Neural correlates of the addictions neuroclinical assessment (ANA) incentive salience factor among individuals with alcohol use disorder.

The Addictions Neuroclinical Assessment (ANA) is a recently-developed framework offering a more holistic understanding of three neurofunctional and behavioral domains that reflect the neurobiological dysfunction seen in alcohol use disorder (AUD). While the ANA domains have been well-validated across independent laboratories, there is a critical need to identify neural markers that subserve the proposed neurofunctional domains. The current study involves secondary data analysis of a two-week experimental medication trial of ibudilast (50 mg BID). Forty-five non-treatment-seeking participants with AUD (17F / 28 M) completed a battery of validated behavioral assessments forming the basis of their incentive salience factor score, computed via factor analysis, as well as a functional neuroimaging (fMRI) task assessing their neural reactivity to visual alcohol cues after being on placebo or ibudilast for 7 days. General linear models were conducted to examine the relationship between incentive salience and neural alcohol cue-reactivity in the ventral and dorsal stratum. Whole-brain generalized linear model analyses were conducted to examine associations between neural alcohol cue-reactivity and incentive salience. Age, sex, medication, and smoking status were included as covariates. Incentive salience was not associated with cue-elicited activation in the dorsal or ventral striatum. Incentive salience was significantly positively correlated (p < 0.05) with alcohol cue-elicited brain activation in reward-learning and affective regions including the insula and posterior cingulate cortices, bilateral precuneus, and bilateral precentral gyri. The ANA incentive salience factor is reflected in brain circuitry important for reward learning and emotion processing. Identifying a sub-phenotype of AUD characterized by increased incentive salience to alcohol cues allows for precision medicine approaches, i.e. treatments specifically targeting craving and reward from alcohol use. This study serves as a preliminary bio-behavioral validation for the incentive salience factor of the ANA. Further studies validating the neural correlates of other ANA factors, as well as replication in larger samples, appear warranted.

Large-scale network abnormality in behavioral addiction.

BACKGROUND: Researchers have endeavored to ascertain the network dysfunction associated with behavioral addiction (BA) through the utilization of resting-state functional connectivity (rsFC). Nevertheless, the identification of aberrant patterns within large-scale networks pertaining to BA has proven to be challenging. METHODS: Whole-brain seed-based rsFC studies comparing subjects with BA and healthy controls (HC) were collected from multiple databases. Multilevel kernel density analysis was employed to ascertain brain networks in which BA was linked to hyper-connectivity or hypo-connectivity with each prior network. RESULTS: Fifty-six seed-based rsFC publications (1755 individuals with BA and 1828 HC) were included in the meta-analysis. The present study indicate that individuals with BAs exhibit (1) hypo-connectivity within the fronto-parietal network (FN) and hypo- and hyper-connectivity within the ventral attention network (VAN); (2) hypo-connectivity between the FN and regions of the VAN, hypo-connectivity between the VAN and regions of the FN and default mode network (DMN), hyper-connectivity between the DMN and regions of the FN; (3) hypo-connectivity between the reward system and regions of the sensorimotor network (SS), DMN and VAN; (4) hypo-connectivity between the FN and regions of the SS, hyper-connectivity between the VAN and regions of the SS. CONCLUSIONS: These findings provide impetus for a conceptual framework positing a model of BA characterized by disconnected functional coordination among large-scale networks.

Neurofeedback for alcohol addiction: Changes in resting state network activity✰.

Alcohol dependence continues to be a major global burden despite significant research progress and treatment development. The aim of this study was to investigate whether neurofeedback training can alter resting state fMRI activity in brain regions that play a crucial role in addiction disorders in patients with alcohol dependence. For this purpose, a total of 52 patients were recruited for the present study, randomized, and divided into an active and a sham group. Patients in the active group received three sessions of neurofeedback training. We compared the resting state data in the active group as part of the NF training on six measurement days. When comparing the results of the active group from neurofeedback day 3 with baseline 1, a significant reduction in activated voxels in the ventral attention network area was seen. This suggests that reduced activity over the course of therapy in subjects may lead to greater independence from external stimuli. Overall, a global decrease in activated voxels within all three analysed networks compared to baseline was observed in the study. The use of resting-state data as potential biomarkers, as activity changes within these networks, may be to help restore cognitive processes and alcohol abuse-related craving and emotions.

Higher striatal glutamate in male youth with internet gaming disorder.

Internet gaming disorder (IGD) was included in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) as a research diagnosis, but little is known about its pathophysiology. Alterations in frontostriatal circuits appear to play a critical role in the development of addiction. Glutamate is considered an essential excitatory neurotransmitter in addictive disorders. This study's aim was to investigate striatal glutamate in youth with IGD compared to healthy controls (HC). Using a cross-sectional design, 25 adolescent male subjects fulfilling DSM-5 criteria for IGD and 26 HC, matched in age, education, handedness and smoking, were included in the analysis. A structural MPRAGE T1 sequence followed by a single-voxel magnetic resonance spectroscopy MEGA-PRESS sequence (TR = 1500 ms, TE = 68 ms, 208 averages) with a voxel size of 20 mm3 were recorded on 3 T Siemens Magnetom Prisma scanner. The voxel was placed in the left striatum. Group comparison of the relative glutamate and glutamine (Glx) was calculated using regression analysis. IGD subjects met an average of 6.5 of 9 DSM-5 IGD criteria and reported an average of 29 h of weekly gaming. Regression analysis showed a significant group effect for Glx, with higher Glx levels in IGD as compared to HC (coef. = .086, t (50) = 2.17, p = .035). Our study is the first to show higher levels of Glx in the striatum in youth with IGD. The elevation of Glx in the striatum may indicate hyperactivation of the reward system in IGD. Thus, results confirm that neurochemical alterations can be identified in early stages of behavioral addictions.

Similarity and difference in large-scale functional network alternations between behavioral addictions and substance use disorder: a comparative meta-analysis.

Behavioral addiction (BA) and substance use disorder (SUD) share similarities and differences in clinical symptoms, cognitive functions, and behavioral attributes. However, little is known about whether and how functional networks in the human brain manifest commonalities and differences between BA and SUD. Voxel-wise meta-analyses of resting-state functional connectivity (rs-FC) were conducted in BA and SUD separately, followed by quantitative conjunction analyses to identify the common and distinct alterations across both the BA and SUD groups. A total of 92 datasets with 2444 addicted patients and 2712 healthy controls (HCs) were eligible for the meta-analysis. Our findings demonstrated that BA and SUD exhibited common alterations in rs-FC between frontoparietal network (FPN) and other high-level neurocognitive networks (i.e. default mode network (DMN), affective network (AN), and salience network (SN)) as well as hyperconnectivity between SN seeds and the Rolandic operculum in SSN. In addition, compared with BA, SUD exhibited several distinct within- and between-network rs-FC alterations mainly involved in the DMN and FPN. Further, altered within- and between-network rs-FC showed significant association with clinical characteristics such as the severity of addiction in BA and duration of substance usage in SUD. The common rs-FC alterations in BA and SUD exhibited the relationship with consistent aberrant behaviors in both addiction groups, such as impaired inhibition control and salience attribution. By contrast, the distinct rs-FC alterations might suggest specific substance effects on the brain neural transmitter systems in SUD.

The severity of addiction mediates loneliness and cortical volume in internet gaming disorder.

Internet gaming disorder (IGD) subjects reported higher loneliness scores than healthy controls. However, the neural correlates underlying the association between loneliness and IGD remain unclear. Thus, the aim of this study was to explore the relationship between loneliness, online gaming addiction and brain structure. In the current study, structural MRI data were acquired from 84 IGD subjects and 103 matched recreational game users (RGUs). We assessed and compared their addiction severity, loneliness scores, and cortical volumes and analyzed the correlations among these values. Significant correlations were found between loneliness scores and brain volumes in the postcentral cortex, the medial orbitofrontal cortex, the rostral anterior cingulate cortex, and the temporal cortex. In addition, the addiction severity scores partly mediated the relationship between loneliness score and cortical volume in IGD. The results showed that participants with extreme loneliness had significant correlations with brain regions responsible for executive control, social threat surveillance and avoidance. More importantly, the severity of addiction mediates loneliness and cortical volume. The findings shed new insight into the neural mechanisms of loneliness and IGD and have implications for potential treatment.

Regional brain activity of resting-state fMRI and auditory oddball ERP with multimodal approach in individuals with internet gaming disorder.

Background and aims: Resting-state brain activity may be associated with the ability to perform tasks; however, a multimodal approach involving resting-state functional magnetic resonance imaging (fMRI) and event-related potentials (ERPs) has not been widely used to investigate addictive disorders. Methods: We explored resting-state fMRI and auditory oddball ERP values from 26 with internet gaming disorder (IGD) patients and 27 age- and intelligence quotient-matched healthy controls (HCs). To assess the characteristics of resting-state fMRI, we calculated regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), and fractional amplitude of low-frequency fluctuation (fALFF); we also calculated the P3 component of the ERPs. Results: Compared with HCs, the individuals with IGD exhibited significant decreases in ReHo and fALFF values in the left inferior occipital gyrus, increased ReHo and ALFF values in the right precuneus, increased ALFF in the left superior frontal gyrus, and lower P3 amplitudes in the midline centro-parietal area during the auditory ERP task. Furthermore, the regional activity of resting-state fMRI in the right inferior temporal gyrus and the occipital regions were positively correlated with the P3 amplitudes in IGD patients, whereas ReHo values of the left hippocampus and the right amygdala were negatively correlated with P3. Discussion and conclusions: Our results suggest that IGD patients have difficulty interacting effectively with cognitive function and sensory processing, although its interpretations need some cautions. The findings in this study will broaden the overall understanding of the neurobiological mechanisms that underlie IGD pathophysiology.

The role of the cerebellum in internet gaming disorder-A systematic review.

Recent studies increasingly highlight involvement of the cerebellum in drug craving and addiction. However, its exact role, that is, whether the cerebellum is a critical component of a brain network underlying addictive behaviour, or whether it rather is a facilitator or mediator, is still unclear. Findings concerning the newly recognized internet gaming disorder (IGD) suggest that changes in cerebellar connectivity and functioning are associated with behavioural/non-substance addiction. Here, we systematically review the literature on IGD and cerebellar involvement following the PRISMA guidelines. A total of 13 neuroimaging studies met the inclusion criteria. Studies utilized a broad range of diagnostic instruments and resulting cut-off criteria, rendering it difficult to compare findings. Results on altered cerebro-cerebellar connectivity in patients with IGD are mixed; most studies report altered or increased functional connectivity. Moreover, decreased cerebellar grey matter volume is reported. Studies have further indicated that differential activation patterns in the cerebellum may enable discrimination between healthy subjects and subjects with IGD, even allowing for prediction of treatment outcomes. Given the strong connectivity between the cerebellum and cerebral regions, the cerebellum may act as an intermediary between regions involved in craving and addiction and consequently affect symptoms of IGD. Results suggest differential involvement of the cerebellar lobes, emphasizing a need for high-resolution parcellation of the cerebellum in future studies. However, the studies included in the present review have small sample sizes and include mostly male participants. Thus, results may have limited generalizability yet highlight a crucial role of the cerebellum in IGD that needs further investigation.

Static and dynamic changes of intrinsic brain local connectivity in internet gaming disorder.

BACKGROUND: Studies have revealed that intrinsic neural activity varies over time. However, the temporal variability of brain local connectivity in internet gaming disorder (IGD) remains unknown. The purpose of this study was to explore the alterations of static and dynamic intrinsic brain local connectivity in IGD and whether the changes were associated with clinical characteristics of IGD. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed on 36 individuals with IGD (IGDs) and 44 healthy controls (HCs) matched for age, gender and years of education. The static regional homogeneity (sReHo) and dynamic ReHo (dReHo) were calculated and compared between two groups to detect the alterations of intrinsic brain local connectivity in IGD. The Internet Addiction Test (IAT) and the Pittsburgh Sleep Quality Index (PSQI) were used to evaluate the severity of online gaming addiction and sleep quality, respectively. Pearson correlation analysis was used to evaluate the relationship between brain regions with altered sReHo and dReHo and IAT and PSQI scores. Receiver operating characteristic (ROC) curve analysis was used to reveal the potential capacity of the sReHo and dReHo metrics to distinguish IGDs from HCs. RESULTS: Compared with HCs, IGDs showed both increased static and dynamic intrinsic local connectivity in bilateral medial superior frontal gyrus (mSFG), superior frontal gyrus (SFG), and supplementary motor area (SMA). Increased dReHo in the left putamen, pallidum, caudate nucleus and bilateral thalamus were also observed. ROC curve analysis showed that the brain regions with altered sReHo and dReHo could distinguish individuals with IGD from HCs. Moreover, the sReHo values in the left mSFG and SMA as well as dReHo values in the left SMA were positively correlated with IAT scores. The dReHo values in the left caudate nucleus were negatively correlated with PSQI scores. CONCLUSIONS: These results showed impaired intrinsic local connectivity in frontostriatothalamic circuitry in individuals with IGD, which may provide new insights into the underlying neuropathological mechanisms of IGD. Besides, dynamic changes of intrinsic local connectivity in caudate nucleus may be a potential neurobiological marker linking IGD and sleep quality.

Abnormal structural alterations and disrupted functional connectivity in behavioral addiction: A meta-analysis of VBM and fMRI studies.

Background: Altered large-scale brain systems, including structural alterations and resting-state functional connectivity (rs-FC) changes, have been demonstrated as effective system-level biomarkers for revealing potential neural mechanism of multiple brain disorders. However, identifying consistent abnormalities of large-scale brain systems in behavioral addictions (BA) is challenging due to varying methods and inconsistent results. Therefore, the aim of this study was to identify the significantly abnormal large-scale brain systems in BA. Method: PubMed, OVID Embase, OVID Medline, and Web of Science were searched with relevant keywords to identify potential studies. A total of 52 studies including 35 rs-FC studies and 17 structural studies were examined by extracting the coordinates of seeds and target brain regions. The seeds were then categorized into predefined seven networks by their locations based on previous parcellations in rs-FC studies, followed by pooling the results in those networks. Results: The rs-FC findings illustrated that BA were characterized as abnormal networks in response to inhibition, salience attribution, self-referential mental process, and reward-driven behaviors. Meanwhile, meta-analysis of structural studies showed decreased gray matter volume in the anterior cingulate cortex, extending to the middle cingulate cortex and the superior frontal gyrus. Importantly, overlapping regions in the cingulate cortex and anterior thalamus projections extending to caudate regions exhibited both dysfunctions in structure and rs-FC. Conclusions: This study highlighted substantial dysconnectivity in BA, which might result in impaired response to inhibition and salience attribution. Therefore, this study might provide novel insights of neural biomarkers for clinical diagnoses and treatment targets for BA.

Functional MRI of inhibitory control processing in problematic mobile video gamers.

With the development of mobile technology, mobile video games provide people with a more convenient way of entertainment, but problematic playing could also bring some negative consequences. Prior studies have indicated that Internet gaming addicts were accompanied by impaired inhibitory control. However, as a relatively new form of problematic game usage based on mobile devices, little is known about the neurobiological underpinnings of inhibitory control in problematic mobile video game (PMVG) users. Adopting an event-related fMRI Stroop task, the present study aimed to examine the different neural correlates of inhibitory control between PMVG and healthy control (HC) subjects. Compared with HC group, PMVG group showed greater brain activities in the right dorsolateral prefrontal cortex (DLPFC) during the Stroop process. Moreover, correlation analysis showed that brain activities extracted from the voxel in the DLPFC cluster had a significantly negative correlation with reward sensitivity. Our current findings may suggest the compensating effect in key brain regions of inhibitory control in problematic mobile video gamers relative to healthy controls.

Reduced loss aversion in value-based decision-making and edge-centric functional connectivity in patients with internet gaming disorder.

Background and aims: Impaired value-based decision-making is a feature of substance and behavioral addictions. Loss aversion is a core of value-based decision-making and its alteration plays an important role in addiction. However, few studies explored it in internet gaming disorder patients (IGD). Methods: In this study, IGD patients (PIGD) and healthy controls (Con-PIGD) performed the Iowa gambling task (IGT), under functional magnetic resonance imaging (fMRI). We investigated group differences in loss aversion, brain functional networks of node-centric functional connectivity (nFC) and the overlapping community features of edge-centric functional connectivity (eFC) in IGT. Results: PIGD performed worse with lower average net score in IGT. The computational model results showed that PIGD significantly reduced loss aversion. There was no group difference in nFC. However, there were significant group differences in the overlapping community features of eFC1. Furthermore, in Con-PIGD, loss aversion was positively correlated with the edge community profile similarity of the edge2 between left IFG and right hippocampus at right caudate. This relationship was suppressed by response consistency3 in PIGD. In addition, reduced loss aversion was negatively correlated with the promoted bottom-to-up neuromodulation from the right hippocampus to the left IFG in PIGD. Discussion and conclusions: The reduced loss aversion in value-based decision making and their related edge-centric functional connectivity support that the IGD showed the same value-based decision-making deficit as the substance use and other behavioral addictive disorders. These findings may have important significance for understanding the definition and mechanism of IGD in the future.

Cognitive domain-independent aberrant frontoparietal network strength in individuals with excessive smartphone use.

Excessive smartphone use (ESU) may fulfill criteria for addictive behavior. In contrast to other related behavioral addictions, particularly Internet Gaming Disorder, little is known about the neural correlates underlying ESU. In this study, we used functional magnetic resonance imaging (fMRI) to acquire task data from three distinct behavioral paradigms, i.e. cue-reactivity, inhibition, and working memory, in individuals with psychometrically defined ESU (n = 19) compared to controls (n-ESU; n = 20). The Smartphone Addiction Inventory (SPAI) was used to quantify ESU-severity according to a novel five-factor model (SPAI-I). A multivariate data fusion approach, i.e. joint Independent Component Analysis (jICA) was employed to analyze fMRI-data derived from three separate experimental conditions, but analyzed jointly to detect converging and domain-independent neural signatures that differ between persons with vs. those without ESU. Across the three functional tasks, jICA identified a predominantly frontoparietal system that showed lower network strength in individuals with ESU compared to n-ESU (p < 0.05 FDR-corrected). Furthermore, significant associations between frontoparietal network strength and SPAI-I's dimensions "time spent" and "craving" were found. The data suggest a frontoparietal cognitive control network as cognitive domain-independent neural signature of excessive and potentially addictive smartphone use.

Opposing associations of Internet Use Disorder symptom domains with structural and functional organization of the striatum: A dimensional neuroimaging approach.

Background: Accumulating evidence suggests brain structural and functional alterations in Internet Use Disorder (IUD). However, conclusions are strongly limited due to the retrospective case-control design of the studies, small samples, and the focus on general rather than symptom-specific approaches. Methods: We here employed a dimensional multi-methodical MRI-neuroimaging design in a final sample of n = 203 subjects to examine associations between levels of IUD and its symptom-dimensions (loss of control/time management, craving/social problems) with brain structure, resting state and task-based (pain empathy, affective go/no-go) brain function. Results: Although the present sample covered the entire range of IUD, including normal, problematic as well as pathological levels, general IUD symptom load was not associated with brain structural or functional alterations. However, the symptom-dimensions exhibited opposing associations with the intrinsic and structural organization of the brain, such that loss of control/time management exhibited negative associations with intrinsic striatal networks and hippocampal volume, while craving/social problems exhibited a positive association with intrinsic striatal networks and caudate volume. Conclusions: Our findings provided the first evidence for IUD symptom-domain specific associations with progressive alterations in the intrinsic structural and functional organization of the brain, particularly of striatal systems involved in reward, habitual and cognitive control processes.

Sex differences in neural substrates of risk taking: Implications for sex-specific vulnerabilities to internet gaming disorder.

Background and aims: Sex differences in internet gaming disorder (IGD) remain unknown. Investigating sex-specific neural features that underlie the core risk factor (i.e., risk-taking) of IGD would help in understanding sex-specific vulnerabilities to IGD and advance sex-specific treatments and prevention for IGD. Methods: 111 participants (28 IGD males, 27 IGD females, 26 recreational game user (RGU) males, 30 RGU females) completed a probability discounting task during fMRI scanning. Results: First, among RGUs, males showed a higher risk-taking tendency and greater neural activation associated with risk/value evaluation for reward (the ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), left putamen) and smaller activation associated with cognitive control (the inferior frontal gyrus) than females during the contrast of risky-safe choices. Moreover, males showed a greater modulatory effect of risky choices on the connection from the vmPFC/ACC to the left putamen than females. Second, IGD males showed decreased activation in the vmPFC/ACC and left putamen compared to RGU males, whereas this decrease did not exist in IGD females. Discussion: Males show a higher risk-taking tendency than females. Altered neural substrates associated with risky decision-making exist in IGD males but not in IGD females. Conclusions: The present findings fill the gap in information on the behavioral and neural substrates underlying IGD among females and demonstrate that a high risk-taking tendency is a risk factor and core symptom only in IGD males but not in IGD females. It is necessary to design and adopt distinct treatments and prevention strategies for IGD in males and females.

Predicting the severity of internet gaming disorder with resting-state brain features: A multi-voxel pattern analysis.

BACKGROUND: Internet gaming disorder (IGD) has become a worldwide mental health concern; however, the neural mechanism underlying this disorder remains unclear. Multivoxel pattern analysis (MVPA), a newly developed data-driven approach, can be used to investigate the neural features of IGD based on massive neural data. METHODS: Resting-state fMRI data from four hundred and two participants with varying levels of IGD severity were recruited. Regional homogeneity (ReHo) and the amplitude of low-frequency fluctuation (ALFF) were calculated and subsequently decoded by applying MVPA. The highly weighted regions in both predictive models were selected as regions of interest for further graph theory and Granger causality analysis (GCA) to explore how they affect IGD severity. RESULTS: The results revealed that the neural patterns of ReHo and ALFF can independently and significantly predict IGD severity. The highly weighted regions that contributed to both predictive models were the right precentral gyrus and left postcentral gyrus. Moreover, topological properties of the right precentral gyrus were significantly correlated with IGD severity; further GCA revealed effective connectivity from the right precentral gyrus to left precentral gyrus and dorsal anterior cingulate cortex, both of which were significantly associated with IGD severity. CONCLUSIONS: The present study demonstrated that IGD has distinctive neural patterns, and this pattern could be found by machine learning. In addition, the neural features in the right precentral gyrus play a key role in predicting IGD severity. The current study revealed the neural features of IGD and provided a potential target for IGD interventions using brain modulation.

Self-control impacts symptoms defining Internet gaming disorder through dorsal anterior cingulate-ventral striatal pathway.

Self-control is important for long-term success and could be a protective factor against maladaptive behaviours such as excessive gaming activity or Internet gaming disorder (IGD). However, the neurobiological basis of self-control and its relationship to IGD remain elusive. Using resting-state fMRI data from 89 participants aged from 18 to 26, we found that self-control and the number of IGD symptoms (IGD-S) were positively and negatively correlated with functional connectivity between right ventral striatum (rVS) and dorsal anterior cingulate cortex (dACC), respectively. A mediation analysis indicated that self-control influenced IGD-S partially through the rVS-dACC connectivity. In addition, step-wise regression analyses revealed that the rVS connectivity in a reward-anticipation limbic pathway contributed to IGD-S but not self-control, independent of the dACC pathway. These results suggest that the cingulate-ventral striatal functional connectivity may serve as an important neurobiological underpinning of self-control to regulate maladaptive behaviours such as these manifesting IGD through striatal circuitry balance.

Neurocognitive Mechanisms Underlying Internet/Smartphone Addiction: A Preliminary fMRI Study.

The present study investigated the neurocognitive mechanisms underlying smartphone/internet addiction. We tested a specific hypothesis that the excessive, uncontrolled use of smartphones should be related to the ability of controlling attention in a purely endogenous and self-regulatory manner. In an fMRI experiment, in which 43 adults participated, we had participants detect and identify specified target stimuli among non-targets. In some trials, 10 s oddball movies were presented as distractors. While the participants try to filter out the distractors and focus their attention on the main task, the activation profiles of the frontoparietal brain regions were examined. The results showed that the people with a higher risk of being addicted to smartphone use failed to filter out distractors via the endogenous control of attention. The neuroimaging data showed that the high-risk group showed significantly lower levels of activation in the frontopolar cortex (FPC). We conclude that people at a high risk of smartphone addiction have difficulty endogenously shifting their attention from distracting stimuli toward goal-directed behavior, and FPC plays a critical role in this self-regulatory control of attention.

The unbalanced behavioral activation and inhibition system sensitivity in internet gaming disorder: Evidence from resting-state Granger causal connectivity analysis.

BACKGROUND: Patients with behavioral or substance addiction show an unbalanced behavioral activation system (BAS) and behavioral inhibition system (BIS) sensitivity. However, the relationship between internet gaming disorder (IGD) and BAS/BIS is obscure and the neurobiological mechanism underlying this relationship remains unclear. METHODS: We recruited 154 IGDs and 229 recreational game users (RGUs) in the current study. First, we explored the relationship between BAS/BIS and IGD. Second, subjects were subdivided into subgroups by BAS/BIS sensitivity. Third, whole-brain Granger causal connectivity (GCC) of striatum and amygdala subdivisions was estimated for the subgroup. Fourth, mediation analysis was performed to explore the role of connectivity in the relationship between IGD and BAS/BIS sensitivity. RESULTS: We found the IGD group scored higher than the RGU on BIS and BASf (fun-seeking) sensitivity. Then, we identified 4 (2*2) subgroups: low/high risk of IGD with low/high BAS/BIS sensitivity groups. Two-way ANCOVA main results of interaction effects showed that in the high BAS/BIS group, the RGU exhibited increased strength in the GCC from the left putamen to the right cuneus, and the IGD exhibited decreased strength in the GCC from the right medial frontal gyrus to the caudate, from the left superior frontal gyrus to the centromedial amygdala, and from the right superior parietal lobule to the left laterobasal amygdala. Moreover, the GCC from the centromedial amygdala to the middle frontal gyrus mediated the directional relationship between BIS and IAT (Young's internet addiction test) scores. CONCLUSIONS: The IGD individuals exhibited higher BIS and BAS-fun seeking sensitivity. Moreover, IGD with unbalanced BAS/BIS sensitivity exhibited alternative connectivity patterns involving amygdala and striatum subdivisions. These findings suggest a neurobiological mechanism for an alternation between IGD and RGU with different BAS/BIS sensitivity.

Compounding Vulnerability in the Neurocircuitry of Addiction: Longitudinal Functional Connectivity Changes in Alcohol Use Disorder.

AIMS: The addiction neurocircuitry model describes the role of several brain circuits (drug reward, negative emotionality and craving/executive control) in alcohol use and subsequent development of alcohol use disorder (AUD). Human studies examining longitudinal change using resting-state functional magnetic resonance imaging (rs-fMRI) are needed to understand how functional changes to these circuits are caused by or contribute to continued AUD. METHODS: In order to characterize how intrinsic functional connectivity changes with sustained AUD, we analyzed rs-fMRI data from individuals with (n = 18; treatment seeking and non-treatment seeking) and without (n = 21) AUD collected on multiple visits as part of various research studies at the NIAAA intramural program from 2012 to 2020. RESULTS: Results of the seed correlation analysis showed that individuals with AUD had an increase in functional connectivity over time between emotionality and craving neurocircuits, and a decrease between executive control and reward networks. Post hoc investigations of AUD severity and alcohol consumption between scans revealed an additive effect of these AUD features in many of the circuits, such that more alcohol consumption or more severe AUD was associated with more pronounced changes to synchronicity. CONCLUSIONS: These findings suggest an increased concordance of networks underlying emotionality and compulsions toward drinking while also a reduction in control network connectivity, consistent with the addiction neurocircuitry model. Further, they suggest a compounding effect of continued heavy drinking on these vulnerabilities in neurocircuitry. More longitudinal research is necessary to understand the trajectories of individuals with AUD not adequately represented in this study, as well as whether this can inform effective harm reduction strategies.