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The purpose of the work is to analyze the technical, methodical and psychological aspects of digitalization in education and, in particular, the methods of ensuring the effectiveness of independent work of students in the conditions of e-learning. The main attention is paid to the problem of the influence of interactive educational technologies on the formation of external and internal motivation of students of economic specialties to study mathematical disciplines. Methodology. In the conditions of e-learning continuous monitoring of the success of students in mastering mathematical methods and their application to solve economic problems was carried out. The success of each student in performing each type of work separately, as well as his overall rating among other students in the group, were determined. These results were supplemented by the results of the students' questionnaire regarding their own attitude towards interactive technologies as a tool aimed at forming motivation for learning. Results. The virtual environment for e-learning was built using Moodle LMS and contained learning digital resources of various levels of interactivity, including electronic multimedia publications. This helped to fully meet the needs of the distance educational process. To form the student's external motivation, the authors used an electronic journal in which the types of current tasks, points for their completion, the student's rating for each type of tasks, as well as for all types of tasks in general, are defined. To support internal motivation, interactive learning elements were developed and implemented. The effectiveness of the use of digital resources was confirmed during the monitoring of students' success and by the results of the survey of the participants of the experiment. Conclusions. A significant advantage of the use of interactive components in the educational process should be considered the creation of conditions for a better understanding of theoretical material and using mathematical apparatus for solving real economic problems. The use of multi-level digital resources gives the student the opportunity to build an individual educational environment that increases internal motivation to study.

Contains fulltext : 291574.pdf (Publisher’s version ) (Open Access) Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.

The theory of systemic and dynamic localization of higher mental functions by Lev Vygotsky and Alexander Luria was based on the data obtained via an original method, syndrome analysis of deficits of higher mental functions in patients with local brain injury. When this theory was being constructed, technical methods for brain investigation were only in their early stages. Although in later years Luria and his disciples pointed out that such methods were prominent for further development of Soviet/Russian neuropsychology, they are still rarely used by the followers of these scientists. In this article, we focus on neuroimaging and neurostimulation methods that are both noninvasive and the most accessible in Russia: structural, diffusion-weighted, and functional magnetic resonance imaging, as well as transcranial magnetic stimulation. We discuss their scope and perspectives for addressing research questions in neuropsychology and describe possible designs for neu­ropsychological studies in patients with local brain injury and healthy individuals.

Статья посвящена изменениям, происходящим в банковском секторе в условиях цифровой трансформации в России. Выявлены основные факторы, обуславливающие цифровизацию банковских услуг. Проведена оценка ее влияния на структуру банковского рынка, на деятельность его участников и на качество банковских услуг. Проанализирована трансформация потребностей клиентов банков.

Special Issue: The ENIGMA Consortium: the first 10 years., Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes., European Community's Seventh Framework Programme, Grant/Award Numbers: 278948, 602450, 603016, 602805; US National Institute of Child Health and Human Development, Grant/Award Numbers: RO1HD050735, 1009064, 496682; QIMR Berghofer Medical Research Institute and the Centre for Advanced Imaging, University of Queensland; ICTSI NIH/NCRR, Grant/Award Number: RR025761; European Community's Horizon 2020 Programme, Grant/Award Numbers: 667302, 643051; Vici Innovation Program, Grant/Award Numbers: #91619115, 016-130-669; NWO Brain & Cognition Excellence Program, Grant/Award Number: 433-09-229; Biobanking and Biomolecular Resources Research Infrastructure (Netherlands) (BBMRI-NL); Spinozapremie, Grant/Award Number: NWO-56-464-14192; Biobanking and Biomolecular Resources Research Infrastructure, Grant/Award Numbers: 184.033.111, 184.021.007; Netherlands Organization for Health Research and Development (ZonMW), Grant/Award Numbers: 480-15-001/674, 024.001.003, 911-09-032, 056-32-010, 481-08-011, 016-115-035, 31160008, 400-07-080, 400-05-717, 451-04-034, 463-06-001, 480-04-004, 904-61-193, 912-10-020, 985-10-002, 904-61-090; NIMH, Grant/Award Number: R01 MH090553; Geestkracht programme of the Dutch Health Research Council, Grant/Award Number: 10-000-1001; FP7 Ideas: European Research Council; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Grant/Award Numbers: NWO/SPI 56-464-14192, NWO-MagW 480-04-004, 433-09-220, NWO 51.02.062, NWO 51.02.061; National Center for Advancing Translational Sciences, National Institutes of Health, Grant/Award Number: UL1 TR000153; National Center for Research Resources; National Center for Research Resources at the National Institutes of Health, Grant/Award Numbers: NIH 1U24 RR025736-01, NIH 1U24 RR021992; NIH Institutes contributing to the Big Data to Knowledge; U.S. National Institutes of Health, Grant/Award Numbers: R01 CA101318, P30 AG10133, R01 AG19771; Medical Research Council, Grant/Award Numbers: U54EB020403, G0500092; National Institute of Mental Health, Grant/Award Numbers: R01MH117014, R01MH042191; Fundación Instituto de Investigación Marqués de Valdecilla, Grant/Award Numbers: API07/011, NCT02534363, NCT0235832; Instituto de Salud Carlos III, Grant/Award Numbers: PI14/00918, PI14/00639, PI060507, PI050427, PI020499; Swedish Research Council, Grant/Award Numbers: 523-2014-3467, 2017-00949, 521-2014-3487; South-Eastern Norway Health Authority; the Research Council of Norway, Grant/Award Number: 223273; South Eastern Norway Regional Health Authority, Grant/Award Numbers: 2017-112, 2019107; Icahn School of Medicine at Mount Sinai; Seventh Framework Programme (FP7/2007-2013), Grant/Award Number: 602450; National Institutes of Health, Grant/Award Numbers: R01 MH116147, R01 MH113619, R01 MH104284; South London and Maudsley NHS Foundation Trust; the National Institute for Health Research (NIHR)

Contains fulltext : 248376.pdf (Publisher’s version ) (Open Access) For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

Recent studies at the interface between psychiatry and neuroscience demonstrate a trend towards the investigation of single significant clinical characteristics of mental disorders in contrast to the analysis of a mental disorder as a homogeneous nosological unit. Thus, a large body of studies is focused on auditory verbal hallucinations (AVH) in schizophrenia, which are one of the core positive symptoms of the disorder and an important diagnostic criterion. Nevertheless, the neuropsychological and neurophysiological mechanisms of AVH in patients with schizophrenia remain debatable. In this paper, we will review the main neurocognitive models of AVH in schizophrenia, including models of intrusive cognitions and poor inhibitory control, a model of attentional shift to inner auditory stimuli and an inability to reallocate its resources, a model of expectation maximization, a model of working memory deficit, a model of poor source-monitoring, models of AVH within cultural-historical approach, and a model of impaired verbal self-monitoring in inner speech. The results of several neuroimaging and neurophysiological studies relevant to the models are also highlighted. We conclude that schizophrenia patients with AVH demonstrate deficits in executive functions and language, or rather a poor cross-functional interaction between them.

ObjectiveSchizophrenia is associated with widespread brain-morphological alterations, believed to be shaped by the underlying connectome architecture. This study tests whether large-scale structural reorganization in schizophrenia relates to normative network architecture, in particular regional centrality/hubness and connectivity patterns. We examine network effects in schizophrenia across different disease stages, and transdiagnostically explore consistency of such relationships in patients with bipolar and major depressive disorder.MethodsWe studied anatomical MRI scans from 2,439 adults with schizophrenia and 2,867 healthy controls from 26 ENIGMA sites. Case-control patterns of structural alterations were evaluated against two network susceptibility models: 1) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; 2) epicenter models, which identify regions whose typical connectivity profile most closely resembles the disease-related morphological alteration patterns. Both susceptibility models were tested across schizophrenia disease stages and compared to meta-analytic bipolar and major depressive disorder case-control maps.ResultsIn schizophrenia, regional gray matter reductions co-localized with interconnected hubs, in both the functional (r=0.58, pspinspin=0.01). Epicenters were identified in temporo-paralimbic regions, extending to frontal areas. We found unique epicenters for first-episode and early stages, and a shift from occipital to temporal-frontal epicenters in chronic stages. Transdiagnostic comparisons revealed shared epicenters in schizophrenia and bipolar, but not major depressive disorders.ConclusionsCortical reorganization over the course of schizophrenia closely reflects brain network architecture, emphasizing marked hub susceptibility and temporo-frontal epicenters. The observed overlapping epicenters for schizophrenia and bipolar disorder furthermore suggest shared pathophysiological processes within the schizophrenia-bipolar-spectrum.

The subject of research in the article is the degeneration of the first form with a monoharmonic change in the form factor and provided that the pulsation frequency of the "forms" of oscillations reaches the second partial frequency. The goal is to assess the possibility of degeneration of the i-th form of oscillations under various laws of change in the exciting effect and to analyze this phenomenon. The objectives of the study are to build principles for assessing the impact of high-frequency pulsations of system parameters on the free oscillations of the latter. Applied methods: description of dynamic models by differential equations; frequency analysis; formation of amplitude-frequency characteristics. The obtained results: for a dynamic model with certain indicators of the leading and driven links, it was determined that with a harmonious change in the motion function with a pulsation frequency that exceeds one, when the ratio of the damping coefficients is greater than one, the effect of degeneration of the first mode of vibration is observed, as a result of which the oscillation frequency of the driven link practically corresponds to the second form. The practical significance of the work lies in the construction of a model for the formation of frequency characteristics of a dynamic model with a high-frequency pulsation of the parameters of the latter. To identify these effects, one has to abandon the traditional ideas about the smallness of inertial components caused by the nonstationarity of vibration modes.

Although facial beauty prediction (FBP) has achieved high accuracy on images captured in a constrained environment, it is still a challenging task on face images in-the-wild. Moreover, there is no FBP benchmark dataset that includes images with various ethnic, age, gender properties and unrestricted in terms of face expression and pose. In this work, the issue of FBP in real-life scenario is addressed and a multi-ethnic facial beauty dataset, namely MEBeauty, is introduced. All face images are captured in an unconstrained environment and rated by volunteers with various ethnicity, age and gender in order to avoid any cultural and social biases in beauty perception. Different well-known CNNs with layer-wise transfer learning are performed on the dataset. Moreover, the evaluation of knowledge learning from the face recognition task across FBP is conducted. The expected high number of aberrant and outlier faces is considered and the use of various robust loss functions in order to learn deep regression networks for facial beauty prediction is evaluated. Several FBP frameworks are performed on the proposed dataset and widely-used SCUT-FBP 5500 in order to compare their effectiveness on face images in constrained and unconstrained environments.

Examines the opportunities that are provided through the using of interactive technologies in the teaching of disciplines of the mathematical cycle. These disciplines are basic in the training of future economists and managers. Examples of the positive impact of using the “flipped” classroom technology on the perception of new material in the context of online learning are given. And also praxis of using elements of gamification for the formation of students’ competencies related to the use of the mathematical apparatus in their future professional activities are demonstrated.

The analysis of heterogeneity in cognition and brain functioning in patients with schizophrenia seems promising for a deeper understanding of the disorder as well as treatment individualization. As language production and its executive control are disturbed in schizophrenia but may be heterogeneous in severity across patients and related to outcome, we aimed to compare the neuropsychological and neuroimaging measures related to these processes in patients with long-term schizophrenia spectrum disorders (mean illness duration of 20.3 ± 6.0 years) characterized by diverse clinical and functional statuses. Forty-four male patients and 18 age-comparable healthy males participated in the study. The participants performed four verbal fluency tasks (VF) and underwent resting-state fMRI. K-means clustering based on PANSS subscales and the PSP total score allocated patients to subgroups with better (S1; n = 15) and worse (S2; n = 29) outcomes. Between-group differences in VF performance and the whole-brain functional connectivity (FC) of the two seeds (the inferior frontal gyrus and the supplementary motor cortex) in the left hemisphere were analyzed. S1 demonstrated better performance in the letter and non-structured VF conditions compared to S2, and S1 did not differ from the healthy controls. Furthermore, S1 had higher FC between the left inferior frontal gyrus and a region in the left postcentral/precentral gyri and superior parietal lobule compared to S2 and the healthy controls. The latter finding merits attention in the context of resilience mechanisms in schizophrenia patients with more benign outcome

We analyzed morphometric MRI parameters indirectly attesting to structural changes in the supragranular layer in 33 non-converted individuals at clinical high risk for endogenous psychosis (follow-up period of 6.7±0.6 years) and in 34 sex- and age-matched healthy controls. In the group of clinical high-risk individuals, changes indicative of potential predominance of supragranular thinning in comparison with a decrease of infragranular cortical layer thickness were revealed. The results are discussed in the context of the concepts of resilience and risk markers of developing endogenous psychosis.

Narrative discourse is investigated in clinical and healthy populations. This study explored the discourse strategies used to tell stories, comparing the patterns of people with left- and right-hemisphere brain damage, as well as healthy speakers. We analyzed picture-elicited discourses by four people with aphasia, two people with right hemisphere damage, and four healthy speakers. We examined their microlinguistic properties, as well as macrolinguistic features, such as the discourse production type of utterances and patterns of story component usage. We identified two storytelling strategies used by the speakers: a narrative strategy marked by a prevalence of narrative discourse production type utterances and scarce use of evaluation clauses, and a quasi-narrative strategy with the opposite pattern. These strategies were used by both healthy speakers and participants with brain damage.

Human monoclonal antibodies from convalescent individuals that target the SARS-CoV-2 spike protein have been deployed as therapeutics against SARS-CoV-2. However, nearly all of these antibodies have been rendered obsolete by SARS-CoV-2 variants that evolved to resist similar, naturally occurring antibodies. Here, we describe the development of human monoclonal antibodies that bind the ACE2 receptor rather than the viral spike protein. These antibodies block infection by all ACE2 binding sarbecoviruses, including emergent SARS-CoV-2 variants. Structural and biochemical analyses revealed that the antibodies target an ACE2 epitope that engages SARS-CoV-2 spike. Importantly, the antibodies do not inhibit ACE2 enzymatic activity, nor do they induce ACE depletion from cell surfaces. The antibodies exhibit favorable pharmacology and protect human ACE2 knock-in mice against SARS-CoV-2 infection. Such antibodies should be useful prophylactic and treatment agents against any current and future SARS-CoV-2 variants, as well as ACE2-binding sarbecoviruses that might emerge as future pandemic threats.

[Background]: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre/perinatal periods may be reflected in individual variations in cortical surface area later in life., [Methods]: Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 individuals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed., [Results]: Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre/perinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth., [Conclusions]: Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy., This work was supported by the German Research Foundation (DFG Grant Nos. HA7070/2-2, HA7070/3, HA7070/4 [to TH]) and IZKF of the medical faculty of Münster (Grants No. Dan3/012/17 [to UD] and MzH 3/020/20 [to TH]), and NHMRC projects (Grant No. 1064643 [to BJH] and 1024570 [to CGD]). The CIAM study was supported by the University of Cape Town Research Committee, South African National Research Foundation, and the South African Medical Research Council (principal investigator [PI], Fleur M. Howells) and Grant No. R01MH117601 (to NJ). This work was funded by the German Research Foundation (Grant Nos. FOR2107 JA 1890/7-1 and FOR2107 JA 1890/7-2 [to AJ]) and Swinburne University scholarship/Australian Postgraduate Award (to JK). Collection of the COGSBD cohort was funded by the Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L Cooper Foundation, and the Society of Mental Health Research (to JK). This work was funded by the German Research Foundation (Grant Nos. FOR2107 KI588/14-1 and FOR2107 KI588/14-2 [to TK]). The St. Göran study was supported by grants from the Swedish Research Council (Grant No. 2018-02653 [to ML]), the Swedish foundation for Strategic Research (Grant No. KF10-0039 [to ML]), the Swedish Brain foundation (Grant No. FO2020-0261 [to ML]), and the Swedish Government under the LUA/ALF agreement (Grant Nos. ALF 20170019 and ALFGBG-716801 [to ML]). This work was supported by RFBR (Grant No. 20-013-00748 [to IL, AST]) and funded by the Health Research Board (Grant No. HRA_POR/2011/100 [to CM]). The Australian Schizophrenia Research Bank (ASRB) was supported by the NHMRC (Enabling Grant No. 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation, and the Schizophrenia Research Institute. Chief investigators for ASRB were VC, US, RSc, AJ, BM, PTM, SVC, FH, and CPa. This work was supported by Deutsche Forschungsgemeinschaft (Grant Nos. DFG NE 2254/2-1, NE 2254/3-1, NE2254/4-1 [to IN]), the University Research Priority Program “Integrative Human Physiology” at the University of Zurich (to ROT), an NHMRC Senior Principal Research Fellowship (Grant No. 1105825 [to CPa]), an NHMRC L3 Investigator Grant (Grant No. 1196508 [to CPa]), and NHMRC Program Grant (Grant No. 1150083 [to CPa]). ASRB was supported by the NHMRC (Enabling Grant No. 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation and the Schizophrenia Research Institute. Chief investigators for ASRB were VC, US, RSc, AJ, BM, PTM, SVC, FH, and CPa. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant (Agreement No. 798181 [to GP]). ASRB was supported by the NHMRC (Enabling Grant, ID 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation and the Schizophrenia Research Institute. Chief investigators for ASRB were VC, US, RSc, AJ, BM, PTM, SVC, FH, and CPa. The Imaging Genetics in Psychosis study was funded by Project Grants from the NHMRC (Grant Nos. APP630471 and APP1081603 [to YQ]) and the Macquarie University’s Australian Research Council (ARC) Centre of Excellence in Cognition and its Disorders (Grant No. CE110001021 [to YQ]). This work was supported by the Spanish Ministry of Science, Innovation and Universities/Economy and Competitiveness/Instituto de Salud Carlos III (Grant Nos. PI11/01766 and CPII19/00009 [to JR]), co-financed by European Regional Development Fund funds from the European Commission (“A Way of Making Europe”). ASRB was supported by the NHMRC (Enabling Grant No. 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation, and the Schizophrenia Research Institute. Chief investigators for ASRB were VC, US, RSc, AJ, BM, PTM, SVC, FH, and CPa. SR was supported by an NHMRC Senior Fellowship (Grant No. GNT1154651). Collection of the COGSBD cohort was funded by the Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L Cooper Foundation, and the Society of Mental Health Research (to SR). This work was supported by NIHR; MRC (to KR), NIH (Grant Nos. MH-094268, MH-105660, and MH-107730 [to ASS]). The Neuroimaging of the Children's Attention Project cohort was funded by NHMRC, Australia (Grant No. 1065895). Earlier funding for the cohort as also provided by NHMRC (Grant No. 1008522) and a grant from the Collier Foundation. The ACPU cohort was funded by NHMRC, Australia (Project Grant Nos. 384419 and 569533 [to TS]). This work was supported by research grants from the National Healthcare Group, Singapore (Grant Nos. SIG/05004, SIG/05028, and SIG /1103), and the Singapore Bioimaging Consortium (RP C009/2006 [to KS]), and the Ministry of Health, Czech Republic - conceptual development of research organization (“Institute for Clinical and Experimental Medicine - IKEM, IN 00023001” [to ASk]). This study was supported by the Italian Ministry of Health (Grant No. RC/17-18-19-20-21/A [to GS]) and Ministry of Health of the Czech Republic (Grant No. NU20-04-00393 [to FS]). The Drakenstein Child Health Study (DCHS) cohort is funded by the Bill and Melinda Gates Foundation (Grant No. OPP 1017641) and the South African Medical Research Council. This DCHS contribution was made possible in part by a grant from Carnegie Corporation of New York. The statements made and views expressed are solely the responsibility of the author (DJS). STRADL study was supported and funded by the Wellcome Trust Strategic Award “Stratifying Resilience and Depression Longitudinally” (Grant No. 104036/Z/14/Z), and the Medical Research Council Mental Health Pathfinder Award “Leveraging routinely collected and linked research data to study the causes and consequences of common mental disorders” (MRC, Grant No. MC_PC_17209). Scottish Bipolar Family Study (SBFS) was supported by National Health Service Research Scotland, through the Scottish Mental Health Research Network (www.smhrn.org.uk), who provided assistance with subject recruitment and assessments. SBFS was conducted at the Brain Research Imaging Centre (http://www.bric.ed.ac.uk), which is supported by SINAPSE (Scottish Imaging Network, a Platform for Scientific Excellence, http://www.sinapse.ac.uk). Processing of the datasets used the resources provided by the Edinburgh Compute and Data Facility (http://www.ecdf.ed.ac.uk/) (ASt). TVR was supported by an NHMRC Early Career Fellowship (Grant No. GNT1088785). Collection of the COGSBD cohort was funded by the Jack Brockhoff Foundation, University of Melbourne, Barbara Dicker Brain Sciences Foundation, Rebecca L Cooper Foundation, and the Society of Mental Health Research (to TVR). EV was supported by the Spanish Ministry of Science and Innovation (PI18/00805) integrated into the Plan Nacional de I+D+I and co-financed by the ISCIII-Subdirección General de Evaluación and the FEDER; the Instituto de Salud Carlos III; the CIBERSAM (Centro de Investigación Biomédica en Red de Salud Mental); by the CERCA Programme/Generalitat de Catalunya and the Secretaria d’Universitats i Recerca del Departament d’Economia I Coneixement (Grant No. 2017SGR1355). This study was also supported by the Departament de Salut de la Generalitat de Catalunya, Pla Estratègic de Recerca i Innovació en Salut (PERIS) 2016-2020 (Grant No. SLT006/17/00345) and the European Union Horizon 2020 research and innovation program (EU.3.1.1. Understanding health, wellbeing and disease: Grant Nos. 754907 and EU.3.1.3 [to EB]; Treating and managing disease: Grant No. 945151 [to EV]). This study was supported by the National Center for Complementary and Integrative Health (Grant Nos. R21AT009173 and R61AT009864 [to TTY]); by the National Center for Advancing Translational Sciences (CTSI), National Institutes of Health, through UCSF-CTSI (Grant No. UL1TR001872 [to TTY]); by the American Foundation for Suicide Prevention (Grant No. SRG-1-141-18 [to TTY]); by UCSF Research Evaluation and Allocation Committee (REAC) and J. Jacobson Fund (to TTY); by the NIMH (Grant No. R01MH085734 [to TTY]); and by the Brain and Behavior Research Foundation (formerly NARSAD) (to TTY). This work was supported by a personal Veni grant to MH from the Netherlands Organization for Scientific Research (NWO, Grant No. 91619115 [to MH]) and European Community’s Horizon 2020 Programme (H2020/2014 – 2020) (Grant Agreements Nos. 667302 [CoCA], 728018 [Eat2beNICE], and 847879 [PRIME] [to BF]). JBu has been supported by the EU-AIMS (European Autism Interventions) and AIMS-2-TRIALS programmes, which receive support from Innovative Medicines Initiative Joint Undertaking Grant Nos. 115300 and 777394, the resources of which are composed of financial contributions from the European Union’s FP7 and Horizon 2020 Programmes, and from the European Federation of Pharmaceutical Industries and Associations companies’ in-kind contributions, and AUTISM SPEAKS, Autistica and SFARI; and by the Horizon 2020–supported programme CANDY (Grant No. 847818 [to JBu]). This work is supported by Grant No. NIA T32AG058507 and NIH Grant No. U54EB020403 from the Big Data to Knowledge (BD2K) Program (to CRKC). ENIGMA MDD work is supported by NIH (Grant Nos. U54 EB020403 [to PT], R01 MH116147 [to PT], and R01 MH117601 [to NJ and LS]). LS was supported by an NHMRC Career Development Fellowship (Grant No. 1140764). This work was supported by the National Center for Research Resources at the NIH (Grant Nos. NIH 1 U24 RR021992 [Function Biomedical Informatics Research Network], NIH 1 U24 RR025736-01 [Biomedical Informatics Research Network Coordinating Center; http://www.birncommunity.org]). TGMvE is supported by ENIGMA’s NIH BD2K initiative (Grant No. U54 EB020403), ENIGMA Sex Differences (Grant No. R01MH116147), and ENIGMA-COINSTAC: Advanced Worldwide Transdiagnostic Analysis of Valence System Brain Circuits (Grant No. R01MH121246). This work was supported by the NIH (Grant No. R01MH121246 [to JT, Calhoun, and TGMvE]). This work was supported in part by NIH (Grant No. U54 EB020403 [to PT]).

The purpose of the article is to analyze the impact of concept mapping on the level and quality of assimilation of learning material in higher mathematics in the process of independent study. Methodology. Based on a review of the main provisions of modern theory of learning and generalization of research results presented in scientific papers on the scope of application of concept maps in the learning process, such a training experiment was conducted. For students of the two experimental groups on a certain topic of the discipline “Higher Mathematics” were offered to build conceptual maps in addition to the common teaching methods. It considered as an independent creative task. In the other two groups, which were under control, students had to study the same topic of the discipline, using traditional methods. Results. It was determined that the results of the colloquium composed of students of experimental groups were significantly higher than those of students of control groups who did not use mapping as a method of learning during independent work. The average score obtained by students of experimental groups for the colloquium was almost 80 points, while for students of control groups it was only 72 points. Using Student’s test, the significance of the difference between the values of the sample averages of these indicators proved. If we compare the average scores for different types of tasks, the most significant was the difference in the performance of heuristic tasks, which reflect the ability to apply the acquired knowledge to solve practical problems of economic content. Conclusions. The positive influence of the use of concept mapping in independent work of students established, which proves the thesis about the feasibility of using concept mapping as a learning tool. Further introduction of concept maps in the educational process should be based on the development of complex theoretical and practical, as well as competency-oriented tasks.

Objective. To determine the neurophysiological features of schizophrenia at late (more than 20 years) follow- up and identify correlations between neurophysiological indicators and the clinical characteristics of the disease. Materials and methods. Patients of three groups were studied: those with a predominance of personality changes (group 1, 17 patients), those with negative disorders (group 2, 23 patients), and those with marked positive and negative disorders (group 3, 40 patients). The main study methods were psychopathological and neurophysiological, with assessment of event-linked potentials. Results and conclusions. A statistically significantly greater θ-rhythm frequency and a significantly lower α-rhythm frequency were found in group 3, the dominant frequency of the θ rhythm showing a correlation (positive) with the total score for positive disorders on the PANSS. No statistically significant between-group differences were seen in measures of the P300 wave of auditory event-related potential recorded in the oddball paradigm. These results are considered in the framework of views of the role of θ activity as a marker for hippocampal-prefrontal interactions.

Current knowledge on morphological and functional abnormalities of the thalamocortical system (TCS) in schizophrenia is incomplete and inconsistent. To study the TСS, 23 young male patients with schizophrenia and 30 healthy males were examined using structural MRI, diffusion-weighted MRI, and EEG. Structural abnormalities in the anterior and posterior thalamic radiations, multiple fronto-parietal cortical regions, and the thalamus and a decrease in α power in a subband of 11–12.5 Hz were observed in the patients with schizophrenia compared with the healthy controls. A reduced thickness of the gray matter in the medial prefrontal cortex inversely correlated with structural abnormalities of the thalamus and anterior thalamic radiation in right hemisphere. The results provide further evidence that widespread structural abnormalities of the TCS occur in early stages of schizophrenia.

Objectives. To seek neurophysiological predictors of the effi cacy of rhythmic transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex in patients with depressive disorders of different nosological categories. Materials and methods. A total of 34 juvenile patients (all male) with protracted treatment-refractory depressive states were studied. Investigation of patients used psychopathological and psychometric methods (Hamilton scale) and electroencephalography. The search for predictors of therapeutic efficacy was carried out using a wide range of neurophysiological indicators and different protocols for high-frequency rTMS (10 and 20 Hz). Results and conclusions. The most significant changes were identified on rTMS at 20 Hz. Favorable treatment effects on the EEG were found to correlate with higher spectral power in the α and β1 subranges.

The present study analyzed diffusion characteristics of white matter tracts and grey matter anatomy in 48 mentally healthy participants, including first-degree relatives of patients with schizophrenia (N=13) and affective spectrum disorders (N=13). The subgroup with familial risk of schizophrenia displayed abnormalities in the structural connectivity and increased cortical thickness in the superior frontal gyrus. No differences in the analyzed characteristics were revealed in the subgroup with familial risk for affective disorders. The results are discussed within the framework of the concepts of endophenotypes and processes reflecting compensatory and protective mechanisms.

Objectives. To identify the neuroanatomical characteristics of the gray matter in individual areas of the prefrontal cortex (PFC) and a number of subcortical formations in patients with juvenile shiftlike schizophrenia (ICD-10, F20) Materials and methods. A total of 43 patients and 54 mentally healthy men, mean age 22 years, were studied. The main methods were psychopathological investigations and MRI brain scans producing high-resolution T1-weighted images. Results. As compared with the control group, the group of patients with schizophrenia showed a decrease in the thickness of the gray matter in all segments of the prefrontal cortex studied, though no between-group differences in the volume of the subcortical formations were seen. No statistically significant correlations between structural changes and measures of the severity of psychopathological disorders were found. Conclusions. The data obtained from these studies show that structural anomalies in the frontal areas of the brain in juvenile shiftlike schizophrenia are not linked with the severity of psychopathological symptoms.

BackgroundPositive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.MethodTo study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.ResultsThe result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.ConclusionThese findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.

Schizophrenia (SZ) is associated with an increased risk of life-long cognitive impairments, age-related chronic disease, and premature mortality. We investigated evidence for advanced brain ageing in adult SZ patients, and whether this was associated with clinical characteristics in a prospective meta-analytic study conducted by the ENIGMA Schizophrenia Working Group. The study included data from 26 cohorts worldwide, with a total of 2803 SZ patients (mean age 34.2 years; range 18-72 years; 67% male) and 2598 healthy controls (mean age 33.8 years, range 18-73 years, 55% male). Brain-predicted age was individually estimated using a model trained on independent data based on 68 measures of cortical thickness and surface area, 7 subcortical volumes, lateral ventricular volumes and total intracranial volume, all derived from T1-weighted brain magnetic resonance imaging (MRI) scans. Deviations from a healthy brain ageing trajectory were assessed by the difference between brain-predicted age and chronological age (brain-predicted age difference [brain-PAD]). On average, SZ patients showed a higher brain-PAD of +3.64 years (95% CI: 3.01, 4.26; I2 = 55.28%) compared to controls, after adjusting for age and sex (Cohen’s d = 0.50). Among SZ patients, brain-PAD was not associated with specific clinical characteristics (age of onset, duration of illness, symptom severity, or antipsychotic use and dose). This large-scale collaborative study suggests advanced structural brain ageing in SZ. Longitudinal studies of SZ and a range of mental and somatic health outcomes will help to further evaluate the clinical implications of increased brain-PAD and its ability to be influenced by interventions.

Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3004 unmedicated healthy individuals (12–68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r = 0.067, pFDR = 0.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r = 0.285, pspin = 0.024), but not BD (r = 0.166, pspin = 0.205) or MDD (r = −0.274, pspin = 0.073). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho = −0.690, pspin = 0.006), BD (rho = −0.672, pspin = 0.009), and MDD (rho = −0.692, pspin = 0.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype.

This paper provides the results that were achieved and shares the drilling unique practices that were implemented to deliver the first complex bilateral extended reach drilling (ERD) well in Odoptu-more field (North Dome). Well design driven by geological objectives considered drilling 215.9mm main and pilot holes (PH). Well complexity was governed by the type of a profile having ERD ratio of 5.22 (main hole) / 4.60 (PH) and trajectory's 3D nature (turn in azimuth of 90 degrees) compared to previous wells in the project drilled mainly with 2D profiles. Apart from the problems connected with drilling and casing upper sections key challenges comprised kicking off in 215.9mm open hole at 5955m MD and 1512m TVD with rotary steerable system, setting cement plugs at shallow true vertical depth (TVD) at 89 degrees of inclination to abandon laterally drilled PH, delivering 168.3mm production liner to bottom with a risk of entering a lateral while running in hole. An effective collaboration between integrated engineering team and customer departments went far beyond ERD standard set of operations already existing in the project thus allowing to break its own records and to set new achievements due to integrated technological approach. The longest 444.5mm section (2975 m) was drilled in one run achieving the record daily drilling rate and rate of penetration (ROP). Cementing of 244.5mm floated liner resulted in the highest good cement bond integrity percentage ever achieved among other wells in project due to new ways of casing standoff and fluid rheology hierarchy modeling. For the first time in the project 215.9mm main horizontal hole in extreme reach ERD well has been drilled by kicking off in open hole from the pilot horizontal one with push-the-bit rotary steerable system without a kickoff plug with pilot hole being abandoned by setting cement plugs. Project-specific risk assessment conducted by team allowed successful deployment of 168.3mm liner into the main hole. Moreover, due to thorough engineering planning electrical submersible pump (ESP) was run without extending 244.5mm liner to surface by tie-back thus saving additional 7 days. Drilling first bilateral ERD well unlocked opportunities for the operator to reach, explore and develop different extended geological targets thus eliminating well construction process of additional wells on drilling upper sections.

IMPORTANCE The ENIGMA clinical high risk (CHR) for psychosis initiative, the largest pooled neuroimaging sample of individuals at CHR to date, aims to discover robust neurobiological markers of psychosis risk.OBJECTIVE To investigate baseline structural neuroimaging differences between individuals at CHR and healthy controls as well as between participants at CHR who later developed a psychotic disorder (CHR-PS+) and those who did not (CHR-PS-).DESIGN, SETTING, AND PARTICIPANTS In this case-control study, baseline T1-weighted magnetic resonance imaging (MRI) data were pooled from 31 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group. CHR status was assessed using the Comprehensive Assessment of At-Risk Mental States or Structured Interview for Prodromal Syndromes. MRI scans were processed using harmonized protocols and analyzed within a mega-analysis and meta-analysis framework from January to October 2020.MAIN OUTCOMES AND MEASURES Measures of regional cortical thickness (CT), surface area, and subcortical volumes were extracted from T1-weighted MRI scans. Independent variables were group (CHR group vs control group) and conversion status (CHR-PS+ group vs CHR-PS- group vs control group).RESULTS Of the 3169 included participants, 1428 (45.1%) were female, and the mean (SD; range) age was 21.1 (4.9; 9.5-39.9) years. This study included 1792 individuals at CHR and 1377 healthy controls. Using longitudinal clinical information, 253 in the CHR-PS+ group, 1234 in the CHR-PS- group, and 305 at CHR without follow-up data were identified. Compared with healthy controls, individuals at CHR exhibited widespread lower CT measures (mean [range] Cohen d = -0.13 [-0.17 to -0.09]), but not surface area or subcortical volume. Lower CT measures in the fusiform, superior temporal, and paracentral regions were associated with psychosis conversion (mean Cohen d = -0.22; 95% CI, -0.35 to 0.10). Among healthy controls, compared with those in the CHR-PS+ group, age showed a stronger negative association with left fusiform CT measures (F = 9.8; P < .001; q < .001) and left paracentral CT measures (F = 5.9; P = .005; q = .02). Effect sizes representing lower CT associated with psychosis conversion resembled patterns of CT differences observed in ENIGMA studies of schizophrenia (rho = 0.35; 95% CI, 0.12 to 0.55; P = .004) and individuals with 22q11.2 microdeletion syndrome and a psychotic disorder diagnosis (rho = 0.43; 95% CI, 0.20 to 0.61; P = .001).CONCLUSIONS AND RELEVANCE This study provides evidence for widespread subtle, lower CT measures in individuals at CHR. The pattern of CT measure differences in those in the CHR-PS+ group was similar to those reported in other large-scale investigations of psychosis. Additionally, a subset of these regions displayed abnormal age associations. Widespread disruptions in CT coupled with abnormal age associations in those at CHR may point to disruptions in postnatal brain developmental processes.Question How are brain morphometric features associated with later psychosis conversion in individuals at clinical high risk (CHR) for developing psychosis?Findings In this case-control study including 3169 participants, lower cortical thickness, but not cortical surface area or subcortical volume, was more pronounced in individuals at CHR in a manner highly consistent with thinner cortex in individuals with established psychosis. Regions that displayed lower cortical thickness in individuals at CHR who later developed a psychotic disorder additionally displayed abnormal associations with age.Meaning In this study, CHR status and later transition to psychosis was robustly associated with lower cortical thickness; abnormal age associations and specificity to cortical thickness may point to aberrant postnatal brain development in individuals at CHR, including pruning and myelination.This case-control study investigates baseline structural magnetic resonance imaging (MRI) differences between individuals at clinical high risk and healthy controls as well as between participants at clinical high risk who later developed a psychotic disorder and those who did not.

There is increasing evidence of white matter (WM) and grey matter pathology in subjects at ultra-high risk of psychosis (UHR), although a limited number of diffusion-weighted magnetic resonance imaging (DW-MRI) and surface-based morphometry (SBM) studies have revealed anatomically inconsistent results. The present multimodal study applies tractography and SBM to analyze WM microstructure, whole-brain cortical anatomy, and potential interconnections between WM and grey matter abnormalities in UHR subjects. Thirty young male UHR patients and 30 healthy controls underwent DW-MRI and T1-weighted MRI. Fractional anisotropy; mean, radial, and axial diffusivity in 18 WM tracts; and vertex-based cortical thickness, area, and volume were analyzed. We found increased radial diffusivity in the left anterior thalamic radiation and reduced bilateral thickness across the frontal, temporal, and parietal cortices. No correlations between WM and grey matter abnormalities were identified. These results provide further evidence that WM microstructure abnormalities and cortical anatomical changes occur in the UHR state. Disruption of structural connectivity in the prefrontal-subcortical circuitry, likely caused by myelin pathology, and cortical thickness reduction affecting the networks presumably involved in processing and coordination of external and internal information streams may underlie the widespread deficits in neurocognitive and social functioning that are consistently reported in UHR subjects.

Special Issue: The ENIGMA Consortium: the first 10 years.-- Karolinska Schizophrenia Project (KaSP)., Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3–90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns., National Institute of Mental Health, Grant/Award Numbers: MH104284, MH116147, R01MH113619, R01 MH090553, R01MH117014, R01MH042191; Karolinska Institutet; Stockholm County Council; Southern and Eastern Norway Regional Health Authority; German Centre for Cardiovascular Research; DZHK; Siemens Healthineers; University of Queensland; US National Institute of Child Health and Human Development, Grant/Award Number: RO1HD050735; Australian National Health and Medical Research Council; Eunice Kennedy Shriver National Institute of Child Health & Human Development; National Institute on Drug Abuse, Grant/Award Numbers: UL1 TR000153, 1 U24 RR025736-01, 1 U24 RR021992; Brain Injury Fund Research Grant Program; Indiana State Department of Health Spinal Cord; Parents Against Childhood Epilepsy; Epilepsy Therapy Project, Fight Against Childhood Epilepsy and Seizures; Epilepsy Foundation; American Epilepsy Society; Knut and Alice Wallenberg Foundation; European Community's Horizon 2020 Programme; Vici Innovation Program; NWO Brain & Cognition Excellence Program; Netherlands Organization for Scientific Research; Hersenstichting Nederland; Netherlands Organization for Health Research and Development; Geestkracht Programme of the Dutch Health Research Council, Grant/Award Number: 10-000-1001; Universiteit Utrecht; FP7 Ideas: European Research Council; Nederlandse Organisatie voor Wetenschappelijk Onderzoek; National Center for Advancing Translational Sciences; National Institutes of Health; National Center for Research Resources; Consortium grant, Grant/Award Number: U54 EB020403; U.S. National Institutes of Health, Grant/Award Numbers: R01 CA101318, P30 AG10133, R01 AG19771; Medical Research Council, Grant/Award Number: G0500092; Fundación Instituto de Investigación Marqués de Valdecilla, Grant/Award Numbers: API07/011, NCT02534363, NCT0235832; Instituto de Salud Carlos III, Grant/Award Numbers: PI14/00918, PI14/00639, PI060507, PI050427, PI020499; the Research Council, Grant/Award Number: 223273; South Eastern Norway Regional Health Authority, Grant/Award Numbers: 2017-112, 2019107; Swedish Research Council; European Community's Seventh Framework Programme, Grant/Award Number: 602450; King's College London; South London and Maudsley NHS Foundation Trust; Biomedical Research Centre; National Institute for Health Research.