The Anxious Brain: The Influence of Stress on the Nervous System.

Anxiety disorders, including generalized anxiety, panic disorder, and post-traumatic stress, constitute the most frequent mental disorders and occur in about 14-18% of the overall population [...].

Group independent components underpin responses to items from a depression scale.

OBJECTIVE: The aim of the present study is to investigate the brain circuits or networks that underpin diagnostically specific tasks by means of group independent component analysis for FMRI toolbox (GIFT). We hypothesised that there will be neural network patterns of activation and deactivation, which correspond to real-time performance on clinical self-evaluation scales. METHODS: In total, 20 healthy controls (HC) and 22 patients with major depressive episode have been included. All subjects were scanned with functional magnetic resonance imaging (fMRI) with paradigm composed of diagnostic clinical self-assessment depression scale contrasted to neutral scale. The data were processed with group independent component analysis for functional MRI toolbox and statistical parametric mapping. RESULTS: The results have demonstrated that there exist positively or negatively modulated brain networks during processing of diagnostic specific task questions for depressive disorder. There have also been confirmed differences in the networks processing diagnostic versus off blocks between patients and controls in anterior cingulate cortex and middle frontal gyrus. Diagnostic conditions (depression scale) when contrasted to neutral conditions demonstrate differential activity of right superior frontal gyrus and right middle cingulate cortex in the comparison of patients with HC. CONCLUSION: Potential neuroimaging of state-dependent biomarkers has been directly linked with clinical assessment self-evaluation scale, administered as stimuli simultaneously with the fMRI acquisition. It may be regarded as further evidence in support of the convergent capacity of both methods to distinguish groups by means of incremental translational cross-validation.

Degeneracy and disordered brain networks in psychiatric patients using multivariate structural covariance analyzes.

Introduction: In this study, we applied multivariate methods to identify brain regions that have a critical role in shaping the connectivity patterns of networks associated with major psychiatric diagnoses, including schizophrenia (SCH), major depressive disorder (MDD) and bipolar disorder (BD) and healthy controls (HC). We used T1w images from 164 subjects: Schizophrenia (n = 17), bipolar disorder (n = 25), major depressive disorder (n = 68) and a healthy control group (n = 54). Methods: We extracted regions of interest (ROIs) using a method based on the SHOOT algorithm of the SPM12 toolbox. We then performed multivariate structural covariance between the groups. For the regions identified as significant in t term of their covariance value, we calculated their eigencentrality as a measure of the influence of brain regions within the network. We applied a significance threshold of p = 0.001. Finally, we performed a cluster analysis to determine groups of regions that had similar eigencentrality profiles in different pairwise comparison networks in the observed groups. Results: As a result, we obtained 4 clusters with different brain regions that were diagnosis-specific. Cluster 1 showed the strongest discriminative values between SCH and HC and SCH and BD. Cluster 2 had the strongest discriminative value for the MDD patients, cluster 3 - for the BD patients. Cluster 4 seemed to contribute almost equally to the discrimination between the four groups. Discussion: Our results suggest that we can use the multivariate structural covariance method to identify specific regions that have higher predictive value for specific psychiatric diagnoses. In our research, we have identified brain signatures that suggest that degeneracy shapes brain networks in different ways both within and across major psychiatric disorders.

Topology switching during window thresholding fMRI-based functional networks of patients with major depressive disorder: Consensus network approach.

We present a novel method for analyzing brain functional networks using functional magnetic resonance imaging data, which involves utilizing consensus networks. In this study, we compare our approach to a standard group-based method for patients diagnosed with major depressive disorder (MDD) and a healthy control group, taking into account different levels of connectivity. Our findings demonstrate that the consensus network approach uncovers distinct characteristics in network measures and degree distributions when considering connection strengths. In the healthy control group, as connection strengths increase, we observe a transition in the network topology from a combination of scale-free and random topologies to a small-world topology. Conversely, the MDD group exhibits uncertainty in weak connections, while strong connections display small-world properties. In contrast, the group-based approach does not exhibit significant differences in behavior between the two groups. However, it does indicate a transition in topology from a scale-free-like structure to a combination of small-world and scale-free topologies. The use of the consensus network approach also holds immense potential for the classification of MDD patients, as it unveils substantial distinctions between the two groups.

Conversion and Obsessive-Phobic Symptoms Predict IL-33 and IL-28A Levels in Individuals Diagnosed with COVID-19.

The first epidemiological wave of the incidence of COVID-19 in Bulgaria was registered in June 2020. After the wave peak, we conducted a study in persons diagnosed with COVID-19 (N = 52). They were assessed with the anxiety-depressive scale (ADS), including basic (BS), vegetative (VS), conversion (CS), obsessive-phobic (OPS), and depressive (DS) symptoms. ADS assessment of individuals diagnosed with SARS-CoV-2 indicated a correlation between OPS and IL-33 values. IL-10 levels were higher than reference ranges in all patients. Multiple linear regression analyses demonstrated that combination of CS and OPS explained 28% of IL-33 levels, while combination of symptoms from all ADS dimensions explained 24% of IL-33 levels. It was also found that 21% of IL-28A levels was explained from the combination by all ADS dimensions, whereas OPS was the predictor for lower concentrations. The obtained results revealed meaningful correlations between psycho neuro-immunological factors in pathogenesis of illness from the coronavirus infection.

Functional Connectivity of the Anterior Cingulate Cortex and the Right Anterior Insula Differentiates between Major Depressive Disorder, Bipolar Disorder and Healthy Controls.

Background: This study aimed to explore possible differences of the whole-brain functional connectivity of the anterior cingulate cortex (ACC) and anterior insula (AI), in a sample of depressed patients with major depressive disorder (MDD), bipolar disorder (BD) and healthy controls (HC). Methods: A hundred and three subjects (nMDD = 35, nBD = 25, and nHC = 43) between the ages of eighteen and sixty-five years old underwent functional magnetic resonance imaging. The CONN Toolbox was used to process and analyze the functional connectivity of the ACC and AI. Results: The comparison between the patients (MDD/BD) and HC yielded increased resting-state functional connectivity (rsFC) between the ACC and the motor and somatosensory cortices (SSC), superior parietal lobule (SPL), precuneus, and lateral occipital cortex, which was driven by the BD group. In addition, hyperconnectivity between the right AI and the motor and SSC was found in BD, as compared to HC. In MDD, as compared to HC, hyperconnectivity between ACC and SPL and the lateral occipital cortex was found, with no statistical rsFC differences for the AI seed. Compared to BD, the MDD group showed ACC-cerebellum hyperconnectivity and a trend for increased rsFC between the right AI and the bilateral superior frontal cortex. Conclusions: Considering the observed hyperconnectivity between the ACC/somatosensory cortex in the patient group, we suggest depression may be related to an impairment of the sensory-discriminative function of the SSC, which results in the phenomenological signature of mental pain in both MDD and BD. These findings suggest that future research should investigate this particular network with respect to motor functions and executive control, as a potential differential diagnostic biomarker for MDD and BD.

Toward interpretability of machine learning methods for the classification of patients with major depressive disorder based on functional network measures.

We address the interpretability of the machine learning algorithm in the context of the relevant problem of discriminating between patients with major depressive disorder (MDD) and healthy controls using functional networks derived from resting-state functional magnetic resonance imaging data. We applied linear discriminant analysis (LDA) to the data from 35 MDD patients and 50 healthy controls to discriminate between the two groups utilizing functional networks' global measures as the features. We proposed the combined approach for feature selection based on statistical methods and the wrapper-type algorithm. This approach revealed that the groups are indistinguishable in the univariate feature space but become distinguishable in a three-dimensional feature space formed by the identified most important features: mean node strength, clustering coefficient, and the number of edges. LDA achieves the highest accuracy when considering the network with all connections or only the strongest ones. Our approach allowed us to analyze the separability of classes in the multidimensional feature space, which is critical for interpreting the results of machine learning models. We demonstrated that the parametric planes of the control and MDD groups rotate in the feature space with increasing the thresholding parameter and that their intersection increases with approaching the threshold of 0.45, for which classification accuracy is minimal. Overall, the combined approach for feature selection provides an effective and interpretable scenario for discriminating between MDD patients and healthy controls using measures of functional connectivity networks. This approach can be applied to other machine learning tasks to achieve high accuracy while ensuring the interpretability of the results.

Retrospective Analysis of the Psychological Predictors of Public Health Support in Bulgarians at the Beginning of the Coronavirus Pandemic.

The earliest critical context of the pandemic, preceding the first real epidemiological wave of contagion in Bulgaria, was examined using a socio-affective perspective. A retrospective and agnostic analytical approach was adopted. Our goal was to identify traits and trends that explain public health support (PHS) of Bulgarians during the first two months of the declared state of emergency. We investigated a set of variables with a unified method within an international scientific network named the International Collaboration on Social & Moral Psychology of COVID-19 (ICSMP) in April and May 2020. A total of 733 Bulgarians participated in the study (67.3% females), with an average age of 31.8 years (SD = 11.66). Conspiracy Theories Beliefs were a significant predictor of lower PHS. Psychological Well-Being was significantly associated with Physical Contact and Anti-Corona Policy Support. Physical Contact was significantly predicted by fewer Conspiracy Theories Beliefs, higher Collective Narcissism, Open-mindedness, higher Trait Self-Control, Moral Identity, Risk Perception and Psychological Well-Being. Physical Hygiene compliance was predicted by fewer Conspiracy Theories Beliefs, Collective Narcissism, Morality-as-Cooperation, Moral Identity and Psychological Well-Being. The results revealed two polar trends of support and non-support of public health policies. The contribution of this study is in providing evidence for the affective polarization and phenomenology of (non)precarity during the outbreak of the pandemic.

Advances in the Diagnosis and Management of Psychosis.

Psychosis research in the contemporary sense of scientific inquiry may be traced as far as the formulation of the "unitary psychosis" concept, or Einheitpsychose, which is usually attributed to Wilhelm Griesinger, Ernst von Zeller, and Heinrich Neumann [...].

Effective Connectivity Between the Orbitofrontal Cortex and the Precuneus Differentiates Major Psychiatric Disorders: Results from a Transdiagnostic Spectral DCM Study.

BACKGROUND & OBJECTIVE: We have previously identified aberrant connectivity of the left precuneus, ventrolateral prefrontal cortex, anterior cingulate cortex, and anterior insula in patients with either a paranoid (schizophrenia), or a depressive syndrome (both unipolar and bipolar). In the current study, we attempted to replicate and expand these findings by including a healthy control sample and separating the patients in a depressive episode into two groups: unipolar and bipolar depression. We hypothesized that the connections between those major nodes of the resting state networks would demonstrate different patterns in the three patient groups compared to the healthy subjects. METHODS: Resting-state functional MRI was performed on a sample of 101 participants, of which 26 patients with schizophrenia (current psychotic episodes), 24 subjects with Bipolar Disorder (BD), 33 with Major Depressive Disorder (MDD) (both BD and MDD patients were in a current depressive episode), and 21 healthy controls. Spectral Dynamic Causal Modeling was used to calculate the coupling values between eight regions of interest, including the anterior precuneus (PRC), anterior hippocampus, anterior insula, angular gyrus, lateral Orbitofrontal Cortex (OFC), middle frontal gyrus, planum temporale, and anterior thalamus. RESULTS & CONCLUSION: We identified disturbed effective connectivity from the left lateral orbitofrontal cortex to the left anterior precuneus that differed significantly between unipolar depression, where the influence was inhibitory, and bipolar depression, where the effect was excitatory. A logistic regression analysis correctly classified 75% of patients with unipolar and bipolar depression based solely on the coupling values of this connection. In addition, patients with schizophrenia demonstrated negative effective connectivity from the anterior PRC to the lateral OFC, which distinguished them from healthy controls and patients with major depression. Future studies with unmedicated patients will be needed to establish the replicability of our findings.

Neural Activation in the Ventromedial Prefrontal Cortex Precedes Conscious Experience of Being in or out of a Transient Hallucinatory State.

BACKGROUND AND HYPOTHESES: Auditory verbal hallucinations (AVHs) is not only a common symptom in schizophrenia but also observed in individuals in the general population. Despite extensive research, AVHs are poorly understood, especially their underlying neuronal architecture. Neuroimaging methods have been used to identify brain areas and networks that are activated during hallucinations. A characteristic feature of AVHs is, however, that they fluctuate over time, with varying frequencies of starts and stops. An unanswered question is, therefore, what neuronal events co-occur with the initiation and inhibition of an AVH episode. STUDY DESIGN: We investigated brain activation with fMRI in 66 individuals who experienced multiple AVH-episodes while in the scanner. We extracted time-series fMRI-data and monitored changes second-by-second from 10 s before to 15 s after participants indicated the start and stop of an episode, respectively, by pressing a hand-held response-button. STUDY RESULTS: We found a region in the ventromedial prefrontal cortex (VMPFC) which showed a significant increase in activation initiated a few seconds before participants indicated the start of an episode, and a corresponding decrease in activation initiated a few seconds before the end of an episode. CONCLUSIONS: The consistent increase and decrease in activation in this area in advance of the consciously experienced presence or absence of the "voice" imply that this region may act as a switch in turning episodes on and off. The activation is unlikely to be confounded by motor responses. The findings could have clinical implications for brain stimulation treatments, like transcranial magnetic stimulation.

Functional magnetic resonance imaging study of group independent components underpinning item responses to paranoid-depressive scale.

BACKGROUND: Our study expand upon a large body of evidence in the field of neuropsychiatric imaging with cognitive, affective and behavioral tasks, adapted for the functional magnetic resonance imaging (MRI) (fMRI) experimental environment. There is sufficient evidence that common networks underpin activations in task-based fMRI across different mental disorders. AIM: To investigate whether there exist specific neural circuits which underpin differential item responses to depressive, paranoid and neutral items (DN) in patients respectively with schizophrenia (SCZ) and major depressive disorder (MDD). METHODS: 60 patients were recruited with SCZ and MDD. All patients have been scanned on 3T magnetic resonance tomography platform with functional MRI paradigm, comprised of block design, including blocks with items from diagnostic paranoid (DP), depression specific (DS) and DN from general interest scale. We performed a two-sample t-test between the two groups-SCZ patients and depressive patients. Our purpose was to observe different brain networks which were activated during a specific condition of the task, respectively DS, DP, DN. RESULTS: Several significant results are demonstrated in the comparison between SCZ and depressive groups while performing this task. We identified one component that is task-related and independent of condition (shared between all three conditions), composed by regions within the temporal (right superior and middle temporal gyri), frontal (left middle and inferior frontal gyri) and limbic/salience system (right anterior insula). Another component is related to both diagnostic specific conditions (DS and DP) e.g. It is shared between DEP and SCZ, and includes frontal motor/language and parietal areas. One specific component is modulated preferentially by to the DP condition, and is related mainly to prefrontal regions, whereas other two components are significantly modulated with the DS condition and include clusters within the default mode network such as posterior cingulate and precuneus, several occipital areas, including lingual and fusiform gyrus, as well as parahippocampal gyrus. Finally, component 12 appeared to be unique for the neutral condition. In addition, there have been determined circuits across components, which are either common, or distinct in the preferential processing of the sub-scales of the task. CONCLUSION: This study has delivers further evidence in support of the model of trans-disciplinary cross-validation in psychiatry.

Resting-State Functional Connectivity Impairment in Patients with Major Depressive Episode.

AIM: This study aims to develop new approaches to characterize brain networks to potentially contribute to a better understanding of mechanisms involved in depression. METHOD AND SUBJECTS: We recruited 90 subjects: 49 healthy controls (HC) and 41 patients with a major depressive episode (MDE). All subjects underwent clinical evaluation and functional resting-state MRI. The data were processed investigating functional connectivity network measures across the two groups using Brain Connectivity Toolbox. The statistical inferences were developed at a functional network level, using a false discovery rate method. Linear discriminant analysis was used to differentiate between the two groups. RESULTS AND DISCUSSION: Significant differences in functional connectivity (FC) between depressed patients vs. healthy controls was demonstrated, with brain regions including the lingual gyrus, cerebellum, midcingulate cortex and thalamus more prominent in healthy subjects as compared to depression where the orbitofrontal cortex emerged as a key node. Linear discriminant analysis demonstrated that full-connectivity matrices were the most precise in differentiating between depression vs. health subjects. CONCLUSION: The study provides supportive evidence for impaired functional connectivity networks in MDE patients.

Perspectives before incremental trans-disciplinary cross-validation of clinical self-evaluation tools and functional MRI in psychiatry: 10 years later.

Translational validity (or trans-disciplinary validity) is defined as one possible approach to achieving incremental validity by combining simultaneous clinical state-dependent measures and functional MRI data acquisition. It is designed under the assumption that the simultaneous administration of the two methods may produce a dataset with enhanced synchronization and concordance. Translational validation aims at "bridging" the explanatory gap by implementing validated psychometric tools clinically in the experimental settings of fMRI and then translating them back to clinical utility. Our studies may have identified common diagnostic task-specific denominators in terms of activations and network modulation. However, those common denominators need further investigation to determine whether they signify disease or syndrome-specific features (signatures), which, at the end of the day, raises one more question about the poverty of current conventional psychiatric classification criteria. We propose herewith a novel algorithm for translational validation based on our explorative findings. The algorithm itself includes pre-selection of a test based on its psychometric characteristics, adaptation to the functional MRI paradigm, exploration of the underpinning whole brain neural correlates in healthy controls as compared to a patient population with certain diagnoses, and finally, investigation of the differences between two or more diagnostic classes.