Multi-Parameter Mapping (MPM) is a comprehensive quantitative neuroimaging protocol that enables estimation of four physical parameters (longitudinal and effective transverse relaxation rates R1 and R2*, proton density PD, and magnetization transfer saturation MTsat) that are sensitive to microstructural tissue properties such as iron and myelin content. Their capability to reveal microstructural brain differences, however, is tightly bound to controlling random noise and artefacts (e.g. caused by head motion) in the signal. Here, we introduced a method to estimate the local error of PD, R1, and MTsat maps that captures both noise and artefacts on a routine basis without requiring additional data. To investigate the method's sensitivity to random noise, we calculated the model-based signal-to-noise ratio (mSNR) and showed in measurements and simulations that it correlated linearly with an experimental raw-image-based SNR map. We found that the mSNR varied with MPM protocols, magnetic field strength (3T vs. 7T) and MPM parameters: it halved from PD to R1 and decreased from PD to MTsat by a factor of 3-4. Exploring the artefact-sensitivity of the error maps, we generated robust MPM parameters using two successive acquisitions of each contrast and the acquisition-specific errors to down-weight erroneous regions. The resulting robust MPM parameters showed reduced variability at the group level as compared to their single-repeat or averaged counterparts. The error and mSNR maps may better inform power-calculations by accounting for local data quality variations across measurements. Code to compute the mSNR maps and robustly combined MPM maps is available in the open-source hMRI toolbox.

There is a vast amount of literature indicating that multiple language expertise leads to positive transfer effects onto other non-language cognitive domains possibly due to enhanced cognitive control. However, there is hardly any evidence about underlying mechanisms on how complex behavior like simultaneous interpreting benefits cognitive functioning in other non-language domains. Therefore, we investigated whether simultaneous interpreters (SIs) exhibit cognitive benefits in tasks measuring aspects of cognitive control compared to a professional multilingual control group. We furthermore investigated in how far potential cognitive benefits are related to brain structure (using voxel-based morphometry) and function (using regions-of-interest-based functional connectivity and graph-analytical measures on low-frequency BOLD signals in resting-state brain data). Concerning cognitive control, the results reveal that SIs exhibit less mixing costs in a task switching paradigm and a dual-task advantage compared to professional multilingual controls. In addition, SIs show more gray matter volume in the left frontal pole (BA 10) compared to controls. Graph theoretical analyses revealed that this region exhibits higher network values for global efficiency and degree and is functionally more strongly connected to the left inferior frontal gyrus and middle temporal gyrus in SIs compared to controls. Thus, the data provide evidence that SIs possess cognitive benefits in tasks measuring cognitive control. It is discussed in how far the central role of the left frontal pole and its stronger functional connectivity to the left inferior frontal gyrus represents a correlate of the neural mechanisms for the observed behavioral effects.

This pilot study aimed to evaluate the feasibility of an assessor-blind, randomised controlled trial of psychodynamic art therapy for the treatment of patients with schizophrenia, and to generate preliminary data on the efficacy of this intervention during acute psychotic episodes. Fifty-eight inpatients with DSM-diagnoses of schizophrenia were randomised to either 12 twice-weekly sessions of psychodynamic group art therapy plus treatment as usual or to standard treatment alone. Primary outcome criteria were positive and negative psychotic and depressive symptoms as well as global assessment of functioning. Secondary outcomes were mentalising function, estimated with the Reading the mind in the eyes test and the Levels of emotional awareness scale, self-efficacy, locus of control, quality of life and satisfaction with care. Assessments were made at baseline, at post-treatment and at 12 weeks' follow-up. At 12 weeks, 55% of patients randomised to art therapy, and 66% of patients receiving treatment as usual were examined. In the per-protocol sample, art therapy was associated with a significantly greater mean reduction of positive symptoms and improved psychosocial functioning at post-treatment and follow-up, and with a greater mean reduction of negative symptoms at follow-up compared to standard treatment. The significant reduction of positive symptoms at post-treatment was maintained in an attempted intention-to-treat analysis. There were no group differences regarding depressive symptoms. Of secondary outcome parameters, patients in the art therapy group showed a significant improvement in levels of emotional awareness, and particularly in their ability to reflect about others' emotional mental states. This is one of the first randomised controlled trials on psychodynamic group art therapy for patients with acute psychotic episodes receiving hospital treatment. Results prove the feasibility of trials on art therapy during acute psychotic episodes and justify further research to substantiate preliminary positive results regarding symptom reduction and the recovery of mentalising function.

In the present longitudinal study, we aimed to investigate video game training associated neuronal changes in reward processing using functional magnetic resonance imaging (fMRI). We recruited 48 healthy young participants which were assigned to one of 2 groups: A group in which participants were instructed to play a commercial video game ("Super Mario 64 DS") on a portable Nintendo DS handheld console at least 30minutes a day over a period of two months (video gaming group; VG) or to a matched passive control group (CG). Before and after the training phase, in both groups, fMRI imaging was conducted during passively viewing reward and punishment-related videos sequences recorded from the trained video game. The results show that video game training may lead to reward related decrease in neuronal activation in the dorsolateral prefrontal cortex (DLPFC) and increase in the hippocampus. Additionally, the decrease in DLPFC activation was associated with gaming related parameters experienced during playing. Specifically, we found that in the VG, gaming related parameters like performance, experienced fun and frustration (assessed during the training period) were correlated to decrease in reward related DLPFC activity. Thus, neuronal changes in terms of video game training seem to be highly related to the appetitive character and reinforcement schedule of the game. Those neuronal changes may also be related to the often reported video game associated improvements in cognitive functions.

Virtual reality (VR) simulates real-world scenarios by creating a sense of presence in its users. Such immersive scenarios lead to behavior that is more similar to that displayed in real world settings, which may facilitate the transfer of knowledge and skills acquired in VR to similar real world situations. VR has already been used in education, psychotherapy, rehabilitation and it comes as an appealing choice for training intervention purposes. The aim of the present study was to investigate to what extent VR technology for games presented via goggles can be used in a magnetic resonance imaging scanner (MRI), addressing the question of whether brain connectivity differs between VR stimulation via goggles and a presentation from a screen via mirror projection. Moreover, we wanted to investigate whether stereoscopic goggle stimulation, where both eyes receive different visual input, would elicit stronger brain connectivity than a stimulation in which both eyes receive the same visual input (monoscopic). To our knowledge, there is no previous research using games and functional connectivity (FC) in MRI to address this question. Multiple analyses approaches were taken so that different aspects of brain connectivity could be covered: fractional low-frequency fluctuation, independent component analysis (ICA), seed-based FC (SeedFC) and graph analysis. In goggle presentation (mono and stereoscopic) as contrasted to screen, we found differences in brain activation in left cerebellum and postcentral gyrus as well as differences in connectivity in the visual cortex and frontal inferior cortex [when focusing on the visual and default mode network (DMN)]. When considering connectivity in specific areas of interest, we found higher connectivity between bilateral superior frontal cortex and the temporal lobe, as well as bilateral inferior parietal cortex with right calcarine and right lingual cortex. Furthermore, we found superior frontal cortex and insula/putamen to be more strongly connected in goggle stereoscopic vs. goggle monoscopic, in line with our hypothesis. We assume that the condition that elicits higher brain connectivity values should be most suited for long-term brain training interventions given that, extended training under these conditions could permanently improve brain connectivity on a functional as well as on a structural level.

While previous attempts to train self-control in humans have frequently failed, we set out to train response inhibition using computer-game elements. We trained older adults with a newly developed game-based inhibition training on a tablet for two months and compared them to an active and passive control group. Behavioural effects reflected in shorter stop signal response times that were observed only in the inhibition-training group. This was accompanied by structural growth in cortical thickness of right inferior frontal gyrus (rIFG) triangularis, a brain region that has been associated with response inhibition. The structural plasticity effect was positively associated with time spent on the training-task and predicted the final percentage of successful inhibition trials in the stop task. The data provide evidence for successful trainability of inhibition when game-based training is employed. The results extend our knowledge on game-based cognitive training effects in older age and may foster treatment research in psychiatric diseases related to impulse control.

Human beings evolved in "natural" environments. Many intervention studies have shown that exposure to natural environments (compared to built/urban environments) reduces stress and increases cognitive functioning. We set out to test differences in fMRI functional connectivity while showing participants photographs from natural versus built environments (matched in terms of scenicness ratings). No differences in self-reported perceived stress, rumination, valence, arousal or dominance were observed. However, functional connectivity was significantly higher when participants saw natural rather than built environmental photographs in circuits consisting of dorsal attention network (DAN) and ventral attention network (VAN), DAN and default mode network (DMN) and DMN and Somatomotor connections. In addition, we observed lower functional connectivity during the natural environment condition correlated with more years that individuals spent in major cities during upbringing. Future studies, linking changes in cognitive functioning due to nature exposure and alterations in functional connectivity, are warranted.

A diagnosis of schizophrenia is associated with a heterogeneous psychopathology including positive and negative symptoms. The disconnection hypothesis, an early pathophysiological framework conceptualizes the diversity of symptoms as a result of disconnections in neural networks. In line with this hypothesis, previous neuroimaging studies of patients with schizophrenia reported alterations within the default mode network (DMN), the most prominent network at rest. The aim of the present study was to investigate the functional connectivity during rest in patients with schizophrenia and with healthy individuals and explore whether observed functional alterations are related to the psychopathology of patients. Therefore, functional magnetic resonance images at rest were recorded of 35 patients with schizophrenia and 41 healthy individuals. Independent component analysis (ICA) was used to extract resting state networks. Comparing ICA results between groups indicated alterations only within the network of the DMN. More explicitly, reduced connectivity in the precuneus was observed in patients with schizophrenia compared to healthy controls. Connectivity in this area was negatively correlated with the severity of negative symptoms, more specifically with the domain of apathy. Taken together, the current results provide further evidence for a role DMN alterations might play in schizophrenia and especially in negative symptoms such as apathy.

In the present study, the brain's response towards near- and supra-threshold infrasound (IS) stimulation (sound frequency < 20 Hz) was investigated under resting-state fMRI conditions. The study involved two consecutive sessions. In the first session, 14 healthy participants underwent a hearing threshold-as well as a categorical loudness scaling measurement in which the individual loudness perception for IS was assessed across different sound pressure levels (SPL). In the second session, these participants underwent three resting-state acquisitions, one without auditory stimulation (no-tone), one with a monaurally presented 12-Hz IS tone (near-threshold) and one with a similar tone above the individual hearing threshold corresponding to a 'medium loud' hearing sensation (supra-threshold). Data analysis mainly focused on local connectivity measures by means of regional homogeneity (ReHo), but also involved independent component analysis (ICA) to investigate inter-regional connectivity. ReHo analysis revealed significantly higher local connectivity in right superior temporal gyrus (STG) adjacent to primary auditory cortex, in anterior cingulate cortex (ACC) and, when allowing smaller cluster sizes, also in the right amygdala (rAmyg) during the near-threshold, compared to both the supra-threshold and the no-tone condition. Additional independent component analysis (ICA) revealed large-scale changes of functional connectivity, reflected in a stronger activation of the right amygdala (rAmyg) in the opposite contrast (no-tone > near-threshold) as well as the right superior frontal gyrus (rSFG) during the near-threshold condition. In summary, this study is the first to demonstrate that infrasound near the hearing threshold may induce changes of neural activity across several brain regions, some of which are known to be involved in auditory processing, while others are regarded as keyplayers in emotional and autonomic control. These findings thus allow us to speculate on how continuous exposure to (sub-)liminal IS could exert a pathogenic influence on the organism, yet further (especially longitudinal) studies are required in order to substantialize these findings.

Patients with borderline personality disorder (BPD) frequently exhibit impulsive behavior, and self-reported impulsivity is typically higher in BPD patients when compared to healthy controls. Previous functional neuroimaging studies have suggested a link between impulsivity, the ventral striatal response to reward anticipation, and prediction errors. Here we investigated the striatal neural response to monetary gain and loss anticipation and their relationship with impulsivity in 21 female BPD patients and 23 age-matched female healthy controls using functional magnetic resonance imaging (fMRI). Participants performed a delayed monetary incentive task in which three categories of objects predicted a potential gain, loss, or neutral outcome. Impulsivity was assessed using the Barratt Impulsiveness Scale (BIS-11). Compared to healthy controls, BPD patients exhibited significantly reduced fMRI responses of the ventral striatum/nucleus accumbens (VS/NAcc) to both reward-predicting and loss-predicting cues. BIS-11 scores showed a significant positive correlation with the VS/NAcc reward anticipation responses in healthy controls, and this correlation, while also nominally positive, failed to reach significance in BPD patients. BPD patients, on the other hand, exhibited a significantly negative correlation between ventral striatal loss anticipation responses and BIS-11 scores, whereas this correlation was significantly positive in healthy controls. Our results suggest that patients with BPD show attenuated anticipation responses in the VS/NAcc and, furthermore, that higher impulsivity in BPD patients might be related to impaired prediction of aversive outcomes.

The formation of coherent multisensory percepts requires integration of stimuli across the multiple senses. Patients with schizophrenia (ScZ) often experience a loss of coherent perception and hence, they might also show dysfunctional multisensory processing. In this high-density electroencephalography study, we investigated the neural signatures of the McGurk illusion, as a phenomenon of speech-specific multisensory processing. In the McGurk illusion lip movements are paired with incongruent auditory syllables, which can induce a fused percept. In ScZ patients and healthy controls we compared neural oscillations and event-related potentials (ERPs) to congruent audiovisual speech stimuli and McGurk illusion trials, where a visual /ga/ and an auditory /pa/ was often perceived as /ka/. There were no significant group differences in illusion rates. The EEG data analysis revealed larger short latency ERPs to McGurk illusion compared with congruent trials in controls. The reversed effect pattern was found in ScZ patients, indicating an early audiovisual processing deficit. Moreover, we observed stronger suppression of medio-central alpha-band power (8-10 Hz, 550-700 ms) in response to McGurk illusion compared with control trials in the control group. Again, the reversed pattern was found in SCZ patients. Moreover, within groups, alpha-band suppression was negatively correlated with the McGurk illusion rate in ScZ patients, while the correlation tended to be positive in controls. The topography of alpha-band effects indicated an involvement of auditory and/or frontal structures. Our study suggests that short latency ERPs and long latency alpha-band oscillations reflect abnormal multisensory processing of the McGurk illusion in ScZ.

Clinical studies suggest aberrant neurotransmitter concentrations in the brains of patients with schizophrenia (SCZ). Numerous studies have indicated deviant glutamate concentrations in SCZ, although the findings are inconsistent. Moreover, alterations in glutamate concentrations could be linked to personality traits in SCZ. Here, we examined the relationships between personality dimensions and glutamate concentrations in a voxel encompassing the occipital cortex (OCC) and another voxel encompassing the left superior temporal sulcus (STS). We used proton magnetic resonance spectroscopy to examine glutamate concentrations in the OCC and the STS in 19 SCZ and 21 non-psychiatric healthy control (HC) participants. Personality dimensions neuroticism, extraversion, openness, agreeableness and conscientiousness were assessed using the NEO-FFI questionnaire. SCZ compared to HC showed higher glutamate concentrations in the STS, reduced extraversion scores, and enhanced neuroticism scores. No group differences were observed for the other personality traits and for glutamate concentrations in the OCC. For the SCZ group, glutamate concentrations in STS were negatively correlated with the neuroticism scores [r = -0.537, p = 0.018] but this was not found in HC [r(19) = 0.011, p = 0.962]. No other significant correlations were found. Our study showed an inverse relationship between glutamate concentrations in the STS and neuroticism scores in SCZ. Elevated glutamate in the STS might serve as a compensatory mechanism that enables patients with enhanced concentrations to control and prevent the expression of neuroticism.

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder, characterized by core symptoms of inattention, hyperactivity and impulsivity. Comorbid depression is commonly observed in ADHD-patients. Psychostimulants are recommended as first-line treatment for ADHD. Aberrant long-range temporal correlations (LRTCs) of neuronal activities in resting-state are known to be associated with disorganized thinking and concentrating difficulties (typical in ADHD) and with maladaptive thinking (typical in depression). It has yet to be examined whether (1) LRTC occur in ADHD-patients, and if so, (2) whether LRTC might be a competent biomarker in ADHD comorbid with current depression and (3) how depression affects psychostimulant therapy of ADHD symptoms. The present study registered and compared LRTCs in different EEG frequency bands in 85 adults with ADHD between groups with (n = 28) and without (n = 57) additional depressive symptoms at baseline. Treatment-related changes in ADHD, depressive symptoms and LRTC were investigated in the whole population and within each group. Our results revealed significant LRTCs existed in all investigated frequency bands. There were, however, no significant LRTC-differences between ADHD-patients with and without depressive symptoms at baseline and no LRTC-changes following treatment. However, depressed ADHD patients did seem to benefit more from the therapy with psychostimulant based on self-report.

Cognitive deficits such as working memory (WM) impairment are core features of schizophrenia. One candidate marker for the integrity of synaptic neurotransmission necessary for cognitive processes is glutamate. It is frequently postulated that antipsychotic medication possibly alters functional mechanisms in the living brain. We tested in vivo for group differences in activation of the dorsolateral prefrontal cortex (DLPFC) during WM performance and the association with glutamate concentration in DLPFC depending on medication status.

Recent behavioral and neuroimaging studies have suggested multisensory processing deficits in patients with schizophrenia (SCZ). Thus far, the neural mechanisms underlying these deficits are not well understood. Previous studies with unisensory stimulation have shown altered neural oscillations in SCZ. As such, altered oscillations could contribute to aberrant multisensory processing in this patient group. To test this assumption, we conducted an electroencephalography (EEG) study in 15 SCZ and 15 control participants in whom we examined neural oscillations and event-related potentials (ERPs) in the sound-induced flash illusion (SIFI). In the SIFI multiple auditory stimuli that are presented alongside a single visual stimulus can induce the illusory percept of multiple visual stimuli. In SCZ and control participants we compared ERPs and neural oscillations between trials that induced an illusion and trials that did not induce an illusion. On the behavioral level, SCZ (55.7%) and control participants (55.4%) did not significantly differ in illusion rates. The analysis of ERPs revealed diminished amplitudes and altered multisensory processing in SCZ compared to controls around 135 ms after stimulus onset. Moreover, the analysis of neural oscillations revealed altered 25-35 Hz power after 100 to 150 ms over occipital scalp for SCZ compared to controls. Our findings extend previous observations of aberrant neural oscillations in unisensory perception paradigms. They suggest that altered ERPs and altered occipital beta/gamma band power reflect aberrant multisensory processing in SCZ.

Pregnancy is accompanied by prolonged exposure to high estrogen levels. Animal studies have shown that estrogen influences navigation strategies and, hence, affects navigation performance. High estrogen levels are related to increased use of hippocampal-based allocentric strategies and decreased use of striatal-based egocentric strategies. In humans, associations between hormonal shifts and navigation strategies are less well studied. This study compared 30 peripartal women (mean age 28years) to an age-matched control group on allocentric versus egocentric navigation performance (measured in the last month of pregnancy) and gray matter volume (measured within two months after delivery). None of the women had a previous pregnancy before study participation. Relative to controls, pregnant women performed less well in the egocentric condition of the navigation task, but not the allocentric condition. A whole-brain group comparison revealed smaller left striatal volume (putamen) in the peripartal women. Across the two groups, left striatal volume was associated with superior egocentric over allocentric performance. Limited by the cross-sectional study design, the findings are a first indication that human pregnancy might be accompanied by structural brain changes in navigation-related neural systems and concomitant changes in navigation strategy.

Previous neuroimaging research has demonstrated that female gonadal hormones can alter the structure and function of adult women's brains. So far, we do not know how hormonal contraceptives affect female brain structure, in part because within-person longitudinal observations are lacking. Here, we compared 28 young women before and after three months of regular contraceptive intake with 28 naturally cycling women of comparable age. The goal was to explore within-person neural change in women using contraceptives. Neuroimaging, hormonal, cognitive, and affect data were collected at two time points for each participant. A voxel-wise whole-brain comparison of both groups revealed decreased gray matter volume in the left amygdala/anterior parahippocampal gyrus in women using contraceptives as compared to the control group. Resting-state functional connectivity of this region with the dorsolateral prefrontal cortex changed from positive to negative connectivity following contraceptive intake whereas the opposite held for the control group. An exploratory analysis revealed that gray matter volume in the left amygdala/anterior parahippocampal gyrus was associated with positive affect at the second time point. There were no systematic differences in cognitive performance change between the groups. These findings provide initial insights into effects of hormonal contraceptives on the human brain and expand previous findings on hormone-related amygdala/hippocampal complex plasticity. The affected brain regions may be related to psychological wellbeing, underlining the importance of future studies on contraceptive-induced brain changes.

Playing video games is a common recreational activity of adolescents. Recent research associated frequent video game playing with improvements in cognitive functions. Improvements in cognition have been related to grey matter changes in prefrontal cortex. However, a fine-grained analysis of human brain structure in relation to video gaming is lacking. In magnetic resonance imaging scans of 152 14-year old adolescents, FreeSurfer was used to estimate cortical thickness. Cortical thickness across the whole cortical surface was correlated with self-reported duration of video gaming (hours per week). A robust positive association between cortical thickness and video gaming duration was observed in left dorsolateral prefrontal cortex (DLPFC) and left frontal eye fields (FEFs). No regions showed cortical thinning in association with video gaming frequency. DLPFC is the core correlate of executive control and strategic planning which in turn are essential cognitive domains for successful video gaming. The FEFs are a key region involved in visuo-motor integration important for programming and execution of eye movements and allocation of visuo-spatial attention, processes engaged extensively in video games. The results may represent the biological basis of previously reported cognitive improvements due to video game play. Whether or not these results represent a-priori characteristics or consequences of video gaming should be studied in future longitudinal investigations.

Impulsiveness is a central domain of human personality and of relevance for the development of substance use and certain psychiatric disorders. This study investigates whether there are overlapping as well as distinct structural cerebral correlates of attentional, motor and nonplanning impulsiveness in healthy adults.

It is a widespread concern that violent video games promote aggression, reduce pro-social behaviour, increase impulsivity and interfere with cognition as well as mood in its players. Previous experimental studies have focussed on short-term effects of violent video gameplay on aggression, yet there are reasons to believe that these effects are mostly the result of priming. In contrast, the present study is the first to investigate the effects of long-term violent video gameplay using a large battery of tests spanning questionnaires, behavioural measures of aggression, sexist attitudes, empathy and interpersonal competencies, impulsivity-related constructs (such as sensation seeking, boredom proneness, risk taking, delay discounting), mental health (depressivity, anxiety) as well as executive control functions, before and after 2 months of gameplay. Our participants played the violent video game Grand Theft Auto V, the non-violent video game The Sims 3 or no game at all for 2 months on a daily basis. No significant changes were observed, neither when comparing the group playing a violent video game to a group playing a non-violent game, nor to a passive control group. Also, no effects were observed between baseline and posttest directly after the intervention, nor between baseline and a follow-up assessment 2 months after the intervention period had ended. The present results thus provide strong evidence against the frequently debated negative effects of playing violent video games in adults and will therefore help to communicate a more realistic scientific perspective on the effects of violent video gaming.