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BACKGROUND: The incidence of invasive fungal diseases (IFDs), represented by Candida albicans infection, is increasing year by year. However, clinically available antifungal drugs are very limited and encounter challenges such as limited efficacy, drug resistance, high toxicity, and exorbitant cost. Therefore, there is an urgent need for new antifungal drugs. PURPOSE: This study aims to find new antifungal compounds from plants, preferably those with good activity and low toxicity, and reveal their antifungal targets. METHODS: In vitro antifungal activities of compounds were investigated using broth microdilution method, spot assay, hyphal growth assay and biofilm formation assay. Synergistic effects were assessed using broth microdilution checkerboard technique. In vivo antifungal activities were evaluated using Galleria mellonella and murine candidiasis models. Cytotoxicity of compounds was investigated using Cell Counting Kit-8 (CCK-8). Discovery and validation of antifungal targets of compounds were conducted by using monoallelic knockout library of C. albicans, haploinsufficiency profiling (HIP), thermal shift assay (TSA), enzyme inhibitory effect assay, molecular docking, and in vitro and in vivo antifungal studies. RESULTS: 814 plant products were screened, among which petroselinic acid (PeAc) was found as an antifungal molecule. As a rare fatty acid isolated from coriander (Coriandrum sativum), carrot (Daucus carota) and other plants of the Apiaceae family, PeAc had not previously been found to have antifungal effects. In this study, PeAc was revealed to inhibit the growth of various pathogenic fungi, exhibited synergistic effects with fluconazole (FLC), inhibited the formation of C. albicans hyphae and biofilms, and showed antifungal effects in vivo. PeAc was less toxic to mammalian cells. Fructose-1,6-bisphosphate aldolase (Fba1p) was identified as a target of PeAc by using HIP, TSA, enzyme inhibitory effect assay and molecular docking methods. PeAc exerted antifungal effects more effectively on fba1Δ/FBA1 than wild-type (WT) strain both in vitro and in vivo. CONCLUSIONS: PeAc is an effective and low toxic antifungal compound. The target of PeAc is Fba1p. Fba1p is a promising target for antifungal drug development.
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A series of "turn off" pH fluorescence probes with chalcone skeleton for basic system have been developed. The molecules emitted bright yellow fluorescence under acidic condition, resulting AIE coupled ESIPT characteristic and ICT process. What's more, the compounds exhibited excellent sensitivity and selectivity for detecting pH as a facile "On-Off" fluorescence probe, and the fluorescence of them were quenched with the ESIPT process interrupted under alkaline condition. Theoretical calculation for the related compounds also performed to verify the electron effect on photophysical properties and confirm the rational speculation on the mechanism.
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OBJECTIVE: To analyze the current treatment status and prognostic regression of the chronic NK cell lymphoproliferative disorder (CLPD-NK). METHODS: We retrospectively analyzed the clinical features, treatment and prognosis of 18 patients with CLPD-NK who were treated at our Hospital between September 2016 and September 2022. RESULTS: Eighteen patients were included: three patients were treated with chemotherapy, five patients underwent immune-related therapy, one patient was treated with glucocorticoids alone, five patients were administered granulocyte colony-stimulating factor, blood transfusion therapy, or anti-infection therapy, followed by observation and follow-up, and four patients were observed without treatment. Fifteen patients survived, including two patients who achieved complete remission (CR) and seven patients who achieved partial remission (PR), of whom one patient progressed to Aggressive NK-cell leukemia (ANKL) and sustained remission after multiple lines of treatment; three patients were not reviewed, of which one patient was still in active disease, three patients developed hemophagocytic syndrome during treatment and eventually died, one of them had positive Epstein-Barr virus (EBV) expression. The 5-years overall survival rate was 83%. CONCLUSION: Most patients with CLPD-NK have inert progression and a good prognosis, whereas some patients have a poor prognosis after progressing to ANKL and combined with hemophagocytic syndrome. Abnormal NK cells invading the center suggest a high possibility of ANKL development, and immunosuppressants and hormones are effective treatments for this disease.
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Infecciones por Virus de Epstein-Barr , Leucemia Linfocítica Granular Grande , Leucemia , Linfohistiocitosis Hemofagocítica , Trastornos Linfoproliferativos , Humanos , Infecciones por Virus de Epstein-Barr/complicaciones , Herpesvirus Humano 4 , Estudios Retrospectivos , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/terapia , Pronóstico , Células Asesinas Naturales/metabolismo , Enfermedad Crónica , Leucemia/metabolismoRESUMEN
Corynespora cassiicola is a common plant pathogen responsible for leaf-spotting diseases in the tropical and subtropical areas. C. cassiicola seldom causes human infections. Here we describe a case of subcutaneous phaeohyphomycosis caused by C. cassiicola in a 76-year-old Chinese man, who presented to our hospital with a purulent discharge and painful sensation on his right leg. Skin biopsy revealed an abscess, and culture confirmed C. cassiicola to be the causative agent. The result was further identified by sequence analysis of the internal transcribed spacer region. The patient was successfully treated with systemic voriconazole and wound debridement: the lesion disappeared after 20 days.
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Ascomicetos , Feohifomicosis , Masculino , Humanos , Anciano , Feohifomicosis/tratamiento farmacológicoRESUMEN
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.
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Conectoma , Matrimonio , Humanos , Matrimonio/psicología , Esposos/psicología , EmocionesRESUMEN
BACKGROUND: Central nervous system lymphoma (CNSL) is an aggressive lymphoma. Orelabrutinib, an oral Bruton tyrosine kinase inhibitor, is a new treatment strategy for CNSL. This study aims to evaluate the efficacy and safety of orelabrutinib-based regimens in the treatment of patients with CNSL. METHODS: Twenty-three patients with CNSL were included in this retrospective study. All patients received the orelabrutinib-based regimen. Efficacy was evaluated based on investigators' assessment of overall response rate (ORR), complete response/unconfirmed complete response (CR/CRu), partial response (PR), stable disease (SD), progressive disease (PD), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). The safety of orelabrutinib-based regimens has also been evaluated. RESULTS: A total of 17.39% of patients received orelabrutinib-based regimens for consolidation therapy, and 82.61% of patients for induction therapy (4 newly diagnosed CNSL, 15 relapsed/refractory CNSL). In the newly diagnosed CNSL group, the ORR was 100% (1 CR, 1 CRu, 2 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 100%, 100%, and 100%, respectively. Of the 15 relapsed/refractory CNSL patients, five therapy regimens were applied (orelabrutinib, n = 3; orelabrutinib/immunotherapy, n = 3; orelabrutinib/chemotherapy, n = 2; orelabrutinib/immunochemotherapy, n = 6; orelabrutinib/radiotherapy, n = 1). The ORR was 60.00% (4 CR, 5 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 92.30%, 67.70%, and 70.00%, respectively. Twenty-one patients reported adverse events (AEs), and 6 patients experienced grade ≥ 3 AEs. CONCLUSION: Orelabrutinib-based regimens were efficacious and well-tolerated in patients with CNSL. These combined therapies offer a new potential therapeutic strategy for patients with CNSL.
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Neoplasias del Sistema Nervioso Central , Linfoma no Hodgkin , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Sistema Nervioso Central , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Humanos , Linfoma no Hodgkin/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/efectos adversos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
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.
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Conducta Adictiva , Juegos de Video , Conducta Adictiva/diagnóstico por imagen , Conducta Adictiva/terapia , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Ansia/fisiología , Señales (Psicología) , Humanos , Internet , Trastorno de Adicción a Internet , Imagen por Resonancia Magnética , MasculinoRESUMEN
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.
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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.
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Conducta Adictiva/fisiopatología , Mapeo Encefálico , Encéfalo/fisiología , Trastorno de Adicción a Internet/fisiopatología , Vías Nerviosas/fisiología , Teorema de Bayes , Cognición , Función Ejecutiva , Humanos , Modelos Lineales , Imagen por Resonancia Magnética , Masculino , Aprendizaje por Probabilidad , Pruebas Psicológicas , Adulto JovenRESUMEN
Burkholderia pseudomallei is an important infectious disease pathogen that can cause melioidosis. Melioidosis is mainly prevalent in Thailand, northern Australia and southern China and has become a global public health problem. Early identification of B. pseudomallei is of great significance for the diagnosis and prognosis of melioidosis. In this study, a simple and visual device combined with lateral flow strip-based recombinase polymerase amplification (LF-RPA) was developed, and the utility of the LF-RPA assay for identifying B. pseudomallei was evaluated. In order to screen out the optimal primer probe, a total of 16 pairs of specific primers targeting the orf2 gene of B. pseudomallei type III secretion system (T3SS) cluster genes were designed for screening, and F1/R3 was selected as an optimal set of primers for the identification of B. pseudomallei, and parameters for LF-RPA were optimized. The LF-RPA can be amplified at 30-45°C and complete the entire reaction in 5-30 min. This reaction does not cross-amplify the DNA of other non-B. pseudomallei species. The limit of detection (LOD) of this assay for B. pseudomallei genomic DNA was as low as 30 femtograms (fg), which was comparable to the results of real-time PCR. Moreover, 21 clinical B. pseudomallei isolates identified by 16S rRNA gene sequencing were retrospectively confirmed by the newly developed LF-RPA system. Our results showed that the newly developed LF-RPA system has a simple and short time of operation and has good application prospect in the identification of B. pseudomallei.
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Burkholderia pseudomallei , Recombinasas , Burkholderia pseudomallei/genética , Técnicas de Amplificación de Ácido Nucleico/métodos , ARN Ribosómico 16S , Recombinasas/genética , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
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.
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Conducta Adictiva/fisiopatología , Conectoma , Trastorno de Adicción a Internet/fisiopatología , Máquina de Vectores de Soporte , Juegos de Video/psicología , Adulto , Encéfalo/fisiopatología , Función Ejecutiva , Humanos , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/fisiopatología , Adulto JovenRESUMEN
Vasoactive intestinal polypeptide receptor (VIP1R) is a widely expressed class B G protein-coupled receptor and a drug target for the treatment of neuronal, metabolic, and inflammatory diseases. However, our understanding of its mechanism of action and the potential of drug discovery targeting this receptor is limited by the lack of structural information of VIP1R. Here we report a cryo-electron microscopy structure of human VIP1R bound to PACAP27 and Gs heterotrimer, whose complex assembly is stabilized by a NanoBiT tethering strategy. Comparison with other class B GPCR structures reveals that PACAP27 engages VIP1R with its N-terminus inserting into the ligand binding pocket at the transmembrane bundle of the receptor, which subsequently couples to the G protein in a receptor-specific manner. This structure has provided insights into the molecular basis of PACAP27 binding and VIP receptor activation. The methodology of the NanoBiT tethering may help to provide structural information of unstable complexes.
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Microscopía por Crioelectrón/métodos , Proteínas de Unión al GTP/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Receptores de Tipo I del Polipéptido Intestinal Vasoactivo/metabolismo , Dispersión Dinámica de Luz , Humanos , Microscopía Electrónica , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/metabolismoRESUMEN
YAP/TAZ and ß-catenin are important effectors in the Hippo and Wnt signaling pathways, respectively, which are involved in the development of human tumors. Using immunohistochemistry, the expression levels of the three proteins were determined in 151 cervical tissue samples (including 28 normal cervical, 31 cervical intraepithelial neoplasia, and 92 cervical squamous cell carcinoma [CSC] tissues), which were excised or biopsied by surgery. The results showed that the three proteins were differently expressed in normal, precancerous, and CSC tissues, and ß-catenin expression positively correlated with both YAP and TAZ expression. By analyzing the relationships between YAP, TAZ, and ß-catenin expression and the clinicopathologic characteristics of patients with CSC, we found that YAP was related to the depth of invasion > 1/2, the diameter of the tumor > 4 cm, and positive lymph nodes; while TAZ and ß-catenin were related to the depth of invasion > 1/2 and positive lymph nodes. Regarding the prognostic factors of patients with CSC, Kaplan-Meier univariate and Cox multivariate regression analysis showed that there were significant correlations between lymph node infiltration; expression of YAP, TAZ, and ß-catenin; and patient mortality (P < 0.05), all of which were independent factors influencing mortality (OR > 1).
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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.
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Encéfalo/fisiopatología , Trastorno de Adicción a Internet/fisiopatología , Recompensa , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Neuroimagen/métodos , Adulto JovenRESUMEN
Tillering is a significant agronomic trait in wheat which shapes plant architecture and yield. Strigolactones (SLs) function in inhibiting axillary bud outgrowth. The roles of SLs in the regulation of bud outgrowth have been described in model plant species, including rice and Arabidopsis. However, the role of SLs genes in wheat remains elusive due to the size and complexity of the wheat genomes. In this study, TaD27 genes in wheat, orthologs of rice D27 encoding an enzyme involved in SLs biosynthesis, were identified. TaD27-RNAi wheat plants had more tillers, and TaD27-B-OE wheat plants had fewer tillers. Germination bioassay of Orobanche confirmed the SLs was deficient in TaD27-RNAi and excessive in TaD27-B-OE wheat plants. Moreover, application of exogenous GR24 or TIS108 could mediate the axillary bud outgrowth of TaD27-RNAi and TaD27-B-OE in the hydroponic culture, suggesting that TaD27-B plays critical roles in regulating wheat tiller number by participating in SLs biosynthesis. Unlike rice D27, plant height was not affected in the transgenic wheat plants. Transcription and gene coexpression network analysis showed that a number of genes are involved in the SLs signalling pathway and axillary bud development. Our results indicate that TaD27-B is a key factor in the regulation of tiller number in wheat.
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Proteínas de Plantas , Triticum , Regulación de la Expresión Génica de las Plantas , Fenotipo , Proteínas de Plantas/genética , Plantas Modificadas Genéticamente , Transducción de Señal/genética , Triticum/anatomía & histología , Triticum/genéticaRESUMEN
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.
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Conducta Adictiva/fisiopatología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Señales (Psicología) , Imagen por Resonancia Magnética/métodos , Juegos de Video/psicología , Adulto , Conducta Adictiva/diagnóstico por imagen , Mapeo Encefálico/métodos , Humanos , Internet , Masculino , Adulto JovenRESUMEN
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.
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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.
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Terapia Conductista , Conducta Adictiva/rehabilitación , Corteza Cerebral/diagnóstico por imagen , Ansia , Internet , Estriado Ventral/diagnóstico por imagen , Juegos de Video , Conducta Adictiva/diagnóstico por imagen , Conducta Adictiva/fisiopatología , Estudios de Casos y Controles , Corteza Cerebral/fisiopatología , Estudios Transversales , Neuroimagen Funcional , Humanos , Imagen por Resonancia Magnética , Masculino , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Estriado Ventral/fisiopatología , Adulto JovenRESUMEN
Difficulties in emotion regulation are commonly reported among individuals with alcohol and drug addictions and contribute to the acquisition and maintenance of addictive behaviors. Alterations in neural processing of negative affective stimuli have further been demonstrated among individuals with addictions. However, it is unclear whether these alterations are a general feature of addictions or are a result of prolonged exposure to drugs of abuse. To test the hypothesis of altered negative affect processing independent of drug effects, this study assessed neural function among drug-naïve youth with a behavioral addiction-Internet gaming disorder (IGD). Fifty-six young adults (28 with IGD, 28 matched controls) participated in fMRI scanning during performance of a well-validated emotion regulation task. Between-group differences in neural activity during task performance were assessed using a whole-brain, mixed-effects ANOVA with correction for multiple comparisons at currently recommended thresholds (voxel-level p<0.001, pFWE<0.05). Compared to controls, youth with IGD exhibited significantly blunted neural responses within distributed subcortical and cortical regions including the striatum, insula, lateral prefrontal cortex and anterior cingulate in response to negative affective cues, as well as during emotion regulation. Independent component analysis (ICA) further identified between-group differences in engagement of a fronto-cingulo-parietal network, involving decreased engagement in IGD youth relative to controls. Study findings are largely consistent with those from prior neuroimaging studies in substance-use disorders, thus raising the possibility that neural processing of negative affect may be blunted across drug and behavioral addictions independent of acute or chronic drug effects.
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Conducta Adictiva/fisiopatología , Encéfalo/fisiopatología , Emociones/fisiología , Juego de Azar/fisiopatología , Internet , Adolescente , Adulto , Conducta Adictiva/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Inteligencia Emocional/fisiología , Juego de Azar/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Adulto JovenRESUMEN
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.