Effects of video game playing on cerebral blood flow in young adults: A SPECT study

Psychiatry Research: Neuroimaging 212 (2013) 65–72

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Effects of video game playing on cerebral blood flow in young adults: A SPECT study Yuan-Hwa Chou a,d,n, Bang-Hung Yang b, Ju-Wei Hsu a, Shyh-Jen Wang b, Chun-Lung Lin c, Kai-Lin Huang a, Alice Chien Chang d, Shin-Min Lee e a

Department of Psychiatry, Taipei Veterans General Hospital & National Yang Ming University, Taipei, Taiwan Departments of Nuclear Medicine, Taipei Veterans General Hospital & National Yang Ming University, Taipei, Taiwan c Department of Psychiatry, Taoyuan Armed Forces General Hospital & National Defense Medical Center, Taoyuan, Taiwan d Institute of Neuroscience, National Yang Ming University, Taipei, Taiwan e Department of Psychiatry, Yu-Li Hospital, Department of Health, Executive Yuan, Taipei, Taiwan b

a r t i c l e i n f o

abstract

Article history: Received 3 February 2012 Received in revised form 10 September 2012 Accepted 11 October 2012

To study the impact of video game playing on the human brain, the effects of two video games playing on cerebral blood flow (CBF) in young adults were determined. Thirty healthy subjects comprising 18 males and 12 females who were familiar with video game playing were recruited. Each subject underwent three sessions of single photon emission computed tomography (SPECT) with a bolus injection of 20 mCi 99mTc ECD IV to measure their CBF. The first measurement was performed as baseline, the second and third measurements were performed after playing two different video games for 30 min, respectively. Statistic parametric mapping (SPM2) with Matlab 6.5 implemented on a personal computer was used for image analysis. CBF was significantly decreased in the prefrontal cortex and significantly increased in the temporal and occipital cortices after both video games playing. Furthermore, decreased CBF in the anterior cingulate cortex (ACC) which was significantly correlated with the number of killed characters was found after the violent game playing. The major finding of hypo-perfusion in prefrontal regions after video game playing is consistent with a previous study showing reduced or abnormal prefrontal cortex functions after video game playing. The second finding of decreased CBF in the ACC after playing the violent video game provides support for a previous hypothesis that the ACC might play a role in regulating violent behavior. & 2012 Elsevier Ireland Ltd. All rights reserved.

Keywords: Video games Cerebral blood flow (CBF) Single photon emission computed tomography (SPECT) Prefrontal cortex Anterior cingulated cortex (ACC)

1. Introduction Video game playing is one of the most popular amusements in modern life, and involves various stimuli and cognitive functions. The popularity of video, computer, online, and virtual reality games has raised concern in both the popular media (Wagner, 2008) and the research community regarding the potential for negative health effects of gaming, including the potential for violent behavior, addiction, and emotional responses (Grusser et al., 2007; Montag et al., 2012). Furthermore, video game playing may influence information processing skills such as those pertinent to spatial ability, which in turn, may have implications for more complex computer use (Goldstein, 1994). Green et al. recently reported that playing an action video game markedly improved subject performance in a range of visual skills related to n Corresponding author at: Taipei Veterans General Hospital & National Yang Ming University, Department of Psychiatry, No 201, Sec 2, Shih-Pai Road, Taipei, Taiwan 112, Taiwan. Tel.: þ886 2 28711290; fax: þ 886 2 28768403. E-mail address: [email protected] (Y.-H. Chou).

0925-4927/$ - see front matter & 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.pscychresns.2012.10.002

detecting objects in briefly flashed displays (Green and Bavelier, 2003). However, it has been reported that violent video game playing may increase the propensity toward aggressive behavior in childhood (Anderson and Murphy, 2003) and, importantly, case reports have demonstrated that video game playing may induce seizures (Fylan et al., 1999). A recent comprehensive metaanalysis study strongly suggests that exposure to violent video games is a causal risk factor for increased aggressive behavior, aggressive cognition, and aggressive affect but no evidence of sex differences in susceptibility (Anderson et al., 2010). This result was also supported by another empirical study which demonstrated the causality of the link between violence exposure in computer games and aggressiveness (Bluemke et al., 2010). Hence, it would be very interesting to directly investigate brain activity after violent and non-violent video game playing. Additionally, it has been reported that the video game playing may have different impact among high school students in terms of gender and problematic video game (Desai et al., 2010), compared with the effect of violent video game playing on the brain activity between males and females might also be valuable to further

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explore the impact of violent video game and aggressiveness between sexes. A growing number of functional imaging studies of normal volunteers have sought to examine the neural substrates of mentalization (Baron-Cohen et al., 1994; Vogeley et al., 2001). Traditional brain imaging studies, such as functional magnetic resonance imaging (fMRI), have mainly focused on brain activity derived from a simple stimulus despite of the graphic complexity or difficulty levels of video games. Although brain activity during complex tasks can be partially inferred by accumulating established fundamental evidence, little is known about the actual overall brain activity after a complex task. Currently, only several studies using fMRI have demonstrated the activities of multiple brain regions such as prefrontal and cingulate cortex after a computer game or violent video game playing (Calhoun et al., 2002; Mathews et al., 2005; Mathiak and Weber, 2006). Interestingly, these brain regions have not only been shown to have a function interaction but also linked to aggressiveness (Blair, 2010; Veit et al., 2010). Nuclear medicine techniques, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT), have been shown to be valuable for measuring human brain activities, including cerebral blood flow (CBF), and metabolism (Coles, 2006; Zipursky et al., 2007). A recently developed SPECT radiotracer, 99mTc ethyl cysteinate dimer (99mTc ECD), has been shown to produce better signal-to-noise ratios than the previously commonly used tracer 99mTc hexamethylpropylene amine oxime (99mTc HMPAO) in CBF studies (Leveille et al., 1989, 1992; Koyama et al., 1997). In the present study, SPECT with 99mTc ECD was used to measure CBF after playing two video games which represent violent and non-violent games, respectively. Based on previous results of fMRI studies, it could be speculated that there might be changes of blood flow in both prefrontal and cingulate cortex after video game playing.

2. Methods 2.1. Subjects This study was approved by the Human Ethical Committee in Taipei Veterans General Hospital. A total of 30 healthy subjects aged 24.6 7 4.7 years were recruited after providing written informed consent. The subjects comprised 18 males aged 23.6 7 4.6 years and 12 females aged 24.6 75.0 years. All subjects were recruited by newspaper and/or internet and most of them (25/30) were university students. All of them had previous experience in playing video games. A mini international neuropsychiatric interview (MINI) (Sheehan et al., 1998) was administered by a trained psychiatrist before recruitment to exclude any major or minor psychiatric disorders and potential addiction of video game playing. To minimize the influence of menstrual cycle on the measurement of CBF, all of the female subjects were measured in the follicular phase of their menstrual cycle and exclude the possibility of pregnancy (determined by self-report).

2.2. Video game playing protocol Each game was played for 30 min and the order of CBF measurement was always baseline, the violent game and the non-violent game. The violent game was called Dynasty Warriors 5 in North America (referred to as Shin Sengoku Musou 4 in Japan), and comprised a 3D action video game presented by Koei Company. The video game described a series of wars that erupted in the islands of Japan in 1467, and its main theme was fighting and killing. Subjects were able to use various weapons during the game, such as shurikens, swords, dirks, spears, guns, and chain blades, to fight against the enemy. The non-violent game was called Super Mario 64 and was part of the 3D platform games presented by Nintendo for the Nintendo 64. This game described an evil spell over Mario Land. In order to stop this evil spell, Mario had to use his mentality to find six golden coins throughout Mario Land in order to gain access to his castle and release the evil spell. The game replaced the previous version involving the linear obstacle courses of traditional platform games with enormous worlds in which the player must complete diverse missions, with an emphasis on exploration. Each course was an enclosed world in which the player was free to wander in all directions and

discover the environment without time limits. The challenges included defeating a boss, solving puzzles, racing an opponent, and gathering coins. Mario needed to use his mentality to gain access to his castle and release the evil spell.

2.3. SPECT acquisition Each subject underwent three sessions of SPECT with 99mTc ECD measurements. The first SPECT measurement was performed as baseline, and the second and third measurements were performed immediately after playing the violent and non-violent video games for 30 min, respectively. Each measurement was two weeks apart. The scanning duration was 30 min. Each subject received a bolus injection of 20 mCi 99mTc ECD IV while lying in the supine position with their eyes closed in a dimly lit and quiet room. SPECT was performed using a two-head system (E-Cam variable angle; Siemens Medical Systems Inc.) equipped with highresolution fan-beam collimators. Data were collected in the step and shoot mode at 31 intervals over 3601 while 30-s projection views were obtained per camera head. The radius of rotation was fixed at 13.5 cm. The image matrix size was 128  128 and the pixel size was 3.9 mm. All images were obtained through a filtered back projection reconstruction algorithm with a Metz filter using a Nyquist frequency cutoff of 0.3 and an order of 10. Attenuation correction was performed by the Chang method (m ¼ 0.15 cm  1) and no scatter correction was employed.

2.4. Image and statistical analysis Imaging data analysis was performed using the free software statistic parametric mapping (SPM2) implemented in Matlab 6.5 on a personal computer. Before determining the statistical differences between baseline and violent or non-violent video game playing, all images were normalized using a template and transformed into standard stereotactic space that was matched to the standard space based on the Talairach and Tournoux atlas. The normalized data were smoothed by convolution with an isotropic Gaussian kernel of 12 mm FWHM to increase the signal-to-noise ratio. Proportional scaling to 50 ml min  1 100 g  1 was applied in order to control for global activity confounds to remove the differences in global CBF between individuals (Worsley et al., 1996). SPM integrated the general linear model to create the statistical map and the random field theory to derive regional effect from statistical inference. After the spatial normalization, smoothing and count normalization, differences across scans were statistically estimated at each voxel using a paired t-test to compare CBF in the baseline and CBF after video game playing. Comparison between males and females were studied by compared populations: 1 scan/subject (two sample ttest) design. The numbers of killed characters related to perfusion in different brain regions were studied on a voxel-wise basis in a correlation design. Linear as well as second-order polynomial voxel-wise regression with the number of killed characters as the covariate was investigated. The resulting set of values for each contrast constituted a statistical parametric map of the t statistic SPM{t}. The SPM{t} maps outliving a threshold ofp o0.005 were further corrected for multiple comparisons, according to the random field theory, considering false positive values within the SPM map. An independent Student’s t-test was used for comparisons of demographic data and continuous variables between sexes. All statistical analyses were performed using the SPSS 11.5 software (SPSS Inc.) on a personal computer. Significance was defined as values of p o 0.05. Data are shown as the mean 7 SD.

3. Results A total of 30 healthy subjects comprising 18 males and 12 females completed the protocol. No any adverse effects could be observed after the SPECT measurements. The demographic data of the subjects are shown in Table 1. There were no significant differences between the male and female subjects, including age, education and handedness. However, the male subjects had significantly higher scores than the female subjects for the total number of killed characters and number of killed characters per session in the violent video game. Although the past experiences in playing video games was not different between male and female group, the hours playing video games per weeks was significantly longer in male than in female group. 3.1. Changes in CBF after video game playing in 30 subjects Spatially normalized SPECT images averaged for the 30 subjects after violent and non-violent video game playing are shown in Fig. 1.

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Table 1 Demographic data of the study subjects.

Sample size Age (years) Education (years) Handedness (L/R) Total number of killed characters Average number of killed characters per session Previous experience for non-violent video games (Y/N) Previous experience for violent video game (Y/N) Duration of video games playing (hours/week)

Total

Males

Females

df

t-values

p values

30 24.6 74.7 13.4 71.8 2/28 3123 7719 627 7349 30/0 28/2 3.1atio

18 23.6 7 4.6 13.4 7 1.8 1/17 3410 7 516 798 7 331 18/0 17/1 4.4atio

12 24.6 7 5.0 13.6 7 1.9 1/11 2692 7 782 371 7 180 12/0 10/2 1.0atio

NA 28 28 1 28 28 NA 1 28

NA 0.016  0.320 0.089  3.034  4.066 NA 0.988  2.617

0.988 0.752 0.765 0.005n 0.0001n 1 0.320 0.005n

Data was shown as Mean7 SD. df: degree of freedom. NA: non-applicable. n

Represents p o 0.05, comparison between males and females using student t-test.

Fig. 1. Normalized SPECT images averaged for 30 healthy subjects after violent and non-violent game playing.

Areas with significantly decreased CBF were mainly found in the dorsolateral prefrontal cortex (BA 46, and 9), temporal cortex (BA 21 and 38), anterior cingulate cortex (ACC; BA 32) and fusiform gyrus (BA 20) after violent video game playing, whereas decreased CBF was found in the dorsolateral prefrontal cortex (BA 46, 9, and 10) after non-violent video game playing (Table 2). A major difference between violent and non-violent video game playing was that decreased CBF in the right dorsal ACC (BA 32) and left fusiform gyrus (BA 20) was found after playing the violent video game, but not the non-violent video game. Furthermore, the decreased CBF in the right dorsal ACC was well correlated with the number of killed characters and showed in Fig. 2. Areas with significantly increased CBF were mainly found in the auditory area, Wernicke’s area (BA 22), motor area (BA 6 and 7) and visual cortex (BA 18, 19, and 36) after violent video game playing, while only areas in the visual cortex (BA 18 and 19) were activated after non-violent video game playing (Table 2).

3.2. Changes in CBF after video game playing in 18 male subjects Spatially normalized SPECT images averaged for the 18 male subjects after violent and non-violent video game playing are shown in Fig. 3. Similar to the results for the total subjects, areas with decreased CBF were mainly found in the frontal gyrus (BA 47) and cingulate gyrus (BA 32) after violent video game playing. However, there were no areas with decreased CBF after non-violent game playing in this group (Table 3). Areas with increased CBF were mainly found in the occipital lobe (BA 18) and temporal lobe (BA 39) after violent video game playing, whereas increased CBF was found in the occipital lobe (BA 18, 19, and 31) and temporal lobe (BA 20, 36, and 38) after non-violent video game playing (Table 3).

3.3. Changes in CBF after video game playing in 12 female subjects Spatially normalized SPECT images averaged for the 12 female subjects after violent and non-violent video game playing are shown in Fig. 4. Areas with significantly decreased CBF were found in the frontal cortex (BA 8, 10, and 11) and temporal cortex (BA 21 and 38) and part of the sub-cortical nucleus after violent video game playing. Similar to the results of violent video game playing, decreased CBF was mainly found in the frontal cortex (BA 6, 8, 9, 10, 11, 44, and 47) and temporal cortex (BA 38) and part of the sub-cortical nucleus after non-violent video game playing. In contrast to the male subjects, decreased CBF in the ACC was not found after violent game playing. The areas with increased CBF were similar to those in the male subjects and mainly found in the occipital cortex (BA 18) and parietal cortex (BA 7) after violent video game playing, whereas increased CBF was found in the occipital cortex (BA 19) and temporal cortex (BA 39) after non-violent video game playing. Interestingly, the cerebellum showed increased CBF in the female subjects after non-violent game playing. This finding was not found in either the female subjects after violent game playing or the male subjects after both violent and non-violent game playing (Table 4). 3.4. Differences in CBF changes between male and female subjects at baseline and after video game playing Spatially normalized SPECT images averaged for the male and female subjects after both violent and non-violent video game playing are shown in Fig. 5. Under the baseline conditions, there were no significant differences in the CBF changes between male and female subjects, except for the right temporal gyrus (BA 21 and 37). After violent video game playing, areas with higher CBF

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Table 2 Changes in CBF in different brain areas after violent and non-violent games playing in 30 healthy subjects. Hypo-perfusion areas

Hyper-perfusion areas X

Violent game o baseline Left middle temporal gyrus (BA 21) Left superior temporal gyrus (BA 38) Left fusiform gyrus (BA 20) Left dorsolateral prefrontal cortex (BA 46) Right dorsal anterior cingulate cortex (BA 32) Left dorsolateral prefrontal cortex (BA 9) Non-violent o baseline Left dorsolateral prefrontal cortex (BA 46) Left dorsolateral prefrontal cortex (BA 9) Right dorsolateral prefrontal cortex (BA 9) Left frontopolar area (BA 10)

Y

Z

t-score Cluster size

429 429 688

Violent game4 baseline Right superior temporal gyrus, Wernicke’s area (BA 22) Right visual association cortex (V2) (BA 18) Left visual association cortex (V2) (BA 18) Left secondary motor cortex (BA 6)

 52  20  16 4.57

429

 30 4  28 3.58  38  12  26 2.99  56 38 12 4.33 10

X

Y

Z

48

 56 14

t-score Cluster size

6.60

11615

32  90  2  4  76 6  22  4 60

5.87 5.67 4.75

11615 11615 429

Right somatosensory association cortex (BA 7)

16

 56 58

4.05

486

20

34

4.09

348

 12 50

28

3.54

324

 32 30

12

4.95

445

Non-violent 4baseline Left visual association cortex (V3) (BA 19)

 26  84 26

5.96

3842

 36 18

28

3.24

445

Left visual association cortex (V2) (BA 18)

 24  76 2

6.11

3842

2

62

34

3.81

327

Right parahippocampal cortex (BA 36)

44

 34  26 6.00

577

0

56

10

3.45

327

Right visual association cortex (V3) (BA 19) Right visual association cortex (V2) (BA 18)

30 32

 78 18  92 2

3851 3851

5.69 5.06

BA, Brodman’s area; x, y, z, coordinates in Talairach space; SPM{t}: t-score Level of significance was 0.5%.

Fig. 2. Correlation of decreased CBF in the right dorsal ACC after violent game playing with the number of killed characters.

Fig. 3. Normalized SPECT images averaged for 18 male healthy subjects.

in female subjects than in male subjects were found in the temporal lobe (BA 21 and 37) and parietal lobe (BA 2, 19, 40, and 39), whereas no areas with higher CBF were found in male

subjects compared with female subjects (Table 5). After nonviolent video game playing, four areas located in the temporal lobe (BA 21, and 7) and parietal lobe (BA 7 and 40) had higher CBF

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Table 3 Changes in CBF in different brain areas after violent and non-violent games playing in 18 male subjects. Hypo-perfusion areas

Violent game obaseline Right inferior frontal gyrus (BA 47) Right cingulate gyrus (BA 32) Left cingulate gyrus (BA 32)

Hyper-perfusion areas X

Y

Z

t-score

Cluster size

22 4 8

20 16 22

 16 36 42

4.94 4.79 3.04

325 248 248

Non-violent gameo baseline N/A

Violent game4baseline Right temporal lobe, middle (BA 39) Left occipital lobe, cuneus (BA 17) Right cuneus (BA 18) Left occipital lobe, cuneus (BA 18) Non-violent game 4baseline Right occipital lobe, middle (BA 19) Right occipital lobe, middle (BA 18) Left occipital lobe, precuneus (BA 31) Left occipital lobe, cuneus (BA 18) Left lingual gyrus Right frontal lobe, rectal gyrus (BA 11) Right temporal lobe, fusiform gyrus (BA 20) Right temporal lobe, fusiform gyrus (BA 36) Right superior temporal gyrus (BA 38)

X

Y

Z

t-score

Cluster size

48  24 26 4

 56  76  96  78

12 4 2 6

6.13 5.57 4.82 4.00

538 4246 4246 4246

30 24  28  22  26 4 54 44 36

 76  86  74  86  74 30  40  34 18

18 20 20 24 2  26  24  26  34

7.35 5.97 7.00 5.99 5.13 5.23 4.99 5.14 4.50

1253 1253 2048 2048 2048 306 435 435 341

BA, Brodman’s area; x, y, z, coordinates in Talairach space; SPM{t}: t-score. Level of significance was 0.5%.

Fig. 4. Normalized SPECT images averaged for 12 female healthy subjects.

in females than in males, whereas the frontal lobe (BA 9, 11, and 46) and limbic areas (BA 13, 19, 32, and 36) had higher CBF in males than in females.

4. Discussion Our study first demonstrated that CBF was significantly decreased in the prefrontal cortex and increased in the temporal and occipital cortices after 30 min of exposure to both violent and non-violent video game playing in young adults. The major areas with decreased CBF were found in the dorsolateral prefrontal cortex (BA 9 and 46), which has been indicated as an important brain region for many higher cognitive functions (Miller and Cohen, 2001). By using near infrared spectroscopy (NIRS), Matsuda et al. detected significant and sustained decreases in oxygenated hemoglobin in the dorsal prefrontal cortex during both violent and non-violent video game playing (Matsuda and Hiraki, 2006). Therefore, our findings were consistent with that study and revealed that both violent and non-violent video game playing may induce hypo-perfusion in frontal region. Meanwhile, previous brain imaging studies have demonstrated hypoperfusion in the dorsolateral prefrontal cortex in patients with mental disorders, which was further linked to the severity of their clinical symptoms (Galynker et al., 1998; Molina et al., 2005). It is common for young adults to play video games for more than 30 min in the real world. It is therefore necessary to be careful about monitoring long-term video game playing and to carry out

a clinical study correlating long-term video game playing and mental disorders in young adulthood. Our second major finding was the detection of significantly decreased CBF in the dorsal ACC in male subjects after violent video game playing, which was not observed in either the male subjects after non-violent video game playing or the female subjects after both violent and non-violent video game playing. The ACC plays an essential role in the regulation of cognitive and emotional behavior (Birbaumer et al., 2005). It is also a core structure for the linkage of cognitive tasks with affective processing (Davidson et al., 2000) and regulates aggressive emotions (Allman et al., 2001). Mathiak et al. recently reported an fMRI study in which violent scenes caused strong deactivation of the rostral part and activation of dorsal parts of the ACC (Mathiak and Weber, 2006). This discrepancy between their and our data for the dorsal part of the ACC is difficult to clarify due to the lower spatial resolution of SPECT compared with fMRI and the different study designs. Our finding indicates the overall effect of violent video game playing on the ACC and may be closer to the situation in the real world. It has been reported that sex may be an important factor in cognitive strategies for video game playing (Goldstein, 1994). One previous study suggested that violent video game playing would result in more aggression than non-violent game playing (Anderson and Murphy, 2003). Furthermore, a model of game and sex interactions revealed that men showed greater violent effects during violent video game playing than women (Bartholow and Anderson, 2002). It is still unclear which neural substrate serves

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Table 4 Changes in CBF in different brain areas after violent and non-violent games playing in 12 female subjects. Hypo-perfusion areas

Hyper-perfusion areas X

Violent game obaseline Left and right sub-lobar, caudate Left sub-lobar, claustrum Left superior frontal gyrus (BA 8, 10, and 11) Left superior temporal gyrus (BA 38) Left middle temporal gyrus (BA 21) Left sub-lobar, lentiform nucleus, putamen Non-violent gameo baseline Right inferior frontal gyrus (BA 44) Right frontal lobe, precentral gyrus (BA 6 and 44) Left and right superior frontal gyrus (BA 10 and 11) Left sub-lobar, claustrum, gray matter Left superior temporal gyrus (BA 38)

Y

Z

 16 2 20  24 12 22  22 36 44

t-score Cluster size

10.19 7.01 6.96

582 582 525

X

Y

Z

t-score Cluster size

Violent game4 baseline Right occipital lobe, fusiform gyrus (BA 18) Right occipital lobe, lingual gyrus (BA 18) Right parietal lobe, postcentral gyrus (BA 7)

30 22 12

 88  14 8.57  72  4 7.24  46 70 4.6

2090 2090 425

Right superior parietal lobule (BA 7)

20

 62 66

4.15

425

 36 24  34 6.84  54 2  10 5.54  22 12  4 4.24

647 647 582

50 52

9.01 5.92

1258 1258

Non-violent game4baseline Left middle occipital gyrus (BA 19) Left temporal lobe, fusiform gyrus (BA 19)

 44  76 6  46  74 12

6.44 4.47

421 421

 30 56  14 8.46

3564

Left superior temporal gyrus (BA 39)

 40  56  18 3.15

421

 28 12  2 6.97  38 22  24 6.13

3564 318

Left cerebellum, anterior lobe Right cerebellum, anterior lobe, cerebellar lingual Left cerebellum, anterior lobe, culmen Right lingual gyrus (BA 18) Left cerebrum, lingual gyrus, gray matter

 12  44  30 5.68 0  46  18 5.19

234 234

 16  38  18 3.83 20  70 0 5.59  18  74 0 5.32

234 613 250

Left inferior frontal gyrus (BA 47)  46 Right middle frontal gyrus (BA 8, and 9) 48 Right superior frontal gyrus (BA 8) 24 Right sub-lobar, caudate 16

4 16 10 6

38 28 48 22

 18 42 40 16

4.14 4.83 5.81 4.75

318 323 306 356

BA, Brodman’s area; x, y, z, coordinates in Talairach space; SPM{t}: t-score. Level of significance was 0.5%.

Fig. 5. Normalized SPECT images averaged for differences between male and female healthy subjects.

the underlying mechanism for aggressive behavior, particularly in men. Functional neuroimaging studies (PET and fMRI focusing on aggressive behavior, without looking at media-related violence exposure) demonstrated reduced or abnormal prefrontal cortical activity in severely aggressive adults compared with control subjects (Raine et al., 1998; Schneider et al., 2000; Mathews et al., 2005), suggesting that prefrontal cortical functions may be worthy of investigation to clarify the link between media-related violence exposure and aggressive behavior. However, our data did not support this idea, since decreased CBF in the prefrontal cortex was found after both violent and non-violent video game playing. Instead, it has been suggested that the ACC may be linked to aggressive behavior in conduct disorders (Stadler et al., 2007). Our data revealed that the major areas with decreased CBF were mainly found in the ACC in male subjects after violent video game playing, whereas the areas with decreased CBF in female subjects were in the fronto-temporal circuit after both violent and nonviolent video game playing. Additionally, the scores for killing characters were significantly higher in male subjects than in female subjects. Therefore, our findings support the hypothesis that the brain responses to video game playing differ between males and females. More importantly, it is likely that the ACC

plays a role in the regulation of violent or aggressive behavior in males. A drawback to the present study was that the two video games used for the comparison were drastically different, not only in their degrees of violence but also in many other aspects. For example, Super Mario used relatively old and simple childish cartoons, while Sengoku Musou used very complex human-like graphics and environments. Therefore, it would be very difficult to directly compare these two video games. Another limitation was that we did not use any questionnaire to evaluate the degree of aggressiveness after violent video game playing. Although the number of killed characters may, to some extents, reflect the aggressiveness after violent video game playing and this result was well correlated with the decreased CBF in ACC in males, it should be noted that this finding may not truly reflect the characteristic of aggressiveness. Third, small sample size and a sequence of presented video games (baseline-violent–non-violent) was lack of theory and could have systemic effect. However, in our study three sessions were performed in one subject, thereby eliminating the individual variation and thus reduce the sample size. A randomized study design could benefit this study to reduce the systemic effect in the future. Therefore, it should keep in mind

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Table 5 Changes in CBF in different brain areas of male and female subjects after violent and non-violent games playing. Perfusion areas Females 4Males

Perfusion areas Males4Females X

Baseline Right middle temporal gyrus (BA 21) Right temporal lobe, fusiform gyrus (BA 37) Violent game Right middle temporal gyrus (BA 21) Right temporal lobe, fusiform gyrus (BA 37) Right parietal lobe, postcentral gyrus (BA 2) Right parietal lobe, precuneus (BA 19) Right inferior parietal lobule (BA 40) Right parietal lobe, angular gyrus (BA 39) Non-violent game Right middle temporal gyrus (BA 21)

Y

Z

t-score Cluster size

62  42 0 48  64 20

5.25 4.48

4279 4279

50 50 58 34 34 54

6.07 4.12 4.00 3.97 3.74 3.14

1466 540 960 1110 1110 1110

5.24

694

Right temporal lobe, fusiform gyrus (BA 37) 50  60  22 4.29

694

Right inferior parietal lobule (BA 40) Right parietal lobe, precuneus (BA 7)

395 540

 14  60  26  68  40  60

 20  22 48 40 50 36

58  32  8

54  48 52 30  48 50

3.76 3.22

X

Y

Z

t-score Cluster size

 18 52

30

5.83

2742

 40 30

34

4.01

2742

4.84 3.05 4.07

2742 1008 535

Baseline N/A Violent game N/A

Non-violent game Left and right superior frontal gyrus (BA 9 and 11) Left and right middle frontal gyrus (BA 9) Left middle frontal gyrus (BA 46) Right sub-lobar, insula (BA 13) Left limbic lobe, parahippocampal gyrus (BA 19) Left limbic lobe, parahippocampal gyrus (BA 36) Left limbic lobe, anterior cingulate (BA 32)

 50 46 20 30 26 16  30  50  6

 40  28  20 3.87

535

4

1027

40

4

3.93

BA, Brodman’s area; x, y, z, coordinates in Talairach space; SPM{t}: t-score. Level of significance was 0.5%.

that any differences in brain activity related to these two video games could be entirely caused by differences in the graphic complexity or difficulty levels between the games (Calhoun et al., 2002) and factors related to study design. This makes it almost impossible to interpret the findings of direct comparisons of CBF between violent and non-violent video game playing. Not surprisingly, CBF was increased in the occipital cortex (BA 18, 19, and 37) due to the complex visual stimulation of video game playing. The major areas of increased CBF were the fusiform gyrus and extrastriate cortex. These areas are cytoarchitecturally assembled together as the accessory visual cortex. Furthermore, it is known that the functions of the fusiform gyrus include processing of color information, as well as face, word and number recognition, whereas the functions of the extrastriate cortex include feature extraction, shape recognition, and attentional and multimodal integrating functions (Schummers et al., 2004). Taking together, it is likely that the increased CBF in temporal– occipital circuit reflects the effect of video game playing. However, it should be noted that the global pattern of prefrontal deactivation and temporal or occipital activation may be a result of a general cognitive pattern of response to visual stimuli not specifically related to videogame playing. In conclusion, our findings indicate that video game playing may induce hypoperfusion of the dorsolateral prefrontal cortex. Furthermore, CBF in the ACC was significantly decreased in male subjects who had higher scores of killing characters compared with female subjects after violent video game playing. Our data support the idea that the ACC may play a role in mediating violent behavior.

Acknowledgment This study was supported by the National Science Council (NSC942314-B-075-057 and NSC95-2314-B-075-010), Taipei, Taiwan.

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