Neuroscience and Biobehavioral Reviews 68 (2016) 20–36

Contents lists available at ScienceDirect

Neuroscience and Biobehavioral Reviews

journal homepage: www.elsevier.com/locate/neubiorev

Review article

Counter striking psychosis: Commercial video games as potential

treatment in schizophrenia? A systematic review of neuroimaging
studies
Claudia Suenderhauf ∗ , Anna Walter, Claudia Lenz, Undine E. Lang, Stefan Borgwardt
Neuropsychiatry and Brain Imaging Group, Department of Psychiatry (UPK), Department of Clinical Research (DKF), Wilhelm Klein-Strasse 27, 4012 Basel,
Switzerland

a r t i c l e i n f o a b s t r a c t

Article history: Schizophrenia is a severe, chronic, and strongly disabling neuropsychiatric disorder, characterized by
Received 19 October 2015 cognitive decline, positive and negative symptoms. Positive symptoms respond well to antipsychotic
Received in revised form 19 February 2016 medication and psycho-social interventions, in contrast to negative symptoms and neurocognitive
Accepted 16 March 2016
impairments. Cognitive deficits have been linked to a poorer outcome and hence specific cognitive reme-
Available online 16 April 2016
diation therapies have been proposed. Their effectiveness is nowadays approved and neurobiological
correlates have been reconfirmed by brain imaging studies. Interestingly, recent MRI work showed that
Keywords:
commercial video games modified similar brain areas as these specialized training programs. If gray
Schizophrenia
Positive and negative symptoms matter increases and functional brain modulations would translate in better cognitive and every day
Video games functioning, commercial video game training could be an enjoyable and economically interesting treat-
Cognitive remediation therapy ment option for patients with neuropsychiatric disorders. This systematic review summarizes advances in
Brain plasticity the area with emphasis on imaging studies dealing with brain changes upon video game training and con-
MRI trasts them to conventional cognitive remediation. Moreover, we discuss potential challenges therapeutic
Video game addiction video game development and research would have to face in future treatment of schizophrenia.
Video game induced violence © 2016 Published by Elsevier Ltd.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
1.1. Neuroimaging and schizophrenia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
1.2. CRT and video games . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
2. Materials and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
2.1. Selection procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
3. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
3.1. Neurobiological impact of CRT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
3.2. Commercial video games . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
3.3. fMRI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
3.3.1. Resting state analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28
3.3.2. Reward task . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.3.3. Incentive cue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.3.4. Go/nogo task . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.4. Structural MRI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.4.1. VBM/Cortical thickness analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
4. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
4.1. Motivation and motivational elements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

∗ Corresponding author.
E-mail address: claudia.suenderhauf@upkbs.ch (C. Suenderhauf).

http://dx.doi.org/10.1016/j.neubiorev.2016.03.018
0149-7634/© 2016 Published by Elsevier Ltd.
 C. Suenderhauf et al. / Neuroscience and Biobehavioral Reviews 68 (2016) 20–36 21

4.2. Video game addiction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

4.3. Video games and aggressive behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
4.4. Limitations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
5. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Appendix A. Supplementary data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33

1. Introduction and treatment monitoring of individual patients were discovered in

psychiatry and psychology so far (Borgwardt and Fusar-Poli, 2012).
Schizophrenia is a severe, chronic, strongly disabling mental Brain imaging, in particular functional and structural magnetic res-
disorder. As the disease typically sets on around early adult- onance imaging (MRI) seems to be the most promising approach to
hood (Möller et al., 2008), it imposes a high burden on disability yield quantifiable measures of neuropsychiatric disease progres-
adjusted life years (Lozano et al., 2012). The mortality of patients sion and treatment response − at least in schizophrenia. There is
with schizophrenia is significantly increased, not only because evidence from structural MRI studies that schizophrenia is neu-
of the high suicidality but also due to a tendency to unhealthy robiologically characterized by a diffuse reduction of cortical gray
lifestyle, under-diagnosed physical illnesses and adverse effects matter, visible as enlargement of the third and lateral ventricles
of antipsychotic medication (Laursen et al., 2012). The incidence (Honea et al., 2005; Shepherd et al., 2012; Vita et al., 2012). More
is homogenously distributed around the world (Jablensky, 1997) specific volume reductions during the early course of the disease
and the world health organization (WHO) estimates that about were observed in the limbic system, as well as in frontal and tempo-
21 Mio patients worldwide suffer from the disease (World Health ral regions (Smieskova et al., 2010; Steen et al., 2006). In functional
Organization (WHO), 2016). MRI (fMRI) studies, abnormal or decreased activation was found in
Despite schizophrenias relevance for public health, options dorsolateral prefrontal cortex and anterior cingulate, both regions
for curing are limited (Davis et al., 2014). While positive symp- which are typically associated with executive and cognitive control
toms, such as delusions, disordered thoughts and speech, and (Dutt et al., 2015; Minzenberg et al., 2014). Altered functioning was
hallucinations respond relatively well to antipsychotic medication, also observable in limbic structures such as amygdala, insula and
negative symptoms, such as anhedonia and social retreat as well hippocampus, reflecting impaired emotional processing (Fusar-Poli
as neurocognitive impairments are hard to tackle (Erhart et al., et al., 2011; Gur et al., 2007). Notably, hippocampal volume reduc-
2006). Unfortunately, negative symptoms and cognitive impair- tion and neuro-functional impairment in frontotemporo-parietal
ments have a great tendency to chronicity and are the major reason networks seemed to be very early neurobiological changes in psy-
for patient’s impaired quality of life (Fusar-Poli et al., 2012; Ventura chosis as they were even detectable in patients with at risk mental
et al., 2009). About 60% of patients with schizophrenia show a state (Smieskova et al., 2012; Walter et al., 2012).
chronic course of the disease and only about 25% recover during The characterization of a neurobiological phenotype in
the first years after diagnosis (van der Heiden and Häfner, 2000). schizophrenia could pave the way for more targeted and objec-
As a rule of thumb, the earlier treatment is initiated and the fewer tive disease monitoring and treatment development. This holds
psychotic episodes a subject experiences, the better is the prognosis also for non-pharmacological treatment alternatives like cognitive
for recovery (Perkins et al., 2005). remediation therapy (CRT), where outcome could not only be mea-
From this follows, that early detection of schizophrenia for sured by clinical observation but also by quantitative visualization
treatment initiation is the most promising approach to improve of changes in brain plasticity and gray matter volume. As a conse-
outcome (Fusar-Poli et al., 2013; Picchioni and Murray, 2007). The quence, brain imaging is increasingly applied to assess therapeutic
majority of patients pass through an unspecific, prodromal phase, response in clinical trials.
which might persist for several years before the full psychotic onset
(Fusar-Poli et al., 2013). To date, clinical detection criteria for this 1.2. CRT and video games
high risk syndrome in help seeking populations are well estab-
lished (Schultze-Lutter et al., 2012). This achievement paves the Cognitive remediation therapy (CRT) consists mainly of
way for early initiation of disease-modifying therapies or effec- clinician-led or computerized behavioral training exercises, which
tive lifestyle interventions to prevent or postpone psychosis onset. target attention, working memory, and executive functioning as
However, as many of these patients with a so called “at risk men- well as social cognition (Harvey and Bowie, 2012). It has been
tal state” do not progress into full psychosis, one would be rather shown that beneficial effects like improved executive functioning
reluctant to introduce preventive drug treatment since the side and working memory are retained for months after treatment with-
effects of antipsychotics might counteract the burden of disease. drawal and that these skills do generalize, reflected in a better every
In particular, there is evidence for antipsychotics not improving day functioning (Hodge et al., 2010). Although CRTs effectiveness in
neuro-degenerative processes in the brain, such as the disease- treatment of schizophrenia is clinically well documented (McGurk
related progressive decrease in grey matter volume (Fusar-Poli et al., 2007; Moritz et al., 2015; Wykes and Dunn, 1992), only
et al., 2013). This holds even more as antipsychotics do not ame- few brain imaging studies were performed to assess its effect on
liorate cognitive deficits or negative symptoms (Keefe et al., 2013). brain plasticity. A recently published meta-analysis, summarizing
Hence powerful and safe treatment alternatives or add-on treat- nine imaging studies assessing pre- and post-training brain activity,
ments are urgently needed in prodromal but also early stages of revealed increased activation in the lateral and medial prefrontal
schizophrenia. cortex, parietal cortex, insula, caudate and thalamus (Ramsay and
MacDonald, 2015). Notably, some of these areas were shown to
1.1. Neuroimaging and schizophrenia be associated with cognitive limitations in schizophrenia as men-
tioned above.
In the strive for new therapeutic approaches, objective measures Although the effects of cognitive remediation therapy seem
for a treatment’s success are crucial. Although well-established in to have a neurobiological correlate, it is hard to discriminate
many other clinical domains, no reliable biomarkers for diagnosis whether individual and specific treatment approaches elicit spe-
22 C. Suenderhauf et al. / Neuroscience and Biobehavioral Reviews 68 (2016) 20–36
cific brain plasticity or whether more general, prolonged and
repeated engagement in (cognitive) activity conveys the observed
effect in patients with psychosis.
It seems that, like in all training tasks, high persistence and fre-
quency of treatment would be a fundamental condition in order to
achieve any sustainable results. It might be owing to these circum-
stances that computerized and clinical CRT has often failed to meet
expectations concerning long-term adherence: educational and
therapeutic aspects might overpower entertainment and immer-
sive quality of the intervention, which leads to loss of motivation
over time and finally, discontinuation of therapy.
Interestingly there is now increasing evidence not only from
behavioral but also from MRI studies, that commercial video games,
have also the potential to impact on brain plasticity (Kühn et al.,
2014a,b). Keeping in mind that persistence and motivation are key
elements for successful training, it seems not surprising that com-
mercial video games − designed for suspense and pleasure—have
the potential to enduringly engage the player. Although there are
not many studies published so far, there is increasing evidence
that effects of commercial video games on the brain go far beyond
improved finger coordination and reaction time. If video gaming
could be successfully used to influence brain structures and induce
functional activation changes in a targeted way, it would qual-
ify as a powerful intervention in neuropsychiatric disease such as
schizophrenia. Considering the typical onset age, at risk mental
state and schizophrenia first episode patients would fit well in the
video game peer group. However, to the best of our knowledge,
there are no published reports on the effects of commercial video
game training in patients with psychosis.
It was the aim of the present systematic review, to summarize
results from currently published video game training studies. We
focused on work applying structural and functional neuroimaging
to compare neurobiological changes induced by commercial video
games and tried to contrast these effects to results from brain imag-
ing studies assessing targeted computerized CRT. In addition we
aimed to discuss the applicability of a potential video game therapy
in schizophrenia, with special emphasis on disease typical vulner-
abilities, such as an increased risk for addictions and aggressive
behavior.
2. Materials and methods
2.1. Selection procedures
We applied a systematic search strategy as recommended by the
PRISMA group (Moher et al., 2015). The PRISMA Statement consists
of an item checklist and a flow diagram essential for transparent
reporting in systematic reviews which we adopted in the present
manuscript.
In a first step, two independent researchers searched the pub-
lic database PubMed to identify relevant studies. Following search
key words were used: “Video games” OR “Online video games” OR
“Serious games” OR “Computerized cognitive remediation therapy”
OR “Cognitive remediation therapy” AND “MRI”. Records dealing
with other conditions than schizophrenia were excluded for CRT
data search. As for video games no literature was available for
patients with schizophrenia; we decided to broaden our litera-
ture search queries to additional populations like healthy control
subjects. Only few studies assessed the influence of video gaming
exclusively in healthy volunteers; but more often; this was done
in context of video game addiction. Since most of these studies
included a healthy control population, we felt that it is reasonable
to extract the data and present it to the reader. Hence we broad-
ened our search to studies assessing healthy controls; frequent
video game players and online/internet gaming addicted patients
to study effects of frequent video game exposure. After checking for
duplicates; the abstracts of 130 articles were screened. They were
excluded if they were either reviews, not referring to any brain
imaging results or assessed other populations than healthy volun-
teers, patients with schizophrenia or video game addicted subjects.
We screened the remaining 38 full text articles; eliminating case
studies and studies assessing acute effects of video gaming or not
sufficiently reporting on imaging results. In addition; we manu-
ally checked the reference list of articles and reviews to check for
any studies not identified by the automated literature search. We
ended up with 30 articles; nine dealing with CRT and 21 dealing
with commercial video games; which were used for the present
review. A schematic representation of our search strategy is given
in Fig. 1.
Our literature search revealed only few brain imaging studies
assessing CRT and video game training effects and our collection
of video game studies followed predominantly a cross-sectional
design and adopted a great heterogeneity of MRI paradigms, which
hampered a meta-analytical comparison. We therefore decided to
summarize our results as a systematic review.
3. Results
3.1. Neurobiological impact of CRT
Table 1 shows the 9 publications found by systematic litera-
ture search matching our inclusion criteria for CRT. Our collection
consisted of seven longitudinal and two crosssectional studies. We
included computerized and clinician-based CRT studies in the same
table. Computerized CRT is an entertaining and automated alter-
native to traditional clinician-based training sessions and strongly
resembles a video game. However, a recent metaanalysis indicated
that there might be no clear superiority of both approaches con-
cerning outcome (Ramsay and MacDonald, 2015). Following the
example of Ramsey and coworkers, we calculated training inten-
sity in training/gaming hours per week to increase inter-study
comparability. Table 2 shows the brain areas and correspond-
ing qualitative effects of CRT training on neuroplasticity. A more
detailed listing of anatomical brain regions involved is given in
supplemental materials.
3.2. Commercial video games
We found imaging studies assessing the brain changes of healthy
subjects, frequent video game players and online/internet gaming
addicted patients. As the later subjects were exposed to intense
video gaming, we hypothesized that MRI studies in this population
might also reveal video game induced brain changes. We therefore
decided to include also studies dealing with online or internet video
game addiction (Beard and Wolf, 2001; Ko et al., 2009; Wölfling
et al., 2011; Young, 1996).
Our literature search revealed 21 studies assessing the effect of
commercial video games meeting our inclusion criteria. Only three
studies were longitudinally designed. An overview of the studies
and their design is given in Table 3. To increase comparability to
CRT studies, we calculated training intensity as playing hours per
week. Structural and functional MRI findings agreed on involve-
ment of temporal and frontal areas as well as hippocampus. Table 4
summarizes these brain areas roughly to improve inter-study com-
parability, but we decided to discuss the results in full depth. A
detailed compilation of studies and brain areas is given in supple-
mental material. For the sake of clarity, we did omit two study arms
of Haier et al. in the table, as they did not show any significant
results. Moreover, comparability of these arms was decreased as
Table 1
Summarizes brain imaging studies assessing the effects of cognitive remediation therapy (CRT). Study size is given as total number of included participants and in brackets, and, if not differently specified, the number of subjects
in treatment group and control group, respectively. If an additional healthy control group was included, the number of participants is given as third number. Two types of magnetic resonance imaging (MRI) were included in
the present review: blood oxygenation level dependent (BOLD) MRI and magnetization prepared rapid gradient echo (MPRAGE). Additionally, we calculated training intensity as hours training per week (h/week) and gave total
training duration in weeks. CRT types were categorized in computer-based (Comp) and clinician-based (Clin) therapy types. When an item was not specified by the authors, we indicated this by the abbreviation “NS”, for “not
specified”. “HC” indicates healthy controls. ROI indicates region of interest analysis.

Author Study size1) MRI Population Control Condition Therapy Name Intensity Duration Treatment CRT Type Paradigm Study design Analytical
(h/week) (weeks) method

Hooker et al. (2012) 22(11/11) BOLD Schizophrenia Unspecific video NS 5 10 CRT, social Comp Facial emotion Longitudinal Whole brain

C. Suenderhauf et al. / Neuroscience and Biobehavioral Reviews 68 (2016) 20–36

gaming cognition recognition task analysis/ROI2)
training
Habel et al. (2010) 30 (10/10/10) BOLD Schizophrenia Treatment as usual TARA) 1.5 6 Training of Clin Facial emotion and Longitudinal NS
and HC affect age recognition
recognition task
(TAR)
Subramaniam et al. 47(16/15/16) BOLD Schizophrenia Unspecific video Videogame like 5 16 CRT Comp Other(Reality Cross-sectional ROI3)
(2012) gaming cognitive training monitoring task)
Vianin et al. (2014) 16(8/8) BOLD Schizophrenia No CRT RECOSB) 3 14 CRT Clin Other(Covert Cross-sectional Whole brain
verbal fluency task) analysis/ROI4)
Wykes and Dunn 18(6/6/6) BOLD Schizophrenia No CRT and HC NS 3.33 12 CRT Clin N-back task Longitudinal ROI5)
(1992)
Bor et al. (2011) 32(8/9/15) BOLD Schizophrenia No CRT and HC Rehacom software 2.33 12 CRT Comp N-Back task Longitudinal Whole brain
analysis
Haut et al. (2010) 27(9/9/9)6) BOLD Schizophrenia Social skills CogPack Marker 5 5 CRT Comp N-Back task Longitudinal Whole brain
training and HC Software analysis/ROI7)
Penades et al. (2013) 45 (17/18/15) BOLD/DTI Schizophrenia Unspecific social NS 2.5 16 Strategy- Clin N-Back task Longitudinal DTI (FA)
skills training and learning-based
HC treatment
Eack et al. (2011) 53(23/30) MPRAGE Schizophrenia, Enriched CRT/Ben-Yishay’s 1.75 45 CRT Comp NS Longitudinal VBM (ROI)
schizoaffective supportive therapy Orientation
disorders Remediation
Module/PSSCogReHab
software

1) Number of included participants. If not declared separately, the number of subjects in treatment group and control group are given in brackets, respectively. If an additional healthy control group was included, the number of
participants in this group is given as third number.
2) ROI was defined according to brain regions where significant group × time interactions occurred.
3) ROI was defined as a spherical region of 20 mm radius according to the medial prefrontal cortex activity.
4) ROI was defined according to significant clusters from baseline assessment.
5) ROI was defined as cortical areas with relevance to the memory component of the task, the perception of the target and the motor response.
6) Participants with schizophrenia or schizoaffective disorder, as well as healthy controls.
7) Functional ROI were defined by assessing all data from all subjects and time points for clusters of interest.
8) ROI was defined as amygdala, caudate, cingulate gyrus, dorsolateral prefrontal cortex, fusiform gyrus, hippocampus, parahippocampal gyrus, putamen, and superior temporal gyrus gray matter.
A) A standardized program for training of affect recognition (TAR).
B) Cognitive Remediation Program for Schizophrenia and other related disorders (RECOS).

23
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Table 2
Summarizes the type of modulation (increase and decrease indicated by arrows), hemisphere (left = l, right = r) and anatomical area of brain changes observed upon cognitive remediation (CRT) training. We only showed significant
results reconfirmed by more than one study. “Type of comparison” indicates the study population and contrasts assessed. We grouped studies according to paradigms and to structural or functional changes. HC abbreviates
healthy control subjects. VBM and ROI indicates voxel based morphometry and region of interest analysis, respectively.

Author Type of Comparison Paradigm Temporal lobe Cingulate Frontal lobe Prefrontal cortex Insula Parietal lobe Occipital lobe

C. Suenderhauf et al. / Neuroscience and Biobehavioral Reviews 68 (2016) 20–36

Hooker et al. (2012) A)
Schizophrenia (group by time interaction), Facial emotion recognition l↑
emotion recognition of anger, disgust, sadness
Schizophrenia (group by time interaction), Facial emotion recognition l&r↑ r↑
emotion recognition of happiness, surprise,
and fear
Habel et al. (2010)A) Schizophrenia (group by time interaction) Facial emotion recognition l&r↑ r↑ l↑
Subramaniam et al. (2012)A) Schizophrenia (CRT training vs unspecific Reality monitoring task l&r↓
computer gaming)
Schizophrenia (CRT training, follow up vs Reality monitoring task (ROI & SVC) l&r↑
baseline)
Schizophrenia (CRT training vs unspecific Reality monitoring task (ROI & SVC) l&r↑
computer gaming: group by session
interaction)
Vianin et al. (2014)A) Schizophrenia (CRT training vs untrained Covert verbal fluency task l&r↑
patients: follow up)
Schizophrenia (CRT training: follow up vs Covert verbal fluency task r↑ l↑ r↑
baseline)
Wykes and Dunn (1992) A)
Schizophrenia (CRT training vs untrained N-back task r↑ l&r↑
patients and HC)
Bor et al. (2011)A) Schizophrenia (CRT training vs untrained N-back task l↑ l↑ l↑
patients)
Haut et al. (2010)A) Schizophrenia (CRT training vs untrained N-back task l&r↑ l&r↑ l↑
patients and HC)
Penades et al. (2013) A)
Schizophrenia (CRT training vs HC) N-back task l&r↑ l&r↑ l&r↑
Schizophrenia (CRT training vs unspecifically N-back task l&r↑ l&r↑ l&r↑ l&r↑
trained patients)
Schizophrenia (CRT training) N-back task l↓ l&r↑ l & r ↑ 1)
Eack et al. (2011)B) Schizophrenia (CRT training vs supportive VBM l↑ l&r↑ r↑
training)

A) Functional MRI.
B) Structural MRI.
1) Generally increased activity in both hemispheres, except decreased activity in billateral precuneus and left hemispheric gyrus submarginalis.
Table 3
Summarizes brain imaging studies assessing the effects of commercial video games and online/internet video games. We give the total number of study participants and in brackets the number of subjects in treatment/affected
group and control group, respectively. Occasionally, an additional study cohort was included which is specified in the footnotes. Magnetic resonance imaging (MRI) types included were blood oxygenation level dependent (BOLD)
and magnetization prepared rapid gradient echo (MPRAGE). Study populations consisted of healthy control subjects (HC), healthy non-addicted frequent or professional video gamers and internet gaming (IGA)/online gaming
(OGA) addicted subjects. The two latter groups refer to the same population, but we decided to keep the original nomenclature of individual authors. “Type of comparisons” indicates the population and contrasts assessed in the
studies. Names of video games played by study cohorts are indicated and corresponding video game genre is given in footnotes. To increase comparability to cognitive remediation studies we calculated video game exposure
intensity as video gaming hours per week (h/week) and gave total exposure duration in weeks. The studies were grouped according to functional or structural assessment and to functional MRI paradigm used. When an item was
not specified by the authors, we indicated this by the abbreviation “NS”, for “not specified”.

Author Study size1) MRI Population Control Game Name Intensity Duration Type of Paradigm Study design Analytical method
Condition (h/week) (weeks) Comparisons

Hahn et al. 27(13/14) BOLD Healthy frequent Healthy World of >4 >52 Frequent World of Resting Cross-sectional ReHo/ROI3)
(2014) video gamers 2) non-gamers WarcraftA) Warcraft players vs state/Reward task
non-gamers
Yuan et al. 36(18/18) BOLD Adolescents with HC5) World of 64.3 >140 Online games Resting state Cross-sectional ALFF
(2013a,b) OGA4) WarcraftA) addicted subjects
vs HC

C. Suenderhauf et al. / Neuroscience and Biobehavioral Reviews 68 (2016) 20–36

Ding et al. 41(17/24) BOLD Internet gaming HC Unspecified Online 26.4 NS Online games Resting state Cross-sectional Seed of posterior
(2013) addiction (IGA)4) games addicted subjects cingulate cortex
vs HC
Dong et al. 29(15/14)6) BOLD Internet gaming HC Unspecified Online NS NS Online games Resting state Cross-sectional ReHo
(2012) addiction (IGA) 4) games addicted subjects
vs HC
Feng et al. 33(15/18) ASL Internet gaming HC Unspecified Online 25.5 NS Online games – Cross-sectional ASL
(2013) addiction (IGA)4) games addicted subjects
vs HC
Chen et al. 81(29/22/30)6)7) BOLD Smokers and HC Unspecified Online NS NS Online games Resting state Cross-sectional Seed of posterior
(2014) non-smokers with games addicted subjects cingulate cortex
Internet gaming vs HC
addiction (IGA)4)
Lorenz et al. 50(25/25) BOLD Healthy volunteers No game Super Mario 64 3.5 8 Video game Reward task Longitudinal Whole brain
(2014) training (DS)B) training vs passive analysis/ROI3)
control group8)
Kühn et al. 152 BOLD/MPRAGE Healthy frequent Infrequent Various genres 12.1 NS Frequent vs Reward task Cross-sectional Whole brain
(2011) video gamers9 ) gamers10 ) infrequent players analysis/ROI3) /VBM
Ko et al. 20(10/10)6) BOLD Online game HC12) World of >30 NS Online games Incentive cue Cross-sectional Whole brain
(2009) addicted WarcraftA) addicted subjects analysis/ROI13)
subjects11) vs HC
Han et al. 196) BOLD Video gamers None War RockC) 9.3 1.4 Intense gamers vs Incentive cue Longitudinal Whole brain
(2012) (healthy general players vs analysis
volunteers) HC
Haier et al. 26(15/11) BOLD/MPRAGE Healthy female No game TetrisD) 1.5 12 Video game Playing Tetris Cross- Whole brain
(2009) children training training vs passive sectional/Longitudinalanalysis/Cortical
control group thickness
Ding et al. 34(17/17) BOLD Internet gaming HC Unspecified Online 27/1014) NS Online games Go/No-Go task Cross-sectional Whole brain
(2014) addiction (IGA)4) games addicted subjects analysis
vs HC
Kühn et al. 48(23/25) MPRAGE Healthy volunteers No game Super Mario 64 3.5 8 Video game – Longitudinal Cortical thickness
(2014a,b)15) training (DS)B) training vs passive
control group8)
Sun et al. 39(18/21) MPRAGE/DKI Internet gaming HC Unspecified Online NS NS Online games – Cross-sectional VBM (whole brain
(2014) addiction (IGA)4) games addicted subjects analysis)/DKI
vs HC
Tanaka et al. 50(17/33)6) MPRAGE Gaming experts16) Infrequent Guilty GearE) 21.4 NS Gaming experts vs – Cross-sectional VBM (whole brain
(2013) gamers17) infrequent gamers analysis)
Han et al. (20/17/18)6)18) MPRAGE Internet gaming HC/Professional Unspecified online 63/65.1/721) 25522) Online games – Cross-sectional VBM (whole brain
(2012) addiction19) gamers games/StarCraft20)F) addicted subjects analysis)
vs Professional
StarCraft gamers vs
HC

25
 26
Table 3 (Continued)

Author Study size1) MRI Population Control Game Name Intensity Duration Type of Paradigm Study design Analytical method
Condition (h/week) (weeks) Comparisons

Kühn et al. 152 MPRAGE 14-year old Infrequent Various genres 12.6 NS Excessive and – Cross-sectional VBM (whole brain
(2014a,b)23) adolsecents24) gamers addicted video analysis)
gamers vs HC
Hong et al. (15/?)6)25) MPRAGE Internet gaming HC Unspecified Online NS NS Online games – Cross-sectional Cortical
(2013) addiction (IGA)4) games addicted subjects thickness/ROI26)
vs HC
Hyun et al. 236) MPRAGE Professional None StarCraftF) 64.4 208 Correlation of – Cross-sectional Cortical thickness
(2013)27) on-line gamers (no Cortical thickness
addiction) and career length
Zhang et al. 45(28/17) DTI Frequent players28) Infrequent World of >=10 >24 Long term video – Cross-sectional DTI (FA)
(2015) players29) WarcraftA) /CrossfireC) /Need game players vs
for Non-video gamers
speedG) /Audition

C. Suenderhauf et al. / Neuroscience and Biobehavioral Reviews 68 (2016) 20–36

dance BattleH)
Dong et al. 31(16/15)6) DTI Internet gaming HC Unspecified Online NS NS Online games – Cross-sectional DTI (FA)
(2012) addiction (IGA)4) games addicted subjects
vs HC

ReHo and ALFF indicate regional homogeneity analysis and amplitude low frequency approach, respectively. ASL and VBM indicate arterial spin labeling and voxel based morphometry, respectively.
1) Total number of participants is given. If not specified else, first and second figure in brackets indicate treatment group and control group size, respectively.
2) Subjects had to play the game at least 4 h/week over one year.
3) Region of interest (ROI) was ventral striatum.
4) Online/Internet gaming addiction (OGA/IGA) according to the modified Young Diagnostic Questionnaire (YDQ) for OGA criteria by Beard and Wolf (Beard and Wolf, 2011).
5) Healthy controls who spent less than 2 h per day on the Internet.
6) Only male subjects.
7) Figure indicates number of smokers, non-smokers, and healthy controls, respectively.
8) Group x time comparison of healthy volunteers.
9) Frequent video gamers played more than 9 h/week.
10) Infrequent video gamers played less than 9 h/week.
11) Online gaming addiction was diagnosed in clinician-led assessment according to DIAC-C criteria (Ko et al., 2009).
12) Internet use and gaming at an intensity <14 h/week.
13) Region of interest (ROI) was not explicitly specified (gaming urge/craving associated brain areas).
14) Figure indicates training intensity of online game addicted subjects and healthy controls, respectively.
15) Study cohort overlapping with Lorenz et al. (2014).
16) Action video game experts was defined as 15.9 years of video game experience and video game tournament wining.
17) Less than 2 h video gaming/week.
18) Figure indicates number of online game addicted subjects, professional gamers, and healthy controls, respectively.
19) Defined as gaming >4 h/d, YIAS score > 50 (Young, 1996), impaired behavior or distress due to maladaptive pattern of video gaming.
20) For addicted subjects no specific video game was indicated. Professional video game players played the video game StarCraft.
21) Figure indicates training intensity of online game addicted subjects, professional gamers, and healthy controls, respectively.
22) Training duration applies for both, online game addicted subjects and professional online gamers.
23) Study cohort overlapping with Kühn et al. (2011).
24) Sample contained 6 addicted and 13 excessive video game players, identified according to a questionnaire assessing computer gaming behavior (Wölfling et al., 2011).
25) Number of healthy control subjects not specified.
26) Region of interest (ROI) was orbitofrontal cortex.
27) Study cohort possibly overlapping with Han et al. (2012).
28) Played at least 10 h/week over 6 months.
29) No video game experience or played less than 1–2 h/week.
A) Massive online role playing game (MORPG).
B) Platformer game.
C) Ego shooter.
D) Puzzle game.
E) Third person action game.
F) Military science fiction real-time strategy video game.
G) Car racing video game.
H) Music multiplayer online game.
Table 4
Summarizes functional and structural brain changes upon video game play in different cohorts. Only significant results reconfirmed by more than one study are shown. Modulation (increase and decrease indicated by arrows),
hemisphere (left = l, right = r) as well as anatomical area of brain changes are given. Individual contrasts are given as “Type of comparison”. We grouped the table according to paradigms and to structural or functional Imaging
study mode rather than according to author. This leads to occasional duplicate occurrence of manuscripts in our table, which we indicated by asterisks. HC abbreviates healthy control subjects. VBM and ROI indicate voxel based
morphometry and region of interest analysis, respectively.

Author Type of Comparison Paradigm Temporal lobe Cingulate Frontal Prefrontal Insula Parietal Occipital Subcortical Cerebellum
lobe cortex lobe lobe

Hahn et al. (2014)A) Healthy Frequent World of Warcraft gamers vs non Resting State r↑X)
gamers
Yuan et al. (2013a,b)A) Online gaming addicted subjects vs HC Resting State r↑ l&r↑ l↑ l↑
Ding et al. (2013)A) Online gaming addicted subjects vs HC Resting State l & r ↑, r↓1) r↓ l&r↑
Dong et al. (2012)A) Online gaming addicted subjects vs HC Resting State l↓ l↑ l ↓↑/r↑2) l↓ l↑
Feng et al. (2013)A) Online gaming addicted subjects vs HC Resting State r ↑/l ↓↑3) l↑/r↓↑4) r↑ l↑ l&r↑ r↑ l↓
Chen et al. (2014)A) Smoking online gaming addicted subjects vs HC Resting State l&r↓ l↑ l&r↓ r↓ l & r ↑Y) l ↓↑/r↑
Non-Smoking online gaming addicted subjects vs Resting State l↓ l↓ r↑ l&r↓ r ↓/l ↓ r ↑Y) l↑
HC
Smoking vs Non-Smoking online gaming addicted Resting State l↑

C. Suenderhauf et al. / Neuroscience and Biobehavioral Reviews 68 (2016) 20–36

subjects
Lorenz et al. (2014)A) Trained healthy volunteers vs HC (whole brain Reward l/&r↑ r↑ l&r↑ r↑X)
analysis)
Trained healthy volunteers vs HC (ROI: Ventral Reward
striatum)
Hahn et al. (2014)A) Healthy frequent World of Warcraft gamers vs Reward l&r↓X)
non-gamers
Kühn et al. (2011)*A) Healthy frequent video gamers vs infrequent Reward l↑X)
gamers
Ko et al. (2009)A) Online gaming addicted subjects vs HC Incentive cue l&r↑ l&r↑ l&r↑ l&r↑ l↑ r↑Y)
Online gaming addicted subjects Incentive cue l&r↑ l&r↑ l&r↑ r↑ r↑ l↑ r↑Y)
Han et al. (2012)A) HC Incentive cue l↑ l↑ l&r↑ l&r↑ l&r↑Z) l&r↑
Healthy frequent video gamers vs infrequent Incentive cue r↑ l&r↑ r↑ l↑
gamers
Ding et al. (2014)A) Online gaming addicted subjects vs HC Other (Go/No-Go task) l&r↓ r↑ l&r↑ l ↑/r ↓
Kühn et al. (2014a,b)B) Trained healthy volunteers vs HC (time × group VBM r↑ l&r↑
interaction)
X)
Kühn et al. (2011)*B) Healthy frequent video gamers vs infrequent VBM l↑
gamers
Sun et al. (2014)*B) Online gaming addicted subjects vs HC VBM r↑ l↓
Tanaka et al. (2013)B) Video game experts vs infrequent gamers VBM r↑
Han et al. (2012)B) Online gaming addicted subjects vs HC VBM l↑ l↑Z)
HC vs Online gaming addicted subjects VBM l&r↑ l&r↑
Professional on-line gamers (no addiction) vs HC VBM l↑ r↑
HC vs Professional, non-addicted online gamers VBM l&r↑ l↑
Professional on-line gamers vs addicted video VBM l↑
gamers
Addicted video gamers vs professional on-line VBM l↑Z)
gamers
Haier et al. (2009)B) Trained HC (follow up vs baseline) Cortical thickness l↑ l↑
Kühn et al. (2014a,b)B) Excessive and addicted video gamers vs HC Cortical thickness l↑
Positive correlation with time playing video games Cortical thickness l↑ l↑
Hong et al. (2013)B) Online gaming addicted subjects vs HC Cortical thickness r↓ r↓ l↓
Hyun et al. (2013)B) Professional, non-addicted online gamers Cortical thickness r↑ r↑

1) Decreased activity in right inferior temporal gyrus.

2) Decreased activity in left postcentral Gyrus.
3) Increased activity in left parahippocampus and inferior temporal gyrus.
4) Increased activity in right anterior cingulate cortex.
A) Functional MRI.
B) Structural MRI.
X) Ventral striatum.
Y) Caudate.

27
Z) Thalamus.
28 C. Suenderhauf et al. / Neuroscience and Biobehavioral Reviews 68 (2016) 20–36
Fig. 1. Work flow of structured literature search.
The number of records at each step of systematic literature search is given and depicted as work flow diagram according to recommendations of the Preferred Reporting
Items for Systematic Reviews and Meta-Analyses work group (PRISMA) (Moher et al., 2015).
the authors did not use common MRI paradigms but rather assessed
subjects while playing a video game.
3.3. fMRI
Although a variety of study designs and analytical techniques
were used, we summarized results from fMRI studies together
in Table 4 and grouped them according to paradigm, type of
comparison, as well as study design and analytical methodology.
Our collection of video game induced brain function modulation
showed considerable heterogeneity. This might partially be owing
to the fact that there were few overlaps in studies design, popula-
tion and methodology. Although a comparison of the different fMRI
paradigms seemed challenging, we tried to group studies according
to paradigm (e.g., resting state, incentive cue) or to assessed neural
systems (e.g., reward).
3.3.1. Resting state analysis
We found six cross-sectional publications assessing the influ-
ence of frequent and excessive video gaming as well as
online/internet video game addiction on resting state func-
tional connectivity. Besides independent component analysis, two
additional methodological approaches were applied to analyze
functional connectivity, namely assessment of regional homogene-
ity (ReHo) and amplitude of low frequency fluctuations (ALFF). Both
methods assess fluctuations in the blood oxygenation level depen-
dent (BOLD) MRI signal and it has been shown that they correlate
reasonably with each other (Yuan et al., 2013a,b). We therefore
showed the results in the same table.
Several authors observed functional connectivity modulations
in online game addicted subjects in left prefrontal cortex, namely
supplementary motoric areas and orbitofrontal cortex, but also in
bilateral cingulate cortex (Feng et al., 2013; Yuan et al., 2013a,b).
Increased connectivity in temporal areas (i.e., parahippocampus)
and decreased connectivity in superior parietal and occipital lobe
were described in several studies although there is some disagree-
ment on the hemispheric distribution (Chen et al., 2014; Ding et al.,
2013; Dong et al., 2012; Feng et al., 2013).
The more controversial results in temporal lobe raised from
varying findings for connectivity in middle and inferior tempo-
ral gyrus. Other areas of disaccord between studies were, middle
frontal gyrus, precuneus, and inferior parietal lobule as well as for
the posterior lobule of cerebellum. Studies disagreed on decrease
or increase of connectivity as well as on hemispheric distribution of
the observed effect (Chen et al., 2014; Ding et al., 2013; Feng et al.,
2013; Yuan et al., 2013a,b).
 C. Suenderhauf et al. / Neuroscience and Biobehavioral Reviews 68 (2016) 20–36
Individual reports revealed increased connectivity in left supe-
rior temporal area anterior cingulate (Feng et al., 2013), right gyrus
precentralis and gyrus rectus, left medial frontal, medial prefrontal
and orbitofrontal area as well as in left postcentral gyrus (Chen
et al., 2014; Yuan et al., 2013a,b). Hahn and coworkers performed
a region of interest analysis (ROI) in healthy non-addicted but fre-
quently playing video gamers and observed significantly increased
regional homogeneity in right ventral striatum (training intensity
of 4 h/week) compared to healthy non-gamers (Hahn et al., 2014).
3.3.2. Reward task
We found three studies assessing the impact of video game
training using monetary incentive delay tasks, which are used to
assess brain activity during reward anticipation (Knutson et al.,
2001; Lorenz et al., 2014). Despite resembling paradigms used, we
found quite heterogeneous results. Increased activation in frontal
and prefrontal areas, as well as insula were only reconfirmed by
Lorenz and coworkers (Lorenz et al., 2014). Moreover we found
quite diverging results for subcortical structures: While Kühn et al.
and Lorenz et al. found increased activity in left and right ventral
striatum, respectively (Kühn et al., 2011; Lorenz et al., 2014), Hahn
et al. (2014) reported a bilateral decrease. Owing to the high par-
ticipant number and intense training applied, there seems to be
more evidence that striatal activity is increased by video gaming.
However, this theory needs to be underlined by additional studies.
It has to be mentioned that Kühn and coworkers performed
their study in 14 years old adolescents and used a cross-sectional
study design, which might impede direct comparability to the
other studies. Despite the fact that adolescents seem to be more
reward sensitive than adults and the results might—owing to the
design—reflect preexisting subpopulation features (i.e., frequent vs
infrequent players), the findings agreed reasonable with the longi-
tudinal work in adults of Lorenz and coworkers.
3.3.3. Incentive cue
Our literature search revealed two studies assessing functional
brain differences in cue-induced desire and addiction to play video
games. Both used in-game pictures as incentive cue stimulus and
unspecific mosaic pictures as negative control and studies were
performed in male subjects exclusively. Although both studies
revealed uniformly increased activity in temporal, frontal, and
parietal lobe as well as in subcortical structures upon incentive
cues, there was disagreement in hemispheric distribution. These
differing reports concerned in more detail parahippocampal and
medial frontal gyrus, inferior parietal lobule, caudate and thala-
mus. These differences might arise from different study designs
and non-overlapping study cohorts: Ko and coworkers performed a
cross-sectional investigation in video gaming addicted subjects and
occasionally gaming healthy controls (Ko et al., 2009). Increased
activity in bilateral cingulate, insula as well as prefrontal cortex
was only reconfirmed for video game addicted subjects. Moreover,
increased activity in bilateral hippocampal gyrus was observed in
addicted subjects contrasted to healthy controls. The authors did
not expect any significant functionality increase in left parahip-
pocampal gyrus compared to addicted subjects. However, Han et al.
performed their study in healthy, non-addicted subjects and found
that parahippocampal activity significantly increased upon incen-
tive cues when they underwent a 10 days video game (ego shooter)
training (Han et al.). Additional areas of increased activation were
found in left frontal, as well as in bilateral parietal and occipital
lobe, thalamus and cerebellum.
Moreover, Han et al. discovered retrospectively a subgroup in
their cohort who played the game more intensely (17.5 h/week)
than the remaining participants (6 h/week). These subjects showed
increased right hemispheric parahippocampal, medial frontal, and
postcentral activation as well as bilateral in precentral gyrus. Unfor-
29
tunately, the authors did not further investigate, whether this
frequent gaming subgroup fulfilled video/online gaming addiction
criteria, which would have yielded the study more comparable to
work of Ko and coworkers. In view of the fact, that video gaming
has an impact on incentive cue processing in healthy controls it
might be likely that effects seen in the cross-sectionally assessed
video game addicted cohort of Ko and coworkers were confound-
ing effects of frequent video gaming and video game addiction.
At least in terms of brain activation pattern, theses frequent and
intense players seemed to differ substantially from the sample of
video game addicted subjects. The latter showed increased acti-
vation in right orbitofrontal, dorsolateral prefrontal, and superior
frontal cortex, right nucleus accumbens and caudatus and bilateral
medial cingulate and medial frontal cortex. The increased recruit-
ment of addiction related networks (nucleus accumbens, prefrontal
and orbitofrontal cortex, and cingulate) seen in these subjects but
not in frequent players might be an indication that intense expo-
sure to video games alone is not sufficient to progress a subject into
video game dependency and additional vulnerabilities have to be
present to trigger compulsive behavior.
3.3.4. Go/nogo task
We found one study assessing the functional difference in
impulse control of online/internet gaming addicted patients to their
healthy counterparts by a go/nogo task (Ding et al., 2014). The
authors found a generally decreased activity in bilateral middle
temporal gyrus, inferior temporal gyrus, and right superior parietal
lobe. Areas of increased activity were found in right hemispheric
anterior cingulate and superior frontal gyrus as well as left hemi-
spheric precentral gyrus, medial frontal gyrus, precuneus, cuneus
and inferior parietal lobule.
3.4. Structural MRI
3.4.1. VBM/Cortical thickness analysis
Notably, studies applying voxel based morphometry (VBM) and
cortical thickness analysis revealed predominantly a gray matter
volume increase upon video gaming, yet only limited regional over-
lap between authors was found. Several studies agreed on volume
increases in prefrontal cortex, temporal (i.e., middle and inferior
temporal gyrus) and frontal lobe (i.e., superior frontal gyrus) as
well as in occipital lobe, but in opposing hemispheres (Han et al.,
2012; Kühn et al., 2014a,b; Sun et al., 2014). Left hemispheric vol-
ume increases in premotor cortex and supplementary motoric area
were reported by several authors (Haier et al., 2009; Kühn et al.,
2014a,b).
Gray matter increases in frontal, parietal and striatal areas were
only reconfirmed by single studies. These areas were namely right
precentral and middle frontal gyrus, right superior and inferior
parietal lobule as well as left ventral striatum. Additionally involved
areas were right hippocampus (Kühn et al., 2014a,b) and parahip-
pocampus (Sun et al., 2014), left superior and temporopolar gyrus
(Haier et al., 2009) as well as bilateral cerebellum (Kühn et al.,
2014a,b). Left anterior cingulate was found to be increased in pro-
fessional but not addicted video gamers. Left angular gyrus as well
as left thalamus was increased in online gaming addicted subjects
(Han et al., 2012). Gray matter volume reductions were exclu-
sively observed in online/internet gaming addiction, namely in left
precentral gyrus (Sun et al., 2014), right posterior cingulate, right
frontal inferior and orbitofrontal gyrus, as well as in left occipital
lobe (Hong et al., 2013).
The heterogeneity of brain areas involved might arise from the
varying games and training intensities as well as from longitudinal
and cross-sectional study designs applied (see Table 3). Longitudi-
nal study designs might reflect treatment effects in a purer manner
than cross-sectional studies as participants could serve as their own
30 C. Suenderhauf et al. / Neuroscience and Biobehavioral Reviews 68 (2016) 20–36
controls and observed effects could be better attributed to inter-
ventions than to preexisting sub-population characteristics (e.g.,
the population of video game addicted patients). In our literature
search, only two out of nine video game studies assessing structural
brain changes applied longitudinal study designs.
The two structural longitudinal studies used two different game
types to train, namely a 3D platformer (Super Mario 64) (Kühn
et al., 2014a,b) and a puzzle game (Tetris) (Haier et al., 2009). The
impact of game genre on location and intensity of brain plastic-
ity modulation was reconfirmed by the cross-sectional assessment
of Kühn and coworkers: Puzzle and platform games were deemed
superior in inducing gray matter increases in entorhinal cortex,
compared to other genres like sport or simulation games (Kühn
and Gallinat, 2014). The same study assessed frequent video game
players (>9 h/week) and revealed increased left striatal grey matter
volumes compared to infrequent gaming subjects, though it cannot
be ruled out that these findings were study group specific precon-
ditions. Our sample contained moreover a study which focused
exclusively on female children (Haier et al., 2009). Thus, one can-
not rule out gender and age specific effects perturbing observations
attributed to video game impact. In addition, we observed a ten-
dency to unbalanced study design in work of Kühn et al. While
the groups of excessive and addicted players consisted of 9 and 5
subjects respectively, the healthy population outweighed them by
48.
4. Discussion
All here presented video game studies were performed in
healthy subjects or excessive video gamers and to the best of our
knowledge, there are no published reports using brain imaging
and commercial video game training in schizophrenia or any other
psychiatric disorder. The age distribution of participants in the
present video game study collection, containing also adolescents,
might only marginally overlap the typical schizophrenia onset age
in early adulthood. Besides the increased vulnerability to risk tak-
ing and increased sensitivity to reward in adolescents, also the fact
that most of them were healthy control subjects could hamper
direct comparisons (DeWitt et al., 2014; Kwon et al., 2014; Spear,
2013). Hence, at the current state of research it cannot be finally
answered what effect video game training would have on patients
with schizophrenia. Nevertheless, it has been shown that not only
healthy but also impaired neural systems show training induced
plasticity (Eack et al., 2011; Subramaniam et al., 2012) and obser-
vations from healthy volunteers might well translate to patients
with schizophrenia.
As juggling involves swift button use on the console to react
on gaming content, it does not surprise that gamers showed
temporo-parietal gray matter increases (i.e., areas involved in
motion perception) and clinically significant improvements in
fine-motor skills (Borecki et al., 2013; Busch et al., 2004). How-
ever, effects of commercial video games on brain plasticity seem
to go beyond improved finger coordination and reaction time
and included connectivity and grey matter volume increases in
schizophrenia-relevant brain areas such as hippocampus, insula,
cingulate and frontotemporal networks.
These brain areas showed a great overlap with our CRT study
collection and recent meta-analytical findings from CRT studies
(Ramsay and MacDonald, 2015). This metaanaylsis reconfirmed
increased activation upon CRT training in brain areas known to be
compromised in schizophrenia: significant clusters were found in
left inferior, middle and superior frontal gyrus, pre- and postcentral
gyrus, as well as in bilateral insula, parietal lobe and medial frontal
gyrus. Notably, in this work, no clear differentiation between vari-
ous training modalities (e.g., computerized vs clinician based) and
intensities became evident.
Although only one report of a retrospective assessment was
available to us, it seems that video game type and genre play a cru-
cial role on the location and intensity of brain plasticity effect (Kühn
and Gallinat, 2014). There was evidence that puzzle-, 3D-platform-
and third person shooter games were most successful to induce
gray matter volume increases, especially in entorhinal cortex and
parahippocampus, regions associated with spatial navigation and
environmental scene recognition (Epstein and Kanwisher, 1998;
Hafting et al., 2005; Kühn and Gallinat, 2014). These game types
involved a third person view on the game character or require
a mental rotation of puzzle pieces. The authors argued that per-
spective rotation required an allocentric view on game content or
pawn, which seemed to stimulate brain regions associated with
navigation. Surprisingly, action based role playing games and ego-
shooters seemed to be negative predictors for entorhinal volume
increases. Why these closely resembling game genres elicited a con-
trasting effect on the entorhinal cortex remained unclear. It might
be interesting for future studies to reconfirm these findings and to
elucidate in more depth the influence of specific game components
on cerebral structures and functioning.
We found two CRT studies, which applied unspecific video gam-
ing as a placebo treatment. Anticipating that CRT and video gaming
affect similar brain regions, one would expect that using video gam-
ing as a control condition reduced observable significant effects
given the same paradigm. In the study of Hooker and coworkers,
subjects showed increased activity in bilateral temporal lobe and
left frontal lobe upon a facial emotion recognition task (Hooker
et al., 2012). A comparable paradigm but different control condi-
tions (treatment as usual and healthy control subjects), revealed
a bilateral frontal activity increase (Habel et al., 2010). This would
suggest that there is indeed an overlapping effect of video gaming
and CRT, visible as increased effect in frontal areas when no video
gaming is used as placebo. However, the study did not reconfirm
any changes in temporal lobe. This incoherence could be caused by
the different training intensities applied. Another reason could be
the potential differences in CRT training modalities or that quickly
changing video games did not elicit sufficient video game training
effects in the unspecific video game control group as the partic-
ipants had to rotate through 16 commercial video games during
study. Unfortunately, we could not clarify this ambiguity by assess-
ing and comparing the effects of unspecific video gaming in the
study of Subramaniam and coworkers to other results from our
literature collection as it was the only study applying a realty mon-
itoring task paradigm (Subramaniam et al., 2012).
Ultimately, cognitive training and remediation should enable a
subject to generalize learned skills to everyday life. Recent imaging
studies underline the evidence for such transfer effects, at least after
training of working memory, which was considered as basis for
many other cognitive tasks (Jaeggi et al., 2011). A recent fMRI study
using the working memory challenging cognitive computer game
“space fortress” confirmed that individual changes in activation
patterns of brain areas typically involved with working memory
were generalizable and correlated with performance changes in
untrained working memory tasks (Nikolaidis et al., 2014). This
underlines that inducing localized functional brain plasticity by
training, improved performance in other, untrained tasks, which
were processed in the same brain areas (Dahlin et al., 2008; Jonides,
2004). A training study using the puzzle video game Tetris in twelve
year old kids indicated that functional integration of game content
was complex and did not exert its effect exclusively on the brain
areas used while playing the game (Haier et al., 2009). Whether
this would be an indication that complex transfer effects could be
evoked by video games, remains to further assessment. The exis-
tence of complex transfer effects would also raises the question
 C. Suenderhauf et al. / Neuroscience and Biobehavioral Reviews 68 (2016) 20–36
whether the overlap in brain regions elicited by video games and
CRT would be indicative for clinical outcome. Whether the video
game induced changes ultimately translate in better outcome for
patients with schizophrenia remains to be answered by clinical
investigations.
4.1. Motivation and motivational elements
Considering the typical onset of schizophrenia in early adult-
hood, at risk mental state and first episode patients would fit well in
the video game peer group. Designed for immersion, patients would
most probably exhibit good compliance to video game training,
although adherence is often reduced in psychosis (Blanchard et al.,
2011). To avoid disengagement, a therapeutic video game would
eventually demand an increased effort in design and motivational
features. It has been shown that besides individual characteristics
of the player, game design elements, such as real-time scoring sys-
tems, theme changes, or prizes substantially influenced motivation
(Jaeggi et al., 2011). However, it seems that not all motivational
features lead to an improved training performance. Katz and
coworkers found that the inclusion of real-time scoring during
play, found in both, entertainment and cognitive training games,
was negatively impacting training improvements over a three day
period in school children (Katz et al., 2014). Whether such game
features lead to an increased motivation or rather to distraction or
even discouragement might strongly depend on the specific target
group a game is designed for. In addition, motivational factors and
beliefs about the subjects own competences and capabilities can
substantially affect learning and training success (Mangels et al.,
2006). Such considerations have to be taken into account, when
video games should be used in vulnerable populations, such as
neuropsychiatric patients.
4.2. Video game addiction
If video game training should be used as therapy, one has to
establish a reasonable profile of the treatments unwished side
effects. Despite of evidence that moderate video game play can have
positive effects, video games were repeatedly accused of causing
addictive behavior (Bailin et al., 2014; Granic et al., 2014; Ng and
Wiemer-Hastings, 2005). Up to date, there are no studies available
estimating the risk to develop video game addiction in patients
with Schizophrenia. However, as the risk of developing addictive
disorders is generally increased in schizophrenia, we feel that if
there would be any connection between video game addiction to
other addictive disorders, video game therapy could impose a risk
to schizophrenic patients (Sara et al., 2015; Selzer and Lieberman,
1993). It seems therefore important to outline the behavioral and
neurobiological characteristics of video game addiction in more
detail to get a clearer risk estimate.
Although experts agree on the existence of problematic video
gaming behavior, the concept of a video game addiction itself
is still strongly debated in the field. In the case of the better-
characterized subgenre internet gaming, addictive video gaming
has not been included in the official part of the 5th edition of
the Diagnostic and Statistical Manual of Mental Disorders of the
American Psychiatric Association (DSM-5), but found entry as “Con-
dition for Further Study” (American Psychiatric Association, 2014).
Some authors classify video game addiction as a result of psychoso-
cial, time management and impulse control issues (Ferguson et al.,
2011; Hellman et al., 2012; Suissa, 2014). Neurobiologically, there
are indications that substance and behavioral addictions, such as
pathologic gambling show the same mesolimbic-prefrontal cortical
circuitry adaptions (Goudriaan et al., 2010; van Holst et al., 2010).
The addictive stimulus enhances the dopaminergic neurotransmis-
sion in the mesolimbic system and induces strong, re-enforcement
31
driven learning (Volkow et al., 2009), which leads to stimulus crav-
ing upon cue exposure and, over time, increasing loss of prefrontal
inhibitory self-control (Volkow et al., 2004). Recent MRI studies
showed that the presentation of video game cues to addicted online
video game players evoked excessive responses in the same brain
structures where cue-induced activity was seen in patients with
substance or behavioral addictions (Han et al., 2012; Ko et al., 2009).
Moreover, online video game addicts responded well to bupro-
pion treatment, indicating that similar dopaminergic changes were
involved in the pathophysiology as in nicotine addiction (Han and
Renshaw, 2012).
Despite this close resemblance, recent imaging studies indicate
also some marked neurobiological differences in problematic video
gaming compared to other addictive behavior: Addicted online
video gamers showed increased activation in orbitofrontal cortex
when winning and decreased anterior cingulate activation when
losing a game (Dong et al., 2011). As both brain structures are
associated with reinforcement-guided decision making involving
reward expectations and cost-benefit considerations (Rushworth
et al., 2007), the authors argued addicted online video gamers
exhibit an enhanced reward sensitivity and an increased frustra-
tion tolerance towards losing a game. This observation stands in
contrast to other addictions including pathologic gambling, where
over time declining reward stimulus (fueling the urge to increase
the stimulus) and reduced frustration tolerance was seen (de Ruiter
et al., 2009). Moreover compulsive video gamers showed unlike
other addictions increased activity in insula at rest (representing
introspective awareness, motoric control, pain experience and the
experience of a number of basic emotions, including anger, fear, dis-
gust, happiness, and sadness (Phan et al., 2002)) and volume gains
in thalamus, which is thought to be involved in filtering peripheral
information for further cortical processing (Han et al., 2012; Park
et al., 2010; Potenza, 2008; Steriade and Llinas, 1988; Volkow et al.,
2006; Vollstädt-Klein et al., 2010). Still it is not clear, whether the
observed gray matter and brain function increases reflected effects
of game addiction or frequent video gaming, as in some studies,
the term video game addiction seems vaguely applied. The dis-
crimination between video game addicted subjects and gamers that
simply spend many hours playing is difficult and most studies used
total gaming time as the only criterion to classify their participants.
This might oversimplify the problem as indicated by a recent study,
which tried to discriminate brain plasticity in online game addicted
subjects from video gamers who played many hours for profes-
sional reasons (Han et al., 2012). The authors found that only the
professional gamers showed increased gray matter volumes. Simi-
lar findings were reported by Kühn and co-workers: Subjects, who
were retrospectively assessed for lifetime video gaming duration
and structural changes in gray matter showed correlations between
ventral striatal volume increases, an area associated with reward-
related processing, and higher ranks in a video game addiction
scores (Kühn and Gallinat, 2014). Notably, there was no correlation
of lifetime video game exposure or excessive video gaming with
ventral striatal volumes or addiction scores, which contradicted
the statement that mere exposure to video games suffices to trigger
addiction (Hellman et al., 2012). This notion was even put further
by recent work showing that time spent on computer games alone
did not have any negative consequences on subjects, while a clear
positive correlation of video game addiction with low academic
achievement, depression and conduct problems was established
(Brunborg et al., 2014).This disposition seemed to be the most
relevant factor for future development of video game addiction:
such subjects were also highly at risk to experience problems in
other areas of life. This observation is highly relevant, when video
game therapy should be evaluated for treatment of schizophrenia.
Compared to healthy and other psychiatric populations, the vul-
nerability for addictive behavior, especially substance addictions,
32 C. Suenderhauf et al. / Neuroscience and Biobehavioral Reviews 68 (2016) 20–36
was particularly increased in patients with schizophrenia (Sara
et al., 2015; Selzer and Lieberman, 1993). There are indications that
reduced functioning of hippocampal- prefrontal circuits typically
seen in psychosis leads to a hyperactive dopamine signaling in the
nucleus accumbens, which is associated with both, positive symp-
toms and addictive behavior (Chambers et al., 2001). Hence, the
reduced inhibitory control over the dopaminergic signaling sensi-
tizes the patient to reward or drug seeking behavior.
Most of our insights into video game addiction were estab-
lished assessing online video game consumption. Whether a game
is played off- or online seems to be quite relevant for the develop-
ment of video game addiction and addicted gamers seem to default
more often to online games. Online games like massive online role
playing games (MORPG) can be played with or against other, real
existing players, 24 h a day. Online games do not stop once a player
is logged out. This leads to a considerable (social) pressure to turn
back to the game. Such behavior was also observed in social media
addiction and pathologic gambling. Online gamblers were at sig-
nificantly higher risk for problematic gambling behavior and drug
abuse as their offline counterparts (Kairouz et al., 2012).
So far, we are not aware of any studies assessing the preva-
lence and characteristics of online or video gaming addictions in
schizophrenia and our ability to estimate the risk for patients with
schizophrenia to develop video game addictions in the absence of
experimental evidence is very limited. However, if an increased
vulnerability for video game addiction would be found in patients
with schizophrenia it might become a particular challenge to design
captivating and immersive games without fostering any unwished
side effects.
Turner and co-workers stated that online video gaming bears
a the danger for lonely and depressed individuals to fuel social
retreat and loss of social competences as the games and especially
online games enable safe and nonthreatening social interactions
(Turner, 2008). This dependence on artificial sociality might then
trigger relapses as no coping strategies for real-life interactions
were established. However, one could also debate the opposite
way: patients with schizophrenia show a reduced capability for
social interaction due to neurobiological impairment and exposure
to online, “safe” social contact might lead to stagnation or at least a
slowing down of social retreat and concomitant stimulus depriva-
tion. Virtual social contact would act as training of remaining social
functioning and bridge the time until real-life integration measures
are imposed.
4.3. Video games and aggressive behavior
As with the concept of game addiction, there is a heated debate
on the subject whether or not video games increase aggression
(Anderson and Bushman, 2001; Kutner et al., 2008). In any case,
it seems that video gaming taken by itself did not foster aggres-
sive or antisocial behavior, but the consumption of violent content
from any kind of media could have detrimental effects on sub-
jects with aggressive dispositions. Especially young children and
persons with preexisting hostile or oppositional-defiant person-
ality traits have been shown to be vulnerable to chronic and to
a lesser extent also acute display of violence (Brockmyer, 2015;
Funk et al., 2003). Typically, desensitization effects, which mani-
fested as reduced empathy and reduced emotional arousal when
confronted with violence were observed. Imaging studies showed
that aggressive behavior was mainly associated with reduced pre-
frontal inhibition of subcortical systems (Bufkin and Luttrell, 2005;
Siever, 2008).
Patients with schizophrenia exhibit a 4–8 times higher risk of
becoming criminal compared to the normal population and sub-
stance abuse and social stress have been identified as influential
covariates (Fazel et al., 2009). Violent behavior in schizophre-
nia manifest mostly in the context of impulsive criminal offences
with strong emotional component in relationship to acute posi-
tive symptoms, more chronic and planned delusional motivated
offences and, in the later course of disease, crimes seeming disso-
cial due to social neglect and reduced capability to cope with stress
(Prüter, 2010). It has been controversially discussed whether the
cognitive impairment itself is a risk factor for aggressive behavior
in schizophrenia.
Neuroimaging studies assessing peculiarities in offensive
patients with schizophrenia showed volume reductions in hip-
pocampus and orbitofrontal gray matter, features also found in
non-violent patients (Soyka, 2011). However, fronto-basal acti-
vation seemed to be even more reduced, when violent patients
showed additionally an antisocial personality disorder and sub-
stance abuse (Joyal et al., 2007). On a functional level, reduced
connectivity between amygdala and prefrontal cortex seemed
to correlate well with higher chance of aggressive behavior in
schizophrenia (Hoptman et al., 2010).
Despite the public perception, offenders with schizophrenia
exhibit low relapse rates and respond well to treatment, suggesting
that supportive care and early detection of subjects at risk could be
an option for violence prevention (Boudriot et al., 2014). However,
considering the vulnerability for aggressive behavior in patients
with schizophrenia, it seems sound to avoid intentional exposition
to any media with violent content, including violent video games.
There are, to the best of our knowledge, no reports to which extent
exposure to violent media content plays a role in the development
of aggressive behavior in schizophrenia. It could be expected that
the excitatory threshold for aggressive behavior might be lower
than in the healthy population, but epidemiologic evidence has to
be established to underline this claim.
Additional concerns could be raised that delusion content is
determined by current cultural beliefs and media. Interestingly, up
to date, video games have not been found to be a frequent subject
of delusions and reports of patients, feeling “caught” in a computer
game are sporadic (Forsyth et al., 2001). Hence, the risk of trigger-
ing video game specific delusions by video game training seems to
be relatively limited. However, for evidence-based estimates epi-
demiological studies of video gaming frequency in patients with
schizophrenia would be needed.
4.4. Limitations
Our systematic literature search revealed a very small database
on the topic of neuroimaging supported studies assessing the
effects of video gaming or CRT on brain plasticity. Although no final
conclusions can be drawn from the present database, we feel that
the present work can inform and induce future work on this area.
However, it is important to note that despite an overlap in brain
regions affected by video gaming and CRT, it is not granted that
patients with schizophrenia would profit from both treatments the
same way. Whether the video game induced changes would ulti-
mately translate in better outcome for patients with schizophrenia
remains to be answered by clinical investigations, assessing both
behavioral and neurobiological parameters
Besides the constrained number of studies available to us, we
anticipated unbalanced prevalence of study designs between CRT
and video game studies, which might additionally limit the gen-
eralizability of our conclusions. While our CRT study collection
consisted mainly of longitudinal designs, we only found three
longitudinal video game studies. Cross-sectional or retrospective
assessments of gaming habits might bear the risk of linking brain
imaging results erroneously to video game specific changes, not
anticipating that these might merely reflect preexisting study
cohort subpopulation features. Longitudinal designs might suffer
less from such shortcomings, however the selection of valid control
 C. Suenderhauf et al. / Neuroscience and Biobehavioral Reviews 68 (2016) 20–36
conditions seems still challenging: Two CRT studies used com-
mercially available computer games as active placebo condition
(Hooker et al., 2012; Subramaniam et al., 2012), which might not
be appropriate as video games were shown to elicit themselves
specific brain plasticity effects. Although the authors stated that
they applied an unspecific video game training, with only short
exposure to individual games, it cannot be ruled out that some
synergistic game effect led to a decrease in observed differences. In
this regard, increased engagement in any specific activity such as
watching DVDs or playing an instrument might bias results. In case
of neuropsychiatric patients, the installation of video game training
on top of standard treatment could be a practical compromise for
an active treatment group. As long as treatment and control group
do keep the same or comparable treatment schedule and are of
sufficient size, brain imaging results should be attributable to the
video game intervention.
In addition, the participant recruitment procedure itself could
introduce bias. For example when subjects knew they were
recruited for their gaming experience or they were informed about
the study purpose. Personal expectations on own performance and
wishes towards study outcome could strongly modulate the par-
ticipants motivation to engage in the study. To counter fight such
shortcomings, sufficient blinding in respect to study purpose or
readouts should be introduced.
Moreover, outcome measures should not be similar to the
training, or bear the risk that study participants have different
expectations on improvement (Boot et al., 2011). This would also
be beneficial to validly quantify potential transfer effects. When
almost identical exercises are used for test and training, statements
on generalizability can no longer be made (Nahum et al., 2014).
Such studies are not only of reduced explanatory power but might
suffer from a strong expectation bias.
5. Conclusions
The present work aimed to present the reader a systematic
overview over a relatively new area of research and intends to
provide a basis for future investigations. Our systematic litera-
ture search reflects an area of research, which is in its beginnings
and more experimental evidence will be needed to ultimately
answer the question whether patients with Schizophrenia would
profit from video game training. Results from brain imaging studies
assessing impact of commercial video games on brain plastic-
ity seem promising as the positively affected brain modulations
showed considerable overlap with brain areas known to be altered
in schizophrenia. If increased brain functioning and grey matter
volumes would translate in better cognitive and every day function-
ing, video game training could be an enjoyable and economically
interesting treatment option for schizophrenia. Moreover, one
could also imagine that regular video game play could enable
home monitoring of patients, if server-based video games would
be used during treatment installation or maintenance. Decreased
login times could then be indicative for diminishing compliance or
worsening of disease. Alarmed by such indicators healthcare pro-
fessionals could initiate at very early stages supportive measures
to avoid relapses.
However, it is still a long way to go as many important questions
remain unanswered: The limited number of video game studies
impedes meta-analytical assessments which would allow to draw
more generalizable qualitative and quantitative conclusions on
the impact of video game training on specific brain structures or
functioning. Moreover, if video games should be considered as a
therapeutic intervention, more epidemiological evidence for pre-
existing vulnerabilities of specific patient groups has to be gained.
Increased vulnerability for addictive behavior might be a particu-
33
lar challenge to design captivating and immersive games without
fostering any unwished side effects.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.neubiorev.2016.
03.018.
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