Predictive neural signature of internet gaming disorder severity revealed by cross-network connectivity

Internet gaming disorder (IGD) and gambling disorder (GD) share similar clinical characteristics but show different brain functional connectivity patterns. Bupropion is known to be effective for the treatment of patients with IGD and GD. We hypothesized that bupropion may be effective for the treatment of Internet-based gambling disorder (ibGD) and IGD and that the connections between the default mode network (DMN) and cognitive control network (CCN) would be different between ibGD and IGD patients after 12 weeks of bupropion treatment. 16 patients with IGD, 15 patients with ibGD, and 15 healthy subjects were recruited in this study. At baseline and after 12 weeks of bupropion treatment, the clinical symptoms of patients with IGD or ibGD were assessed, and brain activity was evaluated using resting state functional magnetic resonance imaging. After the 12-week bupropion treatment, clinical symptoms, including the severity of IGD or GD, depressive symptoms, attention, and impulsivity improved in both groups. In the IGD group, the functional connectivity (FC) within the posterior DMN as well as the FC between the DMN and the CCN decreased following treatment. Moreover, the FC within the DMN in the IGD group was positively correlated with changes in Young Internet Addiction Scale scores after the bupropion treatment period. In the ibGD group, the FC within the posterior DMN decreased while the FC within the CCN increased after the bupropion treatment period. Moreover, the FC within the CCN in the ibGD group was significantly greater than that in the IGD group. Bupropion was effective in improving clinical symptoms in patients with IGD and ibGD. However, there were differences in the pharmacodynamics between the two groups. After 12 weeks of bupropion treatment, the FC within the DMN as well as between the DMN and CCN decreased in patients with IGD, whereas the FC within the CCN increased in patients with ibGD.

Cognitive, functional, and structural brain factors involving frontal executive and striatal reward networks have been implicated in Internet gaming disorder (IGD). However, frontostriatal network connectivity and its association with addiction severity are poorly understood in IGD. Resting-state fMRI data from 337 subjects (130 with IGD, 207 with recreational game use [RGU]) were collected. Striatal-cortical communications were measured with resting-state functional connectivity (FC) using coherent spontaneous fluctuations in the blood-oxygenation-level-dependent fMRI signal. Correlations were calculated between FC measures and IGD-related assessments (addiction severity and craving scores). Decreased FC was predominantly observed in IGD subjects, with IGD subjects showing decreased FC between the putamen and superior frontal gyrus (SFG), middle frontal gyrus (MFG), and inferior frontal gyrus (IFG) and the ventral striatum and IFG, superior temporal gyrus, and MFG. Disorder severity and craving scores were negatively correlated with FC between striatal and frontal brain regions. Associations between diminished FC in corticostriatal circuitry and clinical features (IGD craving, severity) suggest potential therapeutic targets for neuromodulation treatments. The extent to which frontostriatal circuits involving executive control over reward processes may be altered to treat IGD warrants additional study.

Individual-Specific Neural Subspaces Reveal Reward Dysregulation and State Transition Vulnerabilities in Internet Gaming Disorder.

This study sought to investigate brain responses to positive and negative events in individuals with internet gaming disorder (IGD) during real gaming as a direct assessment of the neural features of IGD. This investigation reflects the neural deficits in individuals with IGD while playing games, providing direct and effective targets for prevention and treatment of IGD. Thirty subjects with IGD and fifty-two matched recreational game use (RGU) subjects were scanned while playing an online game. Abnormal brain activities during positive and negative events were detected using a general linear model. Functional connectivity (FC) and correlation analyses between neural features and addiction severity were conducted to provide additional support for the underlying neural features. Compared to the RGU subjects, the IGD subjects exhibited decreased activation in the dorsolateral prefrontal cortex (DLPFC) during positive events and decreased activation in the middle frontal gyrus (MFG), precentral gyrus and postcentral gyrus during negative events. Decreased FC between the DLPFC and putamen during positive events and between the MFG and amygdala during negative events were observed among the IGD subjects. Neural features and addiction severity were significantly correlated. Individuals with IGD exhibited deficits in regulating game craving, maladaptive habitual gaming behaviors and negative emotions when experiencing positive and negative events during real game-playing compared to RGU gamers. These abnormalities in neural substrates during real gaming provide direct evidence for explaining why individuals with IGD uncontrollably and continuously engage in game playing, despite negative consequences.

Background and aimsAlthough the Internet has provided convenience and efficiency in many areas of everyday life, problems stemming from Internet use have also been identified, such as Internet gaming disorder (IGD). Internet addiction, which includes IGD, can be viewed as a behavioral addiction or impulse control disorder. This study investigated the altered functional and effective connectivity of the core brain networks in individuals with IGD compared to healthy controls (HCs).MethodsForty-five adults with IGD and 45 HCs were included in this study. To examine the brain networks related to personality traits that influence problematic online gaming, the left and right central executive network (CEN) and the salience network (SN) were included in the analysis. Also, to examine changes in major brain network topographies, we analyzed the default mode network (DMN).ResultsIGD participants showed lower functional connectivity between the dorsal lateral prefrontal cortex (DLPFC) and other regions in the CEN than HC participants during resting state. Also, IGD participants revealed reduced functional connectivity between the dorsal anterior cingulate cortex and other regions in the SN and lower functional connectivity in the medial prefrontal cortex of the anterior DMN. Notably, in IGD individuals but not HC individuals, there was a positive correlation between IGD severity and effective connectivity and a positive correlation between reward sensitivity and effective connectivity within the ventral striatum of the SN.ConclusionsProblematic online gaming was associated with neurofunctional alterations, impairing the capacity of core brain networks.

Regardless of whether it is conceptualized as a behavioral addiction or an impulse-control disorder, internet gaming disorder (IGD) has been speculated to be associated with impaired cognitive control. Efficient cognitive behavior involves the coordinated activity of large-scale brain networks, however, whether the interactions among these networks during resting state modulated cognitive control behavior in IGD adolescents remain unclear. Twenty-eight IGD adolescents and twenty-five age-, gender-, and education-matched healthy controls participated in our study. Stroop color-word task was conducted to evaluate the cognitive control deficits in IGD adolescents. Functional connectivity and Granger Causal Analysis were employed to investigate the functional and effective connections within and between the salience, central executive, and default mode networks. Meanwhile, diffusion tensor imaging was used to assess the structural integrity of abnormal network connections. The abnormal functional connectivity within central executive networks and effective connectivity within salience network in IGD adolescents were detected. Moreover, the inefficient interactions between these two brain networks were observed. In addition, we identified reduced fractional anisotropy in salience network, right central executive network tracts, and between-network (the anterior cingulate cortex-right dorsolateral prefrontal cortex tracts) pathways in IGD individuals. Notably, we observed a significant correlation between the effective and structural connection from salience network to central executive network and the number of errors during incongruent condition in Stroop task in both IGD and control subjects. Our results suggested that impaired cognitive control in IGD adolescents is likely to be mediated through the abnormal interactions and structural connection between intrinsic large-scale brain networks.

Deficient dynamics of prefrontal-striatal and striatal-default mode network (DMN) neural circuits in 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.

Animal models suggest transitions from non-addictive to addictive behavioral engagement are associated with ventral-to-dorsal striatal shifts. However, few studies have examined such features in humans, especially in internet gaming disorder (IGD), a proposed behavioral addiction. We recruited 418 subjects (174 with IGD; 244 with recreational game use (RGU)). Resting-state fMRI data were collected and functional connectivity analyses were performed based on ventral and dorsal striatal seeds. Correlations and follow-up spectrum dynamic causal model (spDCM) analyses were performed to examine relationships between the ventral/dorsal striatum and middle frontal gyrus (MFG). Longitudinal data were also analysed to investigate changes over time. IGD relative to RGU subjects showed lower ventral-striatum-to-MFG (mostly involving supplementary motor area (SMA)) and higher dorsal-striatum-to-MFG functional connectivity. spDCM revealed that left dorsal-striatum-to-MFG connectivity was correlated with IGD severity. Longitudinal data within IGD and RGU groups found greater dorsal striatal connectivity with the MFG in IGD versus RGU subjects. These findings suggest similar ventral-to-dorsal striatal shifts may operate in IGD and traditional addictions.

Diminished cognitive control in Internet gaming disorder: A multimodal approach with magnetic resonance imaging and real-time heart rate variability

Gender-related differences in involvement of addiction brain networks in internet gaming disorder: Relationships with craving and emotional regulation

Altered gray matter density and disrupted functional connectivity of the amygdala in adults with Internet gaming disorder.

Dopamine projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) and from the substantia nigra (SN) to the dorsal striatum are involved in addiction. However, relatively little is known about the implication of these circuits in Internet gaming disorder (IGD). This study examined the alteration of resting-state functional connectivity (RSFC) and diffusion tensor imaging (DTI) -based structural connectivity of VTA/SN circuits in 61 young male participants (33 IGD and 28 healthy controls). Correlation analysis was carried out to investigate the relationship between the neuroimaging findings and the behavioral Internet Addiction Test (IAT). Both the NAc and medial orbitofrontal cortex (mOFC) showed lower RSFC with VTA in IGD subjects compared with controls. Moreover, the RSFC strength of VTA-right NAc and VTA-left mOFC correlated negatively with IAT in IGD subjects. The IGD subjects also showed lower structural connectivity in bilateral VTA-NAc tracts compared with controls, but the connectivity did not correlate with IAT in IGD. We provide evidence that functional and structural connectivity of the VTA-NAc pathway, and functional connectivity of the VTA-mOFC pathway are implicated in IGD. Since these pathways are important for dopamine reward signals and salience attribution, the findings suggest involvement of the brain DA reward system in the neurobiology of IGD. The association of functional but not structural connectivity of VTA circuits with IAT suggests that while lower structural connectivity might underlie vulnerability for IGD, lower functional connectivity may modulate severity. These results strengthen the evidence that IGD shares similar neuropathology with other addictions.

Depression is one of the most common comorbid conditions in Internet Gaming Disorder (IGD). Although there have been many studies on the pathophysiology of IGD, the neurobiological basis underlying the close association between depression and IGD has not been fully clarified. Previous neuroimaging studies have demonstrated functional and structural abnormalities in the anterior cingulate cortex (ACC) in IGD patients. In this study, we explored functional connectivity (FC) abnormalities involving subregions of the ACC in IGD subjects with comorbid depression. We performed a resting state seed-based FC analysis of 21 male young adults with IGD with comorbid depression (IGDdep+ group, 23.6 ± 2.4 years), 22 male young adults without IGD with comorbid depression (IGDdep− group, 24.0 ± 1.6 years), and 20 male age-matched healthy controls (24.0 ± 2.2 years). ACC-seeded FC was evaluated using the CONN-fMRI FC toolbox. The dorsal ACC (dACC), the pregenual ACC (pgACC), and the subgenual ACC (sgACC) were selected as seed regions. Both IGD groups had stronger pgACC FC with the right precuneus, the posterior cingulate cortex, and the left inferior frontal gyrus/insula than the control group. The IGDdep+ group had stronger dACC FC with the left precuneus and the right cerebellar lobule IX than the control and IGDdep- groups. The IGDdep+ group also had weaker pgACC FC with the right dorsomedial prefrontal cortex and the right supplementary motor area and had weaker sgACC FC with the left precuneus, the left lingual gyrus, and the left postcentral gyrus than the other groups. The strength of the connectivity between the sgACC and the left precuneus correlated positively with a higher omission error rate in the continuous performance test in the IGDdep+ group. In addition, the IGDdep– group had stronger sgACC FC with the left dorsolateral prefrontal cortex than the other groups. Our findings suggest that young males with IGD comorbid with depression have FC alterations of the default mode network and diminished FC with the prefrontal cortex. This altered FC pattern may be involved in the close association of IGD and depression.

Approach bias modification training reduces gaming severity and improves brain network topology in internet gaming disorder.