Efficacy and Neural Mechanisms of Mindfulness Meditation Among Adults With Internet Gaming Disorder

Key Points Question Is mindfulness meditation (MM) an effective treatment for adults with internet gaming disorder (IGD), and what neural mechanisms underlie MM? Findings In this randomized clinical trial of 64 participants, IGD severity and craving decreased among participants who received the MM intervention but not those treated with progressive muscle relaxation. The MM intervention was associated with decreased brain activation in the bilateral lentiform nuclei, insula, and medial frontal gyrus. Meaning These findings indicate that MM may be an effective treatment for adults with IGD and may exert its effects by altering frontopallidal pathways.


Introduction
[3][4][5] In the past decade, notable advances have improved understanding of the neural features underlying IGD.Altered brain activation has been observed in frontal brain regions related to executive control. 6ese regions include the dorsolateral prefrontal cortex and orbitofrontal cortex, 7,8 which are also implicated in craving.0][11] Beyond regional activation and consistent with dual-process models of addiction, altered connectivity among brain regions involved in executive control and reward processing have been reported in individuals with IGD. 12,13Despite increased understanding of the neurobiology of IGD, treatment development efforts in the behavioral, pharmacologic, and neuromodulatory domains have been arguably slower. 146][17][18] Although treatments are reported to decrease gaming craving or shorten gaming time, gaming recurrence after treatment may be high. 19udies of substance use disorders (SUDs) suggest that craving after cessation is a main reason for relapse. 20,21Craving has also been implicated in IGD, and the presence of gaming cues may be difficult to avoid, given how individuals currently use digital devices.Furthermore, games have been used for educational purposes, with schools incorporating games to promote learning. 22,23Internet gaming may improve visuospatial ability 24 and motor skills 25 and may promote well-being.However, gaming exposure may lead to craving and dysfunction among individuals with IGD.
Mindfulness meditation (MM) has attracted recent public and scientific interest.This treatment has been incorporated into clinical interventions and examined with neuroimaging. 26Compared with other treatments, MM has the advantages of versatility and social acceptance, which may increase the likelihood that individuals will engage with and adhere to MM and may overcome some existing barriers to treatment. 27,28The practice of MM may extend beyond treating clinical conditions and promote well-being in general populations. 29,30To our knowledge, MM has not been systematically investigated to examine its efficacy and tolerability in the treatment of IGD.In MM, individuals are instructed to attend in a nonjudgmental way while maintaining a relaxed vigilance for distractions. 31ndfulness meditation can increase attention and self-regulation, 32 which often are areas of concern for individuals with IGD.Mindfulness meditation may support sustained improvement by strengthening the ability to monitor and cope with discomfort (craving or negative affect), thus supporting longer-term outcomes. 33These characteristics suggest that MM may be beneficial in the treatment of individuals with IGD.Specific brain mechanisms may underlie the systematic training of attention and self-control with an attitude of acceptance and openness to internal and external experiences inherent to MM. 32,34 Brain mechanisms implicated in attentional control (alerting, orienting, and conflict monitoring), 35,36  present-moment experiences) 37,38 have been linked to MM. Specific brain regions implicated include the anterior cingulate cortex, striatum and other limbic regions, prefrontal cortex, insula, posterior cingulate cortex, and precuneus. 32,34Thus, MM may alter responses to cues that lead to craving and engagement in addictive behaviors in a manner different from other therapies. 39,40udies of addiction have emphasized a key role for craving. 41,42Craving contributes to the development and maintenance of addictive behaviors. 43Impaired control over craving has been linked to engagement in addictive behaviors despite adverse consequences.Mindfulness meditation promotes improved attention and self-control 35,38 and may decrease craving, 44,45 perhaps by directly altering responses to environmental and internal factors. 44Altered activity in the anterior cingulate cortex and prefrontal cortex has been observed in randomized studies of mindfulness training involving individuals who smoke tobacco 46 or use other drugs. 47In previous studies, MM decreased craving and substance use among individuals who used drugs, 37 with longer-term effects on reduced craving. 33milar to individuals with SUDs, those with IGD often experience impaired executive control over gaming craving [9][10][11] and alterations in interactions between brain regions involved in executive control and reward processing.

Participants
To determine the required sample size, we used G*Power, version 3.1.9.7 (University of Dusseldorf), with an effect size f equal to 0.25 and α error probability equal to .05.The required sample size was 66. Eligible participants were aged 18 years or older.Potential participants were instructed to complete the online Internet Addiction Test (IAT) (revised for IGD). 50,51Individuals with an IAT score greater than 50 were interviewed by a psychiatrist to diagnose IGD according to the proposed criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), which includes 9 items. 52We used a threshold of at least 6 inclusion criteria having been met to ensure IGD of substantial severity. 53Psychiatric disorders were also assessed using the Mini-International Neuropsychiatric Interview (MINI). 54l participants completed a pretest safety screening questionnaire for functional magnetic resonance imaging (fMRI).Individuals were excluded if they met any of the following criteria: (

Task-Based Brain Responses
Participants performed a cue-craving task during fMRI as described previously. 58eFigure 1B in Supplement 2 describes the tasks and timeline for 1 trial.First, participants were asked to fixate their sight on a cross located at the center of the screen for 500 milliseconds.Then cues were presented for approximately 3000 milliseconds, and participants were instructed to respond to whether there was a face in each picture by pressing button 1 (yes) or 2 (no).Each cue was terminated by pressing a button.If participants did not respond for 3000 milliseconds, the trial was considered missed.
After participants pressed the button, a black screen was presented for 3000 milliseconds.Finally, a black screen was shown for 1500 to 3500 milliseconds before the next trial.The task included 80 trials, with the entire task lasting approximately 12 minutes.
Of the 80 pictures shown in the task, 40 were related to gaming and 40 were related to typing (eFigure 1B in Supplement 2).In each category, half of the pictures had a face and the other half had a hand.In gaming-related pictures, a person was shown gaming in front of a computer.Typingrelated pictures were considered neutral stimuli.For our study, we created 2 copies (A and B) of the tasks for pretest and posttest.To avoid having a difference between A and B (although we tried to make them similar), some of the participants used copy A for the pretest and copy B for the posttest; the other participants used copy B for the pretest and copy A for the posttest.This is known as the AB/BA experimental design.

Mindfulness Training Sessions
All The training procedure's design was based on specified theoretical content. 59

Parameters and Preprocessing of fMRI Scans
Structural images were obtained using a T1-weighted,

Secondary Analysis
First, we identified voxels that showed a main effect in the gaming trials compared with the neutral trials.Second, we determined voxels that were significantly different in pretest vs posttest BOLD signals.We identified clusters of contiguous and significantly different voxels at an uncorrected threshold of P < .001(2-sided).Finally, these clusters were tested for cluster-level familywise error correction at P < .005(2-sided).Specifically, the estimate obtained using the AlphaSim correction method indicated that the cluster extent of 26 adjoining voxels would achieve a familywise error threshold of P < .005(2-sided) effectively.The smoothing kernel applied in simulating false-positive (noise) maps using AlphaSim was 8.4 mm, which was estimated from residual fields of the contrast maps pooled into the 1-sample t test.

Analysis of variance (ANOVA) of group (MM or PMR) × time (pretest [baseline] or posttest
[outcome]) interactions were performed.Post hoc analyses were performed for further testing.
P < .05 was considered statistically significant, and all significance tests were 2 tailed.

Functional Connectivity Among Implicated Brain Regions
We used brain regions implicated in the cue-craving task as regions of interest (ROIs) in group comparisons and calculated the functional connectivity (FC) among these ROIs.Correlations between pretest vs posttest changes in FC values and changes in gaming craving scores were calculated.
Statistical analysis was performed using the CONN toolbox, release 22a. 64Data analysis was conducted on December 1, 2023.
Similar findings were observed for IAT scores (Figure 2B) and craving (Figure 2C) for the MM group but not for the PMR group.In the MM group, there were significant decreases in IAT scores When posttest results were compared between the MM and PMR groups, statistically significant differences were found between groups for IGD severity (mean [SD], 3.6 [0.8] vs 6.0   2D presents changes in craving scores for the MM group from pretest assessment at baseline to 1 month after posttest assessment.

Task-Based Brain Responses
The ANOVA results showed that brain responses in the bilateral lentiform nuclei, left medial frontal gyrus (MFG), right insula, and right sublobar region decreased after MM treatment compared with baseline, with greater effects than PMR (Figure 3 and eTable in Supplement 2).In the comparison of β weights in different conditions, these features were related to decreased brain responses after MM treatment (Figure 3).Regarding relationships between pretest vs posttest changes in brain response and craving scores, positive correlations were observed in the lentiform nuclei (r = 0.40; 95% CI, 0.19 to 0.60; P = .02),insula (r = 0.35; 95% CI, 0.09 to 0.60; P = .047),and MFG (r = 0.43; 95% CI, 0.16 to 0.70; P = .01)(Figure 3).Findings for the fusiform and sublobar regions are presented in eFigure 4 in Supplement 2.

FC Among Implicated Brain Regions
eFigure 5 in Supplement 2 describes the ROIs selected for FC calculation.Functional connectivity between the left MFG and left lentiform increased after MM (Figure 4).Changes in MFG-lentiform FC mediated the relationship between changes in mindfulness and gaming craving scores in the MM group (task A-B = −0.17;95% CI, −0.32 to −0.08; P = .03;eFigure 6 in Supplement 2).

Discussion
In this study of adults with IGD, MM was superior to PMR in reducing craving and IGD severity.
Furthermore, frontopallidal brain mechanisms were implicated, with changes in MFG-lentiform FC mediating the relationship between increased mindfulness and decreased craving.Implications of these findings are discussed next.

Pretest vs Posttest Assessments
Most pretest vs posttest indicators of IGD used in this study (ie, IAT scores, number of DSM-5-TR proposed criteria met, and craving scores) decreased in both the MM and PMR groups.These findings highlight the importance of including a control PMR group to identify effects specific to MM.  sessions reduced gaming craving to a significantly greater extent than PMR, supporting the promise of MM in treating individuals with IGD.

Brain Responses
According to our group comparisons, MM decreased activation in brain regions previously implicated in craving, including the lentiform nuclei, MFG, and insula.The lentiform nucleus is a key node of dopaminergic circuitry implicated in craving and reward processing. 65,66Cue-induced craving often involves lentiform activation, including in individuals with IGD 42,67 and those with SUDs. 68,69covery and decreased addiction severity have been associated with decreased lentiform activation in cue-craving tasks. 67In line with these prior reports, positive correlations between gaming craving and lentiform activation were observed in this study, with decreased activation after MM treatment.
Taken together, cue-related lentiform activation may represent a potential biomarker of treatment outcome for IGD, with MM serving to decrease such activation.
In this study, the MFG also demonstrated decreased cue-related activation after MM.In a previous meta-analysis, MFG activation was implicated in cue-induced drug craving. 70The MFG shows temporal dynamics in drug-cue responses 71 and is also implicated in executive control. 65,724][75] Mindfulness meditation may operate, in part, by altering cue reactivity and thus increasing behavioral control. 32,34e features of MM linked to cue responsivity warrant consideration.Mindfulness meditation involves systematic training of attention and self-control with an attitude of acceptance and openness to internal and external experiences. 32,34One key feature of MM involves accepting the present situation in a nonjudgmental fashion while maintaining a relaxed vigilance for distractions. 31 the case of craving, MM may involve considering cravings or urges as current phenomena, observing them with curiosity as mental events, and not suppressing them or thinking about the past or the future. 76With respect to IGD, MM may involve accepting gaming cravings and not engaging in gaming or combatting the urges.Previous randomized MM studies have observed reduced resting brain activity in cortical regions of individuals with tobacco use disorder 46 or other SUDs, 47 consistent with findings that individuals who are experienced in meditation show relatively reduced activity in cortical regions, especially in regions of the default mode network such as the MFG and posterior cingulate cortex. 37As such, the brain mechanisms underlying MM may differ from those of other behavioral treatments such as cognitive behavior therapy or motivational interviewing, although some common elements (eg, decreased neural craving responses to cues) may be shared. 77,78 this study, decreased insula activation was observed after MM in the experimental group during the fMRI craving task.The insula, like the lentiform nuclei and cortical regions, has been implicated in craving 79,80 and has thus been proposed as a treatment target for addiction. 81Nicotine withdrawal has been associated with greater activation of the anterior insula, 82 and individuals with stroke lesions in the insula have spontaneously quit smoking. 83,84The insula has been linked to reactivity to gaming cues.However, among individuals with IGD, relatively increased activation to gaming cues was observed after a craving behavioral intervention (involving elements of mindfulness and cognitive behavior therapy), although decreased connectivity between the insula and regions implicated in craving like the precuneus was also observed. 85,86Additionally, relatively decreased insula activity has been observed in individuals with IGD in response to affective stimuli. 87From this perspective, the insula has been implicated in complex or mixed functions in IGD.In this study, the correlation between changes in insula activation and gaming craving scores suggests that MM may reduce craving in part by reducing insular activation to gaming cues, similar to observations for SUDs.

MM and Changes in FC
In this study, both the MFG and lentiform nuclei showed relatively decreased cue-related activity after MM, with increased MFG-lentiform FC.These findings suggest that concurrent reductions within the frontopallidal circuitry may be related to decreased cue reactivity and craving after MM.
Consistent with this notion, we observed that FC changes between the MFG and lentiform nuclei mediated the relationship between changes in mindfulness and gaming craving.As discussed earlier, FC between the MFG and lentiform nuclei reflects the coupling between these 2 measures.Addiction may involve an imbalance between control and reward systems, which may be structurally independent but functionally coordinated 88 ; in addition, top-down regulation of craving in addiction may involve cortical control over subcortical drives. 89Although the results for MM in this study suggest such processes, a perhaps more plausible explanation given the fMRI task administered suggests that MM may directly alter cortical-subcortical systems underlying craving.Future studies involving different tasks, such as regulation-of-craving tasks, 72 particularly those modified to examine mindful vs cognitive regulation, may help provide further clarity.

Limitations
This study had several limitations.First, this study included only gaming cue task-based brain responses.Data from other tasks or resting-state data may have provided additional insight.Second, the pretest and posttest assessments were not linked to specific MM modules.Future studies may consider more precisely the elements of MM that may reflect its active ingredients.Third, follow-up of these participants would provide valuable information about the recurrence of gaming addiction after MM training.

Conclusions
In this randomized clinical trial of adults with IGD, MM was more effective in decreasing addiction severity and gaming cravings compared with PMR.In addition, MM decreased activation in cortical and subcortical brain regions previously implicated in craving responses, with coordinated reductions linking relationships between changes in mindfulness and decreases in cue-induced craving.These findings suggest that MM may alter frontopallidal responses underlying craving in IGD, and they provide preliminary support for the use of MM to treat IGD and suggest possible neural mechanisms for its efficacy.
MM and PMR training sessions were performed in separate rooms, in which all participants had a seat or yoga mat.Beyond MM and PMR training, no specific requirements were set for participants regarding their gaming behaviors.The interventions are described next.eFigure 1 in Supplement 2 presents the MM (experimental) and PMR (control) training interventions.Training lasted for 4 weeks, with 2 sessions (each 2.5-3.5 hours) per week.We required participants to attend all training and fMRI scanning sessions.The MM training sessions typically included 10 to 20 participants and were led by 2 MM trainers.(The PMR training sessions were open at the same time and were led by 2 PMR trainers.)During the training sessions, trainers observed participants and answered questions after training completion.

Figure 2 .
Figure 2. Pretest and Posttest Assessments of Mindfulness Meditation (MM) and Progressive Muscle Relaxation (PMR) The ANOVA of group (MM or PMR) × time (pretest or posttest) interactions indicated superiority of MM on outcome measures related to craving and IGD severity.The results suggest that 8 MM training

JAMA Network Open | Substance Use and Addiction Efficacy
emo34on regulation,32,34and self-awareness (self-reference and awareness of and Neural Mechanisms of Mindfulness Meditation for Internet Gaming Disorder JAMA Network Open.2024;7(6):e2416684.doi:10.1001/jamanetworkopen.2024.16684(Reprinted) June 18, 2024 2/15 Downloaded from jamanetwork.comby guest on 06/29/2024 12,13The aforementioned findings of efficacy in SUD treatment suggest that MM may be effective in treating individuals with IGD by decreasing cue-related craving and IGD severity.This study aimed to investigate the efficacy of MM in treating adults with IGD and to explore the potential underlying neural mechanisms of MM.Because some prior studies have been criticized for lack of randomization and weak control conditions, 32,34 we included an active control

JAMA Network Open | Substance Use and Addiction
Behavioral measurements were collected 1 hour before the pretest assessment.Craving scores for gaming were collected immediately after each MM or PMR session.Data at the posttest assessment were collected immediately after participants finished the eighth MM or PMR session.Addiction severity was measured with the DSM-5-TR proposed criteria for IGD and with IAT scores.Craving was last 12 months before recruitment;(7)regular used any psychotropic medication; and (8) had any prior mindfulness training experiences.After careful selection, 80 individuals were included in this study.All eligible participants were randomly allocated (1:1) to either MM (experimental group) or progressive muscle relaxation (PMR) (control group).Men and women were arranged into experimental and control groups separately, according to their registration sequence (odd for experimental and even for control).The CONSORT flow diagram is presented in Figure 1, and the task procedures are described in eFigure 1A in Supplement 2. measured with the Questionnaire for Gaming Urges (adapted from the Tiffany Questionnaire for Smoking Urges 57 ) before the first training, after each training, and 1 month after the entire training period.

JAMA Network Open | Substance Use and Addiction Efficacy
Lost to follow-up (missed follow-up fMRI scan) and Neural Mechanisms of Mindfulness Meditation for Internet Gaming Disorder Figure 1.CONSORT Flow Diagram 542 Potential participants assessed for eligibility 462 Excluded 411 Did not meet inclusion criteria 51 Refused to participate or declined due to MM scheduling conflicts 2 Excluded due to head movement 4 Excluded due to head movement 80 Randomized 32 Included in analysis 32 Included in analysis 6 Lost to follow-up (missed follow-up fMRI scan) 4 JAMA Network Open.2024;7(6):e2416684.doi:10.1001/jamanetworkopen.2024.16684(Reprinted) June 18, 2024 4/15 Downloaded from jamanetwork.comby guest on 06/29/2024 Functional Imaging Laboratory, UCL Queen Square Institute of Neurology), 62 then co-registered and normalized to the Montreal Neurological Institute brain template and smoothed using a 4-mm 3 isotropic gaussian kernel.Six participants (4 in the MM group and 2 in the PMR group) were excluded from analyses due to head movement (3 mm in directional movement or 2°in rotational movement).Detailed procedures and parameters are provided in the eAppendix in Supplement 2.Efficacy and Neural Mechanisms of Mindfulness Meditation for Internet Gaming Disorder and GLMs included a constant term per run.Head movement parameters and a highpass filter (0.01-0.1 Hz) for 128 seconds were included as regressions of no interest.The GLM approach was used to identify voxels that were significantly activated for each event during the response stage.