Tobias Gleich

Playing Super Mario induces structural brain plasticity: Gray matter changes resulting from training with a commercial video game

Video gaming is a highly pervasive activity, providing a multitude of complex cognitive and motor demands. Gaming can be seen as an intense training of several skills. Associated cerebral structural plasticity induced has not been investigated so far. Comparing a control with a video gaming training group that was trained for 2 months for at least 30 min per day with a platformer game, we found significant gray matter (GM) increase in right hippocampal formation (HC), right dorsolateral prefrontal cortex (DLPFC) and bilateral cerebellum in the training group. The HC increase correlated with changes from egocentric to allocentric navigation strategy. GM increases in HC and DLPFC correlated with participants’ desire for video gaming, evidence suggesting a predictive role of desire in volume change. Video game training augments GM in brain areas crucial for spatial navigation, strategic planning, working memory and motor performance going along with evidence for behavioral changes of navigation strategy. The presented video game training could therefore be used to counteract known risk factors for mental disease such as smaller hippocampus and prefrontal cortex volume in, for example, post-traumatic stress disorder, schizophrenia and neurodegenerative disease.

Aberrant Salience Is Related to Reduced Reinforcement Learning Signals and Elevated Dopamine Synthesis Capacity in Healthy Adults

The striatum is known to play a key role in reinforcement learning, specifically in the encoding of teaching signals such as reward prediction errors (RPEs). It has been proposed that aberrant salience attribution is associated with impaired coding of RPE and heightened dopamine turnover in the striatum, and might be linked to the development of psychotic symptoms. However, the relationship of aberrant salience attribution, RPE coding, and dopamine synthesis capacity has not been directly investigated. Here we assessed the association between a behavioral measure of aberrant salience attribution, the salience attribution test, to neural correlates of RPEs measured via functional magnetic resonance imaging while healthy participants (n = 58) performed an instrumental learning task. A subset of participants (n = 27) also underwent positron emission tomography with the radiotracer [18F]fluoro-l-DOPA to quantify striatal presynaptic dopamine synthesis capacity. Individual variability in aberrant salience measures related negatively to ventral striatal and prefrontal RPE signals and in an exploratory analysis was found to be positively associated with ventral striatal presynaptic dopamine levels. These data provide the first evidence for a specific link between the constructs of aberrant salience attribution, reduced RPE processing, and potentially increased presynaptic dopamine function.

Aberrant Salience Is Related to Dysfunctional Self-Referential Processing in Psychosis

BACKGROUND A dysfunctional differentiation between self-relevant and irrelevant information may affect the perception of environmental stimuli as abnormally salient. The aberrant salience hypothesis assumes that positive symptoms arise from an attribution of salience to irrelevant stimuli accompanied by the feeling of self-relevance. Self-referential processing relies on the activation of cortical midline structures which was demonstrated to be impaired in psychosis. We investigated the neural correlates of self-referential processing, aberrant salience attribution, and the relationship between these 2 measures across the psychosis continuum. METHODS Twenty-nine schizophrenia patients, 24 healthy individuals with subclinical delusional ideation, and 50 healthy individuals participated in this study. Aberrant salience was assessed behaviorally in terms of reaction times to task irrelevant cues. Participants performed a self-reference task during fMRI in which they had to apply neutral trait words to them or to a public figure. The correlation between self-referential processing and aberrant salience attribution was tested. RESULTS Schizophrenia patients displayed increased aberrant salience attribution compared with healthy controls and individuals with subclinical delusional ideation, while the latter exhibited intermediate aberrant salience scores. In the self-reference task, schizophrenia patients showed reduced activation in the ventromedial prefrontal cortex (vmPFC), but individuals with subclinical delusional ideation did not differ from healthy controls. In schizophrenia patients, vmPFC activation correlated negatively with implicit aberrant salience attribution. CONCLUSIONS Higher aberrant salience attribution in schizophrenia patients is related to reduced vmPFC activation during self-referential judgments suggesting that aberrant relevance coding is reflected in decreased neural self-referential processing as well as in aberrant salience attribution.

Reward anticipation in the adolescent and aging brain

Processing of reward is the basis of adaptive behavior of the human being. Neural correlates of reward processing seem to be influenced by developmental changes from adolescence to late adulthood. The aim of this study is to uncover these neural correlates during a slot machine gambling task across the lifespan. Therefore, we used functional magnetic resonance imaging to investigate 102 volunteers in three different age groups: 34 adolescents, 34 younger adults, and 34 older adults. We focused on the core reward areas ventral striatum (VS) and ventromedial prefrontal cortex (VMPFC), the valence processing associated areas, anterior cingulate cortex (ACC) and insula, as well as information integration associated areas, dorsolateral prefrontal cortex (DLPFC), and inferior parietal lobule (IPL). Results showed that VS and VMPFC were characterized by a hyperactivation in adolescents compared with younger adults. Furthermore, the ACC and insula were characterized by a U‐shape pattern (hypoactivation in younger adults compared with adolescents and older adults), whereas the DLPFC and IPL were characterized by a J‐shaped form (hyperactivation in older adults compared with younger groups). Furthermore, a functional connectivity analysis revealed an elevated negative functional coupling between the inhibition‐related area rIFG and VS in younger adults compared with adolescents. Results indicate that lifespan‐related changes during reward anticipation are characterized by different trajectories in different reward network modules and support the hypothesis of an imbalance in maturation of striatal and prefrontal cortex in adolescents. Furthermore, these results suggest compensatory age‐specific effects in fronto‐parietal regions. Hum Brain Mapp 35:5153–5165, 2014.

Video game training and the reward system

Video games contain elaborate reinforcement and reward schedules that have the potential to maximize motivation. Neuroimaging studies suggest that video games might have an influence on the reward system. However, it is not clear whether reward-related properties represent a precondition, which biases an individual toward playing video games, or if these changes are the result of playing video games. Therefore, we conducted a longitudinal study to explore reward-related functional predictors in relation to video gaming experience as well as functional changes in the brain in response to video game training. Fifty healthy participants were randomly assigned to a video game training (TG) or control group (CG). Before and after training/control period, functional magnetic resonance imaging (fMRI) was conducted using a non-video game related reward task. At pretest, both groups showed strongest activation in ventral striatum (VS) during reward anticipation. At posttest, the TG showed very similar VS activity compared to pretest. In the CG, the VS activity was significantly attenuated. This longitudinal study revealed that video game training may preserve reward responsiveness in the VS in a retest situation over time. We suggest that video games are able to keep striatal responses to reward flexible, a mechanism which might be of critical value for applications such as therapeutic cognitive training.

Prefrontal and Striatal Glutamate Differently Relate to Striatal Dopamine: Potential Regulatory Mechanisms of Striatal Presynaptic Dopamine Function?

Theoretical and animal work has proposed that prefrontal cortex (PFC) glutamate inhibits dopaminergic inputs to the ventral striatum (VS) indirectly, whereas direct VS glutamatergic afferents have been suggested to enhance dopaminergic inputs to the VS. In the present study, we aimed to investigate relationships of glutamate and dopamine measures in prefrontostriatal circuitries of healthy humans. We hypothesized that PFC and VS glutamate, as well as their balance, are differently associated with VS dopamine. Glutamate concentrations in the left lateral PFC and left striatum were assessed using 3-Tesla proton magnetic resonance spectroscopy. Striatal presynaptic dopamine synthesis capacity was measured by fluorine-18-l-dihydroxyphenylalanine (F-18-FDOPA) positron emission tomography. First, a negative relationship was observed between glutamate concentrations in lateral PFC and VS dopamine synthesis capacity (n = 28). Second, a positive relationship was revealed between striatal glutamate and VS dopamine synthesis capacity (n = 26). Additionally, the intraindividual difference between PFC and striatal glutamate concentrations correlated negatively with VS dopamine synthesis capacity (n = 24). The present results indicate an involvement of a balance in PFC and striatal glutamate in the regulation of VS dopamine synthesis capacity. This notion points toward a potential mechanism how VS presynaptic dopamine levels are kept in a fine-tuned range. A disruption of this mechanism may account for alterations in striatal dopamine turnover as observed in mental diseases (e.g., in schizophrenia). SIGNIFICANCE STATEMENT The present work demonstrates complementary relationships between prefrontal and striatal glutamate and ventral striatal presynaptic dopamine using human imaging measures: a negative correlation between prefrontal glutamate and presynaptic dopamine and a positive relationship between striatal glutamate and presynaptic dopamine are revealed. The results may reflect a regulatory role of prefrontal and striatal glutamate for ventral striatal presynaptic dopamine levels. Such glutamate–dopamine relationships improve our understanding of neurochemical interactions in prefrontostriatal circuits and have implications for the neurobiology of mental disease.

Interactions between glutamate, dopamine, and the neuronal signature of response inhibition in the human striatum

Response inhibition is a basic mechanism in cognitive control and dysfunctional in major psychiatric disorders. The neuronal mechanisms are in part driven by dopamine in the striatum. Animal data suggest a regulatory role of glutamate on the level of the striatum. We used a trimodal imaging procedure of the human striatum including F18‐DOPA positron emission tomography, proton magnetic resonance spectroscopy, and functional magnetic resonance imaging of a stop signal task. We investigated dopamine synthesis capacity and glutamate concentration in vivo and their relation to functional properties of response inhibition. A mediation analysis revealed a significant positive association between dopamine synthesis capacity and inhibition‐related neural activity in the caudate nucleus. This relationship was significantly mediated by striatal glutamate concentration. Furthermore, stop signal reaction time was inversely related to striatal activity during inhibition. The data show, for the first time in humans, an interaction between dopamine, glutamate, and the neural signature of response inhibition in the striatum. This finding stresses the importance of the dopamine–glutamate interaction for behavior and may facilitate the understanding of psychiatric disorders characterized by impaired response inhibition. Hum Brain Mapp 36:4031–4040, 2015.

Frontal glutamate and reward processing in adolescence and adulthood

The fronto-limbic network interaction, driven by glutamatergic and dopaminergic neurotransmission, represents a core mechanism of motivated behavior and personality traits. Reward seeking behavior undergoes tremendous changes in adolescence paralleled by neurobiological changes of this network including the prefrontal cortex, striatum and amygdala. Since fronto-limbic dysfunctions also underlie major psychiatric diseases beginning in adolescence, this investigation focuses on network characteristics separating adolescents from adults. To investigate differences in network interactions, the brain reward system activity (slot machine task) together with frontal glutamate concentration (anterior cingulate cortex, ACC) was measured in 28 adolescents and 26 adults employing functional magnetic resonance imaging and magnetic resonance spectroscopy, respectively. An inverse coupling of glutamate concentrations in the ACC and activation of the ventral striatum was observed in adolescents. Further, amygdala response in adolescents was negatively correlated with the personality trait impulsivity. For adults, no significant associations of network components or correlations with impulsivity were found. The inverse association between frontal glutamate concentration and striatal activation in adolescents is in line with the triadic model of motivated behavior stressing the important role of frontal top–down inhibition on limbic structures. Our data identified glutamate as the mediating neurotransmitter of this inhibitory process and demonstrates the relevance of glutamate on the reward system and related behavioral traits like impulsivity. This fronto-limbic coupling may represent a vulnerability factor for psychiatric disorders starting in adolescence but not in adulthood.

Subjective illusion of control modulates striatal reward anticipation in adolescence.

The perception of control over the environment constitutes a fundamental biological adaptive mechanism, especially during development. Previous studies comparing an active choice condition with a passive no-choice condition showed that the neural basis of this mechanism is associated with increased activity within the striatum and the prefrontal cortex. In the current study, we aimed to investigate whether subjective belief of control in an uncertain gambling situation induces elevated activation in a cortico-striatal network. We investigated 79 adolescents (age range: 13-16years) during reward anticipation with a slot machine task using functional magnetic resonance imaging. We assessed post-experimentally whether the participants experienced a subjective illusion of control on winning or losing in this task that was objectively not given. Nineteen adolescents experienced an illusion of control during slot machine gambling. This illusion of control group showed an increased neural activity during reward anticipation within a cortico-striatal network including ventral striatum (VS) as well as right inferior frontal gyrus (rIFG) relative to the group reporting no illusion of control. The rIFG activity was inversely associated with impulsivity in the no illusion of control group. The subjective belief about control led to an elevated ventral striatal activity, which is known to be involved in the processing of reward. This finding strengthens the notion that subjectively perceived control, not necessarily the objective presence of control, affects striatal reward-related processing.

Internal and external attention and the default mode network

Abstract Focused attention meditations have been shown to improve psychological health and wellbeing and are nowadays an integral part of many psychotherapies. While research on the neural correlates of focused attention meditation is increasing, findings vary on whether meditations are associated with high or low activity in the default mode network (DMN). To clarify the relationship between focused attention meditation and the activity in DMN regions, it may be helpful to distinguish internal and external attention as well as different phases within one meditation: During focused attention meditation, the practitioner switches between mindful attention, mind‐wandering and refocusing. Here, we employed a thought‐probe paradigm to study the neural correlates of these different phases. Twenty healthy, meditation naïve participants were introduced to external (mindfulness of sound) and internal (mindfulness of breathing) attention meditation and then practiced the meditation at home for four consecutive days. They then performed the same focused attention meditations during fMRI scanning, in four runs alternating between internal and external attention. At pseudorandom intervals, participants were asked whether they had just been focused on the task (mindful attention) or had been distracted (mind‐wandering). During mindful attention, brain regions typically associated with the DMN, such as the medial prefrontal cortex, posterior cingulate cortex and left temporoparietal junction showed significantly less neural activation compared to mind‐wandering phases. Reduced activity of the DMN was found during both external and internal attention, with stronger deactivation in the posterior cingulate cortex during internal attention compared to external attention. Moreover, refocusing after mind‐wandering was associated with activity in the left inferior frontal gyrus. Our results support the theory that mindful attention is associated with reduced DMN activity compared to mind‐wandering, independent of the practitioners attention focus (i.e., internal vs. external). HighlightsWe assessed neural correlates of mindful and mind‐wandering trials during internal and external meditation.Mindfulness was associated with relative decrease in DMN activity.Relative reduction in PCC activity was stronger during internal meditation.Findings demonstrate the association between state of mind and DMN activity