Neural correlates of social exclusion and overinclusion in patients with borderline personality disorder: an fMRI study.

BACKGROUND: Interpersonal difficulties of patients with borderline personality disorder (BPD) are closely related to rejection sensitivity. The aim of the present study was to gain further insight into the experience and cerebral processing of social interactions in patients with BPD by using fMRI during experimentally induced experiences of social exclusion, inclusion, and overinclusion. METHODS: The study involved 30 participants diagnosed with BPD (29 female and 1 male; age: M = 24.22, SD = 5.22) and 30 healthy controls (29 female and 1 male; age: M = 24.66, SD = 5.28) with no current or lifetime psychiatric diagnoses. In the fMRI session, all participants were asked to complete a Cyberball task that consisted of an alternating sequence of inclusion, exclusion, and overinclusion conditions. RESULTS: Compared to healthy controls, participants with BPD reported higher levels of inner tension and more unpleasant emotions across all experimental conditions. At the neural level, the participants with BPD showed lower recruitment of the left hippocampus in response to social exclusion (relative to the inclusion condition) than the healthy controls did. Lower recruitment of the left hippocampus in this contrast was associated with childhood maltreatment in patients with BPD. However, this difference was no longer significant when we added the covariate of hippocampal volume to the analysis. During social overinclusion (relative to the inclusion condition), we observed no significant differences in a group comparison of neural activation. CONCLUSIONS: The results of our study suggest that patients with BPD experience more discomfort than do healthy controls during social interactions. Compared to healthy participants, patients with BPD reported more inner tension and unpleasant emotions, irrespective of the extent to which others included them in social interactions. At a neural level, the participants with BPD showed a lower recruitment of the left hippocampus in response to social exclusion than the healthy controls did. The reduced activation of this neural structure could be related to a history of childhood maltreatment and smaller hippocampal volume in patients with BPD.

Selected neuroendocrine factors as potential molecular biomarkers of early non-affective psychosis course in relation to treatment outcome: A pilot study.

The aim of this pilot study was to find whether the dysregulation of neuroendocrine biomarker signaling pathways in the first episode of non-affective psychosis is a predictive factor of treatment outcome. Patients with the first episode of non-affective psychosis (N = 29) were examined at admission, at discharge, and at follow-up (N = 23). The biomarkers included serum aldosterone, cortisol, free thyroxine, thyroid stimulating hormone, and prolactin. We revealed lower baseline aldosterone and higher baseline cortisol concentrations in patients with very good outcome compared to those with good outcome after one year. We failed to reveal any significant association between treatment outcome and neurohumoral biomarkers in the whole sample at 1-year follow-up. However, baseline aldosterone concentrations negatively correlated with total PANSS scores at the discharge. Lower baseline aldosterone and higher baseline cortisol concentrations have the potential to predict a more favorable outcome for patients with the first episode of psychosis.

A preliminary choroid plexus volumetric study in individuals with psychosis.

The choroid plexus (ChP) is part of the blood-cerebrospinal fluid barrier, regulating brain homeostasis and the brain's response to peripheral events. Its upregulation and enlargement are considered essential in psychosis. However, the timing of the ChP enlargement has not been established. This study introduces a novel magnetic resonance imaging-based segmentation method to examine ChP volumes in two cohorts of individuals with psychosis. The first sample consists of 41 individuals with early course psychosis (mean duration of illness = 1.78 years) and 30 healthy individuals. The second sample consists of 30 individuals with chronic psychosis (mean duration of illness = 7.96 years) and 34 healthy individuals. We utilized manual segmentation to measure ChP volumes. We applied ANCOVAs to compare normalized ChP volumes between groups and partial correlations to investigate the relationship between ChP, LV volumes, and clinical characteristics. Our segmentation demonstrated good reliability (.87). We further showed a significant ChP volume increase in early psychosis (left: p < .00010, right: p < .00010) and a significant positive correlation between higher ChP and higher LV volumes in chronic psychosis (left: r = .54, p = .0030, right: r = .68; p < .0010). Our study suggests that ChP enlargement may be a marker of acute response around disease onset. It might also play a modulatory role in the chronic enlargement of lateral ventricles, often reported in psychosis. Future longitudinal studies should investigate the dynamics of ChP enlargement as a promising marker for novel therapeutic strategies.

Structural MRI-Based Schizophrenia Classification Using Autoencoders and 3D Convolutional Neural Networks in Combination with Various Pre-Processing Techniques.

Schizophrenia is a severe neuropsychiatric disease whose diagnosis, unfortunately, lacks an objective diagnostic tool supporting a thorough psychiatric examination of the patient. We took advantage of today's computational abilities, structural magnetic resonance imaging, and modern machine learning methods, such as stacked autoencoders (SAE) and 3D convolutional neural networks (3D CNN), to teach them to classify 52 patients with schizophrenia and 52 healthy controls. The main aim of this study was to explore whether complex feature extraction methods can help improve the accuracy of deep learning-based classifiers compared to minimally preprocessed data. Our experiments employed three commonly used preprocessing steps to extract three different feature types. They included voxel-based morphometry, deformation-based morphometry, and simple spatial normalization of brain tissue. In addition to classifier models, features and their combination, other model parameters such as network depth, number of neurons, number of convolutional filters, and input data size were also investigated. Autoencoders were trained on feature pools of 1000 and 5000 voxels selected by Mann-Whitney tests, and 3D CNNs were trained on whole images. The most successful model architecture (autoencoders) achieved the highest average accuracy of 69.62% (sensitivity 68.85%, specificity 70.38%). The results of all experiments were statistically compared (the Mann-Whitney test). In conclusion, SAE outperformed 3D CNN, while preprocessing using VBM helped SAE improve the results.

Clozapine Reverses Dysfunction of Glutamatergic Neurons Derived From Clozapine-Responsive Schizophrenia Patients.

The cellular pathology of schizophrenia and the potential of antipsychotics to target underlying neuronal dysfunctions are still largely unknown. We employed glutamatergic neurons derived from induced pluripotent stem cells (iPSC) obtained from schizophrenia patients with known histories of response to clozapine and healthy controls to decipher the mechanisms of action of clozapine, spanning from molecular (transcriptomic profiling) and cellular (electrophysiology) levels to observed clinical effects in living patients. Glutamatergic neurons derived from schizophrenia patients exhibited deficits in intrinsic electrophysiological properties, synaptic function and network activity. Deficits in K+ and Na+ currents, network behavior, and glutamatergic synaptic signaling were restored by clozapine treatment, but only in neurons from clozapine-responsive patients. Moreover, neurons from clozapine-responsive patients exhibited a reciprocal dysregulation of gene expression, particularly related to glutamatergic and downstream signaling, which was reversed by clozapine treatment. Only neurons from clozapine responders showed return to normal function and transcriptomic profile. Our results underscore the importance of K+ and Na+ channels and glutamatergic synaptic signaling in the pathogenesis of schizophrenia and demonstrate that clozapine might act by normalizing perturbances in this signaling pathway. To our knowledge this is the first study to demonstrate that schizophrenia iPSC-derived neurons exhibit a response phenotype correlated with clinical response to an antipsychotic. This opens a new avenue in the search for an effective treatment agent tailored to the needs of individual patients.

Derivation and Molecular Characterization of a Morphological Subpopulation of Human iPSC Astrocytes Reveal a Potential Role in Schizophrenia and Clozapine Response.

Astrocytes are the most abundant cell type in the human brain and are important regulators of several critical cellular functions, including synaptic transmission. Although astrocytes are known to play a central role in the etiology and pathophysiology of schizophrenia, little is known about their potential involvement in clinical response to the antipsychotic clozapine. Moreover, astrocytes display a remarkable degree of morphological diversity, but the potential contribution of astrocytic subtypes to disease biology and drug response has received little attention. Here, we used state-of-the-art human induced pluripotent stem cell (hiPSC) technology to derive a morphological subtype of astrocytes from healthy individuals and individuals with schizophrenia, including responders and nonresponders to clozapine. Using functional assays and transcriptional profiling, we identified a distinct gene expression signature highly specific to schizophrenia as shown by disease association analysis of more than 10 000 diseases. We further found reduced levels of both glutamate and the NMDA receptor coagonist d-serine in subtype astrocytes derived from schizophrenia patients, and that exposure to clozapine only rescued this deficiency in cells from clozapine responders, providing further evidence that d-serine in particular, and NMDA receptor-mediated glutamatergic neurotransmission in general, could play an important role in disease pathophysiology and clozapine action. Our study represents a first attempt to explore the potential contribution of astrocyte diversity to schizophrenia pathophysiology using a human cellular model. Our findings suggest that specialized subtypes of astrocytes could be important modulators of disease pathophysiology and clinical drug response, and warrant further investigations.

The association of matrix metalloproteinase 9 (MMP9) with hippocampal volume in schizophrenia: a preliminary MRI study.

Matrix metalloproteinases 9 (MMP9) are enzymes involved in regulating neuroplasticity in the hippocampus. This, combined with evidence for disrupted hippocampal structure and function in schizophrenia, has prompted our current investigation into the relationship between MMP9 and hippocampal volumes in schizophrenia. 34 healthy individuals (mean age = 32.50, male = 21, female = 13) and 30 subjects with schizophrenia (mean age = 33.07, male = 19, female = 11) underwent a blood draw and T1-weighted magnetic resonance imaging. The hippocampus was automatically segmented utilizing FreeSurfer. MMP9 plasma levels were measured with ELISA. ANCOVAs were conducted to compare MMP9 plasma levels (corrected for age and sex) and hippocampal volumes between groups (corrected for age, sex, total intracranial volume). Spearman correlations were utilized to investigate the relationship between symptoms, medication, duration of illness, number of episodes, and MMP9 plasma levels in patients. Last, we explored the correlation between MMP9 levels and hippocampal volumes in patients and healthy individuals separately. Patients displayed higher MMP9 plasma levels than healthy individuals (F(1, 60) = 21.19, p < 0.0001). MMP9 levels correlated with negative symptoms in patients (R = 0.39, p = 0.035), but not with medication, duration of illness, or the number of episodes. Further, patients had smaller left (F(1,59) = 9.12, p = 0.0040) and right (F(1,59) = 6.49, p = 0.013) hippocampal volumes. Finally, left (R = -0.39, p = 0.034) and right (R = -0.37, p = 0.046) hippocampal volumes correlated negatively with MMP9 plasma levels in patients. We observe higher MMP9 plasma levels in SCZ, associated with lower hippocampal volumes, suggesting involvement of MMP9 in the pathology of SCZ. Future studies are needed to investigate how MMP9 influences the pathology of SCZ over the lifespan, whether the observed associations are specific for schizophrenia, and if a therapeutic modulation of MMP9 promotes neuroprotective effects in SCZ.

Hemodynamic and white blood cells parameters in patients with first-episode psychosis: a pilot longitudinal study.

OBJECTIVE: Patients with schizophrenia are at higher risk of cardiovascular (CVS) related mortality. Close attention is being paid to the clinical utility of readily available CVS markers. METHODS: A pilot one-year longitudinal study in inpatients with first-episode psychosis (FEP) was carried out to determine markers of inflammation and endothelial dysfunction (monocyte- and neutrophil-to-lymphocyte ratios) and basal blood pressure, pulse, and derived hemodynamic parameters (PP: pulse pressure; RPP: rate pressure product; and MAP: mean arterial pressure). RESULTS: After one year, PP and RPP increased, as did systolic blood pressure and heart rate. Systolic blood pressure, PP, total white blood cells, and neutrophils correlated with weight gain. After one year, correlations between monocyte-to-lymphocyte ratio and RPP and MAP were observed. CONCLUSION: Our study indicates worsening CVS health over the first year of treatment and emphasises the importance of early monitoring of CVS status using easily accessible parameters to prevent CVS-related mortality.Key pointsPatients with schizophrenia are at higher risk of cardiovascular mortality.The CVS risk could be evaluated using affordable, routinely available CVS markers such as monocyte- and neutrophil-to-lymphocyte ratios, blood pressure, and pulse together with the derived parameters.Our pilot study in first-episode psychosis patients indicates worsening of CVS health based on these parameters during the first year of treatment, the early monitoring of CVS status is highly relevant in clinical practice.

Electrodermal Response to Mirror Exposure in Relation to Subjective Emotional Responses, Emotional Competences and Affectivity in Adolescent Girls With Restrictive Anorexia and Healthy Controls.

Objective: Body image disturbances and the attendant negative emotions are two of the major clinical symptoms of eating disorders. The objective of the present experimental study was to shed more light on the degree of association or dissociation between the physiological and emotional response to mirror exposure in patients with restrictive mental anorexia, and on the relationships between the physiological response and characteristics connected with emotional processing. Materials and Methods: Thirty adolescent girls with the restrictive type of anorexia and thirty matched healthy controls underwent bilateral measurement of skin conductance (SC) during rest, neutral stimulus exposure, and mirror exposure, and completed a set of measures focused on emotion regulation competencies, affectivity, and eating disorder pathology. Results: Compared to healthy controls, girls with restrictive anorexia rated mirror exposure as a subjectively more distressful experience. Differences in skin conductance response (SCR) were not significant; however, variance in SCR was substantially greater in the group of anorexia patients as compared to healthy controls. The overall skin conductance level (SCL) was lower in anorexia patients. Increase in SCR during mirror exposure, as opposed to exposure to neutral stimuli, was positively related to the tendency to experience negative emotions, interoceptive sensitivity, body dissatisfaction and suppression, but not to other symptoms of eating pathology or emotional awareness. A post hoc analysis suggested that physiological reactivity might be associated with interoceptive sensitivity to mirror exposure especially in anorectic patients. Conclusion: The study seems to demonstrate some degree of dissociation between psychophysiological reactivity and subjective response to body exposure in patients with restrictive anorexia. Factors affecting differences in psychophysiological responsiveness to body exposure in anorectic patients require further exploration.

Emotional Awareness in Schizophrenia Is Associated With Gray Matter Volume of Right Precuneus.

Objectives: We assessed the relationship between emotional awareness (e.g., the ability to identify and differentiate our own feelings and feelings of others) and regional brain volumes in healthy and in schizophrenia groups. Methods: Magnetic resonance images of 29 subjects with schizophrenia and 33 matched healthy controls were acquired. Brain gray matter was parcellated using FreeSurfer and 28 regions of interest associated with emotional awareness were analyzed. All participants were assessed using the Levels of Emotional Awareness Scale (LEAS) of Self and of Other. LEAS scores were correlated with gray matter volume for each hemisphere on the 14 brain regions of the emotional awareness network. Results: Individuals with schizophrenia showed decreased emotional awareness on both LEAS Self and LEAS Other compared to healthy controls. There were no statistically significant between-group differences in gray matter volumes of the emotional awareness network. The performance on LEAS Other correlated negatively with right precuneus gray matter volume only in the schizophrenia group. Conclusion: Our findings suggest a relationship between gray matter volume of the right precuneus and deficits in understanding of emotional states of others in schizophrenia.

Processing of emotionally ambiguous stimuli in eating disorders: an fMRI pilot study.

PURPOSE: People with eating disorders (EDs) have difficulties understanding their own emotions and recognizing the emotions of others, especially in ambiguous settings. We examined the neuronal mechanisms underlying the emotion processing of ambiguous interpersonal stimuli in EDs and healthy controls (HCs). METHODS: The fMRI data were acquired by a blocked experimental design with 28 women (14 EDs) during the visual presentation of a modified Thematic Apperception Test. RESULTS: EDs showed very strong associations between experienced and inferred emotions evoked by the stimuli; no such relationship was found in HCs. HCs displayed elevated left anterior insula activity during the mentalizing condition; EDs showed increased activity in the right supramarginal gyrus and medial prefrontal cortex. CONCLUSION: The two groups seem to apply different strategies for judging emotionally ambiguous stimuli, albeit resulting in equivalent judgments. We assume that activity in the supramarginal gyrus and insula in EDs is linked with suppressing their own perspective while considering emotional states, probably due to alexithymia and the lack of awareness of their own mental states. We hypothesize that the strong correlation between experienced and inferred emotions in EDs could reflect their tendency to use others as a reference point for perceiving themselves and gaining information about their affective state. LEVEL OF EVIDENCE: No level of evidence, this is a basic science study.

Dimensions of Impulsivity in Healthy People, Patients with Borderline Personality Disorder, and Patients with Attention-Deficit/Hyperactivity Disorder.

Objective: Impulsivity, observed in patients with various psychiatric disorders, is a heterogeneous construct with different behavioral manifestations. Through confirmatory factor analysis (CFA), this study tests hypotheses about relationships between dimensions of impulsivity measured using personality questionnaires and behavioral tests. Method: The study included 200 healthy people, 40 patients with borderline personality disorder, and 26 patients with attention-deficit/hyperactivity disorder (ADHD) who underwent a comprehensive impulsivity test battery including the Barratt Impulsiveness Scale (BIS), UPPS-P Impulsive Behavior Scale, a Go-NoGo task, a stop-signal task, and a delay discounting task. Results: A CFA model comprising three self-reported and three behavioral latent variables reached a good fit. Both patient groups scored higher in the self-reported dimensions and impulsive choice; only the ADHD patients displayed impaired waiting and stopping impulsivity. Conclusions: Using the developed CFA model, it is possible to describe relations between impulsivity dimensions and show different impulsivity patterns in patient populations.

Brain Connectivity and Symptom Changes After Transcranial Magnetic Stimulation in Patients With Borderline Personality Disorder.

OBJECTIVES: Repetitive transcranial magnetic stimulation (rTMS) is an innovative method in the treatment of borderline personality disorder (BPD). We hypothesized that prefrontal rTMS in patients with BPD leads to improved BPD symptoms and that these effects are associated with brain connectivity changes. METHODS: Fourteen patients with BPD received 15 sessions of individually navigated prefrontal rTMS over the right dorsolateral prefrontal cortex. Clinical effects were measured by the Borderline Symptom List 23, UPPS-P, the Difficulties in Emotion Regulation Scale (DERS), the Zung Self-Rating Anxiety Scale (SAS), and the Montgomery and Åsberg Depression Rating Scale (MADRS). Effects of rTMS on brain connectivity were observed with a seed correlation analysis on resting-state fMRI and with a beta series correlation analysis on Go/No Go tasks during fMRI. Assessments were made before and immediately after the treatment. RESULTS: The assessments after rTMS showed significant reductions in two subscales of UPPS-P, and in DERS, SAS, and MADRS. The brain connectivity analysis revealed significant decreases in amygdala and insula connectivity with nodes of the posterior default mode network (pDMN; precuneus, posterior cingulate cortex, parietal lobules). Connectivity changes were observed both in the resting state and during inhibition. The decrease of amygdala-pDMN connectivity was positively correlated with reduced depression and lack of premeditation after rTMS. CONCLUSIONS: Despite the study limitations (open single-arm study in a small sample), our findings suggest a possible neural mechanism of rTMS effect in BPD, reduced amygdala connectivity with the pDMN network, which was positively associated with symptom reduction.

Identification of Laminar Composition in Cerebral Cortex Using Low-Resolution Magnetic Resonance Images and Trust Region Optimization Algorithm.

Pathological changes in the cortical lamina can cause several mental disorders. Visualization of these changes in vivo would enhance their diagnostics. Recently a framework for visualizing cortical structures by magnetic resonance imaging (MRI) has emerged. This is based on mathematical modeling of multi-component T1 relaxation at the sub-voxel level. This work proposes a new approach for their estimation. The approach is validated using simulated data. Sixteen MRI experiments were carried out on healthy volunteers. A modified echo-planar imaging (EPI) sequence was used to acquire 105 individual volumes. Data simulating the images were created, serving as the ground truth. The model was fitted to the data using a modified Trust Region algorithm. In single voxel experiments, the estimation accuracy of the T1 relaxation times depended on the number of optimization starting points and the level of noise. A single starting point resulted in a mean percentage error (MPE) of 6.1%, while 100 starting points resulted in a perfect fit. The MPE was <5% for the signal-to-noise ratio (SNR) ≥ 38 dB. Concerning multiple voxel experiments, the MPE was <5% for all components. Estimation of T1 relaxation times can be achieved using the modified algorithm with MPE < 5%.

Medical Students' Career Choice and Attitudes Toward Psychiatry: Case of the Czech Republic.

OBJECTIVE: A survey among medical students of all medical schools in the Czech Republic was conducted to investigate attitudes and views of psychiatry and career choice of psychiatry. METHODS: A Czech version of the Attitudes to Psychiatry Scale (APS) and a questionnaire surveying demographic characteristics and choices of future specialty were distributed to all medical students of eight medical schools in the Czech Republic via the schools' internal communication systems in the form of an anonymous online questionnaire. RESULTS: Out of a total of 10,147 medical students in the Czech Republic (academic year 2019/2020), 2418 students participated in the survey (response rate 23.8%). Psychiatry as a non-exclusive career choice was considered by 31.3% respondents; child and adolescent psychiatry was considered by 15.4% respondents. Psychiatry as the only choice was considered by 1.6%, and child and adolescent psychiatry was not considered at all. The interest in both specialties was declining since the first year of study. The status of psychiatry among other medical specialties was perceived as low; students were rather discouraged from entering psychiatry by their families. They did not feel encouraged by their teachers to pursue career in psychiatry despite the fact that they were interested in psychiatry. They also felt uncomfortable with patients with mental illness. CONCLUSIONS: Despite high enthusiasm for psychiatry in the first year of medical school, only a small proportion of medical students consider to choose psychiatry, and especially child and adolescent psychiatry, as a career at the end of medical school.

Impulsivity in patients with borderline personality disorder: a comprehensive profile compared with healthy people and patients with ADHD.

BACKGROUND: Impulsivity is a core symptom of borderline personality disorder (BPD). Impulsivity is a heterogeneous concept, and a comprehensive evaluation of impulsivity dimensions is lacking in the literature. Moreover, it is unclear whether BPD patients manifest impaired cognitive functioning that might be associated with impulsivity in another patient group, such as ADHD, a frequent comorbidity of BPD. METHODS: We tested 39 patients with BPD without major psychiatric comorbidities and ADHD, 25 patients with ADHD, and 55 healthy controls (HC) using a test battery consisting of a self-report measure of impulsivity (UPPS-P questionnaire), behavioral measures of impulsivity - impulsive action (Go/NoGo task, stop signal task) and impulsive choice (delay discounting task, Iowa gambling task), and standardized measures of attention (d2 test), working memory (digit span), and executive functioning (Tower of London). RESULTS: Patients with BPD and ADHD, as compared with HC, manifested increased self-reported impulsivity except sensation seeking and increased impulsive choice; patients with ADHD but not BPD showed increased impulsive action and deficits in cognitive functioning. Negative urgency was increased in BPD as compared to both HC and ADHD groups and correlated with BPD severity. CONCLUSIONS: Patients with BPD without ADHD comorbidity had increased self-reported impulsivity and impulsive choice, but intact impulsive action and cognitive functioning. Controlling for ADHD comorbidity in BPD samples is necessary. Negative urgency is the most diagnostically specific impulsivity dimension in BPD.

Processing of Emotions in Functional Movement Disorder: An Exploratory fMRI Study.

Background: Affective dysregulation and impaired cognitive control are implicated in the pathology of functional neurological disorders (FNDs). However, voluntary regulation of emotions has seldom been researched in this group of patients. We hypothesized that patients with FNDs use inefficient voluntary emotion regulation strategies and regulate emotional reactions via increased motor activation. Methods: Fifteen patients with functional movement disorder (FMD) and fifteen healthy subjects matched by age, sex, and education underwent an emotion regulation task in fMRI. For stimuli, we used neutral and negative pictures from the International Affective Picture System. There was no restriction on their emotion regulation strategy. Both patients and healthy subjects were asked about the strategies they had used in a post-scanning interview. Participant levels of depression, trait anxiety, and alexithymia were assessed. Results: There were no significant differences in the emotion regulation strategies used by patients and healthy subjects, nor in levels of reported alexithymia and depression. However, patients showed increased activation in several brain areas when observing negative pictures, notably in the post-central gyrus, precuneus, posterior cingulate cortex (PCC) and cerebellar vermis, and also in their emotion regulation condition, particularly in the precuneus and post-central gyrus. Alexithymia was negatively associated with left insular activation during the observation of unpleasant stimuli only in the patient group. Conclusions: Our findings may implicate areas associated with self-referential processing in voluntary emotional regulation and lower emotional awareness as having a role in patients with functional movement disorders. However, our findings must be replicated with larger sample.

fMRI neurofeedback in emotion regulation: A literature review.

OBJECTIVES: Emotion regulation is one of the most prevalent objectives for real-time fMRI neurofeedback (rt-fMRI-NF) studies. The existing studies differ in a number of methodological parameters. This study provides a literature review of the main parameters and results of studies using rt-fMRI-NF for emotion regulation enhancement. METHOD: A search of the Web of Science database up through November 8, 2018, identified 144 articles written in English, 89 of which were excluded as irrelevant for this study. The remaining 51 original studies and four secondary analyses of previously published original studies were included in the literature review. The selection of target brain areas, target populations, emotion regulation protocols, NF presentation, control group types, and emotion regulation instructions were examined in relation to achieved brain regulation and changes in cognitive or clinical outcomes. Study results were evaluated in terms of their statistical robustness. RESULTS: The results show that healthy people are able to regulate their brain activity in the presence of rt-fMRI-NF from various brain regions related to emotion regulation, including the amygdala, anterior insula, and anterior cingulate cortex. The regulation of brain activity using rt-fMRI-NF from prefrontal-limbic connectivity or from individually navigated brain areas is feasible as well. Most studies that used a control group show that rt-fMRI-NF actually induces some effects on brain regulation, cognitive variables, and clinical variables. Generally, the success of ROI regulation during NF training is related to the combination of target brain region, the type of emotion regulation task, and the population undergoing the training. In terms of patient groups, the strongest support for the beneficial effects of rt-fMRI-NF has been shown in increased positive emotion experiencing in patients with depression and in decreased anxiety in patients with anxiety disorders. Symptom reduction following NF training has been also reported in patients with PTSD, BPD, and schizophrenia, but direct comparisons with control groups in these studies makes it impossible to evaluate the added value of NF. Studies often do not report all the relevant analyses for evaluating NF success and many studies lack statistical robustness. CONCLUSIONS: Overall, rt-fMRI-NF seems a promising tool for emotion regulation enhancement with the potential to induce long-term symptom reduction in patients with various mental disorders. Preplanning of statistical analyses, careful interpretations of the results, and evaluations of the NF effect on symptom reduction in patient groups is recommended.

Brain Morphometry Methods for Feature Extraction in Random Subspace Ensemble Neural Network Classification of First-Episode Schizophrenia.

Machine learning (ML) is a growing field that provides tools for automatic pattern recognition. The neuroimaging community currently tries to take advantage of ML in order to develop an auxiliary diagnostic tool for schizophrenia diagnostics. In this letter, we present a classification framework based on features extracted from magnetic resonance imaging (MRI) data using two automatic whole-brain morphometry methods: voxel-based (VBM) and deformation-based morphometry (DBM). The framework employs a random subspace ensemble-based artificial neural network classifier-in particular, a multilayer perceptron (MLP). The framework was tested on data from first-episode schizophrenia patients and healthy controls. The experiments differed in terms of feature extraction methods, using VBM, DBM, and a combination of both morphometry methods. Thus, features of different types were available for model adaptation. As we expected, the combination of features increased the MLP classification accuracy up to 73.12%-an improvement of 5% versus MLP-based only on VBM or DBM features. To further verify the findings, other comparisons using support vector machines in place of MLPs were made within the framework. However, it cannot be concluded that any classifier was better than another.