rg
e,
he
, Kao
Shi
l Uni
t Roa
gYuh-Ing Junior College of Health Care and Management, No.15 Lane 420 Dachang 2nd Road, Sanmin District, Kaohsiung 807, Taiwan
a r t i c l e i n f o
clude: preoccupation, uncontrolled impulse, using more than in-
tended, tolerance, withdrawal, impairment of control, excessive
time and effort devoted to the internet, impaired decision-making
and impaired function. Six or more symptoms must occur for diag-
nosis as Internet addiction. Although the core symptoms are nearly
identical to the diagnostic criteria for substance dependence and
pathological gambling, the underlying neural mechanism of Inter-
net addiction has not been completely evaluated. Since subjective
(Franken, 2003). The cue-reactivity has been suggested to be the
most reliable and ecologically valid paradigm to evaluate craving
(Wilson et al., 2004), and it has been utilized to evaluate craving
for substance, food, and gambling (Wilson et al., 2004; Potenza
et al., 2003; Pelchat et al., 2004). In functional magnetic resonance
imaging (fMRI) studies of cue-induced brain reactivity for sub-
stance craving, the most reported regions include the nucleus
accumbens, amygdala, striatum, anterior cingulate cortex, orbito-
frontal cortex, and dorsolateral prefrontal cortex (Wilson et al.,
2004; Franken, 2003). The fMRI study based on cue-reactivity par-
adigm also demonstrates the hippocampus, insula, and caudate
* Corresponding author. Tel.: +886 7 3121101x7702; fax: +886 7 3154208.
Journal of Psychiatric Research xxx (2008) xxx–xxx
Contents lists availab
hi
lse
ARTICLE IN PRESSE-mail address: cyberko@cc.kmuh.org.tw (W.-C. Lin).urge/craving. Thus, the results suggest that the gaming urge/craving in online gaming addiction and crav-
ing in substance dependence might share the same neurobiological mechanism.
 2008 Elsevier Ltd. All rights reserved.
1. Introduction
Internet addiction is a maladaptive internet use that occurs all
over the world (Chou et al., 2005). It has been labeled as a behavior
addiction (Holden, 2001) and classified as one type of impulse con-
trol disorder (Sadock and Sadock, 2007). Recently, however, the
‘‘Diagnostic Criteria for Internet Addiction for College Students”
(DCIA-C) has been proposed by Ko et al. (in press). The criteria in-
craving has been regarded as the central phenomenon of substance
use disorder and pathological gambling, it is necessary to evaluate
the mechanism of craving in Internet addiction to develop neuro-
biological models of addiction and provide guidance for its
treatments.
Craving had been defined as the accompanied emotional state
or a strong desire that is produced by conditioned stimuli that
are associated with the reward effects of substance or behaviorArticle history:
Received 20 April 2008
Received in revised form 28 September
2008
Accepted 29 September 2008
Available online xxxx
Keywords:
Internet addiction
Gaming urge
fMRI
Nucleus accumbens
Caudate nucleus0022-3956/$34.00  2008 Elsevier Ltd. All rights rese
doi:10.1016/j.jpsychires.2008.09.012
Please cite this article in press as: Ko C-H
chiatric Research (2008), doi:10.1016/j.jpsa b s t r a c t
The aim of this study was to identify the neural substrates of online gaming addiction through evaluation
of the brain areas associated with the cue-induced gaming urge. Ten participants with online gaming
addiction and 10 control subjects without online gaming addiction were tested. They were presented
with gaming pictures and the paired mosaic pictures while undergoing functional magnetic resonance
imaging (fMRI) scanning. The contrast in blood-oxygen-level dependent (BOLD) signals when viewing
gaming pictures and when viewing mosaic pictures was calculated with the SPM2 software to evaluate
the brain activations. Right orbitofrontal cortex, right nucleus accumbens, bilateral anterior cingulate and
medial frontal cortex, right dorsolateral prefrontal cortex, and right caudate nucleus were activated in the
addicted group in contrast to the control group. The activation of the region-of-interest (ROI) defined by
the above brain areas was positively correlated with self-reported gaming urge and recalling of gaming
experience provoked by the WOW pictures. The results demonstrate that the neural substrate of cue-
induced gaming urge/craving in online gaming addiction is similar to that of the cue-induced craving
in substance dependence. The above-mentioned brain regions have been reported to contribute to the
craving in substance dependence, and here we show that the same areas were involved in online gamingeGraduate Institute of Behavioral Science, Kaohsiung Medical University, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan
fDepartment of Psychiatry, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, 482 Shan-ming Road Hsiao kang, Kaohsiung 812, TaiwanBrain activities associated with gaming u
Chih-Hung Ko a,b,c, Gin-Chung Liu b,d, Sigmund Hsiao
Wei-Chen Lin d,*, Cheng-Fang Yen a,c, Cheng-Sheng C
aDepartment of Psychiatry, Kaohsiung Medical University Hospital, 100 Tzyou 1st Road
bGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 100
cDepartment of Psychiatry, Faculty of Medicine, College of Medicine, Kaohsiung Medica
dDepartment of Medical Imaging, Kaohsiung Medical University Hospital, 100 Tzyou 1s
Journal of Psyc
journal homepage: www.erved.
et al., Brain activities associ
ychires.2008.09.012e of online gaming addiction
Ju-Yu Yen a,b,f, Ming-Jen Yang g,
n a,b,c
hsiung 807, Taiwan
h-Chuan 1st Road, Kaohsiung 807, Taiwan
versity, 100 Shih-Chuan 1st Road, Kaohsiung 807, Taiwan
d, Kaohsiung 807, Taiwan
le at ScienceDirect
atric Research
vier .com/locate / jpsychiresated with gaming urge of online gaming addiction, Journal of Psy-

correspond to food craving (Pelchat et al., 2004). This paradigm has
also been used to observe cue-induced brain activity in pathologi-
cal gambling. Potenza et al. (2003) found that the activation of
frontal and orbitofrontal cortex, caudate/basal ganglia, and thala-
mus decreased initially while viewing gambling scenarios. How-
ever, Crockford et al. (2005) found greater activity over the right
dorsolateral prefrontal cortex, and right medial frontal cortex, right
parahippocampal gyrus and left fusiform gyrus. Thus, cue-reactiv-
ity paradigm could be suggested to evaluate the neurobiological
mechanism of Internet addiction and compare the results to previ-
ous reported substance or behavior addiction.
In order to examine the relationship between cue-induced brain
activation and gaming urge/craving, this fMRI study evaluated the
brain activation regions of cases with online gaming addiction
when viewing the gaming-related cue. Based on previous fMRI
study focus on substance craving, food craving, and gambling urge,
we hypothesized the nucleus accumbens, amygdala, caudate nu-
cleus, anterior cingulate cortex, orbitofrontal cortex, and dorsolat-
eral prefrontal cortex would be activated by the gaming-related
cue.
2. Methods and materials
2.1. Study design
Cue-reactivity paradigm involves exposing addicted individuals
sponse to the cues, but not to irrelevant stimuli and the response
should be only found in participants with online gaming, but not
participants without this potential. Accordingly, the brain activa-
tions corresponding to gaming urge/craving were designed to re-
sponse only under designed gaming cues but not paired control
stimuli and to response only in the case, but not control groups.
2.2. Participants
All participants were recruited via advertising post on the Bul-
letin Board System (BBS) and the campus. In order to increase
the homogeneity of the brain responses, we restricted the case
group to those who were addicted to the specific game, World of
Warcraft (WOW), which was popular in Taiwan. Case group re-
sponse to the post for ‘‘Advanced WOW player (at the top level)
with heavy time use on it (more than 30 h per week)” and control
group response to ‘‘Non-heavy Internet use (less than 2 h per day)”.
Since there is gender difference on the mechanism for gaming
addiction and males had higher potential to be addicted to gaming
(Ko et al., 2005), only male gamers were recruited in the study. All
recruited participants were screened to be Chinese speaking, male,
never had illegal substance use, and right-handed. After the com-
plete description of the study was given to the subjects, written in-
formed consent was obtained. The inclusive criteria for the case
group were: (a) diagnosed of online gaming addiction based on
DCIA-C (Ko et al., in press) and; (b) addicted to the selected specific
game. The subjects in the control group were diagnosed to have no
tim
e.
pic
2 C.-H. Ko et al. / Journal of Psychiatric Research xxx (2008) xxx–xxx
ARTICLE IN PRESSto stimuli designed to elicit craving while assessing concomitant
changes in one or more response systems (Wilson et al., 2004).
The paradigm was associated with the learned response that links
the cue to a pleasurable or an intensely overpowering experience.
Based on this model, if we could provide gaming-related cues
which could bring back the memory and provoke the urge to gam-
ing and the concomitant brain activation could be investigated, the
neurobiological mechanism of gaming urge/craving could be eval-
uated. Thus, the cues should be screened to provoke the designed
response. Besides, the gaming urge/craving should be the only re-
Table 1
The demographic data, score of Chen Internet Addiction Scale, withdrawal time, gaming
case and control groups.
Groups ELa Age CIASb WTc GTd
Control 1 14 21 42 No
Control 2 16 25 52 No
Control 3 16 22 57 No
Control 4 16 22 27 No
Control 5 14 22 62 No
Control 6 16 23 26 No
Control 7 16 22 39 No
Control 8 18 25 68 No
Control 9 16 23 44 No
Control 10 16 22 37 No
Case 1 15 24 76 1 >40
Case 2 16 22 78 4 31–40
Case 3 15 22 79 30 21–30
Case 4 13 20 73 9 11–20
Case 5 15 21 73 16 21–30
Case 6 13 22 63 20 31–40
Case 7 15 21 80 12 31–40
Case 8 15 21 95 2 31–40
Case 9 16 22 82 8 31–40
Case 10 16 25 72 5 31–40
a EL: educational level.
b The score of Chen Internet Addiction Scale.
c WT: withdrawal time: hours of abstinence from WOW (World of Warcraft) gam
d GT: gaming time: hours paid for WOW game every week.
e Gaming urge: the level of intention to play WOW game after viewing the WOW
f Recalling gaming experience of WOW after viewing the WOW pictures.
g Score of Fagerstrom test for nicotine dependence = 1; score of alcohol use disorders
h Score of alcohol use disorders identification test = 2.
Please cite this article in press as: Ko C-H et al., Brain activities associ
chiatric Research (2008), doi:10.1016/j.jpsychires.2008.09.012online gaming addiction and gaming was not a major online activ-
ity. Exclusion criteria included: lifetime substance use disorder
(other than nicotine dependence), lifetime illegal substance use,
current major depressive episode, current psychotropic medication
use, history of bipolar I disorder, psychotic disorder, neurological
illness and injury, mental retardation, and intolerability of mag-
netic resonance imaging (see Table 1). Ten men with online gaming
addiction and 10 controls were recruited after the above process
and were compatible to sample size of previous fMRI studies of
e, gaming motivation after viewing picture, and history of substance exposure among
GUe RGEf Smoking Alcohol Illegal substance
0 0 No No No
0 0 Yesg Yesg No
0 3 No No No
0 0 No No No
0 0 No No No
0 0 No No No
0 0 No No No
5 3 No No No
2 1 No No No
0 0 No No No
3 8 No No No
8 8 No Yesh No
7 9 No No No
7 9 No No No
7 10 No No No
0 8 No No No
7 9 No No No
8 8 No No No
5 4 No No No
9 10 No No No
tures (Ranging 0–10).identification test: 6.
ated with gaming urge of online gaming addiction, Journal of Psy-