Neurocognitive Measures Research Articles

Single Ventricle Reconstruction III: Brain Connectome and Neurodevelopmental Outcomes: Design, Recruitment, and Technical Challenges of a Multicenter, Observational Neuroimaging Study.

Patients with hypoplastic left heart syndrome who have been palliated with the Fontan procedure are at risk for adverse neurodevelopmental outcomes, lower quality of life, and reduced employability. We describe the methods (including quality assurance and quality control protocols) and challenges of a multi-center observational ancillary study, SVRIII (Single Ventricle Reconstruction Trial) Brain Connectome. Our original goal was to obtain advanced neuroimaging (Diffusion Tensor Imaging and Resting-BOLD) in 140 SVR III participants and 100 healthy controls for brain connectome analyses. Linear regression and mediation statistical methods will be used to analyze associations of brain connectome measures with neurocognitive measures and clinical risk factors. Initial recruitment challenges occurred that were related to difficulties with: (1) coordinating brain MRI for participants already undergoing extensive testing in the parent study, and (2) recruiting healthy control subjects. The COVID-19 pandemic negatively affected enrollment late in the study. Enrollment challenges were addressed by: (1) adding additional study sites, (2) increasing the frequency of meetings with site coordinators, and (3) developing additional healthy control recruitment strategies, including using research registries and advertising the study to community-based groups. Technical challenges that emerged early in the study were related to the acquisition, harmonization, and transfer of neuroimages. These hurdles were successfully overcome with protocol modifications and frequent site visits that involved human and synthetic phantoms.

Efficacy of Functional Remediation on Cognitive and Psychosocial Functioning in Patients with Bipolar Disorder: Study Protocol for a Randomized Controlled Study.

Neurocognitive impairment is a prominent characteristic of bipolar disorder (BD), linked with poor psychosocial functioning. This study's purpose is to evaluate the effectiveness of functional remediation (FR) in enhancing neurocognitive dysfunctions in a sample of remitted patients with diagnosis of BD in comparison to treatment as usual-TAU. To quantify the neurocognitive damage, the Brief Assessment of Cognition in Affective Disorders (BAC-A) will be used, and the overall psychosocial functioning will be measured with the Functioning Assessment Short Test-FAST. The randomized, rater-blinded, controlled study will include two arms (1:1) encompassing 54 outpatients with diagnosis of BD-I and BD-II, as defined by the DSM-5 criteria. In the experimental phase, remitted patients aged 18-55 years will be involved. At the baseline, at the end of intervention and at the 6-month follow-up, patients will be evaluated using clinical scales (Young Mania Rating Scale (Y-MRS) and Hamilton Depression Rating Scale (HAM-D)). Neurocognitive measurements and psychosocial functioning will be valued, respectively, with BAC-A and FAST. The primary expected outcome is that following FR intervention, patients will exhibit improved cognitive abilities and psychosocial outcomes compared to the participants in the TAU group. It is now recognized that neurocognitive deficits are potential predictors of functional outcome in patients with BD. In recent years, there has been a growing interest in the implementation of interventions that, in addition to symptomatic remission, are also aimed at neurocognitive dysfunctions in order to achieve a recovery of psychosocial functioning.

Comparison of Social-Evaluative Anxiety and Theory of Mind Functions in Social Anxiety Disorder, Schizophrenia, and Healthy Controls

Introduction: Despite the similarities in poor social competence and clinical manifestations of poor social behavior, no study has compared the theory of mind performance between social anxiety disorder (SAD) and schizophrenia, considering the effect of social-evaluative anxiety and neurocognitive functions. In our study, we aimed to compare the theory of mind functions and social-evaluative anxiety between patients with SAD and schizophrenia and healthy controls and to examine the relationship between the theory of mind, neurocognitive skills, and social-evaluative anxiety. Methods: Thirty-four consecutive patients with schizophrenia, 29 patients with SAD, and 30 controls matched by age, education level, and sex were enrolled in the study. Structured Clinical Interview for DSM, Beck Depression Inventory, Liebowitz Social Anxiety Scale, Theory of Mind measures (Reading the Mind in the Eyes Test, Hinting Task, Faux Pas Test), Social Appearance Anxiety Scale, Fear of Positive Evaluation Scale, Fear of Negative Evaluation Scale-Short Form, and neuropsychological tests were administered to all participants. Results: A greater significant deterioration in theory of mind and neurocognitive functions was found in patients with schizophrenia compared to those with SAD and healthy controls. Social evaluation anxiety was highest in patients with SAD. Although social-evaluative anxiety was associated with the theory of mind function in schizophrenia, only fear of positive evaluation was associated with SAD. In all groups, neither theory of mind nor neurocognitive ability measures were correlated with social anxiety levels and related symptoms. Conclusions: The impaired theory of mind functioning detected in our study is more prominent in the schizophrenia group and largely independent of anxiety in schizophrenia and SAD. Although social evaluation anxiety, as a transdiagnostic concept, seems to be independent of theory of mind function in general, fear of positive evaluation seems to be associated with hinting in both disorders.

Features of cognitive functioning in older people with COVID 19

The results of studies on elderly patients with COVID-19 indicate presence of serious comorbidities, including cerebrovascular disease, infection of the central nervous system, and cognitive deficits. Impaired cognitive functioning may be due to neurological damage, combined and potentially reversible effects of depression, anxiety and sleep disturbances.The purpose of the study: to identify characteristics of cognitive impairment of elderly patients hospitalized for COVID-19.Material and methods: the study involved 35 patients: 15 men and 20 women (median age 61.0 years, interquartile range (IQR, 25.0-75.0 percentiles) — 50.0-69.0 years, established clinical diagnosis: “New coronavirus infection COVID-19 (PCR+)”. Inclusion criteria were: 1) confirmation of the diagnosis of COVID-19 by clinical and PCR methods, 2) absence of mental disorders, incl. cognitive impairment prior to COVID-19. The exclusion criterion was age under 40 and over 90 years. The severity of COVID-19 was assessed in accordance with the criteria of the Interim Guidelines of the Ministry of Health of the Russian Federation. Clinical and psychopathological method, psychometric testing using the MMSE scale were used. Monitoring of current physical condition was carried out using The National Early Warning Score (NEWS2) for COVID-19. MMSE testing and monitoring of NEWS2 were carried out twice: upon presentation of cognitive complaints in the first days of hospitalization (1st measurement) and at discharge (2nd time point) Statistical processing was carried out using the STATISTICA 12 package. When comparing features, two-tailed Fisher’s test and Wilcoxon’s test were used. Correlation analysis was carried out using Kendall’s test. The level of statistical significance was p<0.05.Results: Comparative analysis between the first and second measurements revealed an improvement in the cognitive performance of elderly patients with COVID-19 by the end of the hospital stay. A significant predominance of median indicators was revealed: orientation (Med 9.0, IQR 8.0-10.0 vs Med 7.0 IQR 6.0-8.0; p=.0000), immediate memory (Med 3.0 IQR 3.0-3.0 vs Med 2.0 IQR 2.0-3.0; p= .0006), attention and counting (Med 2.0 IQR 2.0-4.0 vs Med 2.0 IQR 1.0-3.0; p=.0000). word reproduction (Med 2.0 IQR 2.0-3.0 vs Med 1.0 IQR 1.0-2.0; p=.0000); speech (Med 6.0 IQR 6.0-8.0 vs Med 5.0 IQR 4.0-5.0; p=.0000). final score (Med 24.0 IQR 23.0-27.0 vs Med 17.0 IQR 15.0-20.0; p=.0000). Correlations between the MMSE scores and anamnestic data were analyzed. Significant negative correlations were found with age, disease severity (only at the 2nd time point), diseases of the nervous, cardiovascular and digestive systems. Statistically significant relationships with gender, disease severity at the first measurement, tumors, diseases of the endocrine, respiratory and genitourinary systems were not obtained.Conclusion. Objective neurocognitive measurements can provide important information for neuropsychiatric sorting and should be included as endpoints in clinical trials.

Functional neural architecture of cognitive control mediates the relationship between individual differences in bilingual experience and behaviour

Bilinguals have often, but not always, been found to outperform monolinguals on domain-general attentional control. Inconsistent findings have been argued to stem, at least partly, from treating bilingualism as a uniform category and from not considering how neural adaptations to bilingual experiences modulate behavioural outcomes. The present study investigated how patterns of language experience, including language switching behaviour, duration and intensity/diversity of bilingual language use, influence the brain processes underlying cognitive control, and how these in turn translate to cognitive control performance. We examined reaction times and spectral dynamics of the electroencephalograms (EEG) of two-hundred-and-thirty-nine participants (about 70% bilinguals) with diverse language experiences during two cognitive control paradigms testing interference suppression (flanker and Simon task). Using structural equation modelling, we found that different bilingual experience factors were related with neurocognitive measures, which in turn were related with behavioural interference effects, for the flanker but not the Simon task. More specifically, increased frequency of language switching and intensity/diversity of bilingual language usage was negatively related to induced top-down control measures (especially midline-frontal theta), which in turn was beneficial for interference control. In contrast, duration of bilingual engagement correlated negatively with evoked bottom-up control measures (especially P3) and was therefore detrimental to interference control. We demonstrate here for the first time how the different factors of bilingual experience lead to different neural adaptations which impact behavioural outcomes. Significance statementLike other intensive experiences, bilingualism leads to brain adaptations. It results in structural changes in language areas, and, due to demands on language control, in brain areas associated with domain-general cognitive control. Related to this, bilinguals often outperform monolinguals on cognitive control tasks. But what is often ignored is that bilingualism is a multi-dimensional phenomenon, with variations such as diversity of language usage and duration of language use. The present large-scale study of neural functioning in bilingualism revealed for the first time how individual differences in bilingual experience lead to adaptations to brain functioning which in turn affect cognitive control behaviour. It exemplifies how the complexity of individual experiences plays a fundamental role in brain function.

374 Identification of Psychosis Risk Biomarkers in 22q11DS for future translational studies

OBJECTIVES/GOALS: 22q.11 deletion syndrome (22q11DS) is a genomic syndrome that elevates risk for psychosis >20-fold. We used a battery of cognitive and psychophysiological psychosis-risk biomarkers in 22q11DS patients and healthy subjects in order to identify biomarkers of psychosis in 22q11DS that could be used as translational targets in intervention studies. METHODS/STUDY POPULATION: We recruited 15 22q11DS individuals (Mean age=30, M/F=9/6) and 19 healthy controls (HCs; Mean age=34, M/F=5/14). Each individual completed the MATRICS Consensus Cognitive Battery (MCCB), the Wechsler Abbreviated Scale of Intelligence, Second edition (WASI-II) Verbal IQ subtests, and the computerized Wisconsin Card Sorting Task (WCST). To examine auditory EEG responses, each participant completed the 'Double-Deviant' target detection paradigm, which presents a pseudorandom sequence of frequent standard tones and infrequent deviant tones. Mismatch negativity (MMN) metrics were generated from this assessment. Welch's t-tests were completed for neurocognitive variables. One-Way ANOVAs were completed to examine EEG results, with sex entered as a separate factor and age entered as a covariate. RESULTS/ANTICIPATED RESULTS: Significant group differences were found in 8 of the 9 neurocognitive measurements (FDR-adjusted p's< 0.02, average Cohen's d=1.62, average observed power= 0.91) indicating widespread cognitive deficits in 22q11DS subjects across multiple domains. The Double-Deviant MMN ERP response was significantly smaller in absolute magnitude in the 22q11DS group (FDR-adjusted p=0.048, Cohen’s d= -0.864, observed power= 0.58). The MMN ERPs for the frequency and duration deviants were not significantly different (FDR-adjusted p's> 0.33). No group by sex interactions were observed in any of the measures. Neurocognitive variables were associated with psychosis positive, negative, general, and disorganized symptom scales. DISCUSSION/SIGNIFICANCE: Our results identify potential psychosis-risk biomarkers in 22q11DS. If replicated, these biomarkers could provide important translational targets for future clinical trials for individuals with 22q11DS and other individuals at-risk for psychosis syndromes.

Investigating the neural correlates of affective mentalizing and their association with general intelligence in patients with schizophrenia.

Mentalizing impairment in schizophrenia has been linked to altered neural responses. This study aimed to replicate previous findings of altered activation of the mentalizing network in schizophrenia and investigate its possible association with impaired domain-general cognition. We analyzed imaging data from two large multi-centric German studies including 64 patients, 64 matched controls and a separate cohort of 300 healthy subjects, as well as an independent Australian study including 46 patients and 61 controls. All subjects underwent functional magnetic resonance imaging while performing the same affective mentalizing task and completed a cognitive assessment battery. Group differences in activation of the mentalizing network were assessed by classical as well as Bayesian two-sample t-tests. Multiple regression analysis was performed to investigate effects of neurocognitive measures on activation of the mentalizing network. We found no significant group differences in activation of the mentalizing network. Bayes factors indicate that these results provide genuine evidence for the null hypothesis. We found a positive association between verbal intelligence and activation of the medial prefrontal cortex, a key region of the mentalizing network, in three independent samples. Finally, individuals with low verbal intelligence showed altered activation in areas previously implicated in mentalizing dysfunction in schizophrenia. Mentalizing activation in patients with schizophrenia might not differ compared to large well-matched groups of healthy controls. Verbal intelligence is an important confounding variable in group comparisons, which should be considered in future studies of the neural correlates of mentalizing dysfunction in schizophrenia.

Application of data harmonization and tract-based spatial statistics reveals white matter structural abnormalities in pediatric patients with focal cortical dysplasia

Our study assessed diffusion tensor imaging (DTI) metrics of fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) in pediatric subjects with epilepsy secondary to Focal Cortical Dysplasia (FCD) to improve our understanding of structural network changes associated with FCD related epilepsy. We utilized a data harmonization (DH) approach to minimize confounding effects induced by MRI protocol differences. We also assessed correlations between DTI metrics and neurocognitive measures of the fluid reasoning index (FRI), verbal comprehension index (VCI), and visuospatial index (VSI). Data (n = 51) from 23 FCD patients and 28 typically developing controls (TD) scanned clinically on either 1.5T, 3T, or 3T-wide-bore MRI were retrospectively analyzed. Tract-based spatial statistics (TBSS) with threshold-free cluster enhancement and permutation testing with 100,000 permutations were used for statistical analysis. To account for imaging protocol differences, we employed non-parametric data harmonization prior to permutation testing. Our analysis demonstrates that DH effectively removed MRI protocol-based differences typical in clinical acquisitions while preserving group differences in DTI metrics between FCD and TD subjects. Furthermore, DH strengthened the association between DTI metrics and neurocognitive indices. Fractional anisotropy, MD, and RD metrics showed stronger correlation with FRI and VSI than VCI. Our results demonstrate that DH is an integral step to reduce the confounding effect of MRI protocol differences during the analysis of white matter tracts and highlights biological differences between FCD and healthy control subjects. Characterization of white matter changes associated with FCD-related epilepsy may better inform prognosis and treatment approaches.

The impact of pre-adulthood urbanicity on hippocampal subfield volumes and neurocognitive abilities in young adults

BackgroundUrbanicity refers to the conditions that are particular to urban areas and is a growing environmental challenge that may affect hippocampus and neurocognition. This study aimed to investigate the effects of the average pre-adulthood urbanicity on hippocampal subfield volumes and neurocognitive abilities as well as the sensitive age windows of the urbanicity effects. Participants and methodsWe included 5,390 CHIMGEN participants (3,538 females; age: 23.69 ± 2.26 years, range: 18–30 years). Pre-adulthood urbanicity of each participant was defined as the average value of annual night-time light (NL) or built-up% from age 0–18, which were extracted from remote-sensing satellite data based on annual residential coordinates of the participants. The hippocampal subfield volumes were calculated based on structural MRI and eight neurocognitive measures were assessed. The linear regression was applied to investigate the associations of pre-adulthood NL with hippocampal subfield volumes and neurocognitive abilities, mediation models were used to find the underlying pathways among urbanicity, hippocampus and neurocognition, and distributed lag models were used to identify sensitive age windows of urbanicity effect. ResultsHigher pre-adulthood NL was associated with greater volumes in the left (β = 0.100, 95%CI: [0.075, 0.125]) and right (0.078, [0.052, 0.103]) fimbria and left subiculum body (0.045, [0.020, 0.070]) and better neurocognitive abilities in information processing speed (-0.212, [-0.240, −0.183]), working memory (0.085, [0.057, 0.114]), episodic memory (0.107, [0.080, 0.135]), and immediate (0.094, [0.065, 0.123]) and delayed (0.087, [0.058, 0.116]) visuospatial recall, and hippocampal subfield volumes and visuospatial memory showed bilateral mediations for the urbanicity effects. Urbanicity effects were greatest on the fimbria in preschool and adolescence, on visuospatial memory and information processing from childhood to adolescence and on working memory after 14 years. ConclusionThese findings improve our understanding of the impact of urbanicity on hippocampus and neurocognitive abilities and will benefit for designing more targeted intervention for neurocognitive improvement.

Neuropsychological Performance and Cardiac Autonomic Function in Blue- and White-Collar Workers: A Psychometric and Heart Rate Variability Evaluation

The 21st century has brought a growing and significant focus on performance and health within the workforce, with the aim of improving the health and performance of the blue- and white-collar workforce. The present research investigated heart rate variability (HRV) and psychological performance between blue and white-collar workers to determine if differences were evident. A total of 101 workers (n = 48 white-collar, n = 53 blue-collar, aged 19-61 years) underwent a three lead electrocardiogram to obtain HRV data during baseline (10 min) and active (working memory and attention) phases. The Cambridge Neuropsychological Test Automated Battery, specifically the spatial working memory, attention switching task, rapid visual processing and the spatial span, were used. Differences in neurocognitive performance measures indicated that white-collar workers were better able to detect sequences and make less errors than blue-collar workers. The heart rate variability differences showed that white-collar workers exhibit lower levels of cardiac vagal control during these neuropsychological tasks. These initial findings provide some novel insights into the relationship between occupation and psychophysiological processes and further highlight the interactions between cardiac autonomic variables and neurocognitive performance in blue and white-collar workers.

The role of targeted therapy and immune therapy in the management of non-small cell lung cancer brain metastases.

Brain metastases are a significant source of morbidity and mortality in patients with non-small cell lung cancer. Historically, surgery and radiation therapy have been essential to maintaining disease control within the central nervous system due to poorly penetrant conventional chemotherapy. With the advent of targeted therapy against actionable driver mutations, there is potential to control limited and asymptomatic intracranial disease and delay local therapy until progression. In this review paper, intracranial response rates and clinical outcomes to biological and immune therapies are summarized from the literature and appraised to assist clinical decision making and identify areas for further research. Future clinical trials ought to prioritize patient-centered quality of life and neurocognitive measures as major outcomes and specifically stratify patients based on mutational marker status, disease burden, and symptom acuity.

Social determinants of neurocognitive and academic performance in sickle cell disease.

Sickle cell disease (SCD) is associated with poor neurocognitive outcomes due to biomedical and psychosocial factors. The aims of this study were to investigate associations between household and neighborhood socioeconomic status (SES) with cognitive and academic outcomes in SCD and to determine if these relationships were modified by sickle genotype, fetal hemoglobin, or age. We prospectively recruited patients to complete a battery of neurocognitive and academic measures. Household SES was measured using the Barratt Simplified Measure of Social Status, a composite index of parent education and occupation. The Social Vulnerability Index was used to classify individuals based on social vulnerabilities at the neighborhood level. Overall, 299 patients between the ages of 4 and 18 (mean=11.4, standard deviation=4.3) years diagnosed with SCD (57% SS/SB0 -thalassemia) completed testing. Stepwise multivariate models demonstrated that patients with low social vulnerability (i.e., high SES) at the neighborhood level displayed intelligence and math scores that were 4.70 and 7.64 points higher than those living in areas with moderate social vulnerability, respectively (p<.05). Reading performance did not differ based on neighborhood SES; however, the effect of neighborhood SES was dependent on age, such that older participants living in neighborhoods with moderate or high levels of social vulnerability displayed poorer reading scores than those with low social vulnerability (p<.05). This study identified patients with SCD at higher risk of poor academic performance based on SES. Interventions addressing academic difficulties should be offered to all children with SCD, but should be emergently offered to this subpopulation.

Representation of an Interdisciplinary Approach for Evaluation of Precision of a Neurocognitive Screening Bundle: A Proposal

Neurocognitive disorders encompass a range of conditions characterized by cognitive impairments, presenting significant challenges to individuals, families, and healthcare systems worldwide. Traditional paper-and-pencil assessments have limitations, including restricted access, limited frequency, and subjective interpretation. This research proposal aims to address these limitations by developing a reliable digital platform, a neurocognitive screening bundle, for year-round monitoring of neurocognitive symptom domains. The proposed research project adopts an interdisciplinary approach by integrating knowledge and expertise from the fields of neurology, psychology, cognitive neuroscience, and computer science. Neurology provides clinical context and expertise in understanding neurocognitive symptom domains, ensuring that the chosen screening bundle aligns with clinical needs. Psychology contributes insights into human behavior and cognitive processes, aiding in the selection, adaptation, or development of assessments targeting specific neurocognitive functions. Additionally, psychologists contribute expertise in data analysis and interpretation, enabling the identification of meaningful patterns within the collected data. Cognitive neuroscience offers a deeper understanding of the underlying neural mechanisms associated with neurocognitive symptom domains. By identifying the neural networks, brain regions, and cognitive processes involved in specific cognitive functions, cognitive neuroscientists bridge the gap between cognitive assessment and neurobiological underpinnings, aiding in the selection and interpretation of neurocognitive measures. Computer science plays a pivotal role in developing and evaluating the digital platform for neurocognitive screening. Computer scientists leverage their expertise in software development, data analysis, and machine learning to design algorithms for data processing, ensure data security and privacy, and develop user-friendly interfaces for assessments. By integrating technical skills with knowledge from other disciplines, computer scientists enhance the accuracy, reliability, and usability of the digital platform. This interdisciplinary research project aims to provide a comprehensive, accessible, and reliable tool for year-round monitoring of neurocognitive symptom domains, surpassing the limitations of traditional assessment methods. By leveraging the expertise from neurology, psychology, cognitive neuroscience, and computer science, this study aims to advance the field and improve clinical outcomes for individuals with neurocognitive disorders. The findings of this research project have the potential to revolutionize neurocognitive assessments, leading to more effective diagnosis and monitoring of these challenging conditions.

Baseline Computerized Neurocognitive Testing and Oculomotor Measures are not Altered by Hormonal Contraceptive Use.

Neurocognitive testing and oculomotor assessment have been an integral component to provide objective measures for sport-related concussion (SRC) detection and management. Hormonal contraceptive (HC) use is common among collegiate female athletes and may modify baseline SRC performance. The purpose was to examine the effects of HC use on baseline computerized neurocognitive testing (CNT) and oculomotor testing in college-aged individuals. A total of 63 participants (22 HC using females, 22 non-HC using females, 19 males) completed a baseline SRC battery consisting of CNT, near point of convergence (NPC), and the King-Devick (KD) test. CNT measures were composite scores of verbal and visual memory, visual motor processing speed and reaction time, impulse control, and cognitive efficiency index (CEI). NPC was measured as the average convergence distance across three trials. KD time was recorded as total time for each of the two trials and best trial marked as baseline. There were no group differences between HC, non-HC, and male control groups on all baseline CNT composite scores (p = .13-.98), impulse control (p = .47), and CEI (p = .49). NPC distance was similar between groups (p = .41), as well as KD time by trial (Trial 1 p = .65; 2 p = .48) and best time (p = .49). HC use does not appear to influence baseline SRC measures of neurocognition and oculomotor assessment. Clinicians should continue to consider the effects of modifying factors at baseline and post-concussion. Additional research is needed to better understand sex hormone levels and SRC performance measures.

Neurocognition and functioning in adolescents at clinical high risk for psychosis

BackgroundOnce psychosis has set in, it is difficult for patients to achieve full recovery. Prevention of psychosis and early intervention are promising for improving the outcomes of this disorder. In the last two decades, neurocognition has been studied as a biomarker for clinical-high risk for psychosis (CHR-P). However, neurocognitive functioning has been under-investigated in adolescents.MethodsWe enrolled 116 adolescents from 12 to 17 years old (mean = 15.27, SD = 1.56; 76 females). This 3-year cohort study aimed to identify differences in neurocognitive and overall functioning in three groups of adolescent patients divided according to the semi-structured interview Comprehensive Assessment of At-Risk Mental States (CAARMS): adolescents with established psychosis, adolescents with CHR-P, and adolescents not meeting either criteria (non-CHR-P). To differentiate the profiles, clinicians administered cognitive evaluation and neuropsychological tasks. Moreover, they filled in scales to assess their global, social, and role functioning and a questionnaire to assess the severity of the disease.ResultsWe made a between-group comparison on neurocognitive measures and found that the CHR-P and the psychosis groups differed in processing speed (TMT-A; p = .002 in BVN categorial fluency (p = .018), and Rey–Osterrieth complex figure drawing from memory task (p = .014), with psychosis group showing worse performance. No differences emerged between non-CHR-P and CHR-P (p = .014) individuals. CHR-P had better functioning than the psychosis group but worse than the non-CHR-P one.ConclusionsThese results confirm that neurocognition can be a helpful biomarker in identifying specific subgroups of adolescents with emerging psychopathology and help clinicians develop stratified preventive approaches.

ERP Indicators of Phonological Awareness Development in Children: A Systematic Review.

Phonological awareness is the ability to correctly recognize and manipulate phonological structures. The role of phonological awareness in reading development has become evident in behavioral research showing that it is inherently tied to measures of phonological processing and reading ability. This has also been shown with ERP research that examined how phonological processing training can benefit reading skills. However, there have not been many attempts to systematically review how phonological awareness itself is developed neurocognitively. In the present review, we screened 224 papers and systematically reviewed 40 papers that have explored phonological awareness and phonological processing using ERP methodology with both typically developing and children with reading problems. This review highlights ERP components that can be used as neurocognitive predictors of early developmental dyslexia and reading disorders in young children. Additionally, we have presented how phonological processing is developed neurocognitively throughout childhood, as well as which phonological tasks can be used to predict the development of phonological awareness prior to developing reading skills. Neurocognitive measures of early phonological processing can serve as supplemental diagnostic sources to behavioral measures of reading abilities because they show different aspects of phonological sensitivity when compared to behavioral measures.

Neurocognitive development after pediatric brain tumor - a longitudinal, retrospective cohort study

ABSTRACT Survivors of Pediatric Brain Tumors (PBTs) treated with cranial radiation therapy (CRT) often experience a decline in neurocognitive test scores. Less is known about the neurocognitive development of non-irradiated survivors of PBTs. The aim of this study was to statistically model neurocognitive development after PBT in both irradiated and non-irradiated survivors and to find clinical variables associated with the rate of decline in neurocognitive scores. A total of 151 survivors were included in the study. Inclusion criteria: Diagnosis of PBT between 2001 and 2013 or earlier diagnosis of PBT and turning 18 years of age between 2006 and 2013. Exclusion criteria: Death within a year from diagnosis, neurocutaneous syndromes, severe intellectual disability. Clinical neurocognitive data were collected retrospectively from medical records. Multilevel linear modeling was used to evaluate the rate of decline in neurocognitive measures and factors associated with the same. A decline was found in most measures for both irradiated and non-irradiated survivors. Ventriculo-peritoneal (VP) shunting and treatment with whole-brain radiation therapy (WBRT) were associated with a faster decline in neurocognitive scores. Male sex and supratentorial lateral tumor were associated with lower scores. Verbal learning measures were either stable or improving. Survivors of PBTs show a pattern of decline in neurocognitive scores irrespective of treatment received, which suggests the need for routine screening for neurocognitive rehabilitation. However, survivors treated with WBRT and/or a VP shunt declined at a faster rate and appear to be at the highest risk of negative neurocognitive outcomes and to have the greatest need for neurocognitive rehabilitation.

Temporal Irreversibility of Large-Scale Brain Dynamics in Alzheimer's Disease.

Healthy brain dynamics can be understood as the emergence of a complex system far from thermodynamic equilibrium. Brain dynamics are temporally irreversible and thus establish a preferred direction in time (i.e., arrow of time). However, little is known about how the time-reversal symmetry of spontaneous brain activity is affected by Alzheimer's disease (AD). We hypothesized that the level of irreversibility would be compromised in AD, signaling a fundamental shift in the collective properties of brain activity toward equilibrium dynamics. We investigated the irreversibility from resting-state fMRI and EEG data in male and female human patients with AD and elderly healthy control subjects (HCs). We quantified the level of irreversibility and, thus, proximity to nonequilibrium dynamics by comparing forward and backward time series through time-shifted correlations. AD was associated with a breakdown of temporal irreversibility at the global, local, and network levels, and at multiple oscillatory frequency bands. At the local level, temporoparietal and frontal regions were affected by AD. The limbic, frontoparietal, default mode, and salience networks were the most compromised at the network level. The temporal reversibility was associated with cognitive decline in AD and gray matter volume in HCs. The irreversibility of brain dynamics provided higher accuracy and more distinctive information than classical neurocognitive measures when differentiating AD from control subjects. Findings were validated using an out-of-sample cohort. Present results offer new evidence regarding pathophysiological links between the entropy generation rate of brain dynamics and the clinical presentation of AD, opening new avenues for dementia characterization at different levels.SIGNIFICANCE STATEMENT By assessing the irreversibility of large-scale dynamics across multiple brain signals, we provide a precise signature capable of distinguishing Alzheimer's disease (AD) at the global, local, and network levels and different oscillatory regimes. Irreversibility of limbic, frontoparietal, default-mode, and salience networks was the most compromised by AD compared with more sensory-motor networks. Moreover, the time-irreversibility properties associated with cognitive decline and atrophy outperformed and complemented classical neurocognitive markers of AD in predictive classification performance. Findings were generalized and replicated with an out-of-sample validation procedure. We provide novel multilevel evidence of reduced irreversibility in AD brain dynamics that has the potential to open new avenues for understating neurodegeneration in terms of the temporal asymmetry of brain dynamics.

The impact of hemodiafiltration on cognitive function in patients with end-stage renal disease.

Patients with end-stage renal disease are more likely to suffer cognitive impairment. Cognitive impairment may lead to long-term severe adverse consequences. To explore the impact of different blood purification therapy on cerebral blood flow and cognitive functions in end-stage renal disease. This prospective study evaluated patients with end-stage renal disease undergoing blood purification from January to March 2021. Matched healthy controls were also included. Participants performed neurocognitive measurements, including a mini-mental state examination, logical memory test-20-minutes delayed, verbal fluency test, digit span test, clock drawing test, and stroop color and word test C. In addition, we tested plasma amyloid-β protein levels, serum Fe and hemoglobin levels in blood samples. Cerebral blood flow was measured using pulsed pseudocontinuous arterial spin labeling. We analyzed and compared the correlation between cognitive function, biomarkers, and cerebral blood flow between patients and healthy subjects, as well as between patients with different treatments. A total of 44 patients with end-stage renal disease (mean age, 57.39 years ± 8.63) and 46 healthy controls (mean age, 56.15 years ± 6.40) were recruited. Patients receive hemodialysis three times a week, and 27 of them have been replaced hemodialysis for hemodiafiltration twice a month. The cognitive function of patients was worse than healthy controls (P < 0.05). The patients showed higher plasma concentrations of amyloid-β40, amyloid-β42, Tau, and pTau181 than healthy controls (P < 0.05). The group receiving both hemodialysis and hemodiafiltration had higher cerebral blood flow signal values in the left caudate nucleus (chuster-level P < 0.05, voxel-level P < 0.001). They also exhibited better verbal fluency function than the hemodialysis-only group (P < 0.05). Patients with the end-stage renal disease showed widespread cognitive declines. Cerebral blood flow generally decreased in the cerebral cortex and increased in subcortical regions. The hemodiafiltration may protect verbal function by increasing cerebral blood flow in the left caudate.

Anatomically interpretable deep learning of brain age captures domain-specific cognitive impairment

The gap between chronological age (CA) and biological brain age, as estimated from magnetic resonance images (MRIs), reflects how individual patterns of neuroanatomic aging deviate from their typical trajectories. MRI-derived brain age (BA) estimates are often obtained using deep learning models that may perform relatively poorly on new data or that lack neuroanatomic interpretability. This study introduces a convolutional neural network (CNN) to estimate BA after training on the MRIs of 4,681 cognitively normal (CN) participants and testing on 1,170 CN participants from an independent sample. BA estimation errors are notably lower than those of previous studies. At both individual and cohort levels, the CNN provides detailed anatomic maps of brain aging patterns that reveal sex dimorphisms and neurocognitive trajectories in adults with mild cognitive impairment (MCI, N = 351) and Alzheimer's disease (AD, N = 359). In individuals with MCI (54% of whom were diagnosed with dementia within 10.9 y from MRI acquisition), BA is significantly better than CA in capturing dementia symptom severity, functional disability, and executive function. Profiles of sex dimorphism and lateralization in brain aging also map onto patterns of neuroanatomic change that reflect cognitive decline. Significant associations between BA and neurocognitive measures suggest that the proposed framework can map, systematically, the relationship between aging-related neuroanatomy changes in CN individuals and in participants with MCI or AD. Early identification of such neuroanatomy changes can help to screen individuals according to their AD risk.