Efficacy of single-session transcranial direct current stimulation on addiction-related inhibitory control and craving: a randomized trial in males with Internet gaming disorder.

BACKGROUND: Transcranial direct current stimulation (tDCS) of the dorsolateral prefrontal cortex (dlPFC) may reduce substance use and other addictive behaviours. However, the cognitive mechanisms that underpin such effects remain unclear. Impaired inhibitory control linked to hypoactivation of the prefrontal cortex may allow craving-related motivations to lead to compulsive addictive behaviours. However, very few studies have examined whether increasing the activation of the dlPFC via anodal tDCS could enhance inhibitory control over addiction-related distractors. The current study aimed to enrich empirical evidence related to this issue. METHODS: Thirty-three males with Internet gaming disorder underwent active (1.5 mA for 20 minutes) and sham tDCS 1 week apart, in randomized order. We assessed inhibitory control over gaming-related distractors and craving pre- and post-stimulation. RESULTS: Relative to sham treatment, active tDCS reduced interference from gaming-related (versus non-gaming) distractors and attenuated background craving, but did not affect cue-induced craving. LIMITATIONS: This study was limited by its relatively small sample size and the fact that it lacked assessments of tDCS effects on addictive behaviour. Future tDCS studies with multiple sessions in larger samples are warranted to examine the effects on addictive behaviours of alterations in addiction-related inhibitory control. CONCLUSION: These findings demonstrate that stimulation of the dlPFC influences inhibitory control over addiction-related cues and addiction-related motivation. This is the first empirical study to suggest that enhanced inhibitory control may be a cognitive mechanism underlying the effects of tDCS on addictions like Internet gaming disorder. Our finding of attenuated background craving replicated previous tDCS studies. Intriguingly, our finding of distinct tDCS effects on 2 forms of craving suggests that they may have disparate underlying mechanisms or differential sensitivity to tDCS. CLINICAL TRIALS #: NCT03352973.

A role for the right dorsolateral prefrontal cortex in enhancing regulation of both craving and negative emotions in internet gaming disorder: A randomized trial.

Reward-seeking and relief from negative emotions are two central motivational drives underlying addictions. Impaired executive control over craving and negative emotions contributes to compulsive addictive behaviors. Neuroimaging evidence has implicated the prefrontal cortex (PFC) in regulating craving or emotions. This study aims at examining whether anodal transcranial direct current stimulation (tDCS) over a specific region of the PFC would enhance both regulation processes. Thirty-three men with internet gaming disorder received active (1.5 mA for 20 minutes) and sham tDCS over the right dorsolateral PFC (dlPFC) one week apart in a randomized order. During each stimulation session, participants regulated craving for gaming during a regulation of craving (ROC) task and negative emotions during an emotion regulation (ER) task using cognitive reappraisal. Subjective ratings of craving and negative emotions and skin conductance responses (SCRs) were recorded. For both craving and negative emotions, tDCS of the right dlPFC facilitated downregulation and upregulation: active relative to sham tDCS decreased ratings (ROC: 95% CI of difference -1.38 to -0.56, p < 0.001; ER: -1.65 to -0.70, p < 0.001) and/or SCRs (ROC: -1.99 to -0.41 µs, p = 0.004) for downregulation, and increased ratings (ROC: 0.24 to 0.82, p = 0.001; ER: 0.26 to 0.72, p < 0.001) for upregulation. These findings provide the first experimental evidence confirming that tDCS of the right dlPFC enhances both craving- and negative-emotion-regulation. This suggests a promising approach for concurrently enhancing executive control over two central motivational drives underlying addictions.

Impaired regulation of both addiction-related and primary rewards in individuals with internet gaming disorder.

Poor executive function (EF) has been implicated in addictions. Among "hot" EFs (i.e., those involving motivations and emotions), poor regulation of craving has been proposed to underlie addiction development in substance-use disorders (SUDs), making such regulation a potential treatment target. However, regulation of craving remains poorly understood in internet gaming disorder (IGD). Additionally, prior studies of cold EFs (e.g., inhibition and cognitive flexibility under neutral conditions) in IGD have provided mixed results and mostly included only male subjects. We addressed these issues by instructing 54 participants (26 with IGD including males and females, and 28 control subjects) to perform a regulation-of-craving (ROC) task and a Stroop color-word-interference task. Compared to control subjects, individuals with IGD revealed deficits in regulation for both gaming- and food-related craving, but no differences in Stroop performance. The current study provides initial empirical support suggesting regulation impairments for both addiction-related and primary rewards among individuals with IGD. The findings are consistent with studies in SUDs, suggesting that impaired regulation of craving may be a relevant transdiagnostic construct across SUDs and behavioral addictions. The findings suggest targeting regulation of "hot" processes should be considered in IGD treatment development.

Is monetary reward processing altered in drug-naïve youth with a behavioral addiction? Findings from internet gaming disorder.

Current models of addiction biology highlight altered neural responses to non-drug rewards as a central feature of addiction. However, given that drugs of abuse can directly impact reward-related dopamine circuitry, it is difficult to determine the extent to which reward processing alterations are a trait feature of individuals with addictions, or primarily a consequence of exogenous drug exposure. Examining individuals with behavioral addictions is one promising approach for disentangling neural features of addiction from the direct effects of substance exposure. The current fMRI study compared neural responses during monetary reward processing between drug naïve young adults with a behavioral addiction, internet gaming disorder (IGD; n = 22), and healthy controls (n = 27) using a monetary incentive delay task. Relative to controls, individuals with IGD exhibited blunted caudate activity associated with loss magnitude at the outcome stage, but did not differ from controls in neural activity at other stages. These findings suggest that decreased loss sensitivity might be a critical feature of IGD, whereas alterations in gain processing may be less characteristic of individuals with IGD, relative to those with substance use disorders. Therefore, classic theories of altered reward processing in substance use disorders should be translated to behavioral addictions with caution.

Functional and structural neural alterations in Internet gaming disorder: A systematic review and meta-analysis.

This meta-analytic study aimed to identify the common and specific neural alterations in Internet gaming disorder (IGD) across different domains and modalities. Two separate meta-analyses for functional neural activation and gray-matter volume were conducted. Sub-meta-analyses for the domains of reward, cold-executive, and hot-executive functions were also performed, respectively. IGD subjects, compared with healthy controls, showed: (1) hyperactivation in the anterior and posterior cingulate cortices, caudate, posterior inferior frontal gyrus (IFG), which were mainly associated with studies measuring reward and cold-executive functions; and, (2) hypoactivation in the anterior IFG in relation to hot-executive function, the posterior insula, somatomotor and somatosensory cortices in relation to reward function. Furthermore, IGD subjects showed reduced gray-matter volume in the anterior cingulate, orbitofrontal, dorsolateral prefrontal, and premotor cortices. These findings suggest that IGD is associated with both functional and structural neural alterations in fronto-striatal and fronto-cingulate regions. Moreover, multi-domain assessments capture different aspects of neural alterations in IGD, which may be helpful for developing effective interventions targeting specific functions.

Network pharmacology exploration reveals endothelial inflammation as a common mechanism for stroke and coronary artery disease treatment of Danhong injection.

Although Danhong injection (DHI) is the most widely prescribed Chinese medicine for both stroke and coronary artery disease (CAD), its underlying common molecular mechanisms remain unclear. An integrated network pharmacology and experimental verification approach was used to decipher common pharmacological mechanisms of DHI on stroke and CAD treatment. A compound-target-disease & function-pathway network was constructed and analyzed, indicating that 37 ingredients derived from DH (Salvia miltiorrhiza Bge., Flos Carthami tinctorii and DHI) modulated 68 common targets shared by stroke and CAD. In-depth network analysis results of the top diseases, functions, pathways and upstream regulators implied that a common underlying mechanism linking DHI's role in stroke and CAD treatment was inflammatory response in the process of atherosclerosis. Experimentally, DHI exerted comprehensive anti-inflammatory effects on LPS, ox-LDL or cholesterol crystal-induced NF-κB, c-jun and p38 activation, as well as IL-1ß, TNF-α, and IL-10 secretion in vascular endothelial cells. Ten of 14 predicted ingredients were verified to have significant anti-inflammatory activities on LPS-induced endothelial inflammation. DHI exerts pharmacological efficacies on both stroke and CAD through multi-ingredient, multi-target, multi-function and multi-pathway mode. Anti-endothelial inflammation therapy serves as a common underlying mechanism. This study provides a new understanding of DHI in clinical application on cardiovascular and cerebrovascular diseases.

The Prognostic Impact of Heat Shock Proteins Expression in Patients with Esophageal Cancer: A Meta-Analysis.

PURPOSE: Heat shock proteins (HSPs) are highly conserved molecular chaperones. There are various studies that assess the prognostic value of HSPs in patients with esophageal cancer, but the conclusion remains controversial. This is the first meta-analysis study aiming to summarize the evidence on the suitability of HSPs to predict patients' survival. MATERIALS AND METHODS: Searching PubMed, Web of science and Medline until May 31, 2014, data were compared for overall survival in patients with down-regulated HSPs level with those with up-regulated level. We conducted a meta-analysis of 9 studies (801 patients) that correlated HSPs levels with overall survival. Data were synthesized with hazard ratios (HRs). RESULTS: The estimated risk of death was 2.93-fold greater in HSP27 negative patients than HSP27 positive patients [95% confidence interval (CI), 1.12-7.62]. When limited to esophageal squamous cell carcinoma (ESCC), the risk of death in HSP27 negative patients seemed more significant (HR, 3.90; 95% CI, 2.35-6.49). Decreased expression of HSP70 was also associated with worse survival in esophageal cancer (HR, 2.83; 95% CI, 1.90-4.23) and, when limited to ESCC, HR was 3.21 (95% CI, 1.94-5.30). Data collected, however, were not sufficient to determine the prognostic value of HSP90 in patients with ESCC nor esophageal adenocarcinomas (EADC). CONCLUSION: In this meta-analysis, reduced HSP27 and HSP70 expressions were associated with poor survival in patients with esophageal cancer, especially esophageal squamous cell carcinoma.

miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy.

MicroRNAs (miRNAs), a class of small non-coding RNAs, mediate gene expression by either cleaving target mRNAs or inhibiting their translation. They have key roles in the tumorigenesis of several cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to investigate the clinical significance of miR-638 in the evaluation of NSCLC patient prognosis in response to chemotherapy. First, we detected miR-638 expression levels in vitro in the culture supernatants of the NSCLC cell line SPC-A1 treated with cisplatin, as well as the apoptosis rates of SPC-A1. Second, serum miR-638 expression levels were detected in vivo by using nude mice xenograft models bearing SPC-A1 with and without cisplatin treatment. In the clinic, the serum miR-638 levels of 200 cases of NSCLC patients before and after chemotherapy were determined by quantitative real-time PCR, and the associations of clinicopathological features with miR-638 expression patterns after chemotherapy were analyzed. Our data helped in demonstrating that cisplatin induced apoptosis of the SPC-A1 cells in a dose- and time-dependent manner accompanied by increased miR-638 expression levels in the culture supernatants. In vivo data further revealed that cisplatin induced miR-638 upregulation in the serum derived from mice xenograft models, and in NSCLC patient sera, miR-638 expression patterns after chemotherapy significantly correlated with lymph node metastasis. Moreover, survival analyses revealed that patients who had increased miR-638 levels after chemotherapy showed significantly longer survival time than those who had decreased miR-638 levels. Our findings suggest that serum miR-638 levels are associated with the survival of NSCLC patients and may be considered a potential independent predictor for NSCLC prognosis.

[Interaction of anti-thrombotic and anti-inflammatory activities of commonly used traditional Chinese medicine for promoting blood circulation and removing blood stasis revealed by network pharmacology analysis].

Chinese traditional patent medicine for promoting blood circulation and removing blood stasis(PBCRBS) originated from traditional Chinese medicine theory and had approved efficacy and safety standards. However, its compatibility regularity and anti-thrombotic mechanism is not clear. To analyze the compatibility regularity and anti-thrombotic mechanism of Chinese traditional patent medicine for PBCRBS, a statistical and bioinformatics analysis was carried out using traditional Chinese medicine inheritance support system (TICMISS, V2.0) and ingenuity pathway analysis (IPA). The compatibility regularity analysis shows that the most commonly used herb combinations are Danshen (Salvia miltiorrhiza Bge.), Chuanxiong (Ligusticum chuanxiong Hort.) and Honghua (Carthamustinctorius L.). The anti-thrombotic mechanism analysis reveals that 25 ingredients have an effect on 29 thrombosis related molecules which 23 molecules are related to inflammation response. Furthermore, there are 5 inflammation molecules (NOS2, PTGS2, IL6, TNF, IL1ß) served as major targets. At the same time, Danshen, Chuangxiong and Honghua mainly used as sovereign herb or minister herb in the application of cardiovascular and cerebrovascular diseases. Therefore, Chinese traditional patent medicine for PBCRBS probably has an effect on anti-thrombotic activity through inhibiting the inflammatory response. In summary, the most commonly used herb combinations of Chinese traditional patent medicine for PBCRBS are Danshen, Chuanxiong and Honghua. Inhibiting inflammatory response, especially inflammation related molecules (NOS2, PTGS2, IL6, TNF and IL1ß), is probably a new starting point to clarify the anti-thrombotic mechanism of Chinese patent medicine for PBCRBS.