Neurobehavioral Domains Research Articles

Neurobehavioral outcomes of neonatal asymptomatic congenital cytomegalovirus infection at 12-months

BackgroundCongenital cytomegalovirus (cCMV) is the most common congenital viral infection in the United States. Symptomatic infections can cause severe hearing loss and neurological disability, although ~ 90% of cCMV infections are asymptomatic at birth. Despite its prevalence, the long-term neurobehavioral risks of asymptomatic cCMV infections are not fully understood. The objective of this work was to evaluate for potential long-term neurobehavioral sequelae in infants with asymptomatic cCMV.MethodsInfants with cCMV were identified from a universal newborn cCMV screening study in a metropolitan area in the midwestern United States. Asymptomatic infants with cCMV were enrolled in a longitudinal neurodevelopmental study (N = 29). Age- and sex-matched healthy control infants (N = 193) were identified from the Baby Connectome Project (BCP), a longitudinal study of brain and behavioral development. The BCP sample supplemented an additional group of healthy control infants (N = 30), recruited from the same participant registry as the BCP specifically for comparison with infants with asymptomatic cCMV. Neurobehavioral assessments and parent questionnaires, including the Mullen Scales of Early Learning, the Repetitive Behavior Scales for Early Childhood (RBS-EC), and the Infant Toddler Social Emotional Assessment (ITSEA) were administered at 12 months of age. Neurobehavioral scores were compared between infants with asymptomatic cCMV and all identified healthy control infants.ResultsInfants with asymptomatic cCMV performed equivalently compared to healthy control infants on the neurobehavioral measures tested at 12 months of age.ConclusionsThese results indicate that at 12 months of age, infants with asymptomatic cCMV are not statistically different from controls in a number of neurobehavioral domains. Although follow-up is ongoing, these observations provide reassurance about neurobehavioral outcomes for infants with asymptomatic cCMV and inform the ongoing discussion around universal screening. Additional follow-up will be necessary to understand the longer-term outcomes of these children.

Epigenetic age acceleration, neonatal morbidities, and neurobehavioral profiles in infants born very preterm

ABSTRACT Epigenetic age acceleration is a risk factor for chronic diseases of ageing and may reflect aspects of biological ageing. However, few studies have examined epigenetic ageing during the early neonatal period in preterm infants, who are at heightened risk of developmental problems. We examined relationships between neonatal age acceleration, neonatal morbidities, and neurobehavioral domains among very preterm (<30 weeks gestation) infants to characterize whether infants with early morbidities or different neurobehavioral characteristics had accelerated or decelerated epigenetic ageing. This study uses data from the Neonatal Neurobehavior and Outcomes in Very Preterm Infants (NOVI) study, restricted to infants with data on variables assessed (n = 519). We used generalized estimating equations to test for differences in age acceleration associated with severe neonatal medical morbidities and neurobehavioral characteristics. We found that infants with neonatal morbidities, in particular, bronchopulmonary dysplasia (BPD), had accelerated epigenetic age – and some evidence that infants with hypertonicity and asymmetric reflexes had increased and decreased age acceleration, respectively. Adjustment for gestational age attenuated some associations, suggesting that the relationships observed may be driven by the duration of gestation. Our most robust finding shows that very preterm infants with neonatal morbidities (BPD in particular) exhibit age acceleration, but most neonatal neurobehavioral characteristics and morbidities are not associated with early life age acceleration. Lower gestational age at birth may be an upstream factor driving these associations.

Cognitive impairment in a sample of adult patients with multiple sclerosis: an Egyptian study

BackgroundMultiple sclerosis is a chronic neuro-inflammatory disease of the brain and central nervous system. We aimed at assessing the cognitive functions present in adult patients with multiple sclerosis in remission phase of the disease comparing them to healthy control group.ResultsThis is a cross sectional study using Penn Computerized Neurocognitive Battery (CNB) to measure performance accuracy and speed on specific neurobehavioral domains comparing MS group to healthy group. The MS group showed lower statistically significant difference in the accuracy of spatial memory, the motor speed, Non-verbal reasoning, Spatial orientation, social cognition, and working memory. Also, MS group showed statistically significant longer reaction time in facial memory, attention, spatial orientation, and non-verbal reasoning.ConclusionsAttention, spatial orientation, non- verbal reasoning, Facial memory, working memory, social cognition and spatial memory were affected in patients with MS during their remission phase. cognitive evaluation should constitute a major part of the clinical examination in MS, especially when impairment seems likely.

Urinary Glyphosate, 2,4-D and DEET Biomarkers in Relation to Neurobehavioral Performance in Ecuadorian Adolescents in the ESPINA Cohort.

Herbicides are the most used class of pesticides worldwide, and insect repellents are widely used globally. Yet, there is a dearth of studies characterizing the associations between these chemical groups and human neurobehavior. Experimental studies suggest that glyphosate and 2,4-dichlorophenoxyacetic acid (2,4-D) herbicides can affect neurobehavior and the cholinergic and glutamatergic pathways in the brain. We aim to assess whether herbicides and insect repellents are associated with neurobehavioral performance in adolescents. We assessed 519 participants (11-17 years of age) living in agricultural communities in Ecuador. We quantified urinary concentrations of glyphosate, 2,4-D, and two N,N-diethyl-meta-toluamide (DEET) insect repellent metabolites [3-(diethylcarbamoyl)benzoic acid (DCBA) and 3-(ethylcarbamoyl)benzoic acid (ECBA)] using isotope-dilution mass spectrometry. We assessed neurobehavioral performance using 9 subtests across 5 domains (attention/inhibitory control, memory/learning, language, visuospatial processing, and social perception). We characterized the associations using generalized estimating equations and multiple imputation for metabolites below detection limits. Models were adjusted for demographic and anthropometric characteristics, urinary creatinine, and sexual maturation. Mediation by salivary cortisol, dehydroepiandrosterone, , and testosterone was assessed using structural equation modeling. The mean of each neurobehavioral domain score was between 7.0 and 8.7 [standard deviation (SD) range: 2.0-2.3]. Glyphosate was detected in 98.3% of participants, 2,4-D in 66.2%, DCBA in 63.3%, and ECBA in 33.4%. 2,4-D was negatively associated with all neurobehavioral domains, but statistically significant associations were observed with attention/inhibition [score difference per 50% higher metabolite concentration 95% confidence interval (CI): , ], language [ (95% CI: , )], and memory/learning [ (95% CI: , 0.01)]. Glyphosate had a statistically significant negative association only with social perception [ (95% CI: , )]. DEET metabolites were not associated with neurobehavioral performance. Mediation by gender and adrenal hormones was not observed. This study describes worse neurobehavioral performance associated with herbicide exposures in adolescents, particularly with 2,4-D. Replication of these findings among other pediatric and adult populations is needed. https://doi.org/10.1289/EHP11383.

Neurobehavioral Symptoms in Children Born Extremely Preterm: A Swedish National Study.

To determine the prevalence of neurobehavioral problems at 6.5 years in children born extremely preterm (EPT, <27 weeks' gestation). Population-based cohort study of infants born EPT in Sweden from 2004 to 2007. Of 486 survivors 375 were assessed and compared with 369 matched term-born controls. EPT children free from neurosensory and intellectual disabilities (NDD-free, n=236) were compared separately. Standardized questionnaires were used to assess parental ratings of hyperactivity and attention, emotional, peer-relation, conduct, and social problems; and deficits in perception, language and memory. EPT children had more reported problems in all assessed neurobehavioral domains than controls, with more than 3 times greater odds for most outcomes. Except for conduct problems, increased problems were identified also in NDD-free children. The odds of having neurobehavioral problems in ≥3 co-occurring domains were five (whole EPT group) and three (NDD-free group) times higher than in controls. EPT children with or without NDD have more neurobehavioral problems in multiple domains than term peers. Ongoing assessments of behavior until school age or beyond should recognize early symptoms of attention, everyday social problems, perceptual, emotional or language difficulties.

Peripheral inflammation is associated with impairments of inhibitory behavioral control and visual sensorimotor function in psychotic disorders.

Elevated markers of peripheral inflammation are common in psychosis spectrum disorders and have been associated with brain anatomy, pathology, and physiology as well as clinical outcomes. Preliminary evidence suggests a link between inflammatory cytokines and C-reactive protein (CRP) with generalized cognitive impairments in a subgroup of individuals with psychosis. Whether these patients with elevated peripheral inflammation demonstrate deficits in specific cognitive domains remains unclear. To examine this, seventeen neuropsychological and sensorimotor tasks and thirteen peripheral inflammatory and microvascular markers were quantified in a subset of B-SNIP consortium participants (129 psychosis, 55 healthy controls). Principal component analysis was conducted across the inflammatory markers, resulting in five inflammation factors. Three discrete latent cognitive domains (Visual Sensorimotor, General Cognitive Ability, and Inhibitory Behavioral Control) were characterized based on the neurobehavioral battery and examined in association with inflammation factors. Hierarchical clustering analysis identified cognition-sensitive high/low inflammation subgroups. Among persons with psychotic disorders but not healthy controls, higher inflammation scores had significant associations with impairments of Inhibitory Control (R2=0.100, p-value=2.69e-4, q-value=0.004) and suggestive associations with Visual Sensorimotor function (R2=0.039, p-value=0.024, q-value=0.180), but not with General Cognitive Ability (R2=0.015, p-value=0.162). Greater deficits in Inhibitory Control were observed in the high inflammation patient subgroup, which represented 30.2% of persons with psychotic disorders, as compared to the low inflammation psychosis subgroup. These findings indicate that inflammation dysregulation may differentially impact specific neurobehavioral domains across psychotic disorders, particularly performance on tasks requiring ongoing behavioral monitoring and control.

Development of informant-report neurobehavioral survey scales for PTEN hamartoma tumor syndrome and related neurodevelopmental genetic syndromes.

There are few well-validated measures that are appropriate for assessing the full range of neurobehavioral presentations in PTEN hamartoma tumor syndrome (PHTS) and other neurodevelopmental genetic syndromes (NDGS). As potential therapeutics are developed, having reliable, valid, free, and easily accessible measures to track a range of neurobehavioral domains will be crucial for future clinical trials. This study focused on the development and initial psychometric evaluation of a set of freely available informant-report survey scales for PHTS-the Neurobehavioral Evaluation Tool (NET). Concept elicitation, quantitative ratings, and cognitive interviewing processes were conducted with stakeholders and clinician-scientist experts, used to identify the most important neurobehavioral domains for this population, and to ensure items were appropriate for the full range of individuals with PHTS. Results of this process identified a PHTS neurobehavioral impact model with 11 domains. The final NET scales assessing these domains were administered to a sample of 384 participants (median completion time = 20.6 min), including 32 people with PHTS, 141 with other NDGS, 47 with idiopathic neurodevelopmental disorder (NDD), and 164 neurotypical controls. Initial psychometric results for the total scores of each scale indicated very good model (ω = 0.83-0.99) and internal consistency reliability (α = 0.82-0.98) as well as excellent test-retest reproducibility at 1-month follow-up (r = 0.78-0.98) and stability at 4-month follow-up (r = 0.76-0.96). Conditional reliability estimates indicated very strong measurement precision in key score ranges for assessing PHTS and other people with NDGS and/or idiopathic NDD. Comparisons across domains between PHTS and the other groups revealed specific patterns of symptoms and functioning, including lower levels of challenging behavior and more developed daily living and executive functioning skills relative to other NDGS. The NET appears to be a reliable and potentially useful tool for clinical characterization and monitoring of neurobehavioral symptoms in PHTS and may also have utility in the assessment of other NDGS and idiopathic NDD. Additional validation work, including convergent and discriminant validity analyses, are needed to replicate and extend these observations.

Triangulating causality between childhood obesity and neurobehavior: Behavioral genetic and longitudinal evidence.

Childhood obesity is a serious health concern that is not yet fully understood. Previous research has linked obesity with neurobehavioral factors such as behavior, cognition, and brain morphology. The causal directions of these relationships remain mostly untested. We filled this gap by using the Adolescent Brain Cognitive Development study cohort comprising 11,875 children aged 9-10. First, correlations between the age- and sex-specific 95th BMI percentile (%BMIp95) and neurobehavioral measures were cross-sectionally analyzed. Effects were then aggregated by neurobehavioral domain for causal analyses. Behavioral genetic Direction of Causation modeling was used to test the direction of each relationship. Findings were validated by longitudinal cross-lagged panel modeling. %BMIp95 correlated with impulsivity, motivation, psychopathology, eating behavior, and cognitive tests (executive functioning, language, memory, perception, working memory). Greater %BMIp95 was also associated with reduced cortical thickness in frontal and temporal brain areas but with increased thickness in parietal and occipital areas. Similar although weaker patterns emerged for cortical surface area and volume. Behavioral genetic modeling suggested causal effects of %BMIp95 on eating behavior (β=0.26), cognition (β=0.05), cortical thickness (β=0.15), and cortical surface area (β=0.07). Personality/psychopathology (β=0.09) and eating behavior (β=0.16) appeared to influence %BMIp95. Longitudinal evidence broadly supported these findings. Results regarding cortical volume were inconsistent. Results supported causal effects of obesity on brain functioning and morphology. The present study highlights the importance of physical health for brain development and may inform interventions aimed at preventing or reducing pediatric obesity. RESEARCH HIGHLIGHTS: A continuous measure related to obesity, %BMIp95, has correlations with various measures of brain functioning and structure Behavioral genetic and longitudinal modeling suggest causal links from personality, psychopathology, and eating behavior to %BMIp95 Results also indicate directional links from %BMIp95 to eating behavior, cognition, cortical thickness, and cortical surface area Obesity may play a role for healthy brain development during childhood.

Current State of Modeling Human Psychiatric Disorders Using Zebrafish.

Psychiatric disorders are highly prevalent brain pathologies that represent an urgent, unmet biomedical problem. Since reliable clinical diagnoses are essential for the treatment of psychiatric disorders, their animal models with robust, relevant behavioral and physiological endpoints become necessary. Zebrafish (Danio rerio) display well-defined, complex behaviors in major neurobehavioral domains which are evolutionarily conserved and strikingly parallel to those seen in rodents and humans. Although zebrafish are increasingly often used to model psychiatric disorders, there are also multiple challenges with such models as well. The field may therefore benefit from a balanced, disease-oriented discussion that considers the clinical prevalence, the pathological complexity, and societal importance of the disorders in question, and the extent of its detalization in zebrafish central nervous system (CNS) studies. Here, we critically discuss the use of zebrafish for modeling human psychiatric disorders in general, and highlight the topics for further in-depth consideration, in order to foster and (re)focus translational biological neuroscience research utilizing zebrafish. Recent developments in molecular biology research utilizing this model species have also been summarized here, collectively calling for a wider use of zebrafish in translational CNS disease modeling.

ZEBRAFISH AS AN EMERGING ALTERNATIVE TOOL FOR STUDYING ANXIETY DISORDERS

Zebrafish are increasingly becoming popular as promising new model species for translational research in a variety of neurological fields. Because of their complex behaviors across all major neurobehavioral domains and strong genetic and physiological similarities to humans, zebrafish are well-suited to modelling many aspects of anxiety-related states. In this paper, we first summarized the behavioral models available in zebrafish, such as novel tank test, light/dark box test, open field test, and social preference test, and their efficacy in discovering anxiety-like indices in zebrafish, followed by highlighting the key neurotransmitter systems, such as glutamate and GABA. In addition, cortisol levels and gene expression were explored as well. Overall, this review discusses the benefits of using the zebrafish model for anxiety research and examines current research in the field.

Development of Novel Tasks to Assess Outcome-Specific and General Pavlovian-to-Instrumental Transfer in Humans

Introduction: The emergence of Pavlovian-to-instrumental transfer (PIT) research in the human neurobehavioral domain has been met with increased interest over the past two decades. A variety of PIT tasks were developed during this time; while successful in demonstrating transfer phenomena, existing tasks have limitations that should be addressed. Herein, we introduce two PIT paradigms designed to assess outcome-specific and general PIT within the context of addiction. Materials and Methods: The single-lever PIT task, based on an established paradigm, replaced button presses with joystick motion to better assess avoidance behavior. The full transfer task uses alcohol and nonalcohol rewards associated with Pavlovian cues and instrumental responses, along with other gustatory and monetary rewards. We constructed mixed-effects models with the addition of other statistical analyses as needed to interpret various behavioral measures. Results: Single-lever PIT: both versions were successful in eliciting a PIT effect (joystick: p < 0.001, η_p² = 0.36, button-box: p < 0.001, η_p² = 0.30). Full transfer task: it was determined that the alcohol and nonalcoholic reward cues selectively primed their respective reward-associated responses (gustatory version: p < 0.001, r = 0.59, and monetary version: p < 0.001, r = 0.84). The appetitive/aversive cues resulted in a general transfer effect (gustatory: p < 0.001, η_p² = 0.09, and monetary: p < 0.001, η_p² = 0.17). Discussion/Conclusion: Single-lever PIT: PIT was observed in both task versions. We posit that the use of a joystick is more advantageous for the analysis of avoidance behavior. It evenly distributes movement between approach and avoid trials, which is relevant to analyzing fMRI data. Full transfer task: While gustatory conditioning has been used in the past to elicit transfer effects, we present the first paradigm that successfully elicits both specific and general transfers in humans with gustatory alcohol rewards.

Implications of attention and executive functioning weaknesses in youth with Fontan circulation

ABSTRACT Youth with Fontan circulation (Fontan) are at-risk for impairments in attention and executive functioning (EF) due to a confluence of genetic, prenatal, surgical, and medical risk factors. We sought to describe attention and EF in this population, measured via standardized performance-based tests and caregiver rating scales. We then examined how weaknesses in attention and EF were related to outcomes in other neurobehavioral domains, including adaptive behavior and academic achievement. Our sample included 93 youth with Fontan who were referred for neuropsychological evaluations as part of standard clinical care. The cohort as a whole measured between 0.18 to 0.99 standard deviations below normative means across domains of attention, EF, academic achievement, and intellectual ability. In addition, caregiver-reported concerns for attention, EF, anxiety, and depression were elevated, and approximately 0.35 to 0.85 standard deviations above normative means. Lastly, caregiver-reported adaptive behavior measured 0.93 to 1.24 standard deviations below normative values. Academic outcomes were differentially affected by demographic and attention/EF variables, while depression and caregiver-reported EF predicted adaptive behavior. Findings from this study underscore the importance of routine neuropsychological evaluation as part of comprehensive, multidisciplinary care for individuals with Fontan, with the goal of enhancing neurobehavioral and functional outcomes across the lifespan.

Childhood lead exposure and sex-based neurobehavioral functioning in adolescence

It is well documented that childhood lead exposure is associated with long-term decreases in intelligence quotients (IQ). Lesser known is the relationship with neurobehavioral domains, especially in adolescence. This study sought to identify cross-sectional and longitudinal associations between lead exposure and adolescent executive and visual-motor functioning and examine sex-based differences. Participants were 681 children from Jintan, China who had their blood lead levels (BLLs) assessed at age 3–5 years and 12 years old and neurobehavioral functioning assessed through the University of Pennsylvania Computerized Neurocognitive Battery (PennCNB) platform http://www.med.upenn.edu/bbl at 12 years old. Mean BLLs were 6.41 mcg/dl at age 3–5 years and 3.10 mcg/dl at 12. BLLs at 3–5 years and 12 years were used as predictors for the individual neurobehavioral domains in general linear models while controlling for father and mother occupation and education, residence location, age, and adolescent IQ. Models were run separately for males and females. In adjusted models, males BLLs at 3–5 years were associated with increased time to correctly complete tasks in multiple domains including abstraction/flexibility (β = 19.90, 95% CI( 4.26, 35.54) and spatial processing (β = 96.00, 95% CI 6.18, 185.82) at 12 years. For females in adjusted models, BLLs at 3–5 years were associated with increasing time to correctly complete tasks on the episodic memory domain task (β = 34.59, 95% CI 5.33, 63.84) at 12 years. Two adolescent cross-sectional relationships remained in the adjusted models for males only, suggesting a positive association between BLLs and increasing time for correct responses on the attentional domain task (β = 15.08, 95% CI 0.65, 29.51) and decreasing time for correct responses on the episodic memory task (β = −73.49, 95% CI −138.91, −8.06) in males at 12 years. These associations remained with and without controlling for IQ. These results suggest that lead exposure is associated with overall deficits in male and female neurobehavioral functioning, though in different domains and different timing of exposure.

Revisiting the seven pillars of RDoC

BackgroundIn 2013, a few years after the launch of the National Institute of Mental Health’s Research Domain Criteria (RDoC) initiative, Cuthbert and Insel published a paper titled “Toward the future of psychiatric diagnosis: the seven pillars of RDoC.” The RDoC project is a translational research effort to encourage new ways of studying psychopathology through a focus on disruptions in normal functions (such as reward learning or attention) that are defined jointly by observable behavior and neurobiological measures. The paper outlined the principles of the RDoC research framework, including emphases on research that acquires data from multiple measurement classes to foster integrative analyses, adopts dimensional approaches, and employs novel methods for ascertaining participants and identifying valid subgroups.DiscussionTo mark the first decade of the RDoC initiative, we revisit the seven pillars and highlight new research findings and updates to the framework that are related to each. This reappraisal emphasizes the flexible nature of the RDoC framework and its application in diverse areas of research, new findings related to the importance of developmental trajectories within and across neurobehavioral domains, and the value of computational approaches for clarifying complex multivariate relations among behavioral and neurobiological systems.ConclusionThe seven pillars of RDoC have provided a foundation that has helped to guide a surge of new studies that have examined neurobehavioral domains related to mental disorders, in the service of informing future psychiatric nosology. Building on this footing, future areas of emphasis for the RDoC project will include studying central-peripheral interactions, developing novel approaches to phenotyping for genomic studies, and identifying new targets for clinical trial research to facilitate progress in precision psychiatry.

Brain Mapping of Behavioral Domains Using Multi-Scale Networks and Canonical Correlation Analysis.

Simultaneous mapping of multiple behavioral domains into brain networks remains a major challenge. Here, we shed some light on this problem by employing a combination of machine learning, structural and functional brain networks at different spatial resolutions (also known as scales), together with performance scores across multiple neurobehavioral domains, including sensation, motor skills, and cognition. Provided by the Human Connectome Project, we make use of three cohorts: 640 participants for model training, 160 subjects for validation, and 200 subjects for model performance testing thus enhancing prediction generalization. Our modeling consists of two main stages, namely dimensionality reduction in brain network features at multiple scales, followed by canonical correlation analysis, which determines an optimal linear combination of connectivity features to predict multiple behavioral performance scores. To assess the differences in the predictive power of each modality, we separately applied three different strategies: structural unimodal, functional unimodal, and multimodal, that is, structural in combination with functional features of the brain network. Our results show that the multimodal association outperforms any of the unimodal analyses. Then, to answer which human brain structures were most involved in predicting multiple behavioral scores, we simulated different synthetic scenarios in which in each case we completely deleted a brain structure or a complete resting state network, and recalculated performance in its absence. In deletions, we found critical structures to affect performance when predicting single behavioral domains, but this occurred in a lesser manner for prediction of multi-domain behavior. Overall, our results confirm that although there are synergistic contributions between brain structure and function that enhance behavioral prediction, brain networks may also be mutually redundant in predicting multidomain behavior, such that even after deletion of a structure, the connectivity of the others can compensate for its lack in predicting behavior.

0283 Neurobehavioral Resilience and Vulnerability to Sleep Loss Differs Between Objective and Self-Rated Metrics Regardless of Categorization Method Utilized

Abstract Introduction Trait-like individual differences in neurobehavioral responses to sleep restriction (SR) and total sleep deprivation (TSD) are robust and phenotypic. We investigated whether the concordance between multiple approaches for defining differential vulnerability depends on the methods and metrics utilized for categorization, including comparisons between objective and self-rated metrics. Trait-like individual differences in neurobehavioral responses to sleep restriction (SR) and total sleep deprivation (TSD) are robust and phenotypic. We investigated whether the concordance between multiple approaches for defining differential vulnerability depends on the methods and metrics utilized for categorization, including comparisons between objective and self-rated metrics. Methods Forty-one adults (33.9±8.9y; 18 females) participated in a 13-day experiment (two baseline nights [10h-12h time-in-bed, TIB], 5 SR nights [4h TIB], 4 recovery nights [12h TIB], and 36h TSD). The 10-minute Psychomotor Vigilance Test (PVT), Digit Symbol Substitution Test (DSST), Digit Span Task (DS), Karolinska Sleepiness Scale (KSS), Profile of Mood States Fatigue (POMS-F) and Vigor (POMS-V) were administered every 2h during wakefulness. Three approaches (Raw Score [average SR score], Change from Baseline [average SR minus average baseline score], and Variance [intraindividual SR score variance]), and six thresholds (±1 standard deviation, and the best and worst performing 12.5%, 20%, 25%, 33%, and 50%) categorized Resilient and Vulnerable groups. Kendall’s tau-b correlations assessed the group categorization’s concordance between pairings of PVT lapses (reaction time [RT]&amp;gt;500ms), PVT mean response speed (1/RT), DSST number correct, DS total number correct, KSS score, POMS-F score, and POMS-V score (tau-b=0.0: zero; 0.1: weak; 0.4: moderate; 0.70: strong; 1.0: perfect). Results Generally, tau-b correlations comparing Resilient and Vulnerable categorizations between two objective metrics (i.e., PVT, DSST, DS) revealed weak to moderate significant relationships (tau-b=0.29-0.53, p&amp;lt;0.001-0.049) between at least two of the approaches at most thresholds. However, comparisons between one objective (i.e., PVT, DSST, DS) and one self-rated metric (i.e., KSS, POMS) revealed a general lack of significant relationships (tau-b=-0.25-0.28, p=0.052-1.00), regardless of approach or threshold. Conclusion Comparisons between two objective metrics revealed significantly concordant Resilient and Vulnerable categorizations, whereas categorizations were generally not significantly correlated between one objective and one subjective metric, regardless of the method utilized. Our findings support and extend previous assertions that SR differentially impacts objective and subjective neurobehavioral domains and have important implications when assessing resilience and vulnerability to sleep loss in both laboratory and applied settings. Support (If Any) ONR Award No. N00014-11-1-0361; NIH UL1TR000003; NASA NNX14AN49G and 80NSSC20K0243; NIH R01DK117488

Neurocognitive Functioning in Adolescents at Risk for Mental Health Problems.

The main goal of the study was to assess the neurocognitive performance in adolescents at high psychometric risk for mental health problems. A sample of 48 participants at high risk for mental disorders and an age-gender matched healthy comparison group of 48 adolescents were identified from a community-derived sample of 1,509 adolescents. The Strengths and Difficulties Questionnaire problems and the University of Pennsylvania Computerized Neuropsychological Test Battery for children (included 14 tasks assessing five neurobehavioral domains: executive functions, episodic memory, complex cognition, social cognition, and sensorimotor speed) were used. Relative to healthy comparison participants, individuals at high risk showed significant impairments across almost all neurocognitive domains (executive functions, episodic memory, complex cognition, social cognition, and sensorimotor speed). These findings demonstrate that neurocognitive impairments can be shown in adolescents at high psychometric risk for mental health problems before the onset of more severe psychological problems.

Functional Connectivity, Physical Activity, and Neurocognitive Performances in Patients with Vascular Cognitive Impairment, No Dementia.

Vascular Cognitive Impairment, No Dementia (VCIND) is a key stage at which early intervention will delay or prevent dementia. The pathophysiology of VCIND posits that a lesion in a single location in the brain has the ability to disrupt brain networks, and the subsequent abnormal Functional Connectivity (FC) of brain networks leads to deficits in corresponding neurobehavioral domains. In this study, we tested the hypothesis that disrupted anterior cingulate cortex and striatal networks mediated the effects of Physical Activity (PA) on neurobehavioral function. In 27 patients with VCIND, FC within the brain networks and neurobehavioral dysfunction were assessed. The relationship between the cognitive scores, FC, and PA was studied. The Fitbit Charge 2 was used to measure step counts, distance, and calories burned. In patients with VCIND, a cross-sectional Spearman's correlation to analyze the relationship among patient-level measures of PA, cognitive function scores, and FC strength within the brain networks. Average step counts and average distance were associated with Trail Making Test B (TMB) time to completion (seconds) and Instrumental Activities of Daily Living (IADL) score (P < 0.05). The average calories burned were associated with IADL score (P = 0.009). The FC within the brain networks anchored by left caudal Anterior Cingulate Cortex (ACC) seeds (x= -5, y= 0, z= 36) and (x= -5, y= -10, z= 47) were positively correlated with average step counts and average distance, were negatively correlated with TMB time to completion (seconds), and were positively correlated with IADL score (P < 0.05). The FC within the brain networks anchored by left subgenual ACC seed (x= -5, y= 25, z= -10) were negatively correlated with average step counts and average distance were positively correlated with TMB time to completion (seconds), and were negatively correlated with IADL score (P < 0.05). The FC within the striatal networks was positively correlated with average calories burned and IADL score (P < 0.05). FC within the brain networks anchored by caudal ACC seeds was positively correlated with more average step counts/average distance and better IADL score; negatively correlated with longer TMB time to completion (seconds), whereas FC of subgenual ACC seed was negatively correlated with the same parameters. FC within the brain networks anchored by putamen rather than caudate or pallidum was positively correlated with average calories burned and IADL score.

Time after a peak-pesticide use period and neurobehavior among ecuadorian children and adolescents: The ESPINA study

BackgroundLimited evidence exists regarding transient neurobehavioral alterations associated with episodic pesticide exposures or agricultural pesticide spray periods. We previously observed that children examined soon after a pesticide spray period (the Mother's Day flower harvest [MDH]) had lower neurobehavioral performance than children examined later. The present study builds on our previous work by incorporating longitudinal analyses from childhood through adolescence. MethodsWe examined participants in agricultural communities in Ecuador (ESPINA study) during three periods: July–August 2008 (N = 313, 4-9-year-olds); April 2016 (N = 330, 11–17-year-olds); July–October 2016 (N = 535, 11–17-year-olds). Participants were examined primarily during a period of low floricultural production. Neurobehavior was assessed using the NEPSY-II (domains: Attention/Inhibitory Control, Language, Memory/Learning, Visuospatial Processing, and Social Perception). Linear regression and generalized linear mixed models were used to examine cross-sectional and longitudinal associations between examination date (days) after the MDH and neurobehavioral outcomes, adjusting for demographic, anthropometric, and socio-economic variables. ResultsParticipants were examined between 63 and 171 days after the MDH. Mean neurobehavioral domain scores ranged from 1.0 to 17.0 (SDrange = 2.1–3.1) in 2008 and 1.0 to 15.5 (SDrange = 2.0–2.3) in 2016. In cross-sectional analyses (2016 only; N = 523), we found significant or borderline positive associations between time after the MDH and Attention/Inhibitory Control (difference/10 days [β] = 0.22 points [95% CI = 0.03, 0.41]) and Language (β = 0.16 points [95% CI = −0.03, 0.34]). We also observed positive, longitudinal associations (2008–2016) with Attention/Inhibitory Control (β = 0.19 points [95% CI = 0.04, 0.34]) through 112 days after the harvest and Visuospatial Processing (β = 3.56, β-quadratic = −0.19 [95% CI: −0.29, −0.09]) through 92 days. ConclusionsChildren examined sooner after the harvest had lower neurobehavioral performance compared to children examined later, suggesting that peak pesticide spray seasons may transiently affect neurobehavior followed by recovery during low pesticide-use periods. Reduction of pesticide exposure potential for children during peak pesticide-use periods is advised.

Iduronate-2-sulfatase transport vehicle rescues behavioral and skeletal phenotypes in a mouse model of Hunter syndrome.

Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder caused by deficiency of the iduronate-2-sulfatase (IDS) enzyme, resulting in cellular accumulation of glycosaminoglycans (GAGs) throughout the body. Treatment of MPS II remains a considerable challenge as current enzyme replacement therapies do not adequately control many aspects of the disease, including skeletal and neurological manifestations. We developed an IDS transport vehicle (ETV:IDS) that is engineered to bind to the transferrin receptor; this design facilitates receptor-mediated transcytosis of IDS across the blood-brain barrier and improves its distribution into the brain while maintaining distribution to peripheral tissues. Here we show that chronic systemic administration of ETV:IDS in a mouse model of MPS II reduced levels of peripheral and central nervous system GAGs, microgliosis, and neurofilament light chain, a biomarker of neuronal injury. Additionally, ETV:IDS rescued auricular and skeletal abnormalities when introduced in adult MPS II mice. These effects were accompanied by improvements in several neurobehavioral domains, including motor skills, sensorimotor gating, and learning and memory. Together, these results highlight the therapeutic potential of ETV:IDS for treating peripheral and central abnormalities in MPS II. DNL310, an investigational ETV:IDS molecule, is currently in clinical trials as a potential treatment for patients with MPS II.