Molecular (2014) 19, 842–847 & 2014 Macmillan Publishers Limited All rights reserved 1359-4184/14 www.nature.com/mp

ORIGINAL ARTICLE Amount of lifetime video gaming is positively associated with entorhinal, hippocampal and occipital volume

SKu¨hn1 and J Gallinat2

Playing video games is a popular leisure activity among children and adults, and may therefore potentially influence brain structure. We have previously shown a positive association between probability of gray matter (GM) volume in the ventral striatum and frequent video gaming in adolescence. Here we set out to investigate structural correlates of video gaming in adulthood, as the effects observed in adolescents may reflect only a fraction of the potential neural long-term effects seen in adults. On magnetic resonance imaging (MRI) scans of 62 male adults, we computed voxel-based morphometry to explore the correlation of GM with the lifetime amount of video gaming (termed joystick years). We found a significant positive association between GM in bilateral parahippocamal region (entorhinal cortex) and left occipital cortex/inferior parietal lobe and joystick years (Po0.001, corrected for multiple comparisons). An exploratory analysis showed that the entorhinal GM volume can be predicted by the genres played, such as logic/ games and platform games contributing positively, and action-based role-playing games contributing negatively. Furthermore, joystick years were positively correlated with hippocampus volume. The association of lifetime amount of video game playing with bilateral entorhinal cortex, hippocampal and occipital GM volume could reflect adaptive neural plasticity related to navigation and visual attention.

Molecular Psychiatry (2014) 19, 842–847; doi:10.1038/mp.2013.100; published online 20 August 2013 Keywords: entorhinal cortex; hippocampus; MRI; video gaming; voxel-based morphometry

INTRODUCTION infrequent video (p9 h per week).3,18 However, video Playing video games has become a popular leisure activity among gaming is not restricted to adolesence. The average age of a children and adults. Today, people spend a collective 3 billion video in the United States was 30 years and he has on hours per week on video gaming.1 It is predicted that the average average played for 12 years in 2012 (according to the young person will spend about 10 000 h gaming by age 21, twice Entertainment Software Association, http://www.theesa.com/ the time it would take to earn a bachelor’s degree.2 This intense facts/gameplayer.asp). As the participants in our previous study exposure is bound to have effects on neural structure and were considerably younger (14 years of age) than the average function. The current psychological literature reports favourable as video gamer, the identified neural correlates of frequent video well as adverse effects of frequent video game playing (for an gaming in ventral striatum may only reflect a small fraction of the overview, see Bavelier et al3). Favourable effects are mainly potential neural long-term effects in adults. We theorized that reported in the cognitive-perceptual domain,4,5 whereas adverse because of the prominent navigation component in many three- effects have been shown in the social-affective domain.6 It has dimensional (3D) video games, the hippocampal formation been demonstrated that video game playing can enhance pro- may be enlarged in frequent gamers. In order to test this babilistic inferences7 as well as visual skills related to attention, hypothesis, we investigated the structural correlates of memory and the spatial resolution of vision.8–11 Furthermore, video gaming in an adult population within the scope of the improvements in higher- cognitive functions such as task present study. Our main goal was to identify brain structures switching,12 working memory and reasoning have been asso- associated with the lifetime amount of video gaming in an adult ciated with video gaming improvements.13 In addition, video population. games have been shown to enhance spatial14 and motor skills such as endoscopic surgical performance in medical doctors.1,15,16 For violent video games, detrimental effects have been reported MATERIALS AND METHODS in the social domain, namely short-term increases in aggression and reductions of empathy and pro-social behaviour.2,6,17 Participants Surprisingly, studies exploring the functional and structural Sixty-two healthy male participants (mean 28.4 years, s.d. 6.07, range 24) neural correlates of frequent video gaming are scarce. We have were recruited by means of newspaper advertisements, announcing the study as a scientific study including an MRI measurement. According to recently collected cross-sectional data in adolescents, in which we personal interviews (Mini-International Neuropsychiatric Interview), parti- investigated the neural correlates of acute amount of video cipants were free of mental disorders. Family history (first degree) of axis I gaming. We found more gray matter (GM) volume in the left disorder were excluded from participation. In addition, exclusion criteria ventral striatum for frequent (49 h per week) compared with for all subjects were abnormalities in the MRI (for example, cysts and

1Max Planck Institute for Human Development, Center for Lifespan , Berlin, Germany and 2Charite´ University Medicine, St Hedwig-Krankenhaus, Clinic for Psychiatry and Psychotherapy, Berlin, Germany. Correspondence: Dr S Ku¨ hn, Max Planck Institute for Human Development, Center for Lifespan Psychology, Lentzeallee 94, 14195 Berlin, Germany. E-mail: [email protected] Received 23 March 2013; revised 9 May 2013; accepted 24 June 2013; published online 20 August 2013 Lifetime video gaming SKu¨hn and J Gallinat 843 enlarged ventricles), general medical disorders, neurological diseases or classification and affine registration. The affine-registered GM and white any clinically relevant abnormalities such as migraine, tinnitus or metal in matter (WM) segmentations were used to a customised DARTEL the body that would prohibit the MRI measurement. The study was (diffeomorphic anatomical registration through exponentiated lie alge- approved by the local ethics committee of the Charite´ University Clinic, bra)13,24 template. Then warped GM and WM segments were created. Berlin. After complete description of the study, the subjects informed Modulation was applied in order to preserve the volume of a particular written consent was obtained. tissue within a voxel by multiplying voxel values in the segmented images by the Jacobian determinants derived from the spatial normalisation step. In effect, the analysis of modulated data tests for regional differences in Scanning procedure the probability of the absolute amount (volume) of GM. Finally, images Structural images were collected on a Tim Trio (Siemens, Erlangen, were smoothed with a full width half maximum kernel of 8 mm. Statistical Germany) 3T scanner and a standard 12-channel head coil was used. analysis was carried out by means of whole-brain correlation of GM/WM The structural images were obtained using a 3D T1-weighted magnetisa- volume and lifetime joystick hours. Age and whole-brain volume were tion-prepared gradient-echo sequence based on the Alzheimer’s Disease entered as covariates of no interest. The resulting maps were thresholded Neuroimaging Initiative protocol (www.adni-info.org) (repetition time ¼ with Po0.001 and the statistical extent threshold was used to correct 2500 ms; echo time ¼ 4.77 ms; inversion time ¼ 1100 ms, acquisition for multiple comparisons combined together with a nonstationary matrix ¼ 256 Â 256 Â 176 flip angle ¼ 71;1 Â 1 Â 1-mm voxel size). smoothness correction.14,25

Questionnaires FreeSurfer subcortical segmentation. Automated segmentation and label- We administered a questionnaire assessing gaming behaviour ling of the hippocampus was performed by means of FreeSurfer (v5.1.0) (adapted version of a previously published video gaming question- which uses an affine rigid linear transformation and combines information naire,4,5,19 comprising the questions: ‘How many days per week do you about voxel intensity relative to a probability distribution for tissue classes play video games?’; ‘How many hours do you play video games on these with information about the spatial relationship of the voxel to the location of neighbouring structures obtained from a manually labelled atlas. Details days on average?’; and ‘How many years have you been playing video 26 games on a regular basis?’. In order to compute a variable that estimates of FreeSurfer subcortical segmentation are described by Fischl et al. Pearson correlations were computed between extracted GM volumes the dosage of video gaming over the lifetime, we multiplied hours  days from significant clusters of the VBM analysis, bilateral hippocampus per week  52 (weeks per year)  years. This variable will be called ‘joystick years’ (in analogy to pack years in the assessment of lifetime cigarette volume estimated by FreeSurfer, as well as the GM volumes extracted from a region of interest (ROI) in left ventral striatum based on our previous consumption) in the following. 18 To explore the associations between video gaming and substance study and the square root of joystick hours. and other dependencies, we administered the following ques- tionnaires: Use Disorder Identification Test (AUDIT,6,20), Fagerstro¨m Test for Dependence (FTND,7,21), the Interned Addiction Test8–11,22 RESULTS and the Beck Inventory (BDI,12,23). On average, participants reported 3844 joystick years (s.d. 5057, range 0–19 890). As the distribution of joystick years was skewed, Data analysis we transformed the joystick-year measure by means of square Voxel-based morphometry (VBM). Structural data was processed by means root, as the variable was not normally distributed (Kolmogorov– of the VBM8 toolbox (http://dbm.neuro.uni-jena.de/vbm.html) by Gaser Smirnov, Z ¼ 1.761, Po0.01). The joystick-year measure was and the SPM8 software package (http://www.fil.ion.ucl.ac.uk/spm) with negatively associated with age (r(62) ¼À0.420, Po0.01), indicat- default parameters. The VBM8 toolbox involves bias correction, tissue ing that participants from younger generations tend to play video

Figure 1. Brain regions showing a significant positive correlation between joystick years (square-root) and GM volume (probability). Upper row: bilateral entorhinal cortex, lower row: occipital cortex. Diamonds in the scatter plots depict participants that show addictive or excessive use of video games as assessed by means of the video gaming questionnaire.

& 2014 Macmillan Publishers Limited Molecular Psychiatry (2014), 842 – 847 Lifetime video gaming SKu¨hn and J Gallinat 844 games more frequently. According to the criteria of the video was identified that contributed negatively to the prediction of gaming questionnaire, five participants showed addiction-like entorhinal GM volume (b ¼À0.40, Po0.05) (total model: video gaming characteristics (score 47) and nine participants R2 ¼ 0.397, Table 1). were excessive users (score 4–7). We found a positive association As the entorhinal cortex is the main interface between between joystick years and alcohol use (AUDIT, r(62) ¼ 0.378, hippocampus and the neocortex,27 we correlated joystick years Po0.01), and the score in the internet addiction test (IAT) with bilateral hippocampus volume, whereas controlling for age (r(61) ¼ 0.365, Po0.01) but not with the Fagerstro¨m nicotine score and intra-cranial volume (FreeSurfer segmentation), and found a (r(62) ¼À0.147, P ¼ 0.26) or depressivity (BDI, r(62) ¼ 0.05, positive correlation (r(57) ¼ 0.285; P ¼ 0.028; five participants were P ¼ 0.70). excluded from the analysis because the FreeSurfer segmentation When correlating the square-rooted joystick years with GM showed errors). The effect was mostly driven by the volume of the segmentations, we found a significant positive association in right hippocampus (r(57) ¼ 0.364; P ¼ 0.005). bilateral parahippocamal region, more specifically the entorhinal In a previous study, we found higher GM volume in the left cortex (Montreal Neurological Institute coordinate: 26, À 22, À 24; ventral striatum for frequent (49 h video game play per week) À 26, À 17, À 24) and a region between occipital cortex and compared with infrequent video gaming adolescents (r9 h video inferior parietal lobe in the left hemisphere ( À 32, À 71, 32; P game play per week), grouped according to a median split (18). o0.001, corrected for multiple comparisons; Figure 1a). No region With the aim to relate the present data to these previously showed a significant negative correlation between GM volume reported findings, we extracted GM volumes in the present data and joystick years, and no significant correlations were found in from the left striatal cluster identified in this previous study. We WM segmentations. found no significant correlation between GM volume in left The video gaming addiction score of the video gaming ventral striatum and joystick years (r(62) ¼ 0.070 P ¼ .588), but a questionnaire was summed and correlated with the GM volume positive correlation with the video gaming questionnaire in bilateral entorhinal cortex and occipital cortex. GM volume in addiction score (r(62) ¼ 0.255 P ¼ 0.046). entorhinal cortex was positively correlated with the addiction score of the video gaming questionnaire (r(62) ¼ 0.261 P ¼ 0.040), whereas occipital cortex was not (r(62) ¼ 0.153 P ¼ 0.235). DISCUSSION In order to ensure that the GM results are not based on the Within the scope of the present study, we investigated structural associated alcohol use and internet addiction, we correlated the correlates of the lifetime video playing time (joystick years) in GM volume extracted from the cluster in bilateral entorhinal male adults. We found a positive association between GM volume cortex with AUDIT and IAT scores, and found no significant in the parahippocampal region, in particular in bilateral entorhinal associations (P40.31). When comparing participants that were cortex, and the occipital lobe/interior parietal lobe. No regions classified as addicted or excessive gamers according to the video with a significant negative association were identified. In addition, gaming questionnaire to participants that were not, we found a the GM volume within the enthorinal cortex cluster was positively significant difference in joystick years (t(61) ¼À4.22, Po0.01) and correlated with the video gaming addiction score. Although we IAT score (t(61) ¼À3.20, Po0.05), indicating that addicted/ found a correlation between alcohol use and internet addiction excessive gamers have played more and have higher internet score and joystick years, these addiction-related variables were addiction scores. The later association with internet addiction not associated with the GM volume effects. Even though previous might be due to the fact that many video games are played online studies reported associations between time spend video gaming so that the total time spend on the internet may actually consist of and depressivity,28 the present study did not replicate this the time in which participants played video games. None of the observation. Entorhinal GM volume could be predicted by the other variables such as AUDIT, Fagerstro¨m nicotine score, played video game genres, logic/puzzle games and platform depressivity (BDI) or extracted GM volumes were different games contributed positively, action-based role-playing games between the two groups (P40.20). contributed negatively. Joystick hours were positively associated In order to explore which video game genres contributed most with hippocampal volume, with a stronger effect for the to the volume increase detected in entorhinal cortex in video right hippocampus. In line with previously published work,18 we game players, we computed a multiple regression analysis in found a positive correlation between GM volume in ventral which the volume measure was predicted by means of the self- striatum and the video game addiction score of the video gaming reported playing or not playing of certain genres. The following questionnaire. genres were enquired about: building games (for example, Anno, The Settlers), simulation games (e.g. Second Life, The Sims), racing games (e.g. and Formula 1), ball games (for Structural correlates of joystick years in adults: bilateral entorhinal example, Football, Baseball and Golf), online role-playing games and left occipital cortex (for example, World of Warcraft and Lord of the Rings), single- Brain regions positively associated with joystick years were player role-playing games (for example, Dragon Age, The Witcher identified in bilateral entorhinal cortex, part of the parahippo- and ), action-based role-playing games (for campal region and a region in the occipital cortex, close to the example, , Mass Effect, Diablo, Borderlands and Dead inferior parietal lobule. The cluster in the entorhinal cortex was Island), click and point adventure games (for example, Monkey likewise associated with the video-gaming addiction score. Island, Indiana Jones and Day of the Tentacle), action adventure The entorhinal cortex occupies a pivotal position within the games (for example, Zelda, Final Fantasy and Tomb Raider), hippocampal formation as it acts as a conduit for sensory platform games (for example, Commander Keen, Super 64, information into the hippocampus and also provides the main Sonic and ), ego shooter games (for example, , route by which the hippocampal formation can influence large , Counter Strike, Call of Duty and ), third person sections of the cortex.29 Largely based on brain recordings from shooter games (for example, GTA, Resident Evil and Assassin´s navigating rodents, it has been theorized that the entorhinal Creed), logic/puzzle games (for example, , Minesweeper and cortex has a critical role in navigation and memory by encoding ) and arcade games (for example, Pakman, attributes of the current behavioural context.30,31 This universal Asteroids and ). GM volume in entorhinal cortex metric for mapping positions and directions is achieved by was significantly predicted from the binary-assessed game genres entorhinal cortex by means of so-called grid cells. What makes logic/puzzle games (b ¼ 0.58, Po0.01) and platform games grid cells special is that the regularity in grid spacing does not (b ¼ 0.42, P o0.05). One genre, namely action-based role-playing, derive from any regularity in the environment or in the sensory

Molecular Psychiatry (2014), 842 – 847 & 2014 Macmillan Publishers Limited Lifetime video gaming SKu¨hn and J Gallinat 845 ability to effectively deploy attention over space,8 as well as Table 1. Results of the linear regression model predicting gray matter the capacity to track multiple object9 and form representations volume in bilateral entorhinal cortex from the video game categories of objects.42 Brain regions within the proximity of the that participants indicated to have played occipital/parietal structural correlate identified in the present Video game categories Beta values study were previously associated with shifts of visual attention and orienting.43–45 To summarise, the brain regions identified Building games (e.g., The Settlers, Anno) 0.27 as structural correlates of the lifetime spent video game playing Simulation games (e.g., Second Life, The À 0.25 are associated with cognitive domains that are potentially Sims) trained in video games. However, whether the volumetric Racing games (e.g., Formula 1, Flight 0.07 effects are a consequence of long-lasting activation during Simulator) video gaming or preconditions that lead to the preoccupation Ball games (e.g., Football, Golf, Baseball) À 0.34 with gaming cannot be determined within the scope of a Online roleplay games (e.g., World of 0.09 Warcraft, Lord of the Rings) cross-sectional study. Single-player roleplay games (e.g., Dragon À 0.02 Age, The Witcher, The Elder Scrolls) Prediction of bilateral entorhinal GM volume by means of played Action-based roleplay games (e.g., Fallout, À 0.40a Mass Effect, Diablo, Borderlands, Dead To get an idea to which video gaming genres the volume in Island) entorhinal cortex is most strongly associated, we computed a Click and point adventure games (e.g., À 0.13 Monkey Island, Indiana Jones, Day of the multiple regression predicting the GM volume of the identified Tentacle) region by means of the game genres participants indicated. Action adventures games (e.g., Zelda, Final À 0.08 Entorhinal GM volume was positively associated with logic and Fantasy, Tomb Raider) puzzle games, as well as platform games, but negatively Platform games (e.g., Commander Keen, 0.42a associated with action-based role-playing games. The logic and Super Mario 64, Sonic) puzzle video game Tetris clearly involves mental rotation. In a Ego shooter games (e.g., Doom, Duke À 0.09 previous functional magnetic resonance imaging study, blood Nukem, Half-Life, Counter Strike, Call of oxygen level dependent activation in the right posterior Duty, Quake) hippocampus has been shown during Tetris performance,46 Third person Shooter games (e.g., GTA, Max 0.30 which in turn has been associated with spatial navigation in a Payne, Resident Evil, Assassin´ s Creed) 47 Logik/puzzle games (e.g., Tetris, Professor 0.58a recent coordinate-based meta-analysis. In platform games or so- Layton, Minesweeper) called platformers, an needs to run and jump through a Arcade games (e.g., Pakman, Asteroids, 0.02 virtual world. Before the 90-s platform games were mostly side- Space Invaders) scrollers, that is, video games in which the game play action is viewed from a side-view camera angle and the onscreen aP 0.05. o characters move from the left side of the screen to the right. Nowadays, video games are mostly situated in 3D virtual worlds.

32 In Super Mario 64, which is one of the examples given, the avatar input available to an animal. Similar to place cells in the navigates in a 3D environment to collect stars and sees a map of hippocampus, grid cells can be used to reconstruct the position of its surrounding to guide orientation. Therefore, it seems plausible the rodent in the environment and thereby function as a map of 33 that platform games could potentially facilitate brain regions the animal’s position. In human subjects, single-unit recording of associated with spatial representation such as the entorhinal entorhinal cortex neurons has identified neurons in which activity cortex with its grid cells. Why action-based role-playing games indicated whether a person was taking a clockwise or counter- contribute negatively to entorhinal volume is currently unclear clockwise path during video game playing. These neurons showed and was not predicted by the authors. this directional activity irrespective of the location of where a person experienced themselves, which contrasts them to place Hippocampus ROI volume correlates with joystick years cells in the hippocampus, which are activated by specific locations.34 As many video games involve orienting or spatial As we hypothesised an enlargement of the hippocampus navigation in virtual worlds, the higher volume observed with due to the strong spatial navigation affordances of many video games and because the entorhinal cortex is strongly connected more joystick years may reflect the result of exercise. Previous 29 studies have shown benefits of frequent video gamers in tasks with the hippocampus, we were particularly interested in that afford spatial navigation skills.15,16,35,36 A behavioural study in the association between video gaming and hippocampal which gaming experience was related to performance in desktop volume. We used FreeSurfer automated segmentations of the 37 hippocampus that have been shown to be a good estimate of virtual environments found that participants with more video 48 game experience were more accurate in pointing to nonvisible manual segmentation. In line with our predictions, we found a targets and showed superior performance in immersive virtual positive correlation between bilateral hippocampal volume and environments and in a dynamic spatial task. Although this study joystick years. The observed effect was driven mainly by the right could not show transfer effects to real life, another study showed hemispheric correlation. This lateralization is very much in transfer effects of video game training onto learning of visuo- agreement with our reasoning that spatial navigation may be spatial science topics.38 the causal factor. We recently published a coordinate-based The higher volume in occipital/parietal cortex associated with meta-analysis showing a strong right lateralization during retrieval,47 corroborating previous notions of right hemispheric joystick years could reflect visuo-spatial expertise. Several 49,50 behavioural studies have shown an enhancement of visual dominance of spatial navigation. processes, in particular of visual attention in association with video games. West et al39 have shown that experience with action Ventral striatum ROI volume correlates with video game video games modulates early sensory processing, resulting in addiction score increased sensitivity to salient visual stimuli. Furthermore, video In a previous study on adolescents, we found structural difference gamers have been shown to be better in contrast sensitivity,11 between frequent and infrequent video gamers.18 Frequent video visual search,40 the ability to divide and switch attention,41 the gamers had higher GM volume in the left ventral striatum. In order

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