration of effective connectivity between thalamic and cortical areas, and the psychomotor vigilance task was used to measure vigilance. Correlation analysis investigated the relationship between the alteration in effective connectivity and vigilance performance. Sleep deprivation significantly decreased the effective connectivity from the thalamus to the nodes in the default mode network, and significantly increased in the effective connectivity from the thalamus to the nodes in the frontal-parietal attention network. Critically, increased thalamus-parietal effective connectivity was correlated with decreased lapses. The findings indicated sleep deprivation induced a robust alteration of the communication from the sub-cortical to cortical regions. The alteration of thalamus-parietal effective connectivity was anti-correlated with sustained attentional impairment after sleep deprivation.

Disrupted dynamic pattern of regional neural activity in early-stage cognitively normal Parkinson's disease.

BACKGROUND: Neuroimaging studies on Parkinson's disease (PD) mainly focus on static neural activity. However, the dynamic pattern of regional brain activity in early-stage cognitively normal PD has rarely been elucidated. PURPOSE: To identify altered dynamic amplitude of low-frequency fluctuation (dALFF) in PD before the onset of cognitive impairment and verify its differentiating ability between patients with PD and healthy controls (HC). MATERIAL AND METHODS: dALFF and static ALFF (sALFF) derived from functional magnetic resonance imaging data of 51 patients with PD and 50 matched HCs were analyzed. The correlations between aberrant regions and clinical performance were investigated using Spearman correlation analysis. Multivariate pattern analysis was conducted to detect the differentiating ability of both ALFF features. RESULTS: Compared with HCs, patients with PD demonstrated reduced dALFF variance in bilateral lingual gyrus, left middle occipital gyrus, left postcentral gyrus (PcG), and right supplementary motor area (SMA); and increased dALFF variability in bilateral parahippocampal gyrus. Besides overlapping with these distributions of altered dALFF, the aberrant regions of sALFF were more extensive with decreased sALFF in the right middle temporal gyrus and right PcG, and increased sALFF in the left inferior temporal gyrus and left thalamus were observed in patients with PD. dALFF values in right SMA and left PcG were correlated with UPDRS-III scores (ρ = -0.29, P = 0.041; ρ = -0.33, P = 0.018, respectively). CONCLUSION: This study provides novel insights into the neural basis underlying PD as well as the potential role of dynamic neural activity in the diagnosis and prediction of the disease.

[Effect of acupuncture on migraine without aura: a resting-state functional magnetic resonance study].

OBJECTIVE: To observe therapeutic effect of acupuncture on migraine without aura and the changes of brain functional connectivity (FC) using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Thirty-four patients with migraine without aura were included into an observation group and treated with acupuncture at Baihui (GV 20), Xuanlu (GB 5), Shuaigu (GB 8), Taiyang (EX-HN 5), etc. Using G6805-Ⅱ electric acupuncture apparatus, the ipsilateral Fengchi (GB 20) and Shuaigu (GB 8) were connected and stimulated with continuous wave, 2 Hz in frequency and 0.1 mA to 1.0 mA in current intensity, depending on patient's tolerance. Acupuncture stimulation lasted 20 min each time, twice weekly (at the interval>2 days). A total of 6 weeks of treatment (12 times) was required. Matching the gender and age as those of the observation group, 16 healthy subjects were recruited into a control group and no any intervention was provided. The headache days, the score of visual analogue scale (VAS) for headache severity, the total score of headache symptoms, the score of migraine-specific quality of life questionnaire (MSQ), the score of self-rating anxiety scale (SAS), and the score of self-rating depression scale (SDS) were compared before and after acupuncture, and the clinical efficacy was assessed in the observation group. The data of the resting-state functional magnetic resonance were collected in the observation group before and after treatment as well as the control group at baseline. The periaqueductal gray (PAG) was taken as the seed to analyze the effect of acupuncture on the brain FC and the correlation between FC and VAS scores, headache days in the patients of migraine without aura. RESULTS: After treatment, the headache days, VAS score, the total score of headache symptoms, SAS score and SDS score were all reduced (P<0.01); and the scores of the restrictive, preventive, and emotional functional domains of the MSQ were increased (P<0.01) in the observation group compared with those before treatment. The total effective rate was 94.1% (32/34). Compared with the control group, FC between PAG and the right cerebellum Ⅷ was decreased in the observation group before treatment (P<0.05). FC of PAG with the bilateral cerebellum Ⅷ and the left precuneus was increased in the observation group after treatment compared with those before treatment (P<0.05). In the observation group, the FC intensity of PAG and the right cerebellum Ⅷ was negatively correlated with VAS score (r =-0.41, P<0.05) before treatment, while the FC intensity of PAG and the left precuneus was positively correlated with the improvement in headache days (r =0.40, P<0.05) after treatment. CONCLUSION: Acupuncture is effective on migraine without aura. The brain functional connectivity is abnormal in the patients. The effect onset of acupuncture is obtained probably by regulating the abnormal brain regions and activating brain regions relevant with pain and emotions.

[Correlations between resting-state brain functional characteristics and TCM syndrome in premature ejaculation patients with heart-kidney disharmony].

OBJECTIVE: To investigate the correlation between the characteristics of resting-state brain function and the types of traditional Chinese medicine (TCM) syndrome in premature ejaculation (PE) patients with heart-kidney disharmony, and the pathogenesis of abnormal ejaculation of the patients. METHODS: We enrolled 33 PE patients with heart-kidney disharmony and 32 healthy controls matched in general demographic data, evaluated the severity of the main and concurrent symptoms of PE using the PE Diagnostic Tool (PEDT) and TCM Syndrome Scale (TCMSS), and obtained the brain structural and functional MRI data. We processed the collected data and calculated the amplitude of low-frequency fluctuations (ALFF), fractional ALFF (fALFF) and regional homogeneity (Reho) of the brain with the DPABI software. Using the REST software package, we compared the significantly different brain areas between the PE and control groups by two-sample t-test and corrected the results for multiple comparisons by AlphaSim, followed by Pearson correlation analysis of ALFF, fALFF and Reho in abnormal brain areas and the PEDT and CMSS scores of the patients. RESULTS: The PE patients showed decreased ALFF values in the bilateral inferior temporal gyrus, left middle frontal gyrus and left orbital part of the inferior frontal gyrus, and increased ALFF values in the bilateral hippocampus, thalamus and precuneus, right inferior occipital gyrus, right calcarine and left inferior parietal, with positive correlations of the ALFF values of the left thalamus with the scores on PEDT (r = 0.35, P < 0.05) and TCMSS (r = 0.44, P < 0.05). The fALFF values of the patients were also decreased in the left temporal pole of the middle temporal gyrus and left anterior cingulate gyrus, but increased in the left inferior temporal gyrus. The Reho values of the patients were decreased as well in the right inferior temporal gyrus, left middle frontal gyrus, right dorsolateral superior frontal gyrus, right middle occipital gyrus, right middle occipital gyrus and right precuneus, but increased in the left temporal pole of the middle temporal gyrus, left middle frontal gyrus and left superior frontal gyrus, with negative correlations between the Reho value of the right superior parietal gyrus and TCMSS scores (r = －0.35, P < 0.05). CONCLUSION: Abnormal brain regions were found in PE patients with heart-kidney disharmony, with might be the pathologically associated with PE symptoms and heart-kidney disharmony of the patients.

[Effect of acupuncture on default mode network in patients with migraine based on functional Magnetic Resonance Imaging: a preliminary study].

OBJECTIVE: To investigate the effect of acupuncture on default mode network (DMN) in migraine patients without aura based on functional Magnetic Resonance Imaging (fMRI). METHODS: Fifteen patients with migraine were included and treated with acupuncture based on "root-knot" theory (Zuqiaoyin [GB 44] for shaoyang headache, Lidui [ST 45] for yangming headache, Zhiyin [BL 67] for taiyang headache, and ashi point), once every other day, three times a week for 4 weeks. The patients received fMRI scanning before and after acupuncture treatment, the effect of acupuncture on DMN in patients with migraine was observed; the frequency of migraine attack, visual analogue scale (VAS) score and the using of analgesic medication before and after treatment were recorded to evaluate the curative effect of acupuncture; the migraine-specific quality of life questionnaire (MSQ), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were used to evaluate the improvements of quality of life and emotional state. RESULTS: Compared before acupuncture, the functional connections of left parahippocampal cortex (PHC) and anterior medial prefrontal cortex (aMPFC), dorsal medial prefrontal cortex (dMPFC) and lateral temporal cortex (LTC) in DMN after acupuncture were weakened (P<0.05), and the functional connections of bilateral posterior cingulate cortex (PCC) and dMPFC were weakened (P<0.05). Compared before treatment, the frequency of migraine attack, VAS, SAS and SDS scores after treatment were decreased (P<0.05), and MSQ score was increased (P<0.05). CONCLUSION: Acupuncture shows good clinical efficacy for migraine without aura, and could adjust the functional connection of DMN.

Acupuncture Treatment Associated with Functional Connectivity Changes in Primary Dysmenorrhea: A Resting State fMRI Study.

Primary dysmenorrhea (PDM) is the most commonly encountered gynecological problem in reproductive-age women. Acupuncture has been suggested as an effective treatment of PDM that may modulate descending pain modulation systems. In the present study, we used resting-state functional magnetic resonance imaging to investigate possible changes in descending pain modulation systems after acupuncture treatment in women with PDM. Thirty-four right-handed adult women with PDM participated in this randomized, single-blinded, sham-controlled study. Each patient was randomly allocated to an 8-week verum or sham acupuncture intervention on the bilateral Sanyinjiao (SP6). Resting-state functional magnetic resonance imaging was conducted before, during, and after the intervention to measure the spontaneous activity in brain. After the 8-week intervention, both verum and sham groups reported decreased menstrual pain. However, the cessation of decreased functional connectivity (FC) between periaqueductal gray matter and the regions associated with affective pain modulation and attention-related pain modulation were found in the verum but not in the sham group after the 8-week intervention. More decreased FC has been found in the region associated with non-specific effects of acupuncture intervention after the early stage of acupuncture intervention. These results indicated that verum acupuncture may intercept the altered FC in descending pain modulation systems in PDM.

A Treatment-Response Comparison Study of Resting-State Functional Magnetic Resonance Imaging Between Standard Treatment of SSRI and Standard Treatment of SSRI Plus Non-dominant Hand-Writing Task in Patients With Major Depressive Disorder.

Background: Researches have recently shifted from functional/structural imaging studies to functional connectivity (FC) studies in major depressive disorder (MDD). We aimed to compare treatment response of two treatment groups before and after treatment, in terms of both with psychiatric evaluation scales and resting-state functional connectivity (RSFC) changes in order to objectively demonstrate the possible contribution of the non-dominant hand-writing exercise (NHE) effect on depression treatment. Methods: A total of 26 patients who were right-handed women with similar sociodemographic characteristics were enrolled. Their pre-treatment resting-state functional magnetic resonance imaging (rs-fMRI) and neuropsychiatric tests were recorded, and then, patients were divided into two groups randomly. A standard treatment (ST) (fix sertraline 50 mg/day) was given to both groups. One randomly selected group was given the NHE in addition to the ST. After 8 weeks of treatment, all patients were reevaluated with rs-fMRI and neuropsychiatric tests. Pre- and post-treatment FC changes within the groups and post-treatment connectivity changes between groups were evaluated. Results: Post-treatment neuropsychiatric tests were significantly different in both groups. Post-treatment, two brain regions' connectivity changed in the ST group, whereas 10 brain regions' connectivity changed significantly in the ST + NHE group. When treatment groups were compared with each other after the treatment, the FC of 13 regions changed in the ST + NHE group compared to the ST group (p-unc/p-PFD <0.05). The density of connectivity changes in the frontal and limbic regions, especially connectivities shown to change in depression treatment, in the ST + NHE group indicates a positive contribution to depression treatment, which is also supported by neuropsychiatric scale changes. Conclusion: NHE, which we developed with inspiration from the Eye Movement Desensitization and Reprocessing (EMDR) method, showed significantly more connecitivity changes related with MDD treatment. Beyond offering a new additional treatment method, our study will also contribute to the current literature with our efforts to evaluate all brain regions and networks that may be related to MDD and its treatment together, without being limited to a few regions. Trial Registration: The rs-fMRI and treatment registers were recorded in the BizMed system, which is the patient registration system of Bezmialem Vakif University Medicine Faculty, under the BAP support project approval code and the registration number 3.2018/8.

Scalp acupuncture enhances local brain regions functional activities and functional connections between cerebral hemispheres in acute ischemic stroke patients.

This study aimed to explore the changes in functional connections between cerebral hemispheres and local brain regions functional activities in patients with acute ischemic stroke (AIS) treated with International Standard Scalp Acupuncture (ISSA). Thirty patients with middle cerebral artery AIS in the dominant hemisphere were selected and randomly divided into two groups such as the control group and the scalp acupuncture group, with 15 patients in each group. Patients in the control group were treated with conventional Western medicine, while patients in the scalp acupuncture group received ISSA (acupuncture at the parietal midline [MS5], acupuncture at the left anterior parietotemporal oblique line [MS6] and acupuncture at the left posterior parietotemporal oblique line [MS7]) for one course of treatment. All patients were evaluated for treatment efficacy and received whole brain resting state functional magnetic resonance imaging (Rs-fMRI) scan before and after treatment. The observational indicators included: (a) the National Institutes of Health Stroke Scale (NIHSS) scores and the simplified Fugl-Meyer Assessment (SFMA) scores; (b) analyses of the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and voxel-mirrored homotopic connectivity (VMHC). The results showed a significant difference in the NIHSS scores before and after treatment in the scalp acupuncture group compared with the control group (p < .05), indicating that patients improved better after scalp acupuncture treatment. Compared with the control group, the VMHC, ALFF and ReHo values in the scalp acupuncture group increased after treatment. The VMHC values increased in the brain regions dominated by bilateral BA6 and BA8; the ALFF values increased in the left BA39 and the adjacent superior temporal gyrus and middle temporal gyrus; and the ReHo values increased in the brain regions extending from left middle temporal gyrus (including BA21) to BA37, and the brain regions extending from the left BA40 and angular gyrus to BA7. The present study indicated that scalp acupuncture can specifically strengthen the functional activities of the brain regions related to sensory integration, language processing and motor coordination in the middle aged and elderly patients with AIS of the dominant cerebral hemisphere, and can strengthen bilateral frontal lobe motor control. This study may provide a scientific basis for the clinical application of ISSA treatment in patients with AIS, and may also provide a preliminary research basis for further animal experiments.

Differential Modulating Effect of Acupuncture in Patients With Migraine Without Aura: A Resting Functional Magnetic Resonance Study.

Introduction: Migraine is a recurrent neurological disorder, the symptoms of which can be significantly relieved by acupuncture. However, the central mechanism via which acupuncture exerts its therapeutic effect in migraine is unclear. The aim of this study was to compare the differences in regional homogeneity (ReHo) between patients with migraine without aura (MwoA) and healthy controls (HCs) and to explore the immediate and cumulative therapeutic effect of acupuncture in patients with MwoA using resting-state functional magnetic resonance imaging (fMRI). Methods: The study subjects were 40 patients with MwoA and 16 matched HCs. The patients with MwoA received acupuncture on 2 days per week for 6 weeks for a total of 12 sessions followed by 24 weeks of follow-up. The primary clinical efficacy outcomes were the number of days with migraine and the average severity of headache. Secondary outcomes were the Migraine-Specific Quality of Life Questionnaire, Self-Rating Anxiety Scale, and Self-Rating Depression Scale scores. In the migraine group, resting-state blood-oxygen-level-dependent fMRI scans were obtained at baseline and after the first and 12th acupuncture sessions to measure the ReHo value. In the HCs, only a baseline resting-state blood-oxygen-level-dependent fMRI scan was obtained. Results: Compared with the control group, the migraine group had a significantly lower ReHo value in the cerebellum, which increased after the first acupuncture session. Long-term acupuncture significantly improved migraine symptoms and mood with a therapeutic effect that lasted for at least 6 months. After 12 acupuncture sessions, there were significant increase of cerebellum and angular gyrus in the migraine group. Conclusion: These findings suggest that migraine is related to cerebellar dysfunction. Acupuncture can relieve the symptoms of migraine, improve dysfunction of cerebellum, and activate brain regions involved in modulation of pain and emotion The cumulative therapeutic effect of acupuncture is more extensive and significant than its immediate effect.

[Mind-regulating and spleen-strengthening needling technique improves abdominal hypersensitivity and emotion by enhancing functional connectivity between hippocampus and brain regions in diarrhea-predominant irritable bowel syndrome patients].

OBJECTIVE: To compare the difference of brain functional connectivity between diarrhea-predominant irritable bowel syndrome (IBS-D) patients and healthy volunteers and changes after acupuncture intervention, so as to investigate the underlying mechanism of acupuncture in regulating functional activities of IBS-D patients by using seed point correlation analysis. METHODS: A total of 25 IBS-D patients and 25 healthy volunteers were recruited in the present study and respectively attributed to acupuncture group and control group. The IBS-D patients received manual acupuncture stimulation of Baihui (GV20), Yintang (EX-HN3), and bilateral Tianshu (ST25), Zusanli (ST36), Shangjuxu (ST37), Sanyinjiao (SP6) and Taichong (LR3) with mind-regulating and spleen-strengthening technique for 30 min, once a day, 3 days a week for 6 weeks. Before and after the intervention, the IBS symptom severity scale (IBS-SSS) was used to assess the patients' state of abdominal pain, distention and defecation, and Hamilton Anxiety Rating Scale (HAMA) employed to evaluate the patients' anxiety severity. The resting state functional magnetic resonance imaging (rs-fMRI) data were acquired and preprocessed by using SPM8 and DPARSE soft-wares. Seeds (bilate-ral hippocampus regions) to whole-brain analysis was performed to obtain the mean time series of the left and right seed regions, followed by making Pearson correlation analysis to obtain the correlation coefficient (time series from each seed region with the rest of the voxels in the brain), and making a multivariate comparative correction to get data of functional connectivity (FC) of bilateral hippocampus regions and to find the related difference in the brain regions. Then, the differences of the FC of brain regions between IBS-D patients and healthy volunteers were compared. RESULTS: Following acupuncture treatment, both the HAMA and IBS-SSS scores were significantly reduced in the acupuncture group compared with its pre-treatment (P<0.01). Compared with the healthy volunteers, there were a reduction in the functional connectivity between the left hippocampus seed region and the right inferior temporal gyrus, left fusiform gyrus and left superior gyrus, and between the right hippocampus region and the right fusiform gyrus, left inferior temporal gyrus, left inferior occipital gyrus, left rectus gyrus, left insula, left precuneus, right angular gyrus, left middle occipital gyrus, right precuneus, and the left superior temporal gyrus, and an increase in the FC between the left hippocampus and left superior temporal gyrus was increased in ISB-D patients. Self-comparison showed that after the treatment, the FC was increased between the left hippocampus seed region and the right inferior temporal gyrus, left fusiform gyrus, bilateral lingual gyrus, left amygdala, right inferior occipital gyrus, right insula, right middle frontal gyrus, left middle frontal gyrus and the left middle occipital gyrus; and between the right hippocampus seed region and the posterior inferior cerebellar lobe, left inferior temporal gyrus, left suboccipital gyrus, right fusiform gyrus, left insula, right inferior frontal gyrus, left superior temporal gyrus, left middle occipital gyrus, right middle frontal gyrus, left supplementary motor area and right supplementary motor area, and decreased between the left hippocampus region and the left anterior cingulate, paracingulate gyrus and the right posterior central gyrus in IBS-D patients. CONCLUSION: Mind-regulating and spleen-strengthening acupuncture intervention may improve the abdominal pain and distension and emotional state in IBS-D patients, which is possibly associated with its effect in enhancing FC between the hippocampus and brain regions.

Network-level functional topological changes after mindfulness-based cognitive therapy in mood dysregulated adolescents at familial risk for bipolar disorder: a pilot study.

BACKGROUND: Given that psychopharmacological approaches routinely used to treat mood-related problems may result in adverse outcomes in mood dysregulated adolescents at familial risk for bipolar disorder (BD), Mindfulness-Based Cognitive Therapy for Children (MBCT-C) provides an alternative effective and safe option. However, little is known about the brain mechanisms of beneficial outcomes from this intervention. Herein, we aimed to investigate the network-level neurofunctional effects of MBCT-C in mood dysregulated adolescents. METHODS: Ten mood dysregulated adolescents at familial risk for BD underwent a 12-week MBCT-C intervention. Resting-state functional magnetic resonance imaging (fMRI) was performed prior to and following MBCT-C. Topological metrics of three intrinsic functional networks (default mode network (DMN), fronto-parietal network (FPN) and cingulo-opercular network (CON)) were investigated respectively using graph theory analysis. RESULTS: Following MBCT-C, mood dysregulated adolescents showed increased global efficiency and decreased characteristic path length within both CON and FPN. Enhanced functional connectivity strength of frontal and limbic areas were identified within the DMN and CON. Moreover, change in characteristic path length within the CON was suggested to be significantly related to change in the Emotion Regulation Checklist score. CONCLUSIONS: 12-week MBCT-C treatment in mood dysregulated adolescents at familial risk for BD yield network-level neurofunctional effects within the FPN and CON, suggesting enhanced functional integration of the dual-network. Decreased characteristic path length of the CON may be associated with the improvement of emotion regulation following mindfulness training. However, current findings derived from small sample size should be interpreted with caution. Future randomized controlled trials including larger samples are critical to validate our findings.

The acts of opening and closing the eyes are of importance for congenital blindness: Evidence from resting-state fMRI.

Volitional eye closure is observed only in conscious and awake humans, and is rare in animals. It is believed that eye closure can focus one's attention inward and facilitate activities such as meditation and mental imagery. Congenital blind individuals are also required to close their eyes for these activities. Resting-state functional magnetic resonance imaging (RS-fMRI) studies have found robust differences between the eyes-closed (EC) and eyes-open (EO) conditions in some brain regions in the sighted. This study analyzed data from 21 congenital blind individuals and 21 sighted controls by using amplitude of low-frequency fluctuation (ALFF) of RS-fMRI. The blind group and the sighted group shared similar pattern of differences between the EC and EO condition: ALFF was higher in the EC condition than the EO condition in the bilateral primary sensorimotor cortex, bilateral supplementary motor area, and inferior occipital cortex, while ALFF was lower in the EC condition than the EO condition in the medial prefrontal cortex, highlighting the "nature" effect on the difference between the EC and EO conditions. The results of other matrices such as fractional ALFF (fALFF) and regional homogeneity (ReHo) showed similar patterns to that of ALFF. Moreover, no significant difference was observed between the EC-EO pattern of the two subgroups of congenital blind (i.e., with and without light perception), suggesting that the EC-EO difference is irrespective of residual light perception which reinforced the "nature" effect. We also found between-group differences, i.e., more probably "nurture effect", in the posterior insula and fusiform. Our results suggest that the acts of closing and opening the eyes are of importance for the congenital blind, and that these actions and their differences might be inherent in the nature of humans.

Cerebral areas affected by unilateral acupuncture on SP3 in healthy volunteers: An explorative resting-state fMRI study.

OBJECTIVE: The study aimed to explore the cerebral areas with changes in regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) values induced by effective acupuncture on the Taibai (SP3) point. METHODS: In the study, 15 healthy right-handed volunteers (seven males and eight females, 20-35 years old) were enrolled. The average ages of the subjects were 28.0 ± 4.24 years for males and 27.4 ± 3.65 years for females. A 3.0T magnetic resonance imaging (MRI) system was used to perform resting-state functional MRI scan after sham and effective acupuncture on the SP3 point. The differences in cerebral ReHo and ALFF values between posteffective acupuncture and postsham acupuncture were compared using the SPM 12 software. RESULTS: ReHo values of bilateral BA18, cuneus, and BA17, along with BA41, BA22, postcentral gyrus, and BA7 on the right side, were decreased by effective SP3 acupuncture. The ALFF values of bilateral BA 30 and left parahippocampal area were increased, whereas the values of bilateral BA18, BA19, cuneus, posterior cingulate gyrus, and BA7, along with the right superior occipital lobule, postcentral gyrus, and left precuneus, were decreased. CONCLUSIONS: The most dominant cerebral areas affected by SP3 acupuncture were bilateral visual-related cortices (lingual gyrus, cuneus, and calcarine), along with the unilateral postcentral gyrus and superior parietal lobule. These findings may be potential explanations for the available clinical reports concerning the efficacy of SP3 acupuncture. Further clinical and experimental studies on SP3 acupuncture are required.