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In This Article

  • Summary
  • Abstract
  • Introduction
  • Protocol
  • Results
  • Discussion
  • Disclosures
  • Acknowledgements
  • Materials
  • References
  • Reprints and Permissions

Summary

We present a protocol and a feasibility study for applying transcranial direct current stimulation (tDCS) and neuroimaging assessment in online gamers.

Abstract

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that applies a weak electric current to the scalp to modulate neuronal membrane potentials. Compared to other brain stimulation methods, tDCS is relatively safe, simple, and inexpensive to administer.

Since excessive online gaming can negatively affect mental health and daily functioning, developing treatment options for gamers is necessary. Although tDCS over the dorsolateral prefrontal cortex (DLPFC) has demonstrated promising results for various addictions, it has not been tested in gamers. This paper describes a protocol and a feasibility study for applying repeated tDCS over the DLPFC and neuroimaging to examine the underlying neural correlates in gamers.

At baseline, individuals who play online games report average weekly hours spent on games, complete questionnaires on addiction symptoms and self-control, and undergo brain 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET). The tDCS protocol consists of 12 sessions over the DLPFC for 4 weeks (anode F3/cathode F4, 2 mA for 30 min per session). Then, a follow-up is conducted using the same protocol as the baseline. Individuals who do not play online games receive only baseline FDG-PET scans without tDCS. Changes of clinical characteristics and asymmetry of regional cerebral metabolic rate of glucose (rCMRglu) in the DLPFC are examined in gamers. In addition, asymmetry of rCMRglu is compared between gamers and non-gamers at baseline.

In our experiment, 15 gamers received tDCS sessions and completed baseline and follow-up scans. Ten non-gamers underwent FDG-PET scans at the baseline. The tDCS reduced addiction symptoms, time spent on games, and increased self-control. Moreover, abnormal asymmetry of rCMRglu in the DLPFC at baseline was alleviated after tDCS.

The current protocol may be useful for assessing treatment efficacy of tDCS and its underlying brain changes in gamers. Further randomized sham-controlled studies are warranted. Moreover, the protocol can be applied to other neurological and psychiatric disorders.

Introduction

In recent years, increasing attention has been paid to excessive online game use since its associations with negative impact on mental health and daily functioning as well as with internet gaming disorder (IGD) have been reported1,2,3. Although several treatment strategies including pharmacotherapy and cognitive-behavioral therapy have been evaluated, evidence for their effectiveness is limited4.

Previous studies have suggested that IGD may share clinical and neurobiological similarities with other behavioral addictions and substance use disorders5,6. It has been reported that the dorsolateral prefrontal cortex (DLPFC) is closely involved in the pathophysiology of substance and behavioral addiction such as craving7, impulse control8, decision making9, and cognitive flexibility10. Several neuroimaging studies on IGD have reported structural and functional impairments in the DLPFC6. In particular, structural neuroimaging studies revealed a reduction in gray matter density in the DLPFC11,12 and a functional magnetic resonance imaging (fMRI) study found an altered cued-induced activity in the DLPFC of patients with IGD13. In addition, functional asymmetry of the brain may contribute to impulsivity and craving in addictions including IGD. For instance, cue-induced craving for online gaming could be related to right prefrontal activations14. However, alterations of regional cerebral metabolic rate of glucose (rCMRglu) associated with excessive online game use or IGD remain to be further investigated compared to other brain deficits15.

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that applies a weak electric current (1-2 mA) through electrodes attached to the scalp to modulate neuronal membrane potentials. Generally, the cortical excitability is increased under the anode electrode and decreased under the cathode electrode16. tDCS has become a popular method because it is simple, inexpensive, and safe to administer compared to other brain stimulation techniques such as transcranial magnetic stimulation (TMS) that uses a magnetic pulse to generate an electrical current in the brain tissue under the coil. According to a recent review, the use of conventional tDCS protocols has not produced any serious adverse effects or irreversible injury and is associated with only mild and transient itching or tingling sensation under the stimulation area17.

Several studies have demonstrated favorable results of tDCS18,19,20 and repetitive TMS21,22 over the DLPFC for treating behavioral and substance addiction. However, further studies are needed to investigate the effects of brain stimulation techniques on online game use and the underlying brain changes.

The aim of this study is to present a protocol for applying repeated sessions of tDCS over the DLPFC and neuroimaging to examine the underlying neural correlates in gamers using 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET), as well as to assess its feasibility. Specifically, we focused on changes in addiction symptoms, average time spent on games, self-control, and asymmetry of rCMRglu in the DLPFC.

Protocol

All experimental procedures presented in this protocol have been approved by the Institutional Review Board and are in accordance with the Declaration of Helsinki.

1. Research Participants

  1. Recruit individuals who report that they play online games (the gamer group) and those who report that they do not play online games (the non-gamer group).
    NOTE: Here, we included individuals with two or more IGD symptoms according to the Diagnostic and Statistical Manual of Mental Disorders-523 or those who play games at least one hour per day on average in the gamer group. The non-gamer group undergoes only baseline brain FDG-PET scans to compare rCMRglu with the gamer group and does not receive tDCS sessions.
  2. For both groups, exclude individuals with (a) major medical, psychiatric, or neurological disorders, (b) history of traumatic brain injury, (c) history of alcohol or other substance abuse or dependence, (d) use of psychotropic medications, or (e) any contraindications for tDCS such as severe headache, metal in the head, history of seizure, epilepsy, or brain surgery, or any lesions or other medical problems on the skin where tDCS electrodes will be attached.
  3. Explain to each participant the aim of the study, the main experimental procedures, and any potential risks associated with participating in the study. After answering any questions, obtain written consent.

2. Baseline Assessment

  1. Evaluate clinical characteristics using the following questionnaires: Internet Addiction Test (IAT)24 and Brief Self Control Scale (BSCS)25. In addition, ask participants to report average weekly hours spent playing games.
    NOTE: The word "Internet" in the IAT is replaced with "online games" to assess severity of online game addiction.
  2. Perform brain FDG-PET scans.
    1. Inject participants with 185 - 222 MBq of FDG and have participants rest for 45 min of an uptake period during which they are awake and resting in supine position in a dark and quiet room with their eyes closed.
    2. Conduct brain FDG-PET scans to acquire transaxial emission images and CT images using a PET-CT scanner in about 15 min. Apply attenuation correction, standard filtering, and standard reconstruction techniques.

3. Application of tDCS

  1. Within a week after the baseline assessment, apply tDCS to participants. Prepare tDCS sessions with following materials: a tDCS device, wet wipes, saline solution, two sponge electrodes (6 cm in diameter), a cable, a headcap, and a headband.
  2. Have the participant sit on a chair.
  3. Set the stimulation parameters for the tDCS device: 2 mA for 30 min (current density = 0.07 mA/cm2). Set the current so it ramps up to 2.0 mA over 30 s, remains at 2.0 mA for 29 min, and ramps down to 0 mA over the last 30 s.
  4. Put the headcap (the International 10-20 system) on the participant’s head and mark the left dorsolateral prefrontal cortex (F3) and the right dorsolateral prefrontal cortex (F4). Then, remove the headcap from the participant's head.
  5. Place two sponge electrodes in the rubber holders of the headband and soak them with saline solution.
  6. Remove any makeup, dirt, or sweat on the scalp where the electrodes will be applied.
  7. Place the headband over the marking points by putting the anodal electrode over the left DLPFC and the cathodal electrode over the right DLPFC.
  8. Connect the electrodes to the tDCS device using the cable and turn on the device.
  9. Ask the participant to report any adverse effects during or after the tDCS session.
  10. At the end of the 30 min of stimulation, turn off the device and remove the electrodes from the participant.
  11. Administer a total of 12 tDCS sessions (3 times per week for 4 weeks).

4. Follow-up Assessment

  1. Perform the follow-up assessment within a week after the last tDCS session using the same protocol as the baseline assessment.

5. Data Analysis

  1. Use an appropriate software package to preprocess the PET images (e.g., Statistical Parametric Mapping 12).
    1. Convert DICOM files to NIFTI files.
    2. Spatially normalize all PET images to the standard PET template.
  2. Create binary masks for the left and right DLPFC (e.g., WFU PickAtlas toolbox). The DLPFC is defined by the middle frontal gyrus in the Automated Anatomical Labeling atlas.
  3. Extract rCMRglu of the left and right DLPFC using the masks (e.g., MarsBaR toolbox). The rCMRglu is normalized to global mean uptake using proportional scaling.
  4. Calculate asymmetry index (AI) of rCMRglu in the DLPFC as (rCMRglu right - rCMRglu left) / [(rCMRglu right + rCMRglu left) / 2] × 100. Positive AI indicates right-greater-than-left asymmetry of glucose metabolism.

Results

A total of 15 gamers (Table 1) and 10 non-gamers were recruited. The mean age of the gamer group (21.3 ± 1.4) was significantly lower than that of the non-gamer group (28.8 ± 7.5) (t = -3.81, p < 0.001). There were 8 men in the gamer group and 6 men in the non-gamer group (χ2 = 0.11, p = 0.74).

Behavioral results using linear mixed models indicate that the tDCS sessions successfully lowered the IAT score (z = -4.29, p < 0.001), weekly hours sp...

Discussion

We have presented a tDCS and neuroimaging protocol for online gamers and assessed its feasibility. The results demonstrated that repeated sessions of tDCS over the DLPFC reduced online game addiction symptoms and average time spent on games and increased self-control. An increase in self-control was correlated with a decrease in addiction symptoms. Moreover, the abnormal asymmetry of rCMRglu in the DLPFC where the right side was greater than the left side was improved after the tDCS sessions in the gamer group. These res...

Disclosures

The City University of New York (CUNY) has IP on neurostimulation system and methods with Marom Bikson as inventor. Marom Bikson has equity in Soterix Medical Inc and serves as a consultant for Boston Scientific Inc. All other authors declare no financial conflicts of interest.

Acknowledgements

This study was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (2015M3C7A1064832, 2015M3C7A1028373, 2018M3A6A3058651) and by the National Institutes of Health (NIHNIMH 1R01MH111896, NIH-NINDS 1R01NS101362).

Materials

NameCompanyCatalog NumberComments
Discovery STE PET/CT Imaging SystemGE Healthcare
MarsBaR region of interest toolbox for SPMMatthew BrettNeuroimaging analysis software; http://marsbar.sourceforge.net/
Statistical Parametric Mapping 12Wellcome Centre for Human NeuroimagingNeuroimaging analysis software; https://www.fil.ion.ucl.ac.uk/spm/software/spm12/
Transcranial direct current stimulation deviceYbrainYDS-301N
WFU_PickAtlasANSIR Laboratory, Wake Forest University School of MedicineNeuroimaging analysis software; https://www.nitrc.org/projects/wfu_pickatlas/

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