Microstate Analyses to Study face Processing in Healthy Individuals and Psychiatric Disorders: A Review of ERP Findings.

Microstates represent brief periods of quasi-stable electroencephalography (EEG) scalp topography, offering insights into dynamic fluctuations in event-related potential (ERP) topographies. Despite this, there is a lack of a comprehensive systematic overview of microstate findings concerning cognitive face processing. This review aims to summarize ERP findings on face processing using microstate analyses and assess their effectiveness in characterizing face-related neural representations. A literature search was conducted for microstate ERP studies involving healthy individuals and psychiatric populations, utilizing PubMed, Google Scholar, Web of Science, PsychInfo, and Scopus databases. Twenty-two studies were identified, primarily focusing on healthy individuals (n = 16), with a smaller subset examining psychiatric populations (n = 6). The evidence reviewed in this study suggests that various microstates are consistently associated with distinct ERP stages involved in face processing, encompassing the processing of basic visual facial features to more complex functions such as analytical processing, facial recognition, and semantic representations. Furthermore, these studies shed light on atypical attentional neural mechanisms in Autism Spectrum Disorder (ASD), facial recognition deficits among emotional dysregulation disorders, and encoding and semantic dysfunctions in Post-Traumatic Stress Disorder (PTSD). In conclusion, this review underscores the practical utility of ERP microstate analyses in investigating face processing. Methodologies have evolved towards greater automation and data-driven approaches over time. Future research should aim to forecast clinical outcomes and conduct validation studies to directly demonstrate the efficacy of such analyses in inverse space.

Glymphatic System and Psychiatric Disorders: A Rapid Comprehensive Scoping Review.

BACKGROUND: Since discovering the glymphatic system, there has been a looming interest in exploring its relationship with psychiatric disorders. Recently, increasing evidence suggests an involvement of the glymphatic system in the pathophysiology of psychiatric disorders. However, clear data are still lacking. In this context, this rapid comprehensive PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) scoping review aims to identify and analyze current evidence about the relation between the glymphatic system and psychiatric disorders. METHODS: We conducted a comprehensive review of the literature and then proceeded to discuss the findings narratively. Tables were then constructed and articles were sorted according to authors, year, title, location of study, sample size, psychiatric disorder, the aim of the study, principal findings, implications. RESULTS: Twenty papers were identified as eligible, among which 2 articles on Schizophrenia, 1 on Autism Spectrum Disorders, 2 on Depression, 1 on Depression and Trauma-related Disorders, 1 on Depression and Anxiety, 2 on Anxiety and Sleep Disorders, 8 on Sleep Disorders, 2 on Alcohol use disorder and 1 on Cocaine Use Disorder. CONCLUSION: This review suggests a correlation between the glymphatic system and several psychiatric disorders: Schizophrenia, Depression, Anxiety Disorders, Sleep Disorders, Alcohol Use Disorder, Cocaine Use Disorder, Trauma-Related Disorders, and Autism Spectrum Disorders. Impairment of the glymphatic system could play a role in Trauma-Related Disorders, Alcohol Use Disorders, Cocaine Use Disorders, Sleep Disorders, Depression, and Autism Spectrum Disorders. It is important to implement research on this topic and adopt standardized markers and radio diagnostic tools.

Aesthetic processing in neurodiverse populations.

Neurodiversity is a perspective on cognition which suggests a non-pathological view of individual cognitive differences. Aesthetics research on neurodivergent brains has generally been limited to neuropsychological cases. Although this research has been integral to establishing the neurological correlates of aesthetic experience, it is crucial to expand this paradigm to more psychologically complex disorders. We offer a review of research on aesthetic preference in neurodivergent brains beyond neuropsychological cases: across populations with psychotic disorder, anhedonia and depression, anxiety disorder, and autism. We identify stable patterns of aesthetic bias in these populations, relate these biases to symptoms at perceptual, emotional, and evaluative levels of cognition, review relevant neurological correlates, and connect this evidence to current neuroaesthetics theory. Critically, we synthesize the reviewed evidence and discuss its relevance for three brain networks regularly implicated in aesthetic processing: the mesocorticolimbic reward circuit, frontolimbic connections, and the default mode network. Finally, we propose that broadening the subject populations for neuroaesthetics research to include neurodiverse populations is instrumental for yielding new insights into aesthetic processing in the brain.

Testing a Conceptual Model of Early Adversity, Neural Function, and Psychopathology: Protocol for a Retrospective Observational Cohort Study.

BACKGROUND: Early adversity, broadly defined as a set of negative exposures during childhood, is extremely common and increases risk for psychopathology across the life span. Previous research suggests that separate dimensions of adversity increase risk through developmental plasticity mechanisms shaping unique neurobiological pathways. Specifically, research suggests that deprivation is associated with deficits in higher order cognition, while threat is associated with atypicality in fear learning and emotion dysregulation. However, most of this research has been conducted in adolescent and adult samples, long after exposure to adversity occurs and far from periods of peak developmental plasticity. OBJECTIVE: The Wellness Health and Life Experiences (WHALE) study examines the neurobiological and behavioral mechanisms by which deprivation, threat, and unpredictability increase risk for psychopathology in early childhood (age 4-7 years) directly following periods of peak developmental plasticity. The objective of this study is to describe the study rationale and aims, the research design and procedures, and the analytical plan to test the study hypotheses. METHODS: This is a retrospective cohort study that examines associations between exposure to deprivation and threat and their hypothesized neurobiological mechanisms, how these neurobiological mechanisms link early adversity and psychopathology, and associations between unpredictability, reward learning, and psychopathology. The sample was a convenience sample of children (aged 4-7 years) and their families, identified through flyers, email blasts to listserves, school-based advertising, and involvement in community events. Data were collected during a home visit, a subsequent laboratory visit, and a final neuroimaging visit. Planned analyses include linear regression, path analyses, and functional magnetic resonance imaging analyses to explore the role of neural function in the association between early adversity and psychopathology. RESULTS: Participants (N=301) have been recruited into the study, and data collection has commenced. The expected results will be available in 2024. CONCLUSIONS: The findings of this study will help elucidate the neurobiological mechanisms by which early adversity increases risk for psychopathology in early childhood. This study represents the earliest test of an influential theory of biological embedding of early adversity. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/59636.

Topological properties of psychopathological networks of healthy and disordered individuals across mental disorders.

The identification of psychopathological markers has been the focus of several scientific fields. The results were inconsistent due to lack of a clear nosology. Network analysis, focusing on the interactions between symptoms, provided important insights into the nosology of mental disorders. These interactions originate several topological properties that could constitute markers of psychopathology. One of these properties is network connectivity, which has been explored in recent years. However, the results have been inconsistent, and the topological properties of psychopathological networks remain largely unexplored and unknown. We compared several topological properties (i.e., connectivity, average path length, assortativity, average degree, modularity, global clustering) of psychopathological networks of healthy and disordered participants across depression (N = 2830), generalized anxiety (N = 13,463), social anxiety (N = 12,814), and obsessive-compulsive disorder (N = 16,426). Networks were estimated using Bayesian Gaussian Graphical Models. The Janson-Shannon measure of divergence was used to identify differences between the network properties. Network connectivity distinguished healthy and disordered participants' networks in all disorders. However, in depression and generalized anxiety, network connectivity was higher in healthy participants. The presence and number of motifs also distinguished the networks of healthy and disordered participants. Other topological properties (i.e., modularity, clustering, average path length and average degree) seem to be disorder-specific. The psychopathological significance of network connectivity must be clarified. Some topological properties of psychopathological networks are promising markers of psychopathology and may contribute to clarifying the nosology of mental disorders.

Mitochondrial dynamics and psychiatric disorders: The missing link.

Elucidating the molecular mechanisms of psychopathology is crucial for optimized diagnosis and treatment. Accumulating data have underlined how mitochondrial bioenergetics affect major psychiatric disorders. However, how mitochondrial dynamics, a term addressing mitochondria quality control, including mitochondrial fission, fusion, biogenesis and mitophagy, is implicated in psychopathologies remains elusive. In this review, we summarize the existing literature on mitochondrial dynamics perturbations in psychiatric disorders/neuropsychiatric phenotypes. We include preclinical/clinical literature on mitochondrial dynamics recalibrations in anxiety, depression, post-traumatic stress disorder (PTSD), bipolar disorder and schizophrenia. We discuss alterations in mitochondrial network, morphology and shape, molecular markers of the mitochondrial dynamics machinery and mitochondrial DNA copy number (mtDNAcn) in animal models and human cohorts in brain and peripheral material. By looking for common altered mitochondrial dynamics patterns across diagnoses/phenotypes, we highlight mitophagy and biogenesis as regulators of anxiety and depression pathophysiology, respectively, as well as the fusion mediator dynamin-like 120 kDa protein (Opa1) as a molecular hub contributing to psychopathology. Finally, we comment on limitations and future directions in this novel neuropsychiatry field.

Sleep apnea evokes right hemisphere dominance and psychological disorders: An exploratory study.

BACKGROUND: Obstructive sleep apnea (OSA) is considered one of the major causes of sleep disorders and psychological disorders in individuals. Brain asymmetry (BA) demonstrates individual hemispheric activity and psychological disorders. This study aimed to explore the characteristics of BA and psychology in OSA. METHODS: Enrolment of patients for sleep assessment at the Sleep Medicine Center. Clinical characteristics, handedness, and psychological scales were prospectively collected from subjects. Subsequently, EEG power in alpha, beta, and theta bilaterally was calculated for the rest and sleep phases. RESULTS: A total of 152 OSA and 21 non-OSA subjects were included in the study. In the frontal, central and occipital regions, OSA exhibited increased interhemispheric asymmetry with increasing apnea-hypopnea index (AHI) during rest and sleep. Simultaneously, the results showed that greater activity in the right hemisphere was positively associated with anxiety and extraversion, while inversely with positive and lie scale. In addition, the results show that OSA contributes to abnormal BA fluctuations during sleep. CONCLUSIONS: Our results suggest that sleep disorders associated with apnea-hypopnea and arousal may contribute to increased BA during sleep. Such changes may persist into wakefulness with psychological traits.

The role of functional emotion circuits in distinct dimensions of psychopathology in youth.

Several mental disorders emerge during childhood or adolescence and are often characterized by socioemotional difficulties, including alterations in emotion perception. Emotional facial expressions are processed in discrete functional brain modules whose connectivity patterns encode emotion categories, but the involvement of these neural circuits in psychopathology in youth is poorly understood. This study examined the associations between activation and functional connectivity patterns in emotion circuits and psychopathology during development. We used task-based fMRI data from the Philadelphia Neurodevelopmental Cohort (PNC, N = 1221, 8-23 years) and conducted generalized psycho-physiological interaction (gPPI) analyses. Measures of psychopathology were derived from an independent component analysis of questionnaire data. The results showed positive associations between identifying fearful, sad, and angry faces and depressive symptoms, and a negative relationship between sadness recognition and positive psychosis symptoms. We found a positive main effect of depressive symptoms on BOLD activation in regions overlapping with the default mode network, while individuals reporting higher levels of norm-violating behavior exhibited emotion-specific lower functional connectivity within regions of the salience network and between modules that overlapped with the salience and default mode network. Our findings illustrate the relevance of functional connectivity patterns underlying emotion processing for behavioral problems in children and adolescents.

Expanding the therapeutic potential of neuro(active)steroids: a promising strategy for hyperdopaminergic behavioral phenotypes.

Imbalances in dopamine activity significantly contribute to the pathophysiology of several neuropsychiatric disorders, including addiction, ADHD, schizophrenia, impulse control disorders, and Parkinson's Disease. Neuro(active)steroids, comprising endogenous steroids that finely modulate neuronal activity, are considered crucial regulators of brain function and behavior, with implications in various physiological processes and pathological conditions. Specifically, subclasses of Neuro(active)steroids belonging to the 5α reductase pathway are prominently involved in brain disorders characterized by dopaminergic signaling imbalances. This review highlights the neuromodulatory effects of Neuro(active)steroids on the dopamine system and related aberrant behavioral phenotypes. We critically appraise the role of pregnenolone, progesterone, and allopregnanolone on dopamine signaling. Additionally, we discuss the impact of pharmacological interventions targeting 5α reductase activity in neuropsychiatric conditions characterized by excessive activation of the dopaminergic system, ranging from psychotic (endo)phenotypes and motor complications to decision-making problems and addiction.

Development of an eye-tracking system based on a deep learning model to assess executive function in patients with mental illnesses.

Patients with mental illnesses, particularly psychosis and obsessive‒compulsive disorder (OCD), frequently exhibit deficits in executive function and visuospatial memory. Traditional assessments, such as the Rey‒Osterrieth Complex Figure Test (RCFT), performed in clinical settings require time and effort. This study aimed to develop a deep learning model using the RCFT and based on eye tracking to detect impaired executive function during visuospatial memory encoding in patients with mental illnesses. In 96 patients with first-episode psychosis, 49 with clinical high risk for psychosis, 104 with OCD, and 159 healthy controls, eye movements were recorded during a 3-min RCFT figure memorization task, and organization and immediate recall scores were obtained. These scores, along with the fixation points indicating eye-focused locations in the figure, were used to train a Long Short-Term Memory + Attention model for detecting impaired executive function and visuospatial memory. The model distinguished between normal and impaired executive function, with an F1 score of 83.5%, and identified visuospatial memory deficits, with an F1 score of 80.7%, regardless of psychiatric diagnosis. These findings suggest that this eye tracking-based deep learning model can directly and rapidly identify impaired executive function during visuospatial memory encoding, with potential applications in various psychiatric and neurological disorders.

Gut microbiota modulates neurotransmitter and gut-brain signaling.

Neurotransmitters, including 5-hydroxytryptamine (5-HT), dopamine (DA), gamma-aminobutyric acid (GABA), and glutamate, are essential transductors in the Gut-Brain Axis (GBA), playing critical roles both peripherally and centrally. Accumulating evidence suggests that the gut microbiota modulates intestinal neurotransmitter metabolism and gut-to-brain signaling, shedding light on the crucial role of the gut microbiota in brain function and the pathogenesis of various neuropsychiatric diseases, such as major depression disorder (MDD), anxiety, addiction and Parkinson's disease (PD). Despite the exciting findings, the mechanisms underlying the modulation of neurotransmitter metabolism and function by the gut microbiota are still being elucidated. In this review, we aim to provide a comprehensive overview of the existing knowledge about the role of the gut microbiota in neurotransmitter metabolism and function in animal and clinical experiments. Moreover, we will discuss the potential mechanisms through which gut microbiota-derived neurotransmitters contribute to the pathogenesis of neuropsychiatric diseases, thus highlighting a novel therapeutic target for these conditions.

Association of Unc-51-like Kinase 4 (ULK4) with the reactivity of the extended reward system in response to conditioned stimuli.

OBJECTIVES: ULK4 is an established candidate gene for mental disorders and antipsychotic treatment response. We investigated the association of functional genetic variation at the ULK4 locus with the human extended dopaminergic reward system using fMRI during the performance of a well-established reward paradigm. METHODS: Two hundred and thirty-four patients were included in this study. Association of genetic variation in the ULK4 gene with reward system functioning were determined using the Desire-Reason-Dilemma (DRD) paradigm which allows to assess brain activation in response to conditioned reward stimuli. RESULTS: Variant prioritisation revealed the strongest functional signatures for the ULK4 variant rs17215589, coding for amino acid exchange Ala715Thr. For rs17215589 minor allele carriers, we detected increased activation responses to conditioned reward stimuli in the ventral tegmental area, nucleus accumbens and several cortical brain regions of the extended reward system. CONCLUSIONS: Our findings provide further evidence in humans that genetic variation in ULK4 may increase the vulnerability to mental disorders, by modulating the extended reward system function. Future studies are needed to confirm the modulation of the extended reward system by ULK4 and to specify the role of this mechanism in the pathogenesis of psychiatric disorders.

Role of mitochondria-endoplasmic reticulum contacts in neurodegenerative, neurodevelopmental and neuropsychiatric conditions.

Mitochondria-endoplasmic reticulum contacts (MERCs) mediate a close and continuous communication between both organelles that is essential for the transfer of calcium and lipids to mitochondria, necessary for cellular signalling and metabolic pathways. Their structural and molecular characterisation has shown the involvement of many proteins that bridge the membranes of the two organelles and maintain the structural stability and function of these contacts. The crosstalk between the two organelles is fundamental for proper neuronal function and is now recognised as a component of many neurological disorders. In fact, an increasing proportion of MERC proteins take part in the molecular and cellular basis of pathologies affecting the nervous system. Here we review the alterations in MERCs that have been reported for these pathologies, from neurodevelopmental and neuropsychiatric disorders to neurodegenerative diseases. Although mitochondrial abnormalities in these debilitating conditions have been extensively attributed to the high energy demand of neurons, a distinct role for MERCs is emerging as a new field of research. Understanding the molecular details of such alterations may open the way to new paths of therapeutic intervention.

Stereo-Electroencephalography-Guided Network Neuromodulation for Psychiatric Disorders: The Neurophysiology Monitoring Unit.

BACKGROUND AND OBJECTIVES: Recent advances in stereotactic and functional neurosurgery have brought forth the stereo-electroencephalography approach which allows deeper interrogation and characterization of the contributions of deep structures to neural and affective functioning. We argue that this approach can and should be brought to bear on the notoriously intractable issue of defining the pathophysiology of refractory psychiatric disorders and developing patient-specific optimized stimulation therapies. METHODS: We have developed a suite of methods for maximally leveraging the stereo-electroencephalography approach for an innovative application to understand affective disorders, with high translatability across the broader range of refractory neuropsychiatric conditions. RESULTS: This article provides a roadmap for determining desired electrode coverage, tracking high-resolution research recordings across a large number of electrodes, synchronizing intracranial signals with ongoing research tasks and other data streams, applying intracranial stimulation during recording, and design choices for patient comfort and safety. CONCLUSION: These methods can be implemented across other neuropsychiatric conditions needing intensive electrophysiological characterization to define biomarkers and more effectively guide therapeutic decision-making in cases of severe and treatment-refractory disease.

Aberrant inhibitory control as a transdiagnostic dimension of mental disorders - A meta-analysis of the antisaccade task in different psychiatric populations.

This meta-analysis examined inhibitory control performance in the antisaccade task across mental disorders. Following PRISMA guidelines, we analyzed data from k = 146 studies (n = 13,807 participants) on antisaccade performance. Effect sizes were estimated using random-effects models and restricted maximum-likelihood estimation, with robustness tests for study heterogeneity and publication bias. Most disorders displayed elevated error rates, with schizophrenia showing the greatest impairments, followed by autism spectrum disorder, bipolar disorder and attention deficit hyperactivity disorder. Small to medium impairments were also found in eating disorders, major depressive disorder, obsessive-compulsive disorder and substance use disorder. Results were robust against corrections for publication bias and largely unaffected by confounding variables. Prolonged latencies were observed in schizophrenia, attention deficit hyperactivity disorder, bipolar disorder and obsessive compulsive disorder, with smaller and less robust effect sizes. Results indicate inhibitory control deficits in the antisaccade task across mental disorders, especially evident for error rates. While present in most disorders, results imply varying degrees of impairments, ranging from small to large in effect sizes, with largest impairments in schizophrenia.

Dynamicity of brain network organization & their community architecture as characterizing features for classification of common mental disorders from whole-brain connectome.

The urgency of addressing common mental disorders (bipolar disorder, attention-deficit hyperactivity disorder (ADHD), and schizophrenia) arises from their significant societal impact. Developing strategies to support psychiatrists is crucial. Previous studies focused on the relationship between these disorders and changes in the resting-state functional connectome's modularity, often using static functional connectivity (sFC) estimation. However, understanding the dynamic reconfiguration of resting-state brain networks with rich temporal structure is essential for comprehending neural activity and addressing mental health disorders. This study proposes an unsupervised approach combining spatial and temporal characterization of brain networks to classify common mental disorders using fMRI timeseries data from two cohorts (N = 408 participants). We employ the weighted stochastic block model to uncover mesoscale community architecture differences, providing insights into network organization. Our approach overcomes sFC limitations and biases in community detection algorithms by modelling the functional connectome's temporal dynamics as a landscape, quantifying temporal stability at whole-brain and network levels. Findings reveal individuals with schizophrenia exhibit less assortative community structure and participate in multiple motif classes, indicating less specialized network organization. Patients with schizophrenia and ADHD demonstrate significantly reduced temporal stability compared to healthy controls. This study offers insights into functional connectivity (FC) patterns' spatiotemporal organization and their alterations in common mental disorders, highlighting the potential of temporal stability as a biomarker.

Cognitive functioning in adult psychiatric patients with and without attention-deficit/hyperactivity disorder.

INTRODUCTION: Studies of cognitive functioning in patients with attention-deficit/hyperactivity disorder (ADHD) have often used healthy comparison groups. The present study examines cognitive profiles, including general intellectual and executive functions, in a young adult psychiatric outpatient clientele with ADHD and evaluates whether their cognitive profiles can help differentiate them from patients with non-ADHD-associated psychiatric disorders. METHODS: The study group comprised 141 young adult psychiatric patients (age range 18-25 years) of whom 78 had ADHD. Comprehensive neuropsychological assessment included the Wechsler Adult Intelligence Scale, 4th version and subtests from Delis-Kaplan Executive Function System. Clinical psychiatric assessments and diagnostic evaluation were performed. RESULTS: The ADHD group (including all subtypes) had significantly lower verbal comprehension and full-scale intelligence quotient than the non-ADHD group. Tests measuring working memory or executive function did not separate those with and without ADHD. CONCLUSION: The results of our study suggest that, except for the need to establish overall cognitive performance level, the clinical implication of testing is small if the purpose is to "rule out" an ADHD diagnosis.

The parental brain, perinatal mental illness, and treatment: A review of key structural and functional changes.

The transition to parenthood is perhaps the only time in adult life when the brain changes to such a significant degree in such a short period, particularly in birthing parents. It is also a time when there is an increased risk of developing a mental illness, which may be due, in part, to the increased neuroplasticity. Thus, we must develop interventions and treatments that support parents and promote parental brain health. This review will highlight key findings from current research on how human brain structure and function are modified with 1) the transition to parenthood, 2) parenting stress and perinatal mental illness, and 3) treatments aimed at promoting perinatal mental health. The focus will be on birthing parents and mothers, but brain changes in non-birthing parents will also be discussed. Improvements in our understanding of the parental brain, in health and with illness, will promote the well-being of generations to come.

Decoding cognition in neurodevelopmental, psychiatric and neurological conditions with multivariate pattern analysis of EEG data.

Multivariate pattern analysis (MVPA) of electroencephalographic (EEG) data represents a revolutionary approach to investigate how the brain encodes information. By considering complex interactions among spatio-temporal features at the individual level, MVPA overcomes the limitations of univariate techniques, which often fail to account for the significant inter- and intra-individual neural variability. This is particularly relevant when studying clinical populations, and therefore MVPA of EEG data has recently started to be employed as a tool to study cognition in brain disorders. Here, we review the insights offered by this methodology in the study of anomalous patterns of neural activity in conditions such as autism, ADHD, schizophrenia, dyslexia, neurological and neurodegenerative disorders, within different cognitive domains (perception, attention, memory, consciousness). Despite potential drawbacks that should be attentively addressed, these studies reveal a peculiar sensitivity of MVPA in unveiling dysfunctional and compensatory neurocognitive dynamics of information processing, which often remain blind to traditional univariate approaches. Such higher sensitivity in characterizing individual neurocognitive profiles can provide unique opportunities to optimise assessment and promote personalised interventions.