Top-down and bottom-up alterations of connectivity patterns of the suprachiasmatic nucleus in chronic insomnia disorder.

The importance of the suprachiasmatic nucleus (SCN, also called the master circadian clock) in regulating sleep and wakefulness has been confirmed by multiple animal research. However, human studies of SCN in vivo are still nascent. Recently, the development of resting-state functional magnetic resonance imaging (fMRI) has made it possible to study SCN-related connectivity changes in patients with chronic insomnia disorder (CID). Hence, this study aimed to explore whether sleep-wake circuitry (i.e., communication between the SCN and other brain regions) is disrupted in human insomnia. Forty-two patients with CID and 37 healthy controls (HCs) underwent fMRI scanning. Resting-state functional connectivity (rsFC) and Granger causality analysis (GCA) were performed to find abnormal functional and causal connectivity of the SCN in CID patients. In addition, correlation analyses were conducted to detect associations between features of disrupted connectivity and clinical symptoms. Compared to HCs, CID patients showed enhanced rsFC of the SCN-left dorsolateral prefrontal cortex (DLPFC), as well as reduced rsFC of the SCN-bilateral medial prefrontal cortex (MPFC); these altered cortical regions belong to the "top-down" circuit. Moreover, CID patients exhibited disrupted functional and causal connectivity between the SCN and the locus coeruleus (LC) and the raphe nucleus (RN); these altered subcortical regions constitute the "bottom-up" pathway. Importantly, the decreased causal connectivity from the LC-to-SCN was associated with the duration of disease in CID patients. These findings suggest that the disruption of the SCN-centered "top-down" cognitive process and "bottom-up" wake-promoting pathway may be intimately tied to the neuropathology of CID.

Inhibitory Deficits of Insomnia Disorder: A Meta-Analysis on Event Related Potentials in Auditory Oddball Task.

BACKGROUND: Despite numerous studies on auditory event-related potentials (ERPs) in insomnia disorder (ID), the results are inconsistent across different ERP components (e.g. N1, P2, P3, and N350), types of auditory stimuli (e.g. standard and deviant), and stages of sleep (e.g. wakefulness, NREM sleep, and REM sleep). In light of this variability, we conducted a systematic meta-analysis of previous auditory ERP studies in ID to provide a quantitative review of the existing literature. METHODS: Relevant literatures were searched on the Embase, PubMed/MEDLINE, PsycINFO and Cochrane Library. A total of 12 studies comprising 497 participants were finally included in this meta-analysis. The study protocol was registered with PROSPERO under the registration number CRD42022308348. RESULTS: We found that patients with ID have significantly decreased N1 (Hedges' g = 0.34, 95%CI [0.04, 0.65]) and P3 (Hedges'g = -1.21, 95%CI [-2.37, -0.06]) amplitudes during wakefulness. In addition, decreases in P2 (Hedges'g = -0.57, 95%CI [-0.96, -0.17]) amplitude during wakefulness and N350 (Hedges' g = 0.73, 95%CI [0.36, 1.09]) amplitude during NREM. CONCLUSIONS: This meta-analysis represents the first systematic investigation of ERP features across different stages of sleep in individuals with ID. Our results suggest that in patients with insomnia, the absence or deficiency of arousal inhibition during the nighttime sleep initiation or maintenance process may interfere with the normal process of sleep.

Frequency-Specific Alterations in Brain Function in Patients with Primary Dysmenorrhea.

OBJECTIVE: Recent neuroimaging studies have found that brain function is abnormal in primary dysmenorrhea (PDM). The present study aimed to explore frequency-specific brain alterations and their occurrence in the PDM. METHODS: Forty-seven patients with PDM and 36 matched healthy controls were enrolled in the study and underwent resting-state functional magnetic resonance imaging. The alterations in brain function in patients with PDM were assessed with different frequency filter bands (Slow5, Slow4, Slow3, and full low frequency) and a functional connectivity density (FCD) approach. The clinical significance of the altered FCD was then explored. Additionally, mediation analysis was used to detect the altered FCD-mediated clinical relationships in PDM. RESULTS: Frequency-specific FCD alterations have been observed in patients with PDM, especially in the central executive, default mode, and sensorimotor networks and in the hippocampus. The altered full low-frequency FCD in the hippocampus was associated with the duration of disease and pain severity scores. The altered Slow5 FCD in the second somatosensory area (S2) was associated with the severity of pain in PDM. Furthermore, the FCD in S2 mediated the duration associated with pain symptoms in PDM. CONCLUSION: The present study identified frequency-specific FCD alterations in PDM and suggested that the S2 area is a potential treatment target for PDM.

Impaired mesocorticolimbic connectivity underlies increased pain sensitivity in chronic low back pain.

Chronic low back pain (cLBP) is a prevalent disorder. A growing body of evidence linking the pathology of the reward network to chronic pain suggests that pain sensitization may contribute to cLBP chronification via disruptions of mesocortical and mesolimbic circuits in the reward system. Resting-state (RS) functional magnetic resonance imaging (fMRI) data was acquired from 90 patients with cLBP and 74 matched pain-free controls (HCs) at baseline and after a manipulation for back pain intensification. The ventral tegmental area (VTA) was chosen as a seed region to perform RS functional connectivity (FC) analysis. Baseline rsFC of both the mesocortical (between the VTA and bilateral rostral anterior cingulate cortex (rACC)/and medial prefrontal cortex (mPFC)) and mesolimbic (between the VTA and bilateral hippocampus/parahippocampus) pathways was reduced in patients with cLBP (vs. HCs). In addition, patients exhibiting higher back pain intensity (compared to the relatively lower back pain intensity condition) also showed increases in both mesocortical and mesolimbic connectivity, implicating these pathways in pain downregulation in cLBP. Mediation analysis further isolated the mesolimbic (VTA-hippocampus/parahippocampus) dysconnectivity as a neural mechanism mediating the association between mechanical pain sensitivity (indexed by P40 pressure) and cLBP severity. In sum, the current study demonstrates deficient mesocorticolimbic connectivity in cLBP, with mesolimbic dysconnectivity potentially mediating the contribution of pain sensitization to pain chronification. These reward network dysfunctions and purportedly, dopaminergic dysregulations, may help us to identify key brain targets of neuromodulation in the treatment of cLBP.

The effects of active acupuncture and placebo acupuncture on insomnia patients: a randomized controlled trial.

The purpose of this study was to observe and compare the clinical efficacy of active acupuncture and placebo acupuncture in the treatment of insomnia and mood disorders. 96 patients with insomnia in Chengdu were randomly divided into two groups (1:1). The active acupuncture group (AA group n = 48) received the tube of Park sham device with deep needle insertion. The placebo acupuncture group (PA group n = 48) received the tube of Park sham device with a retractable needle shaft and a blunt tip. The same acupuncture points and treatment cycles were used in both groups. The overall score for the Pittsburgh Sleep Quality Index (PSQI) is the primary outcome. Secondary outcomes recorded sleep rate, self-reported depression scale (SDS), self-assessment anxiety scale (SAS), the 'six component' scores of PSQI, and 'Deqi' scale scores. Eventually, 90 patients completed the study. After 2 weeks of treatment, the total score of PSQI in the AA group was 4.6 ± 2.4 and in the PA group was 12.9 ± 1.8 (ES = 3.91, p < .1). The SAS, SDS score in the AA group were 39.9 ± 5.6/39.9 ± 5.9 and in the PA group were 59.7 ± 6.1/61.2 ± 4.4 (ES = 3.38/4.9, p < .1). The sleep rate were 93.8% and 25.0% (p < .1). During the 1 month follow-up period, the PSQI total score in the AA group (5.2 ± 1.9) was superior to the PA group (13.1 ± 1.8) (ES = 4.27, p < .1). The SAS, SDS score in the AA group were 40.4 ± 5.1/42.7 ± 6.6 and in the PA group were 63.7 ± 6.6/63.5 ± 4.8 (ES = 3.95/3.60, p < .1). Throughout the study period, the 'six component' scores of PSQI in the AA group was superior to the PA group (each p < .1). Except for tingling and cooling, other acupuncture sensations were significant differences (each p < .1). Compared to the placebo acupuncture, active acupuncture can significantly improve insomnia, and clinical efficacy is maintained for at least 6 weeks.

Moderate alteration to gut microbiota brought by colorectal adenoma resection.

BACKGROUND AND AIM: Microbial dysbiosis is involved in the development of colorectal cancer and its most common precancerous lesion, colorectal adenoma. Endoscopic resection is one of the procedures for primary prevention of colorectal cancer, yet little is known about how the endoscopic therapy influences gut microbiota. METHODS: We conducted a prospective study of 20 patients who underwent endoscopic resection of colorectal adenoma and analyzed the fecal microbiota before and 3 months after adenoma resection. MiSeq sequencing of 16S rRNA genes was performed to determine the alterations in microbial diversity and structure. To discriminate the microbiota of the two groups, random forest and receiver operating characteristic analysis were applied, and a genus-based microbiota signature was obtained. RESULTS: Despite few alterations in overall microbial structure after adenoma resection, the abundance of Parabacteroides revealed a significant increase postoperatively (3.8% vs 1.5%, 0.1160), and the microbiota signature of Parabacteroides, Streptococcus, and Ruminococcus showed an optimal discriminating performance of postoperative status with the area under the curve 0.788, P < 0.001. CONCLUSION: Fecal microbial alterations indicate the moderate influence of adenoma resection on gut microbiota and lay the groundwork for microbial prediction of adenoma recurrence. Larger sample studies are further required to validate the findings.

Acupuncture for hypertension.

BACKGROUND: Elevated blood pressure (hypertension) affects about one billion people worldwide. It is important as it is a major risk factor for stroke and myocardial infarction. However, it remains a challenge for the medical profession as many people with hypertension have blood pressure (BP) that is not well controlled. According to Traditional Chinese Medicine theory, acupuncture has the potential to lower BP. OBJECTIVES: To assess the effectiveness and safety of acupuncture for lowering blood pressure in adults with primary hypertension. SEARCH METHODS: We searched the Hypertension Group Specialised Register (February 2017); the Cochrane Central Register of Controlled Trials (CENTRAL) 2017, Issue 2; MEDLINE (February 2017); Embase (February 2017), China National Knowledge Infrastructure (CNKI) (January 2015), VIP Database (January 2015), the World Health Organisation Clinical Trials Registry Platform (February 2017)and ClinicalTrials.gov (February 2017). There were no language restrictions. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) that compared the clinical effects of an acupuncture intervention (acupuncture used alone or add-on) with no treatment, a sham acupuncture or an antihypertensive drug in adults with primary hypertension. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies according to inclusion and exclusion criteria. They extracted data and assessed the risk of bias of each trial, and telephoned or emailed the authors of the studies to ask for missing information. A third review author resolved disagreements. Outcomes included change in systolic blood pressure (SBP), change in diastolic blood pressure (DBP), withdrawal due to adverse effects, and any adverse events. We calculated pooled mean differences (MD) with 95% confidence intervals (CI) for continuous outcomes using a fixed-effect or random-effects model where appropriate. MAIN RESULTS: Twenty-two RCTs (1744 people) met our inclusion criteria. The RCTs were of variable methodological quality (most at high risk of bias because of lack of blinding). There was no evidence for a sustained BP lowering effect of acupuncture; only one trial investigated a sustained effect and found no BP lowering effect at three and six months after acupuncture. Four sham acupuncture controlled trials provided very low quality evidence that acupuncture had a short-term (one to 24 hours) effect on SBP (change) -3.4 mmHg (-6.0 to -0.9) and DBP -1.9 mmHg (95% CI -3.6 to -0.3). Pooled analysis of eight trials comparing acupuncture with angiotensin-converting enzyme inhibitors and seven trials comparing acupuncture to calcium antagonists suggested that acupuncture lowered short-term BP better than the antihypertensive drugs. However, because of the very high risk of bias in these trials, we think that this is most likely a reflection of bias and not a true effect. As a result, we did not report these results in the 'Summary of findings' table. Safety of acupuncture could not be assessed as only eight trials reported adverse events. AUTHORS' CONCLUSIONS: At present, there is no evidence for the sustained BP lowering effect of acupuncture that is required for the management of chronically elevated BP. The short-term effects of acupuncture are uncertain due to the very low quality of evidence. The larger effect shown in non-sham acupuncture controlled trials most likely reflects bias and is not a true effect. Future RCTs must use sham acupuncture controls and assess whether there is a BP lowering effect of acupuncture that lasts at least seven days.

Management of an Esophago-pleural Fistula after Emergent Endoscopic Variceal Injectional Sclerotherapy: A Case Report And Literature Review.

A 48-year-old man developed sudden-onset haematemesis and melena after decompensated posthepatitic cirrhosis. Endoscopic variceal injectional sclerotherapy was emergently performed. However, the patient developed esophago-pleural fistula, empyema, and liver failure. He thus received symptomatic treatments and nasojejunal feedings, which failed to restore the nutrition as the gastroesophageal reflux exacerbated the hydrothorax. Percutaneous endoscopic gastro-jejunal (PEG-J) was therefore carefully performed for enteral nutrition support. The patient had recovered from the fistula at a six-month follow-up, which allowed the resumption of an oral diet. Our literature review revealed that PEG-J is a feasible approach to treating esophago-pleural fistula, a rare but lethal complication of endoscopic sclerotherapy.

Sex-Specific Entorhinal Cortex Functional Connectivity in Cognitively Normal Older Adults with Amyloid-ß Pathology.

Sex and apolipoprotein E (APOE) genotype have been shown to influence the risk and progression of Alzheimer's disease (AD). However, the impact of these factors on the functional connectivity of the entorhinal cortex (ERC) in clinically unpaired older adults (CUOA) with amyloid-ß (Aß +) pathology remains unclear. A total of 1022 cognitively normal older adults with Aß + (603 females and 586 APOE ε4 +) from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) study were included in this study. The 2 × 2 (gender, 2 APOE genotypes) analysis of covariance was performed to compare the demographic information, cognitive performance, and volumetric MRI data among these groups. Voxel-wise comparisons of bilateral ERC functional connectivity (FC) were conducted, and partial correlation analyses were used to explore the associations between cognitive performance and ERC-FC strength. We found that the APOE genotype influenced ERC functional connectivity mainly in the sensorimotor network (SMN). Males exhibited higher ERC-FC in the salience network (SN), while females displayed higher ERC-FC in the default mode network (DMN), executive control network (ECN), and reward network. The interplay of sex and APOE genotype on ERC-FC was observed in the SMN and cerebellar lobe. The ERC-FC was associated with executive function and memory performance in individuals with CUOA-Aß + . Our findings provide evidence of sex-specific ERC functional connectivity compensation mechanism in cognitively normal older adults with Aß + pathology. This study may contribute to a better understanding of the mechanisms underlying the early stages of AD and may help develop personalized interventions in preclinical AD.

[Neuroimaging-based study of scalp acupuncture targets for common psychiatric diseases (Part 2)].

In this study, based on the neuroimaging literature Meta analysis retrieved from Neurosynth platform, the scalp stimulation targets for common psychiatric diseases are developed, which provided the stimulation target protocols of scalp acupuncture for attention deficit hyperactivity disorder, autism spectrum disorder, obsessive-compulsive disorder and schizophrenia. The paper introduces the functions of the brain areas that are involved in each target and closely related to the diseases, and lists the therapeutic methods of common acupuncture/scalp acupuncture and common neuromodulation methods for each disease so as to provide the references for clinical practice. Based on the study results above, the paper further summarizes the overlapped stimulation targets undergoing the intervention with scalp acupuncture for common psychiatric diseases, and the potential relationship between these stimulation targets and treatments with acupuncture and moxibustion.

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OBJECTIVES: Scalp acupuncture is a unique acupuncture method developed based on brain functional and pathophysiological knowledge. In past decades, there has been significant development in the understanding of the brain pathology of many neurological disorders through cutting-edge brain imaging techniques. Yet, these findings have not been incorporated into scalp acupuncture. In the present paper, we aimed to initiate an attempt to develop/identify scalp acupuncture targets based on neuroimaging findings. METHODS: Based on the meta-analysis of neuroimaging studies in the Neurosynth database platform (http：//neurosynth.org/), the brain clusters related to neurological disorders were automatically identified according to the search terms "Parkinson's disease"(PD), "chronic pain"(CP), "aphasia"(APH), "dyslexia"(DYS), "mild cognitive impairment", "Alzheimer's disease" and "dementia". Subsequently, the discovered brain region clusters projected onto the brain surface and scalp surface were listed, and the peak points of the clusters projected to the scalp surface were proposed as the potential stimulation targets for the corresponding diseases. Further, by combining the traditional scalp acupoints (including the scalp acupuncture lines) with 10-20 EEG system sites, we made localization suggestions for scalp stimulation targets and made acupuncture operation suggestions by combining with the shape of the brain region clusters. The literature search was conducted on July 30, 2022. RESULTS: The localization and manipulation suggestions of neuroimage-based scalp acupuncture targets were introduced in two parts. This part (part 1) includes PD, CP, APH, and DYS. Here are 3 target examples of each of these 4 diseases simply introduced due to word limitation. 1) PD. Based on the 175 articles retrieved from Neurosynth, we identified 7 potential scalp acupuncture targets for PD, the locations of the acupuncture stimulation and the recommended acupuncture needle operation (RANO) as well as the corresponding brain regions (CBRs) respectively are as below. PD1：about 0.5 cun (1 cun≈33.3 mm) superior-posterior to the left Xuanlu (GB5)；puncturing subcutaneously and forward-upward；the left premotor area, subfrontal cortex of the island, inferior frontal gyrus and middle frontal gyrus. PD2：about 1 cun lateral-inferior to the left Chengling (GB18)；puncturing subcutaneously and backward-upward；the inferior parietal lobule and postcentral gyrus. PD3：about 0.5 cun lateral-anterior to the left GB18；puncturing subcutaneously and inward-backward；left anterior central gyrus and posterior central gyrus. 2) CP. Based on the retrieved 92 articles, we identified 8 potential scalp acupuncture targets, the location of the acupuncture stimulation and the RANO, and CBRs respectively are as below. CP1：about 1 cun anterior-inferior to the left Xuanli (GB8)；puncturing subcutaneously and backward-inwards；the left inferior frontal gyrus orbitalis and pars triangularis. CP2：about 0.5 cun posterior-superior to the left GB5；puncturing subcutaneously and forward-upward；the left anterior central gyrus and premotor area. CP3：about 0.5 cun posterior-superior to the left GB8；puncturing subcutaneously and forward；left inferior central area/central sulci operculum (second somatosensory area). 3) APH. Based on the retrieved 82 papers, we identified 7 potential scalp acupuncture targets for APH, their locations, RANO, and CBRs respectively are as below. APH1：close to the left GB5；puncturing subcutaneously and forward-downward；left subfrontal gyrus operculi/triangularis. APH2：about 0.5 cun posterior to the left Hanyan (GB4)；puncturing subcutaneously and backward-upward；the left anterior central gyrus and posterior central gyrus. APH3：about 0.5 cun anterior-inferior to the left Qubin (GB7)；puncturing subcutaneously and backward-downward；left medial/superior temporal gyrus. 4) DYS. Based on the retrieved 76 researches, we identified 8 potential scalp acupuncture targets for DYS, their locations, RANO and CBRs respectively are as below. DYS1：about 1 cun anterior-inferior to the left GB5；puncturing subcutaneously and forward-upward；the pars triangularis of the left inferior frontal gyrus. DYS2：about 0.5 cun posterior-superior to the left GB5；puncturing subcutaneously and forward-downward；the left subfrontal gyrus operculum, pars triangularis and anterior central gyrus. DYS3：the midpoint between the left GB5 and GB18；puncturing subcutaneously and forward；the left anterior central gyrus and posterior central gyrus. CONCLUSIONS: We identified scalp acupuncture targets for several common neurological disorders based on neuroimaging evidence for clinical application and research. The proposed targets may also be used for treating these disorders using brain stimulation methods.

[Neuroimaging-based study of scalp acupuncture targets for common psychiatric diseases].

Scalp acupuncture is a unique acupuncture method, developed based on the cerebral cortex localization. Neuroimaging technology enables the combination of contemporary brain science findings with the studies of scalp stimulation sites. In this study, based on the neuroimaging literature retrieved from Neurosynth platform, the scalp stimulation targets of common psychiatric diseases are developed, which provides the stimulation target protocol of scalp acupuncture for anxiety, bipolar disorder, major depressive disorder and post-traumatic stress disorder. The paper introduces the functions of the brain areas that are involved in each target and closely related to the diseases, and lists the therapeutic methods of common acupuncture and scalp acupuncture for each disease so as to provide the references for clinical practice. These targets can be used not only for the stimulation of scalp acupuncture, but also for the different neuromodulation techniques to treat related diseases.

Deficits in brain default mode network connectivity mediate the relationship between poor sleep quality and anxiety severity.

STUDY OBJECTIVES: Chronic insomnia disorder (CID) is a prevalent sleep disorder that frequently cooccurs with anxiety. The association between insomnia and anxiety has been established; however, the neurobiological basis of this relationship remains unclear. This study aimed to investigate the neural markers of CID patients with and without anxiety and to determine whether specific neural connectivity mediates the relationship between insomnia and anxiety. METHODS: This study included 180 participants, comprising CID patients with anxiety (CID-A), CID patients without anxiety (CID-NA), and good sleep controls. All participants completed self-reported measures of sleep quality and anxiety severity and underwent functional magnetic resonance imaging. Brain functional integration was measured using functional connectivity density (FCD) and resting-state functional connectivity (rsFC). Correlation and mediation analyses were used to examine the relationships among brain connectivity, sleep quality, and anxiety severity. RESULTS: The CID-NA and CID-A groups showed decreased local FCD in the medial prefrontal cortex (mPFC) and disrupted rsFC between the precuneus and other brain regions. Only the CID-A group exhibited altered long-range FCD in the precuneus and the rsFC between the anterior default mode network (DMN, e.g. mPFC) and posterior DMN (e.g. precuneus). Mediation analysis revealed DMN dysconnectivity underlying the association between poor sleep quality and anxiety symptoms. CONCLUSIONS: This study identified shared and distinct brain circuit disruptions in the CID-NA and CID-A groups, with deficits in DMN connectivity as a potential neural mechanism through which disrupted sleep augments anxiety. These findings may facilitate the development of personalized therapies for insomnia and associated anxiety problems.

Neural mechanisms of attentional bias to emotional faces in patients with chronic insomnia disorder.

OBJECTIVE: This study used event-related potential (ERP) and resting-state functional connectivity (rs-FC) approaches to investigate the neural mechanisms underlying the emotional attention bias in patients with chronic insomnia disorder (CID). METHODS: Twenty-five patients with CID and thirty-three demographically matched healthy controls (HCs) completed clinical questionnaires and underwent electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) scans. EEG analysis examined the group differences in terms of reaction times, P3 amplitudes, event-related spectral perturbations, and inter-trial phase synchrony. Subsequently, seed-based rs-FC analysis of the amygdala nuclei (including the central-medial amygdala [CMA] and basolateral amygdala [BLA]) was performed. The relationship between P3 amplitude, rs-FC and clinical symptom severity in patients with CID was further investigated by correlation analysis. RESULTS: CID patients exhibited shorter reaction times than HCs in both standard and deviant stimuli, with the abnormalities becoming more pronounced as attention allocation increased. Compared to HCs, ERP analysis revealed increased P3 amplitude, theta wave power, and inter-trial synchrony in CID patients. The rs-FC analysis showed increased connectivity of the BLA-occipital pole, CMA-precuneus, and CMA-angular gyrus and decreased connectivity of the CMA-thalamus in CID patients. Notably, correlation analysis of the EEG and fMRI measurements showed a significant positive correlation between the P3 amplitude and the rs-FC of the CMA-PCU. CONCLUSION: This study confirms an emotional attention bias in CID, specifically in the neural mechanisms of attention processing that vary depending on the allocation of attentional resources. Abnormal connectivity in the emotion-cognition networks may constitute the neural basis of the abnormal scalp activation pattern.

Electroencephalography connectome changes in chronic insomnia disorder are correlated with neurochemical signatures.

STUDY OBJECTIVES: This study aimed to investigate the alterations in resting-state electroencephalography (EEG) global brain connectivity (GBC) in patients with chronic insomnia disorder (CID) and to explore the correlation between macroscale connectomic variances and microscale neurotransmitter distributions. METHODS: We acquired 64-channel EEG from 35 female CID patients and 34 healthy females. EEG signals were source-localized using individual brain anatomy and orthogonalized to mitigate volume conduction. Correlation coefficients between band-limited source-space power envelopes of the DK 68 atlas were computed and averaged across regions to determine specific GBC values. A support vector machine (SVM) classifier utilizing GBC features was employed to differentiate CID patients from controls. We further used Neurosynth and a 3D atlas of neurotransmitter receptors/transporters to assess the cognitive functions and neurotransmitter landscape associated with CID cortical abnormality maps, respectively. RESULTS: CID patients exhibited elevated GBC within the medial prefrontal cortex and limbic cortex, particularly at the gamma carrier frequency, compared to controls (pFDR<0.05). GBC patterns were found to effectively distinguish CID patients from controls with a precision of 90.8% in the SVM model. The cortical abnormality maps were significantly correlated with meta-analytic terms like "cognitive control" and "emotion regulation." Notably, GBC patterns were associated with neurotransmitter profiles (pspin<0.05), with neurotransmitter systems such as norepinephrine, dopamine, and serotonin making significant contributions. CONCLUSIONS: This work characterizes the EEG connectomic profile of CID, facilitating the cost-effective clinical translation of EEG-derived markers. Additionally, the linkage between GBC patterns and neurotransmitter distribution offers promising avenues for developing targeted treatment strategies for CID.

Larger hypothalamic subfield volumes in patients with chronic insomnia disorder and relationships to levels of corticotropin-releasing hormone.

The hypothalamus is a well-established core structure in the sleep-wake cycle. While previous studies have not consistently found whole hypothalamus volume changes in chronic insomnia disorder (CID), differences may exist at the smaller substructural level of the hypothalamic nuclei. The study aimed to investigate the differences in total and subfield hypothalamic volumes, between CID patients and healthy controls (HCs) in vivo, through an advanced deep learning-based automated segmentation tool. A total of 150 patients with CID and 155 demographically matched HCs underwent T1-weighted structural magnetic resonance scanning. We utilized FreeSurfer v7.2 for automated segmentation of the hypothalamus and its five nuclei. Additionally, correlation and causal mediation analyses were performed to investigate the association between hypothalamic volume changes, insomnia symptom severity, and hypothalamus-pituitary-adrenal (HPA) axis-related blood biomarkers. CID patients exhibited larger volumes in the right anterior inferior, left anterior superior, and left posterior subunits of the hypothalamus compared to HCs. Moreover, we observed a positive association between blood corticotropin-releasing hormone (CRH) levels and insomnia severity, with anterior inferior hypothalamus (a-iHyp) hypertrophy mediating this relationship. In conclusion, we found significant volume increases in several hypothalamic subfield regions in CID patients, highlighting the central role of the HPA axis in the pathophysiology of insomnia.

Altered cognitive control network mediates the association between long-term pain and anxiety symptoms in primary dysmenorrhea.

Neuroimaging studies have demonstrated the association of the cognitive control network (CCN) with the maintenance of chronic pain. However, whether and how dorsolateral prefrontal cortex (DLPFC), a key region within the CCN, is altered in menstrual pain is unclear. In this study, we aimed to investigate alterations in the DLPFC functional connectivity network in patients with primary dysmenorrhea (PDM). The study comprised 41 PDM patients and 39 matched healthy controls (HCs), all of whom underwent a resting-state functional MRI scan during the menstrual stage. All participants were instructed to complete the clinical assessment before the MRI scan. We used the DLPFC as the seed in resting-state functional connectivity (rsFC) analysis to investigate the difference between PDM patients and HCs. Compared to HCs, PDM patients showed increased right DLPFC rsFC at the bilateral lingual gyrus, dorsal anterior cingulate cortex (dACC), and middle cingulate cortex, and decreased left DLPFC rsFC at the right orbital frontal cortex. In addition, increased right DLPFC-bilateral dACC connectivity mediated the association between disease duration and the self-rating anxiety scale (SAS) scores in PDM patients. We confirmed that the DLPFC-dACC rsFC was associated with higher SAS scores, which could mediate the association between disease duration and anxiety symptoms in patients with PDM. Our findings provide central pathological evidence for an abnormal rsFC of the CCN in PDM patients, which may contribute to a better understanding of the neuropathophysiological mechanisms underlying PDM.

Berberine ameliorates nonalcoholic fatty liver disease-induced bone loss by inhibiting ferroptosis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) may contribute to osteoporosis. Berberine is a traditional Chinese medicine and was recently shown to be beneficial in NAFLD. However, little is known about its impact on bone loss induced by NAFLD. AIM: We aimed to explore the role of berberine in bone loss and determine its underlying mechanisms in NAFLD. METHODS: C57BL/6 mice were fed a high-fat high-fructose high-glucose diet (HFFGD) for 16 weeks to establish a NAFLD mouse model. The mice were administered berberine (300 mg/kg/d) by gavage, and fatty liver levels and bone loss indicators were tested. RESULTS: Berberine significantly improved HFFGD-induced weight gain, hepatic lipid accumulation and increases in serum liver enzymes, thereby alleviating NAFLD. Berberine increased trabecular number (Tb. N), trabecular thickness (Tb. Th), bone volume to tissue volume ratio (BV/TV), and decreased trabecular separation (Tb. Sp) and restored bone loss in NAFLD. Mechanistically, berberine significantly inhibited ferroptosis and 4-hydroxynonenal (4-HNE), prostaglandin-endoperoxide synthase 2 (PTGS2), and transferrin (TF) levels and increased ferritin heavy chain (FTH) levels in the femurs of HFFGD-fed mice. Moreover, berberine also activated the solute carrier family 7 member 11 (SLC7A11)/glutathione (GSH)/glutathione peroxidase 4 (GPX4) signaling pathway. CONCLUSION: Berberine significantly ameliorates bone loss induced by NAFLD by activating the SLC7A11/GSH/GPX4 signaling pathway and inhibiting ferroptosis. Therefore, berberine may serve as a therapeutic agent for NAFLD-induced bone loss.

Transcutaneous electrical acupoint stimulation benefits postoperative pain relief of oocyte retrieval: A randomized controlled trial.

BACKGROUND: Transvaginal oocyte retrieval is frequently followed by adverse events related to anesthesia and the procedure. Some research showed that transcutaneous electrical acupoint stimulation (TEAS) can relieve intraoperative pain and postoperative nausea. OBJECTIVE: This study examined whether TEAS can alleviate pain and relieve adverse symptoms after oocyte retrieval. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Altogether 128 patients were randomly divided into the TEAS group and the mock TEAS group. The two groups received a 30-minute-long TEAS or mock TEAS treatment that began 30 min after oocyte retrieval. MAIN OUTCOME MEASURES: The primary outcome was the visual analog scale (VAS) pain score. Secondary outcomes were pressure pain threshold, McGill score, pain rating index (PRI), present pain intensity (PPI), VAS stress score, VAS anxiety score, and postoperative adverse symptoms. RESULTS: The baseline characteristics of the two groups were comparable (P > 0.05). The VAS pain scores of the TEAS group were lower than those of the mock TEAS group at 60 and 90 min after oocyte retrieval (P < 0.05). The McGill score, PRI and PPI in the TEAS group were significantly lower than those in the control group at 60 min after oocyte retrieval (P < 0.05). However, the two groups had equivalent beneficial effects regarding the negative emotions, such as nervousness and anxiety (P > 0.05). The TEAS group was superior to the mock TEAS group for relieving postoperative adverse symptoms (P < 0.05). CONCLUSION: TEAS treatment can relieve postoperative pain and postoperative adverse symptoms for patients undergoing oocyte retrieval. Please cite this article as: Liu LY, Su Y, Wang RR, Lai YY, Huang L, Li YT, Tao XY, Su MH, Zheng XY, Huang SC, Wu YN, Yu SY, Liang FR, Yang J. Transcutaneous electrical acupoint stimulation benefits postoperative pain relief of oocyte retrieval: A randomized controlled trial. J Integr Med. 2024; 22(1): 32-38.