Introduction. Vagal nerve stimulation (VNS) is a therapeutical option for the treatment of drug-resistant epileptic patients. The response to VNS varies from patient to patient and is difficult to predict. The proposed study is based on our previous work, identifying relative mean power in pre-implantation EEG as a reliable marker for VNS efficacy prediction in adult patients. Our study has two main tasks. Firstly, to confirm the utility of relative mean power as a feature correlating with VNS efficacy in children. The second is to validate the applicability of our prediction classifier, Pre-X-Stim, in the pediatric population. Material and Methods. We identified a group of children with drug-resistant epilepsy. We included only children in whom EEG contained photic stimulation (Task 1) or was recorded based on the defined acquisition protocol used for development Pre-X-Stim (Task 2). Relative mean powers were calculated. VNS responders and non-responders were compared based on relative mean powers' values. In the next step, we evaluate the utility of our classifier, Pre-X-Stim, in the children population. Results: We identified 57 children treated with VNS - 17 patients were recruited for the Task 1 and 7 patients for the Task 2. When focusing on relative mean powers in EEG spectra, we observed statistically significant differences in theta range. The Pre-X-Stim algorithm was able to predict VNS efficacy correctly in 6 out of 7 patients (the accuracy 83.3%, the sensitivity 75%, the specificity 100%). Conclusions. Based on our results, it seems that children and adults share a similar pattern of EEG relative mean power changes. These changes can be used for pre-implantation prediction of VNS efficacy.

• MeSH
• Child MeSH
• Electroencephalography * methods   MeSH
• Epilepsy * therapy   physiopathology   MeSH
• Humans MeSH
• Adolescent MeSH
• Child, Preschool MeSH
• Drug Resistant Epilepsy * therapy   physiopathology   MeSH
• Scalp MeSH
• Vagus Nerve Stimulation * methods   MeSH
• Treatment Outcome MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Child, Preschool MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Modafinil is primarily used to treat narcolepsy but is also used as an off-label cognitive enhancer. Functional magnetic resonance imaging studies indicate that modafinil modulates the connectivity of neocortical networks primarily involved in attention and executive functions. However, much less is known about the drug's effects on subcortical structures. Following preliminary findings, we evaluated modafinil's activity on the connectivity of distinct cerebellar regions with the neocortex. We assessed the spatial relationship of these effects with the expression of neurotransmitter receptors/transporters. METHODS: Patterns of resting-state functional magnetic resonance imaging connectivity were estimated in 50 participants from scans acquired pre- and postadministration of a single (100 mg) dose of modafinil (n = 25) or placebo (n = 25). Using specific cerebellar regions as seeds for voxelwise analyses, we examined modafinil's modulation of cerebellar-neocortical connectivity. Next, we conducted a quantitative evaluation of the spatial overlap between the modulation of cerebellar-neocortical connectivity and the expression of neurotransmitter receptors/transporters obtained by publicly available databases. RESULTS: Modafinil increased the connectivity of crus I and vermis IX with prefrontal regions. Crus I connectivity changes were associated with the expression of dopaminergic D2 receptors. The vermis I-II showed enhanced coupling with the dorsal anterior cingulate cortex and matched the expression of histaminergic H3 receptors. The vermis VII-VIII displayed increased connectivity with the visual cortex, an activity associated with dopaminergic and histaminergic neurotransmission. CONCLUSIONS: Our study reveals modafinil's modulatory effects on cerebellar-neocortical connectivity. The modulation mainly involves crus I and the vermis and spatially overlaps the distribution of dopaminergic and histaminergic receptors.

• MeSH
• Adult MeSH
• Humans MeSH
• Magnetic Resonance Imaging * MeSH
• Young Adult MeSH
• Modafinil * pharmacology   administration & dosage   MeSH
• Cerebellum * drug effects   diagnostic imaging   metabolism   MeSH
• Neocortex drug effects   metabolism   diagnostic imaging   MeSH
• Neural Pathways drug effects   metabolism   MeSH
• Wakefulness-Promoting Agents pharmacology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Randomized Controlled Trial MeSH

This study explored how the human cortical folding pattern composed of convex gyri and concave sulci affected single-subject morphological brain networks, which are becoming an important method for studying the human brain connectome. We found that gyri-gyri networks exhibited higher morphological similarity, lower small-world parameters, and lower long-term test-retest reliability than sulci-sulci networks for cortical thickness- and gyrification index-based networks, while opposite patterns were observed for fractal dimension-based networks. Further behavioral association analysis revealed that gyri-gyri networks and connections between gyral and sulcal regions significantly explained inter-individual variance in Cognition and Motor domains for fractal dimension- and sulcal depth-based networks. Finally, the clinical application showed that only sulci-sulci networks exhibited morphological similarity reductions in major depressive disorder for cortical thickness-, fractal dimension-, and gyrification index-based networks. Taken together, these findings provide novel insights into the constraint of the cortical folding pattern to the network organization of the human brain.

• MeSH
• Depressive Disorder, Major pathology   diagnostic imaging   MeSH
• Adult MeSH
• Connectome * MeSH
• Humans MeSH
• Magnetic Resonance Imaging * MeSH
• Young Adult MeSH
• Cerebral Cortex * diagnostic imaging   anatomy & histology   MeSH
• Nerve Net * diagnostic imaging   anatomy & histology   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

N-Methyl-d-aspartate receptors (NMDARs) play a crucial role in excitatory neurotransmission, with numerous pathogenic variants identified in the GluN subunits, including their ligand-binding domains (LBDs). The prevailing hypothesis postulates that the endoplasmic reticulum (ER) quality control machinery verifies the agonist occupancy of NMDARs, but this was tested in a limited number of studies. Using microscopy and electrophysiology in the human embryonic kidney 293 (HEK293) cells, we found that surface expression of GluN1/GluN2A receptors containing a set of alanine substitutions within the LBDs correlated with the measured EC50 values for glycine (GluN1 subunit mutations) while not correlating with the measured EC50 values for l-glutamate (GluN2A subunit mutations). The mutant cycle of GluN1-S688 residue, including the pathogenic GluN1-S688Y and GluN1-S688P variants, showed a correlation between relative surface expression of the GluN1/GluN2A receptors and the measured EC50 values for glycine, as well as with the calculated ΔGbinding values for glycine obtained from molecular dynamics simulations. In contrast, the mutant cycle of GluN2A-S511 residue did not show any correlation between the relative surface expression of the GluN1/GluN2A receptors and the measured EC50 values for l-glutamate or calculated ΔGbinding values for l-glutamate. Coexpression of both mutated GluN1 and GluN2A subunits led to additive or synergistic alterations in the surface number of GluN1/GluN2A receptors. The synchronized ER release by ARIAD technology confirmed the altered early trafficking of GluN1/GluN2A receptors containing the mutated LBDs. The microscopical analysis from embryonal rat hippocampal neurons (both sexes) corroborated our conclusions from the HEK293 cells.

• MeSH
• Glycine metabolism   MeSH
• HEK293 Cells MeSH
• Hippocampus cytology   metabolism   MeSH
• Rats MeSH
• Glutamic Acid metabolism   MeSH
• Humans MeSH
• Ligands MeSH
• Mutation genetics   MeSH
• Protein Domains MeSH
• Nerve Tissue Proteins MeSH
• Receptors, N-Methyl-D-Aspartate * metabolism   genetics   chemistry   MeSH
• Protein Transport physiology   genetics   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Length of stay (LoS) is a critical parameter of inpatient forensic treatment functioning. Inpatient forensic LoS in Czechia varies across hospitals with the number of patients per 100,000 inhabitants and the treatment duration. We aimed to analyse these inter-hospital differences and provide relevant sociodemographic and treatment-related data. METHODS: We collected descriptive parameters from 841 forensic inpatients from 13 hospitals in Czechia, with follow-up data collection after 6 months (N = 800). Data from eight hospitals with > 50 patients (N = 765) were entered into linear regression analyses with subsequent resampling to identify differences in LoS associated with index offence, diagnosis, and treatment type, thereby highlighting interhospital variations. RESULTS: The cohort comprised predominantly males (mean age, 41.84 years; standard deviation [SD] 3.63) with extended mental health histories; the mean main diagnosis length was 13.2 years (SD 12.18). Most inmates committed violent offences, with psychotic, substance use, or paraphilic disorders predominating. Family contact remained common despite the patients' poor socioeconomic status. The mean LoS was 1,327.58 (SD 1642.41) days. We observed significant differences in LoS among patients from the same diagnostic group. Within the whole system, patients with substance abuse disorders, psychotic disorders, and intellectual disabilities stayed for 760, 1490, and 2441 days, respectively. Violent index offences increased LoS in most hospitals, as did sexual offences, but "other" minor criminal offences (non-violent, non-sexual) were associated with increased LoS only in some hospitals. Sex offender treatment significantly affected LoS in some hospitals, while enrolment into substance use programmes shortened it. CONCLUSIONS: Our study revealed significant inter-hospital variations in LoS associated with index offences, diagnoses, or treatment programs, which could be related to previously unrecognised institutional factors. Regular evaluation of treatment outcomes and implementation of standardised guidelines across the entire system is necessary to balance these differences. The insights provided into inpatient treatment in Czechia can be used to guide policy and practice improvements, enhancing the quality of forensic psychiatric care and ensuring the rights and well-being of the patients. The study addressed the knowledge gap existing in the available literature regarding previously unrecognised factors influencing the LoS at the system "mezzo" level.

• Publication type
• Journal Article MeSH

Schizophrenia, a profoundly impactful neuropsychiatric disorder, has been the subject of extensive research using animal models. However, certain important aspects remain understudied, including assumed long-term consequences of psychotic episodes on negative symptoms development and progression. Addressing these limitations, we proposed a novel animal model in male rats based on early postnatal immune activation triggered by lipopolysaccharide (LPS), serving as the predisposing factor (1st hit). As the 2nd hit, representing psychotic-like episodes, we implemented a multi-episodic co-treatment with dizocilpine (MK-801) and amphetamine (AMP), spanning multiple developmental periods. The animals were tested in two social behavioral assays in adolescence and adulthood to investigate whether a social deficit would arise. In addition, we evaluated the level of oxytocin (OT), a neuropeptide relevant to social behavior, in selected brain regions. In the social interaction test, when animals could freely interact in the open field and express their social behavioral profile entirely, social behavior decreased in adolescent experimental animals. In the social approach test in the Y maze, all animals, irrespective of treatment, preferred conspecific over an indifferent object and novel rat over a familiar rat. Further, the results revealed that the OT content in the hypothalamus increased with age. In the proposed model, social interaction in the open field was decreased in adolescent but not in adult rats, indicating that the pharmacological manipulations caused only transient age-dependent changes. The study was thus in certain aspects successful in creating a novel approach to model social deficit potentially relevant to schizophrenia; other findings require further investigation.

• Publication type
• Journal Article MeSH

BACKGROUND: Several findings indicate that stress may influence epileptiform discharges manifesting in temporal-limbic areas, which may become a potential trigger of psychosis that may manifest without neurologically diagnosed epilepsy. Some findings suggest that measures assessing levels of inter-hemispheric information connection may reveal the spread of subclinical epileptiform neural activity associated with psychotic and seizure-like symptoms. Recent research also suggests that electrodermal activity (EDA), which is related to limbic activations, may allow indirect measurement of interhemispheric information transmission. These findings about the interhemispheric spread of information suggest a hypothesis that heightened spread of information between the brain hemispheres might indirectly indicate epileptiform discharges spreading between hemispheres. METHODS: We have analyzed and measured EDA and also cognitive and affective epileptic-like symptoms (CPSI, complex partial seizure-like symptoms), symptoms of chronic stress (Trauma Symptoms Checklist-40, TSC-40), and psychotic symptoms in 31 schizophrenia patients and compared these data with 31 healthy controls. RESULTS: The results indicate that in schizophrenia patients, the values of pointwise transinformation (PTI) calculated from right and left EDA time series are related to CPSI symptoms (Spearman correlation between CPSI and PTI is R = 0.48; p < 0.01) and symptoms of chronic stress (Spearman correlation between TSC-40 and PTI is R = 0.37, p < 0.05); both during mild stress conditions caused by conflicting (incongruent) Stroop task. CONCLUSION: The analysis indicates potentially diagnostically useful results suggesting that heightened PTI values may reflect autonomic activations that hypothetically might be linked to higher interhemispheric transmission related to spreading of epileptiform discharges between hemispheres.

• Publication type
• Journal Article MeSH

5-MeO-DMT is a short-acting psychedelic that is anecdotally reported to induce a radical disruption of the self and a paradoxical quality of aroused, waking awareness that is nevertheless devoid of any specific perceptual contents. Here, we conducted an exploratory observational study of the phenomenological and neuronal effects of this compound. We collected micro-phenomenological interviews, psychometric questionnaires, and electroencephalography (EEG) in naturalistic ceremonial settings where 5-MeO-DMT was ingested. Results revealed that the 5-MeO-DMT experience followed a dynamic progression that-only in the most extreme cases-manifested as a complete absence of self-experience and other phenomenal content with preserved awareness. Furthermore, visual imagery, bodily self-disruption, narrative self-disruption, and reduced phenomenal distinctions occurred in a variable fashion. EEG analyses revealed the 5-MeO-DMT experience was characterised by (global) alpha and (posterior) beta power reductions, implying a mode of brain functioning where top-down models are inhibited. Our preliminary phenomenological findings confirm the potential utility of 5-MeO-DMT as a pharmacological model for deconstructed consciousness while noting the limitations of employing retrospective questionnaires for this purpose. Considering the exploratory nature of this study and its limitations inherent to its naturalistic nature, further research employing real-time experience sampling and phenomenologically trained participants in controlled environments could expand our findings to meaningfully inform the potential of this tool for the scientific study of consciousness.

• Publication type
• Journal Article MeSH

In recent decades, neuroscience has advanced with increasingly sophisticated strategies for recording and analysing brain activity, enabling detailed investigations into the roles of functional units, such as individual neurons, brain regions and their interactions. Recently, new strategies for the investigation of cognitive functions regard the study of higher order interactions-that is, the interactions involving more than two brain regions or neurons. Although methods focusing on individual units and their interactions at various levels offer valuable and often complementary insights, each approach comes with its own set of limitations. In this context, a conceptual map to categorize and locate diverse strategies could be crucial to orient researchers and guide future research directions. To this end, we define the spectrum of orders of interaction, namely, a framework that categorizes the interactions among neurons or brain regions based on the number of elements involved in these interactions. We use a simulation of a toy model and a few case studies to demonstrate the utility and the challenges of the exploration of the spectrum. We conclude by proposing future research directions aimed at enhancing our understanding of brain function and cognition through a more nuanced methodological framework.

• MeSH
• Cognition physiology   MeSH
• Humans MeSH
• Models, Neurological MeSH
• Brain * physiology   MeSH
• Neurons physiology   MeSH
• Neurosciences * methods   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Good brain health plays a significant role in an individual's well-being and profoundly impacts the collective economy and society. Brain development does not stop at birth, and some aspects continue throughout childhood and adolescence, allowing the full development of cognitive functions. Different determinants related to physical health, healthy environments, safety and security, life-long learning and social connection as well as access to quality services influence the way our brains develop, adapt and respond to stress and adversity. Ongoing progress in neurobiology and cognitive neuroscience allows the design of better prevention and intervention strategies to help avoid brain deficits and/or limit their impact and maintain brain health. The European Brain Council (EBC) convened an expert meeting during the Federation of European Neuroscience Societies (FENS) Forum 2024 to address youth brain health challenges. In recent years, the importance of brain health has garnered significant attention across scientific, medical and policy-making communities. Although much focus has traditionally been on neurodegenerative conditions affecting the elderly, a paradigm shift towards prioritizing brain health in youth is both timely and necessary. This shift can profoundly impact individual lives and society, necessitating an interdisciplinary approach that brings neuroscience to the forefront of public health and informs evidence-based policy. The topic is of utmost importance as EBC launched this year a new campaign on No Health Without Brain Health rallying support with its member organizations and the wider brain community for the increased prioritization of brain health on EU health and research agendas.

• MeSH
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Brain * physiology   MeSH
• Neurosciences * MeSH
• Societies, Scientific MeSH
• Check Tag
• Child MeSH
• Humans MeSH
• Adolescent MeSH
• Publication type
• Editorial MeSH
• Geographicals
• Europe MeSH