The dorsomedial prefrontal cortex represents subjective value across effort-based and risky decision-making.

Decisions that require taking effort costs into account are ubiquitous in real life. The neural common currency theory hypothesizes that a particular neural network integrates different costs (e.g., risk) and rewards into a common scale to facilitate value comparison. Although there has been a surge of interest in the computational and neural basis of effort-related value integration, it is still under debate if effort-based decision-making relies on a domain-general valuation network as implicated in the neural common currency theory. Therefore, we comprehensively compared effort-based and risky decision-making using a combination of computational modeling, univariate and multivariate fMRI analyses, and data from two independent studies. We found that effort-based decision-making can be best described by a power discounting model that accounts for both the discounting rate and effort sensitivity. At the neural level, multivariate decoding analyses indicated that the neural patterns of the dorsomedial prefrontal cortex (dmPFC) represented subjective value across different decision-making tasks including either effort or risk costs, although univariate signals were more diverse. These findings suggest that multivariate dmPFC patterns play a critical role in computing subjective value in a task-independent manner and thus extend the scope of the neural common currency theory.

Altered intrinsic connectivity distribution in internet gaming disorder and its associations with psychotherapy treatment outcomes.

Alterations in brain connectivity have been implicated in internet gaming disorder (IGD). However, little is known about alterations in whole-brain connectivity and their associations with long-term treatment outcomes. Here, we used a relatively new analytic approach, intrinsic connectivity distribution (ICD) analysis, to examine brain connectivity in 74 IGD participants and 41 matched healthy controls (HCs) and conducted post hoc seed-based resting-state functional connectivity (rsFC) analyses based on the ICD findings. We also examined how these findings related to outcomes involving a craving behavioral intervention (CBI) for IGD. IGD participants showed less whole-brain connectivity in the left angular gyrus and ventromedial prefrontal cortex (vmPFC) compared with HC participants. Seed-based rsFC analyses revealed that the left angular gyrus in the IGD group showed less connectivity with areas involved in the default-mode network and greater connectivity with areas in the salience and executive control networks. CBI was associated with improved connectivity within regions in the default-mode network and regions across the default-mode and salience networks. ICD-identified connectivity differences in the left angular gyrus and vmPFC were related to changes in craving and severity of addiction 6 months after the intervention. The findings suggest that IGD is associated with alterations in brain connectivity that may be sensitive to interventions. Thus, the findings have implications for understanding mechanisms underlying CBI effects and for further treatment development.

Resting-state connectome-based support-vector-machine predictive modeling of internet gaming disorder.

Internet gaming disorder (IGD), a worldwide mental health issue, has been widely studied using neuroimaging techniques during the last decade. Although dysfunctions in resting-state functional connectivity have been reported in IGD, mapping relationships from abnormal connectivity patterns to behavioral measures have not been fully investigated. Connectome-based predictive modeling (CPM)-a recently developed machine-learning approach-has been used to examine potential neural mechanisms in addictions and other psychiatric disorders. To identify the resting-state connections associated with IGD, we modified the CPM approach by replacing its core learning algorithm with a support vector machine. Resting-state functional magnetic resonance imaging (fMRI) data were acquired in 72 individuals with IGD and 41 healthy comparison participants. The modified CPM was conducted with respect to classification and regression. A comparison of whole-brain and network-based analyses showed that the default-mode network (DMN) is the most informative network in predicting IGD both in classification (individual identification accuracy = 78.76%) and regression (correspondence between predicted and actual psychometric scale score: r = 0.44, P < 0.001). To facilitate the characterization of the aberrant resting-state activity in the DMN, the identified networks have been mapped into a three-subsystem division of the DMN. Results suggest that individual differences in DMN function at rest could advance our understanding of IGD and variability in disorder etiology and intervention outcomes.

Craving behavioral intervention for internet gaming disorder: remediation of functional connectivity of the ventral striatum.

Psychobehavioral intervention is an effective treatment of Internet addiction, including Internet gaming disorder (IGD). However, the neural mechanisms underlying its efficacy remain unclear. Cortical-ventral striatum (VS) circuitry is a common target of psychobehavioral interventions in drug addiction, and cortical-VS dysfunction has been reported in IGD; hence, the primary aim of the study was to investigate how the VS circuitry responds to psychobehavioral interventions in IGD. In a cross-sectional study, we examined resting-state functional connectivity of the VS in 74 IGD subjects (IGDs) and 41 healthy controls (HCs). In a follow-up craving behavioral intervention (CBI) study, of the 74 IGD subjects, 20 IGD subjects received CBI (CBI+) and 16 IGD subjects did not (CBI-). All participants were scanned twice with similar time interval to assess the effects of CBI. IGD subjects showed greater resting-state functional connectivity of the VS to left inferior parietal lobule (lIPL), right inferior frontal gyrus and left middle frontal gyrus, in positive association with the severity of IGD. Moreover, compared with CBI-, CBI+ showed significantly greater decrease in VS-lIPL connectivity, along with amelioration in addiction severity following the intervention. These findings demonstrated that functional connectivity between VS and lIPL, each presumably mediating gaming craving and attentional bias, may be a potential biomarker of the efficacy of psychobehavioral intervention. These results also suggested that non-invasive techniques such as transcranial magnetic or direct current stimulation targeting the VS-IPL circuitry may be used in the treatment of Internet gaming disorders.

Activation of the ventral and dorsal striatum during cue reactivity in Internet gaming disorder.

Studies conducted in drug addiction suggest a transition in processing of drug-related cues from the ventral to the dorsal component of the striatum. However, this process has not been studied in a behavioral addiction. Assessment of this process in a non-drug addiction can provide insight into the pathophysiology of both substance and behavioral addictions. Thirty-nine male Internet gaming disorder (IGD) subjects and 23 male matched healthy controls (HCs) participated in functional magnetic resonance imaging during performance of a cue-reactivity task involving alternating presentation of Internet gaming-related stimuli (game cues) and general Internet surfing-related stimuli (control cues). Cue-induced neural activations in the ventral and dorsal striatum (DS) were compared between IGD and HC participants. Associations between cue-reactivity within these regions and cue-induced craving and severity and duration of IGD were also explored. IGD participants exhibited higher cue-induced activations within both the ventral and DS when compared with HCs. Within the IGD group, activity within the left ventral striatum (VS) was correlated negatively with cue-induced craving; positive associations were found between activations within the DS (right putamen, pallidum and left caudate) and duration of IGD. Cue-induced activity within the left putamen was negatively associated with right VS volumes among IGD participants. Consistent with studies in substance addictions, our results suggest that a transition from ventral to dorsal striatal processing may occur among individuals with IGD, a condition without the impact of substance intake.

Altered resting-state functional connectivity of the insula in young adults with Internet gaming disorder.

The insula has been implicated in salience processing, craving, and interoception, all of which are critical to the clinical manifestations of drug and behavioral addiction. In this functional magnetic resonance imaging (fMRI) study, we examined resting-state functional connectivity (rsFC) of the insula and its association with Internet gaming characteristics in 74 young adults with Internet gaming disorder (IGD) and 41 age- and gender-matched healthy control subjects (HCs). In comparison with HCs, IGD subjects (IGDs) exhibited enhanced rsFC between the anterior insula and a network of regions including anterior cingulate cortex (ACC), putamen, angular gyrus, and precuneous, which are involved in salience, craving, self-monitoring, and attention. IGDs also demonstrated significantly stronger rsFC between the posterior insula and postcentral gyrus, precentral gyrus, supplemental motor area, and superior temporal gyrus (STG), which are involved in interoception, movement control, and auditory processing. Furthermore, IGD severity was positively associated with connectivity between the anterior insula and angular gyrus, and STG, and with connectivity between the posterior insula and STG. Duration of Internet gaming was positively associated with connectivity between the anterior insula and ACC. These findings highlight a key role of the insula in manifestation of the core symptoms of IGD and the importance to examine functional abnormalities of the anterior and posterior insula separately in IGDs.

Decreased functional connectivity between ventral tegmental area and nucleus accumbens in Internet gaming disorder: evidence from resting state functional magnetic resonance imaging.

BACKGROUND: Internet gaming disorder (IGD) has become an increasing mental health problem worldwide. Decreased resting-state functional connectivity (rsFC) between the ventral tegmental area (VTA) and the nucleus accumbens (NAcc) has been found in substance use and is thought to play an important role in the development of substance addiction. However, rsFC between the VTA and NAcc in a non-substance addiction, such as IGD, has not been assessed previously. The current study aimed to investigate: (1) if individuals with IGD exhibit alterations in VTA-NAcc functional connectivity; and (2) whether VTA-NAcc functional connectivity is associated with subjective Internet craving. METHODS: Thirty-five male participants with IGD and 24 healthy control (HC) individuals participated in resting-state functional magnetic resonance imaging. Regions of interest (left NAcc, right NAcc and VTA) were selected based on the literature and were defined by placing spheres centered on Talairach Daemon coordinates. RESULTS: In comparison with HCs, individuals with IGD had significantly decreased rsFC between the VTA and right NAcc. Resting-state functional connectivity strength between the VTA and right NAcc was negatively correlated with self-reported subjective craving for the Internet. CONCLUSIONS: These results suggest possible neural functional similarities between individuals with IGD and individuals with substance addictions.

Compulsivity-related behavioral features of problematic usage of the internet: A scoping review of paradigms, progress, and perspectives.

Background and aims: Compulsivity contributes to the development and maintenance of multiple addictive disorders. However, the relationship between compulsivity-related cognitive features and problematic usage of the internet (PUI), an umbrella term for various internet use disorders/interfering behaviors, remains largely unclear, partly due to the multidimensional nature of compulsivity. This scoping review utilized a four-domain framework of compulsivity to consider this topic and aimed to summarize available evidence on compulsivity-related neuropsychological characteristics in PUI based on this framework. Methods: A systematic literature search was conducted by applying the combination of search term to the search engines of PubMed, PsycINFO and Web of Science. A four-domain framework of compulsivity, involving cognitive flexibility, set-shifting, attentional bias, and habit learning, was used to consider its complex structure and frequently used tasks. Main findings in related PUI studies were summarized based on this framework. Our secondary aim was to compare compulsivity-related features between different PUI subtypes. Results: Thirty-four empirical studies were retained, comprising 41 task-results and 35 independent data sets. Overall, individuals with PUI showed more consistent deficits in attentional biases and were relatively intact in set-shifting. Few studies have examined cognitive flexibility and habit learning, and more evidence is thus needed to establish reliable conclusions. Moreover, most studies focused on internet gaming disorder, whereas other PUI sub-types were not sufficiently examined. Conclusion: This systematic review highlights the use of the four-domain framework for advancing understanding of mechanisms underlying compulsivity in PUI. Related therapeutic implications and future directions are discussed.

Subgroups of internet gaming disorder based on addiction-related resting-state functional connectivity.

AIMS: To identify subgroups of people with internet gaming disorder (IGD) based on addiction-related resting-state functional connectivity and how these subgroups show different clinical correlates and responses to treatment. DESIGN: Secondary analysis of two functional magnetic resonance imaging (fMRI) data sets. SETTING: Zhejiang province and Beijing, China. PARTICIPANTS: One hundred and sixty-nine IGD and 147 control subjects. MEASUREMENTS: k-Means algorithmic and support-vector machine-learning approaches were used to identify subgroups of IGD subjects. These groups were examined with respect to assessments of craving, behavioral activation and inhibition, emotional regulation, cue-reactivity and guessing-related measures. FINDINGS: Two groups of subjects with IGD were identified and defined by distinct patterns of connectivity in brain networks previously implicated in addictions: subgroup 1 ('craving-related subgroup') and subgroup 2 ('mixed psychological subgroup'). Clustering IGD on this basis enabled the development of diagnostic classifiers with high sensitivity and specificity for IGD subgroups in 10-fold validation (n = 218) and out-of-sample replication (n = 98) data sets. Subgroup 1 is characterized by high craving scores, cue-reactivity during fMRI and responsiveness to a craving behavioral intervention therapy. Subgroup 2 is characterized by high craving, behavioral inhibition and activations scores, non-adaptive emotion-regulation strategies and guessing-task fMRI measures. Subgroups 1 and 2 showed largely opposite functional-connectivity patterns in overlapping networks. CONCLUSIONS: There appear to be two subgroups of people with internet gaming disorder, each associated with differing patterns of brain functional connectivity and distinct clinical symptom profiles and gender compositions.

Meta-analysis of the efficacy of acupuncture in the treatment of the vascular cognitive impairment associated with cerebral small vessel disease.

OBJECTIVE: To systematically evaluate the efficacy and safety of acupuncture in the treatment of the vascular cognitive impairment (VCI) associated with cerebral small vessel disease (CSVD-VCI) and to provide a theoretical basis for clinical acupuncture treatment for CSVD-VCI. METHOD: Various databases, including China National Knowledge Infrastructure, Wanfang Data, Chinese Science and Technology Journal Database, Chinese BioMedical Literature Service System, PubMed, the Cochrane Library, and EBSCOhost, were searched for randomized controlled trials (RCTs) related to acupuncture treatment for CSVD-VCI. The quality of the included trials was evaluated, and a meta-analysis was conducted using the Review Manager 5.4 software. RESULTS: Ten articles on RCTs were included, involving 761 patients, i.e., 381 in the acupuncture group and 380 in the control group. The meta-analysis results indicated that the use of acupuncture alone and acupuncture alongside other therapies for CSVD-VCI could improve the overall clinical response rate [odds ratio = 3.51, 95% confidence interval (CI) = (2.05, 6.00), P < 0.00001], increase the patients' Montreal Cognitive Assessment scores [mean difference (MD) = 3.33, 95%CI (2.98, 3.68), P < 0.00001], Mini-Mental State Examination scores [MD = 2.78, 95%CI (2.51, 3.06), P < 0.00001], and activities of daily living scores [MD = 6.30, 95%CI (4.22, 8.37), P < 0.00001], and shorten the latency of auditory evoked potential P300 [MD = -14.67, 95%CI (-19.54, -9.80), P < 0.00001]. CONCLUSION: Acupuncture alone and acupuncture alongside other therapies are superior to non-acupuncture-based therapies in the treatment of CSVD-VCI. However, due to the small number of relevant available articles and their general low quality, this conclusion may be biased. More clinical RCTs with a larger sample size and higher quality are needed to support this theory.

Reward-related decision-making deficits in internet gaming disorder: a systematic review and meta-analysis.

AIMS: To estimate the aggregated effect sizes of reward-related decision-making deficits in internet gaming disorder (IGD) and to explore potential moderators on the variability of effect sizes across studies. DESIGN: Review of peer-reviewed studies comparing reward-related decision-making performance between IGD and control participants identified via PubMed, Web of Science and ProQuest databases. Random-effects modeling was conducted using Hedge's g as the effect size (ES). The effects of decision-making situation, valence, sample type, testing environment, IGD severity and self-reported impulsivity on decision-making differences were examined by moderator analyses. SETTING: No restrictions on location. PARTICIPANTS: Twenty-four studies (20 independent samples) were included in the meta-analysis, resulting in 604 IGD and 641 control participants and 35 ESs. MEASURES: Reward-related decision-making differences between IGD and control groups. FINDINGS: The overall ES for decision-making deficits in IGD was small (g = -0.45, P < 0.01). The effects were comparable across risky, ambiguous and inter-temporal decision-making. Larger aggregate ESs were identified for pure-gain and mixed compared with pure-loss decision-making. Studies based on clinical and community samples showed similar effects. No significant difference between behavioral studies and those with extra measurements was observed. Decision-making alterations were not closely associated with IGD severity or self-reported impulsivity differences at the study level. CONCLUSIONS: Internet gaming disorder appears to be consistently associated with reward-related decision-making deficits.

Connectome-based prediction of marital quality in husbands' processing of spousal interactions.

Marital quality may decrease during the early years of marriage. Establishing models predicting individualized marital quality may help develop timely and effective interventions to maintain or improve marital quality. Given that marital interactions have an important impact on marital well-being cross-sectionally and prospectively, neural responses during marital interactions may provide insight into neural bases underlying marital well-being. The current study applies connectome-based predictive modeling, a recently developed machine-learning approach, to functional magnetic resonance imaging (fMRI) data from both partners of 25 early-stage Chinese couples to examine whether an individual's unique pattern of brain functional connectivity (FC) when responding to spousal interactive behaviors can reliably predict their own and their partners' marital quality after 13 months. Results revealed that husbands' FC involving multiple large networks, when responding to their spousal interactive behaviors, significantly predicted their own and their wives' marital quality, and this predictability showed gender specificity. Brain connectivity patterns responding to general emotional stimuli and during the resting state were not significantly predictive. This study demonstrates that husbands' differences in large-scale neural networks during marital interactions may contribute to their variability in marital quality and highlights gender-related differences. The findings lay a foundation for identifying reliable neuroimaging biomarkers for developing interventions for marital quality early in marriages.

Neural classification of internet gaming disorder and prediction of treatment response using a cue-reactivity fMRI task in young men.

BACKGROUND: Neural mechanisms underlying internet gaming disorder (IGD) are important for diagnostic considerations and treatment development. However, neurobiological underpinnings of IGD remain relatively poorly understood. METHODS: We employed multi-voxel pattern analysis (MVPA), a machine-learning approach, to examine the potential of neural features to statistically predict IGD status and treatment outcome (percentage change in weekly gaming time) for IGD. Cue-reactivity fMRI-task data were collected from 40 male IGD subjects and 19 male healthy control (HC) subjects. 23 IGD subjects received 6 weeks of craving behavioral intervention (CBI) treatment. MVPA was applied to classify IGD subjects from HCs and statistically predict clinical outcomes. RESULTS: MVPA displayed a high (92.37%) accuracy (sensitivity of 90.00% and specificity of 94.74%) in the classification of IGD and HC subjects. The most discriminative brain regions that contribute to classification were the bilateral middle frontal gyrus, precuneus, and posterior lobe of the right cerebellum. MVPA statistically predicted clinical outcomes in the craving behavioral intervention (CBI) group (r = 0.48, p = 0.0032). The most strongly implicated brain regions in the prediction model were the right middle frontal gyrus, superior frontal gyrus, supramarginal gyrus, anterior/posterior lobes of the cerebellum and left postcentral gyrus. CONCLUSIONS: The findings about cue-reactivity neural correlates could help identify IGD subjects and predict CBI-related treatment outcomes provide mechanistic insight into IGD and its treatment and may help promote treatment development efforts.

Efficient Brain Connectivity Reconfiguration Predicts Higher Marital Quality and Lower Depression.

Social-information processing is important for successful romantic relationships and protecting against depression, and depends on functional connectivity (FC) within and between large-scale networks. Functional architecture evident at rest is adaptively reconfigured during task and there were two possible associations between brain reconfiguration and behavioral performance during neurocognitive tasks (efficiency effect and distraction-based effect). This study examined relationships between brain reconfiguration during social-information processing and relationship-specific and more general social outcomes in marriage. Resting-state FC was compared with FC during social-information processing (watching relationship-specific and general emotional stimuli) of 29 heterosexual couples, and the FC similarity (reconfiguration efficiency) was examined in relation to marital quality and depression 13 months later. The results indicated wives' reconfiguration efficiency (globally and in visual association network) during relationship-specific stimuli processing was related to their own marital quality. Higher reconfiguration efficiency (globally and in medial frontal, frontal-parietal, default mode, motor/sensory and salience networks) in wives during general emotional stimuli processing was related to their lower depression. These findings suggest efficiency effects on social outcomes during social cognition, especially among married women. The efficiency effects on relationship-specific and more general outcome are respectively higher during relationship-specific stimuli or general emotional stimuli processing.

Altered functional network activities for behavioral adjustments and Bayesian learning in young men with Internet gaming disorder.

BACKGROUND AND AIMS: Deficits in cognitive control represent a core feature of addiction. Internet Gaming Disorder (IGD) offers an ideal model to study the mechanisms underlying cognitive control deficits in addiction, eliminating the confounding effects of substance use. Studies have reported behavioral and neural deficits in reactive control in IGD, but it remains unclear whether individuals with IGD are compromised in proactive control or behavioral adjustment by learning from the changing contexts. METHODS: Here, fMRI data of 21 male young adults with IGD and 21 matched healthy controls (HC) were collected during a stop-signal task. We employed group independent component analysis to investigate group differences in temporally coherent, large-scale functional network activities during post-error slowing, the typical type of behavioral adjustments. We also employed a Bayesian belief model to quantify the trial-by-trial learning of the likelihood of stop signal - P(Stop) - a broader process underlying behavioral adjustment, and identified the alterations in functional network responses to P(Stop). RESULTS: The results showed diminished engagement of the fronto-parietal network during post-error slowing, and weaker activity in the ventral attention and anterior default mode network in response to P(Stop) in IGD relative to HC. DISCUSSION AND CONCLUSIONS: These results add to the literatures by suggesting deficits in updating and anticipating conflicts as well as in behavioral adjustment according to contextual information in individuals with IGD.

The effects of amiloride, a Na+-H+ exchange inhibitor, on iliac artery stenosis after balloon injury in rabbits.

This study was designed to explore the effects of amiloride, a Na+-H+ exchange (NHE) inhibitor, on vessel stenosis by observing the expression of NHE-1 protein in vascular smooth muscle (VSM) after balloon injury and the effects of amiloride on VSM cell proliferation, migration, and excretion of extracellular matrices (ECMs). A total of 32 adult male New Zealand white rabbits were randomly divided into a balloon injury group (BG), an amiloride-treated group (AG), and a sham-operated group (SG). The left iliac artery was injured by inflating a 2.5 mm x 20 mm Foley catheter in BG and AG rabbits; in SG rabbits, the Foley catheter was inserted but not inflated. Amiloride (5 mg x kg(-1) x d(-1)) was injected intraperitoneally in AG and the same volume of distilled water was used in BG 3 days before balloon injury and for 28 days after the injury. The left iliac artery was stained by hematoxylin-eosin, alpha-actin, and Masson's trichrome to observe the vessel cava, neointima, media layer, and ECMs. NHE-1 proteins of the VSM were detected by Western blotting. A narrowing of the arterial cava, neointima formation, and thickened VSM layer were observed 28 days after balloon injury in BG and AG. However, in AG, the vessel cava was not as narrowed as that of BG and the intimal areas were to a lesser extent than in BG. In AG, the alpha-actin-positive areas and the ECM areas in the neointima were increased compared with SG, but to a lesser extent than in BG. The expression of NHE-1 protein in VSM was increased in BG and AG after balloon injury; however, the levels in AG were significantly less than in BG. In conclusion, VSM cell proliferation, migration, and excretion of ECMs contributed to vessel stenosis in the BG and AG rabbits. The expression of NHE-1 protein in VSM increased after balloon injury. Amiloride, an inhibitor of NHE-1, can limit the development of vessel stenosis through inhibition of VSM cell proliferation, migration, and excretion of ECMs.

Alterations in functional networks during cue-reactivity in Internet gaming disorder.

BACKGROUND: Cue-induced brain reactivity has been suggested to be a fundamental and important mechanism explaining the development, maintenance, and relapse of addiction, including Internet gaming disorder (IGD). Altered activity in addiction-related brain regions has been found during cue-reactivity in IGD using functional magnetic resonance imaging (fMRI), but less is known regarding the alterations of coordinated whole brain activity patterns in IGD. METHODS: To investigate the activity of temporally coherent, large-scale functional brain networks (FNs) during cue-reactivity in IGD, independent component analysis was applied to fMRI data from 29 male subjects with IGD and 23 matched healthy controls (HC) performing a cue-reactivity task involving Internet gaming stimuli (i.e., game cues) and general Internet surfing-related stimuli (i.e., control cues). RESULTS: Four FNs were identified that were related to the response to game cues relative to control cues and that showed altered engagement/disengagement in IGD compared with HC. These FNs included temporo-occipital and temporo-insula networks associated with sensory processing, a frontoparietal network involved in memory and executive functioning, and a dorsal-limbic network implicated in reward and motivation processing. Within IGD, game versus control engagement of the temporo-occipital and frontoparietal networks were positively correlated with IGD severity. Similarly, disengagement of temporo-insula network was negatively correlated with higher game-craving. DISCUSSION: These findings are consistent with altered cue-reactivity brain regions reported in substance-related addictions, providing evidence that IGD may represent a type of addiction. The identification of the networks might shed light on the mechanisms of the cue-induced craving and addictive Internet gaming behaviors.

Hypoxia-inducible factor-1alpha induces the coronary collaterals for coronary artery disease.

BACKGROUND: Marked variability exists in coronary artery collaterals in patients with ischemic heart disease. Multiple factors are thought to play a role in collateral development; however, the contribution of hypoxia inducible factor-1alpha (HIF-1alpha), which is a transcriptional activator that functions as a master regulator of oxygen homeostasis, is not completely clear. It could play an important role in modulating collateral development. OBJECTIVE: The objective of this study is to investigate the changes and significance of expression of HIF-1alpha in patients with coronary artery collaterals. METHODS: Collateral vessels were determined in 98 patients with >or=70% narrowing of at least one coronary artery without earlier revascularization, 42 patients with coronary artery collaterals and 56 patients with no coronary artery collaterals. Extent of collaterals was expressed as scores according to the Rentrop scoring system. Another 50 cases with normal coronary arteries were selected as control. The levels of HIF-1alpha protein expression in monocyte and lymphocyte in the participants were tested by immunohistochemistry (IHC) and western blot; mRNA levels were measured using reverse transcriptase PCR technique. RESULTS: Compared with the control with normal coronary artery, the patients had higher expression of HIF-1alpha protein tested by IHC and western blot (52.6+/-10.2 vs. 13.7+/-6.2 by IHC, 50.8+/-4.5 vs. 6.5+/-1.8 by western blot); furthermore, significantly higher HIF-1alpha expression was observed in patients with collaterals compared with patients with no collaterals (81.5+/-11.8 vs. 20.7+/-9.4 by IHC; 87.2+/-6.5 vs. 9.5+/-1.4 by western blot). On the transcriptional levels of HIF-1alpha, the result was the same as the protein, there was significant difference of HIF-1alpha between the three groups. The patients with collaterals were the highest (127.3+/-23.9), followed by patients with no collaterals (35.7+/-12.3), and the control were the lowest (23.5+/-9.3). A highly positive correlation was observed between the expression/transcription of HIF-1alpha and collateral score (P<0.01, IHC: r1=0.78, reverse transcriptase PCR: r2=0.69, western blot: r3=0.84). CONCLUSION: These data suggest that higher inductions of HIF-1alpha are associated with coronary collaterals, thus implying that HIF-1alpha may promote coronary collateral formation. Detection of HIF-1alpha expression might be helpful to predict prognosis of patients with coronary artery disease.

The Comorbidity Between Internet Gaming Disorder and Depression: Interrelationship and Neural Mechanisms.

Internet gaming disorder (IGD) is characterized by cognitive and emotional deficits. Previous studies have reported the co-occurrence of IGD and depression. However, extant brain imaging research has largely focused on cognitive deficits in IGD. Few studies have addressed the comorbidity between IGD and depression symptoms and underlying neural mechanisms. Here, we systematically investigated this issue by combining a longitudinal survey study, a cross-sectional resting-state functional connectivity (rsFC) study and an intervention study. Autoregressive cross-lagged modeling on a longitudinal dataset of college students showed that IGD severity and depression are reciprocally predictive. At the neural level, individuals with IGD exhibited enhanced rsFC between the left amygdala and right dorsolateral prefrontal cortex (DLPFC), inferior frontal and precentral gyrus, compared with control participants, and the amygdala-frontoparietal connectivity at the baseline negatively predicted reduction in depression symptoms following a psychotherapy intervention. Further, following the intervention, individuals with IGD showed decreased connectivity between the left amygdala and left middle frontal and precentral gyrus, as compared with the non-intervention group. These findings together suggest that IGD may be closely associated with depression; aberrant rsFC between emotion and executive control networks may underlie depression and represent a therapeutic target in individuals with IGD. Registry name: The behavioral and brain mechanism of IGD; URL: https://www.clinicaltrials.gov/ct2/show/NCT02550405; Registration number: NCT02550405.

Craving Behavior Intervention in Ameliorating College Students' Internet Game Disorder: A Longitudinal Study.

Craving, as a central feature of addiction and a precursor of relapse, is targeted recently in addiction intervention. While Internet gaming disorder (IGD), conceptualized as a behavioral addiction, is lack of effective treatment practice and exploration of its mechanism. This research aims to test the effectiveness and detect the active ingredients of craving behavior intervention (CBI) in mitigation of IGD among young adults. A total of 63 male college students with IGD were assigned into the intervention group (six-session CBI intervention) or the waiting-list control group. Structured questionnaires were administered at pre-intervention (T1), post-intervention (T2), 3-month follow-up (T3), and 6-month follow-up (T4). Compared to the control group, a significant decrease in the severity of IGD in intervention group was found at post-intervention and lasting to 6 months after intervention. The value changes of craving could partially mediate the relationship between intervention and changes of IGD among all effects tests (immediate, T2-T1; short-term, T3-T1; and long-term effects, T4-T1). Further, explorations of the active ingredients of intervention found depression relief and shift of psychological needs from Internet to real life significantly predict craving amelioration at both post-intervention and 6-month follow-up. Although preliminary, the current study provides evidence for the value of craving-aimed intervention practice in IGD treatment and identifies two potential active ingredients for mitigation of craving, and the long-term therapeutic benefits are further conferred. Registry name: The behavioral and brain mechanism of IGD; URL: https://www.clinicaltrials.gov/ct2/show/NCT02550405; Registration number: NCT02550405.