Effects on resting-state EEG phase-amplitude coupling in insomnia disorder patients following 1 Hz left dorsolateral prefrontal cortex rTMS.

Despite burgeoning evidence for cortical hyperarousal in insomnia disorder, the existing results on electroencephalography spectral features are highly heterogeneous. Phase-amplitude coupling, which refers to the modulation of the low-frequency phase to a high-frequency amplitude, is probably a more sensitive quantitative measure for characterizing abnormal neural oscillations and explaining the therapeutic effect of repetitive transcranial magnetic stimulation in the treatment of patients with insomnia disorder. Sixty insomnia disorder patients were randomly divided into the active and sham treatment groups to receive 4 weeks of repetitive transcranial magnetic stimulation treatment. Behavioral assessments, resting-state electroencephalography recordings, and sleep polysomnography recordings were performed before and after repetitive transcranial magnetic stimulation treatment. Forty good sleeper controls underwent the same assessment. We demonstrated that phase-amplitude coupling values in the frontal and temporal lobes were weaker in Insomnia disorder patients than in those with good sleeper controls at baseline and that phase-amplitude coupling values near the intervention area were significantly enhanced after active repetitive transcranial magnetic stimulation treatment. Furthermore, the enhancement of phase-amplitude coupling values was significantly correlated with the improvement of sleep quality. This study revealed the potential of phase-amplitude coupling in assessing the severity of insomnia disorder and the efficacy of repetitive transcranial magnetic stimulation treatment, providing new insights on the abnormal physiological mechanisms and future treatments for insomnia disorder.

The potential of electroencephalography coherence to predict the outcome of repetitive transcranial magnetic stimulation in insomnia disorder.

BACKGROUND: It is unknown whether repetitive Transcranial Magnetic Stimulation (rTMS) could improve sleep quality by modulating electroencephalography (EEG) connectivity of insomnia disorder (ID) patients. Great heterogeneity had been found in the clinical outcomes of rTMS for ID. The study aimed to investigate the potential mechanisms of rTMS therapy for ID and develop models to predict clinical outcomes. METHODS: In Study 1, 50 ID patients were randomly divided into active and sham groups, and subjected to 20 sessions of treatment with 1 Hz rTMS over the left dorsolateral prefrontal cortex. EEG during awake, Polysomnography, and clinical assessment were collected and analyzed before and after rTMS. In Study 2, 120 ID patients were subjected to active rTMS stimulation and were then separated into optimal and sub-optimal groups due to the median of Pittsburgh Sleep Quality Index reduction rate. Machine learning models were developed based on baseline EEG coherence to predict rTMS treatment effects. RESULTS: In Study 1, decreased EEG coherence in theta and alpha bands were observed after rTMS treatment, and changes in theta band (F7-O1) coherence were correlated with changes in sleep efficiency. In Study 2, baseline EEG coherence in theta, alpha, and beta bands showed the potential to predict the treatment effects of rTMS for ID. CONCLUSION: rTMS improved sleep quality of ID patients by modulating the abnormal EEG coherence. Baseline EEG coherence between certain channels in theta, alpha, and beta bands could act as potential biomarkers to predict the therapeutic effects.

Reconfigurations of Dynamic Functional Network Connectivity in Large-scale Brain Network after Prolonged Abstinence in Heroin Users.

BACKGROUND: Brain recovery phenomenon after long-term abstinence had been reported in substance use disorders. Yet, few longitudinal studies have been conducted to observe the abnormal dynamic functional connectivity (dFNC) of large-scale brain networks and recovery after prolonged abstinence in heroin users. OBJECTIVE: The current study will explore the brain network dynamic connection reconfigurations after prolonged abstinence in heroin users (HUs). METHODS: The 10-month longitudinal design was carried out for 40 HUs. The 40 healthy controls (HCs) were also enrolled. Group independent component analysis (GICA) and dFNC analysis were employed to detect the different dFNC patterns of addiction-related ICNs between HUs and HCs. The temporal properties and the graph-theoretical properties were calculated. Whether the abnormalities would be reconfigured in HUs after prolonged abstinence was then investigated. RESULTS: Based on eight functional networks extracted from GICA, four states were identified by the dFNC analysis. Lower mean dwell time and fraction rate in state4 were found for HUs, which were increased toward HCs after prolonged abstinence. In this state, HUs at baseline showed higher dFNC of RECN-aSN, aSN- aSN and dDMN-pSN, which decreased after protracted abstinence. A similar recovery phenomenon was found for the global efficiency and path length in abstinence HUs. Mean while, the abnormal dFNC strength was correlated with craving both at baseline and after abstinence. CONCLUSION: Our longitudinal study observed the large-scale brain network reconfiguration from the dynamic perspective in HUs after prolonged abstinence and improved the understanding of the neurobiology of prolonged abstinence in HUs.

Partial recovery of the left DLPFC-right insula circuit with reduced craving in abstinent heroin users: a longitudinal study.

The phenomenon of brain recovery after long-term abstinence has been reported in substance use disorders. However, few longitudinal studies have been conducted to observe the potential recovery in heroin users, and little is known about the neural mechanism underlying the decreased craving after prolonged abstinence. The 8-month longitudinal study was carried out in 29 heroin users and 30 healthy controls. By choosing the L_DLPFC, which was activated by the heroin cue as the seeding region, different brain connection patterns were compared between healthy controls and heroin users by using Granger causality analysis (GCA) at baseline. Then, a paired t test was employed to detect the potential recovery of L_DLPFC circuits after prolonged abstinence. The visual analog scale (VAS) and trail-making test-A (TMT-A) were adopted to investigate craving and cognitive control impairment, respectively. The neuroimaging changes were then correlated with behavioral improvements. Similar analyses were applied for the mirrored right DLPFC to verify the lateralization hypothesis of the DLPFC in addiction. In the longitudinal study, enhanced GCA coefficients were observed in the L_DLPFC-R_insula circuit of heroin users after long-term abstinence and were associated with craving score changes. At baseline, decreased GCA coefficients from the left DLPFC to the bilateral SMA and right putamen, together with the reduced GCA strength from the bilateral OFC to the left DLPFC, were found between HUs and HCs. Our findings extended the brain recovery phenomenon into the field of heroin and suggested that the increased regulation of the L_DLPFC over the insula after prolonged abstinence was important for craving inhibition.

Effects of harmaline on cell growth of human liver cancer through the p53/p21 and Fas/FasL signaling pathways.

The effects of harmaline on the viability and apoptosis of human liver carcinoma were investigated in vitro. HepG2 cells were treated with harmaline (0-10 µM), and the proliferation and apoptosis of HepG2 cells were investigated using an MTT assay and flow cytometry, respectively. The protein expression of cellular tumor antigen p53 (p53), cyclin-dependent kinase inhibitor 1 (p21), tumor necrosis factor receptor superfamily member 6 (Fas), Fas ligand (FasL) and caspase-8 was subsequently measured using western blotting. In addition, an ELISA was used to analyze caspase-8/3 activity. Harmaline significantly increased p53, p21, Fas and FasL protein expression in HepG2 cells. Additionally, treatment with harmaline significantly increased the expression of caspase-8 and caspase-8/3 activity. The results from the present study suggest that harmaline suppresses the viability, but induces the apoptosis, of human liver carcinoma cells through upregulation of the p53/p21 and Fas/FasL signaling pathways.

Iodine-125 implantation plus transarterial chemoembolization for the treatment of hepatocellular carcinoma of 3-5cm: A propensity score matching study.

BACKGROUND: Both iodine-125 implantation and transarterial chemoembolization (TACE) are feasible options for hepatocellular carcinoma (HCC). The aim of the research is to investigate whether iodine-125 implantation combined with TACE could improve the overall survival of patients with HCC of 3-5cm. METHODS: 144 patients with HCC of 3-5cm who underwent iodine-125 implantation plus TACE and TACE alone were retrospectively enrolled in this study. To reduce the selection bias, 55 matched pairs of patients were generated by propensity score matching (PSM). Their overall survival was compared by the Kaplan-Meier method. Independent prognostic factors were identified by Cox proportional hazards regression model. RESULTS: patients receiving iodine-125 implantation plus TACE have significantly better overall survival than patients receiving TACE alone (P<0.001). After PSM, treatment of iodine-125 plus TACE still provide better survival (1-year, 89.1% vs. 65.5%; 3-year, 51.0% vs. 7.4%; P<0.001). In multivariate analysis, BCLC stage, vascular invasion and treatment modality independently predicted the prognosis. No severe adverse events occurred in both groups. CONCLUSION: for HCC patients of 3-5cm for whom surgical intervention is not an option, iodine-125 implantation combined with TACE might be an effective and viable alternative to provide better overall survival.