Cortico-limbic connectivity in MAOA-L carriers is vulnerable to acute tryptophan depletion.

INTRODUCTION: A gene-environment interaction between expression genotypes of the monoamine oxidase A (MAOA) and adverse childhood experience increases the risk of antisocial behavior. However, the neural underpinnings of this interaction remain uninvestigated. A cortico-limbic circuit involving the prefrontal cortex (PFC) and the amygdala is central to the suppression of aggressive impulses and is modulated by serotonin (5-HT). MAOA genotypes may modulate the vulnerability of this circuit and increase the risk for emotion regulation deficits after specific life events. Acute tryptophan depletion (ATD) challenges 5-HT regulation and may identify vulnerable neuronal circuits, contributing to the gene-environment interaction. METHODS: Functional magnetic resonance imaging measured the resting-state state activity in 64 healthy males in a double-blind, placebo-controlled study. Cortical maps of amygdala correlation identified the impact of ATD and its interaction with low- (MAOA-L) and high-expression variants (MAOA-H) of MAOA on cortico-limbic connectivity. RESULTS: Across all Regions of Interest (ROIs) exhibiting an ATD effect on cortico-limbic connectivity, MAOA-L carriers were more susceptible to ATD than MAOA-H carriers. In particular, the MAOA-L group exhibited a larger reduction of amygdala connectivity with the right prefrontal cortex and a larger increase of amygdala connectivity with the insula and dorsal PCC. CONCLUSION: MAOA-L carriers were more susceptable to a central 5-HT challenge in cortico-limbic networks. Such vulnerability of the cortical serotonergic system may contribute to the emergence of antisocial behavior after systemic challenges, observed as gene-environment interaction. Hum Brain Mapp 38:1622-1635, 2017. © 2016 Wiley Periodicals, Inc.

Age- and gender-related variations of emotion recognition in pseudowords and faces.

UNLABELLED: BACKGROUND/STUDY CONTEXT: The ability to interpret emotionally salient stimuli is an important skill for successful social functioning at any age. The objective of the present study was to disentangle age and gender effects on emotion recognition ability in voices and faces. METHODS: Three age groups of participants (young, age range: 18-35 years; middle-aged, age range: 36-55 years; and older, age range: 56-75 years) identified basic emotions presented in voices and faces in a forced-choice paradigm. Five emotions (angry, fearful, sad, disgusted, and happy) and a nonemotional category (neutral) were shown as encoded in color photographs of facial expressions and pseudowords spoken in affective prosody. RESULTS: Overall, older participants had a lower accuracy rate in categorizing emotions than young and middle-aged participants. Females performed better than males in recognizing emotions from voices, and this gender difference emerged in middle-aged and older participants. The performance of emotion recognition in faces was significantly correlated with the performance in voices. CONCLUSION: The current study provides further evidence for a general age and gender effect on emotion recognition; the advantage of females seems to be age- and stimulus modality-dependent.

Quetiapine modulates functional connectivity in brain aggression networks.

Aggressive behavior is associated with dysfunctions in an affective regulation network encompassing amygdala and prefrontal areas such as orbitofrontal (OFC), anterior cingulate (ACC), and dorsolateral prefrontal cortex (DLPFC). In particular, prefrontal regions have been postulated to control amygdala activity by inhibitory projections, and this process may be disrupted in aggressive individuals. The atypical antipsychotic quetiapine successfully attenuates aggressive behavior in various disorders; the underlying neural processes, however, are unknown. A strengthened functional coupling in the prefrontal-amygdala system may account for these anti-aggressive effects. An inhibition of this network has been reported for virtual aggression in violent video games as well. However, there have been so far no in-vivo observations of pharmacological influences on corticolimbic projections during human aggressive behavior. In a double-blind, placebo-controlled study, quetiapine and placebo were administered for three successive days prior to an fMRI experiment. In this experiment, functional brain connectivity was assessed during virtual aggressive behavior in a violent video game and an aggression-free control task in a non-violent modification. Quetiapine increased the functional connectivity of ACC and DLPFC with the amygdala during virtual aggression, whereas OFC-amygdala coupling was attenuated. These effects were observed neither for placebo nor for the non-violent control. These results demonstrate for the first time a pharmacological modification of aggression-related human brain networks in a naturalistic setting. The violence-specific modulation of prefrontal-amygdala networks appears to control aggressive behavior and provides a neurobiological model for the anti-aggressive effects of quetiapine.

Brain networks underlying mental imagery of auditory and visual information.

Mental imagery is a complex cognitive process that resembles the experience of perceiving an object when this object is not physically present to the senses. It has been shown that, depending on the sensory nature of the object, mental imagery also involves correspondent sensory neural mechanisms. However, it remains unclear which areas of the brain subserve supramodal imagery processes that are independent of the object modality, and which brain areas are involved in modality-specific imagery processes. Here, we conducted a functional magnetic resonance imaging study to reveal supramodal and modality-specific networks of mental imagery for auditory and visual information. A common supramodal brain network independent of imagery modality, two separate modality-specific networks for imagery of auditory and visual information, and a common deactivation network were identified. The supramodal network included brain areas related to attention, memory retrieval, motor preparation and semantic processing, as well as areas considered to be part of the default-mode network and multisensory integration areas. The modality-specific networks comprised brain areas involved in processing of respective modality-specific sensory information. Interestingly, we found that imagery of auditory information led to a relative deactivation within the modality-specific areas for visual imagery, and vice versa. In addition, mental imagery of both auditory and visual information widely suppressed the activity of primary sensory and motor areas, for example deactivation network. These findings have important implications for understanding the mechanisms that are involved in generation of mental imagery.

Supramodal representation of emotions.

Supramodal representation of emotion and its neural substrates have recently attracted attention as a marker of social cognition. However, the question whether perceptual integration of facial and vocal emotions takes place in primary sensory areas, multimodal cortices, or in affective structures remains unanswered yet. Using novel computer-generated stimuli, we combined emotional faces and voices in congruent and incongruent ways and assessed functional brain data (fMRI) during an emotional classification task. Both congruent and incongruent audiovisual stimuli evoked larger responses in thalamus and superior temporal regions compared with unimodal conditions. Congruent emotions were characterized by activation in amygdala, insula, ventral posterior cingulate (vPCC), temporo-occipital, and auditory cortices; incongruent emotions activated a frontoparietal network and bilateral caudate nucleus, indicating a greater processing load in working memory and emotion-encoding areas. The vPCC alone exhibited differential reactions to congruency and incongruency for all emotion categories and can thus be considered a central structure for supramodal representation of complex emotional information. Moreover, the left amygdala reflected supramodal representation of happy stimuli. These findings document that emotional information does not merge at the perceptual audiovisual integration level in unimodal or multimodal areas, but in vPCC and amygdala.

Signal quality and Bayesian signal processing in neurofeedback based on real-time fMRI.

Real-time fMRI allows analysis and visualization of the brain activity online, i.e. within one repetition time. It can be used in neurofeedback applications where subjects attempt to control an activation level in a specified region of interest (ROI) of their brain. The signal derived from the ROI is contaminated with noise and artifacts, namely with physiological noise from breathing and heart beat, scanner drift, motion-related artifacts and measurement noise. We developed a Bayesian approach to reduce noise and to remove artifacts in real-time using a modified Kalman filter. The system performs several signal processing operations: subtraction of constant and low-frequency signal components, spike removal and signal smoothing. Quantitative feedback signal quality analysis was used to estimate the quality of the neurofeedback time series and performance of the applied signal processing on different ROIs. The signal-to-noise ratio (SNR) across the entire time series and the group event-related SNR (eSNR) were significantly higher for the processed time series in comparison to the raw data. Applied signal processing improved the t-statistic increasing the significance of blood oxygen level-dependent (BOLD) signal changes. Accordingly, the contrast-to-noise ratio (CNR) of the feedback time series was improved as well. In addition, the data revealed increase of localized self-control across feedback sessions. The new signal processing approach provided reliable neurofeedback, performed precise artifacts removal, reduced noise, and required minimal manual adjustments of parameters. Advanced and fast online signal processing algorithms considerably increased the quality as well as the information content of the control signal which in turn resulted in higher contingency in the neurofeedback loop.

Lateralization of amygdala activation in fMRI may depend on phase-encoding polarity.

OBJECT: Susceptibility artifacts along the phase-encoding (PE) direction impact the activation pattern in the amygdala and may lead to systematic asymmetries. We implemented a triple-echo echo-planar imaging (EPI) sequence, acquiring opposite PE polarities along left-right PE direction in a single shot, to investigate its effects on amygdala lateralization. MATERIALS AND METHODS: Twelve subjects viewed emotional faces to evoke amygdala activation. RESULTS AND CONCLUSION: A region of interest analysis revealed that the lateralization of amygdala responses depended on the PE polarity thus representing a pure method artifact. Alternating PE with multi-echo EPI reduced the artifact. Lateralized fMRI activation in areas with magnetic field inhomogeneities need to be interpreted with caution.

Reward system and temporal pole contributions to affective evaluation during a first person shooter video game.

BACKGROUND: Violent content in video games evokes many concerns but there is little research concerning its rewarding aspects. It was demonstrated that playing a video game leads to striatal dopamine release. It is unclear, however, which aspects of the game cause this reward system activation and if violent content contributes to it. We combined functional Magnetic Resonance Imaging (fMRI) with individual affect measures to address the neuronal correlates of violence in a video game. RESULTS: Thirteen male German volunteers played a first-person shooter game (Tactical Ops: Assault on Terror) during fMRI measurement. We defined success as eliminating opponents, and failure as being eliminated themselves. Affect was measured directly before and after game play using the Positive and Negative Affect Schedule (PANAS). Failure and success events evoked increased activity in visual cortex but only failure decreased activity in orbitofrontal cortex and caudate nucleus. A negative correlation between negative affect and responses to failure was evident in the right temporal pole (rTP). CONCLUSIONS: The deactivation of the caudate nucleus during failure is in accordance with its role in reward-prediction error: it occurred whenever subject missed an expected reward (being eliminated rather than eliminating the opponent). We found no indication that violence events were directly rewarding for the players. We addressed subjective evaluations of affect change due to gameplay to study the reward system. Subjects reporting greater negative affect after playing the game had less rTP activity associated with failure. The rTP may therefore be involved in evaluating the failure events in a social context, to regulate the players' mood.

Neuromagnetic oscillations and hemodynamic correlates of P50 suppression in schizophrenia.

Behavioral and electrophysiological data indicate compromised stimulus suppression in schizophrenia. The physiological basis of this effect and its contributions to the etiology of the disease are poorly understood. We examined neural and metabolic measures of P50 suppression in 12 patients with schizophrenia and controls. First, whole-head magnetoencephalography (MEG) assessed amplitudes of left- and right-hemispheric evoked responses and induced oscillations. Secondly, functional magnetic resonance imaging (fMRI) measured the hemodynamic responses to pairs of beeps with a short interval (500ms) as compared with those with a long interval (1500ms). The suppression of alpha power (8-13Hz) time-locked to the stimuli was negatively correlated with the suppression of evoked components and the hemodynamic measures. Remarkably, the suppression of alpha power was reduced in the patients already prior to stimulus onset. Conceivably, alpha oscillations play a central role in stimulus adaptation of neuronal networks and reflect an active mechanism for sensory suppression. The reduced stimulus suppression in schizophrenia seems to be in part due to impaired generation of alpha oscillations in the auditory cortex, resulting in higher metabolic demand as detected by fMRI. Delayed recovery of alpha rhythm may reflect an impaired gating function and contribute to sensory and cognitive deficits in schizophrenia.

Real-time noise cancellation for speech acquired in interactive functional magnetic resonance imaging studies.

PURPOSE: To present online scanner noise cancellation for speech acquired in functional magnetic resonance imaging (fMRI) studies. MATERIALS AND METHODS: An online active noise cancellation method for speech acquired in fMRI studies was developed. The approach consists of two automated steps: 1) creation of an MR noise template in a short "test" fMRI scan; 2) application of the template for automatic recognition and subtraction of the MR noise from the acquired microphone signal during an fMRI study. The method was applied in an experimental paradigm where a subject and an investigator communicated in an interactive verbal generation task during fMRI. RESULTS: By applying online active noise cancellation, the quality of the subject's speech was substantially improved. The present approach was found to be flexible, reliable, and easy to implement, providing a method for fMRI studies that investigate the neural correlates of interactive speech communication. CONCLUSION: Using online noise cancellation it is possible to improve the quality of acquired speech in fMRI. This approach may be recommended for interactive fMRI studies.

Quality of life in childhood epilepsy with lateralized epileptogenic foci.

BACKGROUND: Measuring quality of life (QOL) helps to delineate mechanisms underlying the interaction of disease and psychosocial factors. In adults, epileptic foci in the left temporal lobe led to lower QOL and higher depression and anxiety as compared to the right-sided foci. No study addressed the development of QOL disturbances depending on the lateralization of epileptogenic focus. The objective of our study was to examine QOL in children with lateralized epileptiform discharges. METHODS: Thirty-one parents of children with epilepsy filled the Health-Related Quality of Life in Childhood Epilepsy Questionnaire (QOLCE). Fifteen children had foci in the left hemisphere and sixteen in the right, as verified with Electroencephalography (EEG) examinations. RESULTS: We found a significant correlation between foci lateralization and reduced QOL (Spearman's rho = 0.361, p < 0.046). Children with right hemispheric foci exhibited lower overall QOL, particularly in five areas: anxiety, social-activities, stigma, general-health, and quality-of-life. CONCLUSIONS: We demonstrated for the first time that in children left- and right-hemispheric foci were associated with discordant QOL scores. Unlike in adults, foci in the right hemisphere led to worse emotional and social functioning demonstrating that seizures impact the brain differentially during development.

Social reinforcement can regulate localized brain activity.

Social learning is essential for adaptive behavior in humans. Neurofeedback based on functional magnetic resonance imaging (fMRI) trains control over localized brain activity. It can disentangle learning processes at the neural level and thus investigate the mechanisms of operant conditioning with explicit social reinforcers. In a pilot study, a computer-generated face provided a positive feedback (smiling) when activity in the anterior cingulate cortex (ACC) increased and gradually returned to a neutral expression when the activity dropped. One female volunteer without previous experience in fMRI underwent training based on a social reinforcer. Directly before and after the neurofeedback runs, neural responses to a cognitive interference task (Simon task) were recorded. We observed a significant increase in activity within ACC during the neurofeedback blocks, correspondent with the a-priori defined anatomical region of interest. In the course of the neurofeedback training, the subject learned to regulate ACC activity and could maintain the control even without direct feedback. Moreover, ACC was activated significantly stronger during Simon task after the neurofeedback training when compared to before. Localized brain activity can be controlled by social reward. The increased ACC activity transferred to a cognitive task with the potential to reduce cognitive interference. Systematic studies are required to explore long-term effects on social behavior and clinical applications.

Selective reward responses to violent success events during video games.

Aggressive behavior in violent video games activates the reward system. However, this effect is closely related to game success. Aim of the present study was to investigate whether aggressive behavior has a rewarding value by itself. Functional magnetic resonance imaging (fMRI) was measured in fifteen right-handed males while playing the video game Carmageddon. Neuroimaging data were analyzed based on violent and non-violent success and failure events. Correlations with subjective game experience measured brain-behavior and -affect relationships. Results revealed a differential involvement of the striatal reward system: non-violent success elicited activation of the ventral striatum, whereas violent success activated specifically the dorsal striatum. Subjective game experience correlated with putamen and medial prefrontal cortex activation specifically for violent success. These results emphasize a differential neural processing of violent and non-violent success events in dorsal and ventral striatum. Virtual violence seems to enable selective responses of the reward system and positive in-game experience.

Psychosocial impairments in children with epilepsy depend on the side of the focus.

This article explores the idea that epileptic activity may interfere with psychosocial functions and development in children. In an adult population with epilepsy, left hemispheric seizure focus predicts worse psychosocial functioning. The developmental aspects of these disturbances require further studies. We studied self-report measures of cognitive (locus of control) and emotional (Beck Youth Inventories of Emotional and Social Impairment) functions in 30 children with partial epilepsy (6-15 years) and 60 healthy matched controls. Multivariate statistics revealed significant lateralization effects, with left-sided foci (n=15) leading to more external locus of control. Opposite to adults, the children with right hemispheric foci (n=15) exhibited more emotional impairments (anger, disruptive behavior) than the left hemispheric group. The cognitive and emotional dysfunctions in epilepsy may result from the interaction of focus lateralization and brain development. The cognitive disturbances beginning in childhood may lead to the stronger emotional impairments observed in adults with left hemispheric seizures.

Predictability modulates motor-auditory interactions in self-triggered audio-visual apparent motion.

We studied an effect of predictability in an audio-visual apparent motion task using magnetoencephalography. The synchronous sequences of audio-visual stimuli were self-triggered by subjects. The task was to detect the direction of the apparent motion in experimental blocks in which the motion either started from the side selected by subjects (predictable condition) or was random (unpredictable condition). Magnetic fields yielded three patterns of activity in the motor, auditory, and visual areas. Comparison of the dipole strength between predictable and unpredictable conditions revealed a significant difference of the preparatory motor activity in the time interval from -450 to -100 ms before self-triggering the stimulus. Perception of the audio-visual apparent motion was also modulated by predictability. However, the modulation was found only for the auditory activity but not for the visual one. The effect of predictability was selective and modulated only the auditory component N1 (100 ms after stimulus), which reflects initial evaluation of stimulus meaning. Importantly, the preparatory motor activity correlates with the following auditory activity mainly in the same hemisphere. Similar modulation by predictability of the motor and auditory activities suggests interactions between these two systems within an action-perception cycle. The mechanism of these interactions can be understood as an effect of anticipation of the own action outcomes on the preparatory motor and perceptual activity.

Impaired Voluntary Control in PTSD: Probing Self-Regulation of the ACC With Real-Time fMRI.

Background: Post-traumatic stress disorder (PTSD) is characterized by deficits in the self-regulation of cognitions and emotions. Neural networks of emotion regulation may exhibit reduced control mediated by the anterior cingulate cortex (ACC), contributing to aberrant limbic responses in PTSD. Methods: Real-time fMRI neurofeedback (rt-fMRI NF) assessed self-regulation of the ACC in nine patients with PTSD after single trauma exposure and nine matched healthy controls. All participants were instructed to train ACC upregulation on three training days. Results: Both groups achieved regulation, which was associated with wide-spread brain activation encompassing the ACC. Compared to the controls, regulation amplitude and learning rate was lower in patients, correlating with symptom severity. In addition, a frontopolar activation cluster was associated with self-regulation efforts in patients. Conclusions: For the first time, we tested self-regulation of the ACC in patients with PTSD. The observed impairment supports models of ACC-mediated regulation deficits that may contribute to the psychopathology of PTSD. Controlled trials in a larger sample are needed to confirm our findings and to directly investigate whether training of central regulation mechanisms improves emotion regulation in PTSD.

Who is telling what from where? A functional magnetic resonance imaging study.

The human central-auditory system exhibits distinct lateralization effects (speech, space) and encompasses different processing pathways (where, what, who). Using spatialized pseudoword utterances, attentional modulation of the networks bound to sound source localization ('where'), voice recognition ('who'), and the encoding of phonetic-linguistic information ('what') was evaluated by silent functional magnetic resonance imaging. The 'where'-pathway was found to be restricted to posterior parts of the left superior temporal gyrus, speaker ('auditory face') identification exclusively activated temporal lobe structures, and the representation of the sound structure of the utterances was associated with hemodynamic activation of Broca's area. Speech perception in space, therefore, engages at least three distinct neural networks. Furthermore, the findings indicate that voice recognition may depend upon template matching within auditory association cortex whereas the sequencing of phonetic-linguistic information extends to frontal areas.

[Polish adaptation and validation of Health-Related Quality of Life in Childhood Epilepsy Questionnaire]. / Kwestionariusz Jakosci Zycia w Padaczce Dzieciecej - polska adaptacja i walidacja kwestionariusza.

BACKGROUND AND PURPOSE: Epilepsy is a frequent chronic disease in children, having a strong impact on a child's psychosocial functioning. Effective therapy must take into account the wide range of physical, psychological and social needs of patients. The importance of assessing patients' quality of life is becoming increasingly acknowledged. In addition to providing better health care, it may reveal how the disease and its psychosocial outcome interact. Quality of life in epilepsy can be assessed most reliably by disease-specific measures. Health-Related Quality of Life in Childhood Epilepsy (QOLCE) is an English parental questionnaire for children aged between 4 and 18 years. It contains 87 questions that fall into five domains: physical function, emotional well-being, cognitive function, social function and behavioural function. The original scale has a well-grounded theoretical background and good psychometric properties. The aim of the study was to create a Polish version of QOLCE and evaluate its psychometric properties. MATERIAL AND METHODS: Parents of 87 patients suffering from epilepsy were recruited in neurological clinics in the Warsaw area. RESULTS: Reliability was very high (Cronbach's alpha = 0.97). The construct validity was confirmed by the correlation between subscales of QOLCE and the Child Behaviour Checklist, as well as selected clinical measures of child's health (duration of disease: r=-0.22, p=0.02; duration of treatment: r=-0.20, p=0.04; number of hospitalizations: r=-0.24, p=0.02). All the psychometric properties were similar to those of the original scale. CONCLUSIONS: A Polish scale examining the quality of life was created that takes into account a wide range of psychosocial problems. We confirmed very high reliability and good validity, and thus we recommend the inventory for both research on and clinical diagnostics of Polish children with epilepsy.

[Polish adaptation and validation of beck youth inventories of emotional and social impairment]. / Kwestionariusz Becka dla Dzieci do oceny zaburzen emocjonalnych i spolecznych--polska adaptacja i walidacja kwestionariusza Beck Youth Inventories of Emotional and Social Impairment.

INTRODUCTION: Psychiatric disorders are common among children and adolescents, affecting about 15-22% of this population. In order to fully develop emotional and cognitive skills, those children require professional care at early stages of the illness. Inventories addressing the broad range of emotional and social impairments, with high reliability and validity, can be of great help in early diagnostics. Self-report scales were proven valuable diagnostic tools even for young children. The Beck Youth Inventories (BYI) are five self-report measures for children between the ages of 7 and 14. They assess a child's experience of self-concept, depression, anxiety, anger and disruptive behaviour. BYI were created in response to epidemiological studies demonstrating significant prevalence of psychiatric disorders in children as well as the U.S. governmental report suggesting a high value of a brief questionnaires for early diagnostics of those disorders. AIM: To our knowledge, there existed no Polish self-report scale for children examining a broad range of psychiatric disturbances. The aim of the study was to create a Polish version of BYI and to examine its psychometric properties. METHOD: Using a culturally-adapted Polish translation, we examined 197 students of three primary schools in Warsaw. RESULTS: The scales had high reliability (Cronbach's alpha from 0.87 to 0.93). The validity was confirmed by intercorrelations between scales. In addition, boys scored higher on theAnger and Disruptive behaviour scales and young children on the Self-concept scale. CONCLUSION: Polish self-report inventories for children, examining emotional and social impairments have been created. Very high reliability and good validity of each scale qualify them as trustworthy tools both in scientific research and in individual diagnostics.

Targeting Treatment-Resistant Auditory Verbal Hallucinations in Schizophrenia with fMRI-Based Neurofeedback - Exploring Different Cases of Schizophrenia.

Auditory verbal hallucinations (AVHs) are a hallmark of schizophrenia and can significantly impair patients' emotional, social, and occupational functioning. Despite progress in psychopharmacology, over 25% of schizophrenia patients suffer from treatment-resistant hallucinations. In the search for alternative treatment methods, neurofeedback (NF) emerges as a promising therapy tool. NF based on real-time functional magnetic resonance imaging (rt-fMRI) allows voluntarily change of the activity in a selected brain region - even in patients with schizophrenia. This study explored effects of NF on ongoing AVHs. The selected participants were trained in the self-regulation of activity in the anterior cingulate cortex (ACC), a key monitoring region involved in generation and intensity modulation of AVHs. Using rt-fMRI, three right-handed patients, suffering from schizophrenia and ongoing, treatment-resistant AVHs, learned control over ACC activity on three separate days. The effect of NF training on hallucinations' severity was assessed with the Auditory Vocal Hallucination Rating Scale (AVHRS) and on the affective state - with the Positive and Negative Affect Schedule (PANAS). All patients yielded significant upregulation of the ACC and reported subjective improvement in some aspects of AVHs (AVHRS) such as disturbance and suffering from the voices. In general, mood (PANAS) improved during NF training, though two patients reported worse mood after NF on the third day. ACC and reward system activity during NF learning and specific effects on mood and symptoms varied across the participants. None of them profited from the last training set in the prolonged three-session training. Moreover, individual differences emerged in brain networks activated with NF and in symptom changes, which were related to the patients' symptomatology and disease history. NF based on rt-fMRI seems a promising tool in therapy of AVHs. The patients, who suffered from continuous hallucinations for years, experienced symptom changes that may be attributed to the NF training. In order to assess the effectiveness of NF as a therapeutic method, this effect has to be studied systematically in larger groups; further, long-term effects need to be assessed. Particularly in schizophrenia, future NF studies should take into account the individual differences in reward processing, fatigue, and motivation to develop individualized training protocols.