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Background: Docosahexaenoic acid (DHA) has been reported to be associated with the children's neurodevelopment, who may be exposed to tobacco smoke simultaneously. The evidence about joint effect of DHA intake and tobacco smoke exposure on children and adolescents' learning disabilities (LD) was limited. The objective of this study was to assess the joint effect of DHA intake and tobacco smoke exposure on children and adolescents' LD., Methods: A cross-sectional analysis of the NHANES 1999-2004 was performed. Children and adolescents aged 6-15 years old were included. The outcome was diagnosed by parental report of ever health professionals or school representative-identified LD. Dietary DHA intake data were obtained by food frequency questionnaire and tobacco smoke exposure levels were evaluated by serum cotinine levels. Weighted univariable and multivariate logistic regression analyses were conducted to determine the joint effect of DHA intake and tobacco smoke exposure on LD in children and adolescents, with odds ratios (ORs) and 95% confidence intervals (CIs). This joint association was further assessed after stratification by age, gender, body mass index, the history of attention deficit disorder and seen mental health professional., Results: We identified 5,247 children and adolescents in present study, of whom 593 (11.30%) had LD. After adjusting covariates, we observed children and adolescents with DHA intake (OR = 0.76, 95%CI: 0.61-0.96) was related to lower incidence of LD; children who exposure to tobacco smoke was related to higher incidence of LD (OR = 1.54, 95%CI: 1.07-2.23); children and adolescents who exposure to tobacco smoke and without DHA intake were related to highest odds of LD (OR = 2.08, 95%CI: 1.37-3.17, P for trend = 0.042), that was, DHA and tobacco smoke exposure may have a joint effect on the odds of LD in children and adolescents. Subgroup analyses suggested this joint effect was robust especially among children and adolescents with normal & underweight BMI and without the history of attention deficit disorder and seen mental health professional., Conclusion: Increasing the DHA intake and reducing tobacco smoke exposure may have a potential role in the prevention of LD in children and adolescents. This joint effect warrants further investigation by large-scale prospective study., (© 2024. The Author(s).)

Alcohol abuse induces various neurological disorders including motor learning deficits, possibly by affecting neuronal and astrocytic activity. Physical exercise is one effective approach to remediate synaptic loss and motor deficits as shown by our previous works. In this study, we unrevealed the role of exercise training in the recovery of cortical neuronal and astrocytic functions. Using a chronic alcohol injection mouse model, we found the hyperreactivity of astrocytes along with dendritic spine loss plus lower neuronal activity in the primary motor cortex. Persistent treadmill exercise training, on the other hand, improved neural spine formation and inhibited reactive astrocytes, alleviating motor learning deficits induced by alcohol exposure. These data collectively support the potency of endurance exercise in the rehabilitation of motor functions under alcohol abuse., (© 2024. The Author(s).)

Purpose: The main aim of this systematic review was to investigate the possible association between hearing loss [and/or history of otitis media with effusion (OME)] and learning difficulties in children. Secondary aims were to: (i) investigate if deaf and hard of hearing (DHH) children with learning difficulties might show different clinical and neuropsychological features compared with those with other neurodevelopmental disorders; (ii) identify possible predictors of learning difficulty in DHH children., Methods: A review was conducted of the scientific literature reported by Pubmed, Cochrane and Scopus databases. The following inclusion criteria were used: (i) studies published after 2000; (ii) studies conducted considering subjects with age < 18 years; (iii) studies considering patients who showed both learning difficulties and hearing loss and/or episodes of OME; (iv) articles written in English. The exclusion criteria were: (i) presence in the studied cohort of any other proven comorbidities, other than hearing loss and/or OME; (ii) non-original studies., Results: A total of 924 studies were identified. Four were reviewed after applying the above criteria. From their analysis it emerged that: (i) children with hearing loss who had undergone a diagnostic and rehabilitation program before 6 months of age had better levels of K readiness and language and literacy skills compared to those who had undergone it after 6 months; (ii) higher frequency of episodes of OME and the presence of a conductive hearing loss during the period of language acquisition was associated to lower scores in reading skills; (iii) reading difficulties found in subjects with hearing loss had similar characteristics to those with language difficulties., Conclusions: There is a dearth of information about this topic. Further investigations are therefore necessary on children of various ages with hearing loss to disclose learning difficulties in reading and writing abilities using current diagnostic tools., Competing Interests: Declaration of competing interest The authors declare no potential conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To examine baseline neurocognitive functioning among adolescent athletes on the autism spectrum based on self-reported level of academic performance., Method: Participants in this cross-sectional, observational study were 6,441 adolescent athletes with a self-reported diagnosis of autism who completed pre-season neurocognitive testing using Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT); 4,742 reported a co-occurring learning disorder (LD), and 6,612 individuals without autism or LD were included as a control group. The majority (57%) self-reported Average Academic Performance, 39% Above Average, and 4% Below Average performance., Results: Athletes with self-reported autism (with or without LD; 12.2%) were 2.74x (95% CI: 2.17-2.82) more likely to fall below cutoffs for ImPACT Embedded Invalidity Indicators (EVIs), with a significant interaction between self-reported Diagnosis and Academic Performance; individuals with co-occurring autism and LD who reported Below Average Academic Performance had the greatest likelihood of scoring below cutoffs (22%), followed by ASD without LD (14.8%) and Controls (14.6%) with Below Average Academic Performance. Analyses of variance (ANOVAs) revealed main effects of Diagnosis and Academic Performance on neurocognitive performance, with interactions on all ImPACT Composite Scores except Processing Speed., Conclusion: Athletes with self-reported ASD are more likely to fall below ImPACT EVIs and score worse on ImPACT, with greater likelihood/worse performance related to level of academic functioning. Academic performance should be considered when interpreting neurocognitive testing data, to best index neuropsychological functioning associated with concussion in this population. The current findings highlight the importance of individual participant baseline neuropsychological testing for individuals on the autism spectrum., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Studies have found maternal smoking during pregnancy was linked to attention-deficit/hyperactivity disorder (ADHD) risk. It is unclear if maternal smoking cessation during pregnancy lowers ADHD and learning disability (LD) risk in offspring. This study aimed to explore the associations between maternal smoking cessation during pregnancy and ADHD and LD risk in offspring., Methods: Data from the National Health and Nutrition Examination Survey 1999-2004 (8,068 participants) were used. Logistic regression was used to analyze the associations between maternal smoking and smoking cessation during pregnancy and ADHD and LD risk in offspring., Results: Compared to non-smokers' offspring, maternal smoking during pregnancy increased the risk of ADHD (odds ratios [OR] = 2.07, 95% confidence interval [CI]: 1.67-2.56) and LD (OR = 1.93, 95% CI: 1.61-2.31) in offspring, even if mothers quit smoking later (OR ADHD  = 1.91, 95%CI ADHD : 1.38-2.65, OR LD  = 1.65, 95%CI LD : 1.24-2.19). Further analysis of the timing of initiation of smoking cessation during pregnancy revealed that, compared to non-smokers' offspring, maternal quitting smoking in the first trimester still posed an increased risk of ADHD (OR = 1.72, 95% CI: 1.41-2.61) and LD (OR = 1.52, 95% CI: 1.06-2.17) in offspring. Maternal quitting smoking in the second or third trimester also had a significantly increased risk of ADHD (OR = 2.13, 95% CI: 1.26-3.61) and LD (OR = 1.82, 95% CI: 1.16-2.87) in offspring. Furthermore, maternal smoking but never quitting during pregnancy had the highest risk of ADHD (OR = 2.17, 95% CI: 1.69-2.79) and LD (OR = 2.10, 95% CI: 1.70-2.58) in offspring. Interestingly, a trend toward a gradual increase in the risk-adjusted OR for ADHD and LD risk was observed among the three groups: maternal quitting smoking in the first trimester, maternal quitting smoking in the second or third trimester, and maternal smoking but never quitting., Conclusion: Maternal smoking cessation in the first trimester still poses an increased risk of ADHD and LD in offspring. Furthermore, it seems that the later the mothers quit smoking during pregnancy, the higher the risk of ADHD and LD in their offspring. Therefore, early intervention of maternal smoking in preconception and prenatal care is vital for offspring neurodevelopment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Cai, Zhou, Ma and Li.)

Objective: A previous investigation of people with newly diagnosed focal epilepsy participating in the Human Epilepsy Project 1 (HEP1) revealed an association between learning difficulties and structural brain differences, suggesting an underlying relationship prior to seizure onset. To investigate physicians' practices of documentation learning difficulties during clinical encounters, we conducted a review of initial epileptologist encounter notes from HEP1 participants who self-reported early life learning difficulties separately as part of study enrollment., Methods: HEP1 enrolled 67 North American participants between June 2012 and November 2017 who self-reported one or more difficulties with learning (i.e., having repeated grade, receiving learning support/remediation, and/or formal diagnosis of a learning disability) prior to epilepsy diagnosis as part of the study enrollment. The epileptologist's initial encounter note was then reviewed in detail for each of these participants. Documentation of learning issues and specific diagnoses of learning disabilities was compared to participant characteristics. Regression analysis was used to test for any independent associations between participant characteristics and physician documentation of learning difficulties., Results: There were significant independent relationships between age, sex, and physician documentation of learning difficulties. On average, participants ages 22 and younger were 12.12 times more likely to have their learning difficulties documented compared to those 23 years and older (95 % CI: 2.226 to 66.02, p = 0.004). Additionally, male participants had 7.2 times greater odds of having their learning difficulty documented compared to female participants (95 % CI: 1.538 to 33.717, p = 0.012). There were no significant independent associations between race, language, employment, or geographical region., Significance: These findings highlight disparities in physician documentation for people with newly diagnosed focal epilepsy and a history of learning difficulties. In the HEP1 cohort, physicians were more likely to document learning difficulties in males and in younger individuals. Systematic practice standards are important for reducing healthcare disparities across populations, improving clinical care to individuals, as well as enabling more accurate retrospective study of clinical phenomenon., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Pyramidal neurons have a pivotal role in the cognitive capabilities of neocortex. Though they have been predominantly modeled as integrate-and-fire point processors, many of them have another point of input integration in their apical dendrites that is central to mechanisms endowing them with the sensitivity to context that underlies basic cognitive capabilities. Here we review evidence implicating impairments of those mechanisms in three major neurodevelopmental disabilities, fragile X, Down syndrome, and fetal alcohol spectrum disorders. Multiple dysfunctions of the mechanisms by which pyramidal cells are sensitive to context are found to be implicated in all three syndromes. Further deciphering of these cellular mechanisms would lead to the understanding of and therapies for learning disabilities beyond any that are currently available., Competing Interests: Declaration of Competing Interest The authors declare no competing interests, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: To investigate the prevalence and clinical manifestations of reading, writing, and mathematics disorders in children with cerebral palsy (CP). We explored how the clinical profile of these children differed from those with specific learning disorders (SLDs), taking into account several factors, particularly IQ scores, neuropsychological aspects, and the presence of a visual impairment., Method: A prospective cross-sectional study was conducted in 42 children with CP (mean age 9 years 8 months; SD = 2 years 2 months) and 60 children with SLDs (mean age 10 years; SD = 1 year 7 months). Clinical characteristics, neuromotor and cognitive profiles, neuropsychological aspects (speech performance, academic skills, visual attention, phonological awareness, working memory), and signs of visual impairment (visual acuity, contrast sensitivity, visual field, oculomotor functions) were assessed. A machine learning approach consisting of a random forest algorithm, where the outcome was the diagnosis and the covariates were the clinical variables collected in the sample, was used for the analyses., Results: About 59% of the children with CP had reading, writing, or mathematics disorders. Children with CP with learning disorders had a low performance IQ, normal phonological awareness, and working memory difficulties, whereas children with SLDs had normal performance IQ, impaired phonological awareness, and mild working memory difficulties. There were no differences in verbal IQ between the two groups., Interpretation: Learning disorders are frequently associated with CP, with different clinical characteristics, compared with SLDs. Assessment of academic skills is mandatory in these children, even if the IQ is normal. At school age, specific interventions to promote academic skills in children with CP could be a major rehabilitative goal., What This Paper Adds: Reading, writing, and mathematics disorders in cerebral palsy have specific clinical characteristics. Their underlying mechanisms differ from those described in specific learning disorders. Working memory impairment can be considered a hallmark of learning disorders in children with cerebral palsy., (© 2023 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

ADHD is a common chronic neurodevelopmental disorder and is characterized by persistent inattention, hyperactivity, impulsivity and are often accompanied by learning and memory impairment. Great evidence has shown that learning and memory impairment of ADHD plays an important role in its executive function deficits, which seriously affects the development of academic, cognitive and daily social skills and will cause a serious burden on families and society. With the increasing attention paid to learning and memory impairment in ADHD, relevant research is gradually increasing. In this article, we will present the current research results of learning and memory impairment in ADHD from the following aspects. Firstly, the animal models of ADHD, which display the core symptoms of ADHD as well as with learning and memory impairment. Secondly, the molecular mechanism of has explored, including some neurotransmitters, receptors, RNAs, etc. Thirdly, the susceptibility gene of ADHD related to the learning and impairment in order to have a more comprehensive understanding of the pathogenesis. Key words: Learning and memory, ADHD, Review.

Purpose: Neurofibromatosis (NF) is associated with low quality-of-life (QoL). Learning disabilities are prevalent among those with NF, further worsening QoL and potentially impacting benefits from mind-body and educational interventions, yet research on this population is scarce. Here, we address this gap by comparing NF patients with and without learning disabilities on QoL at baseline and QoL-related gains following two interventions., Methods: Secondary analysis of a fully-powered RCT of a mind-body program (Relaxation Response Resiliency Program for NF; 3RP-NF) versus an educational program (Health Enhancement Program for NF; HEP-NF) among 228 adults with NF. Participants reported QoL in four domains (Physical Health, Psychological, Social Relationships, and Environmental). We compare data at baseline, post-treatment, and 12-month follow-up, controlling for intervention type., Results: At baseline, individuals with NF and learning disabilities had lower Psychological (T = -3.0, p = .001) and Environmental (T = -3.8, p < .001) QoL compared to those without learning disabilities. Both programs significantly improved all QoL domains (ps < .0001-0.002) from baseline to post-treatment, regardless of learning disability status. However, those with learning disabilities exceeded the minimal clinically important difference in only one domain (Psychological QoL) compared to three domains in individuals without learning disabilities. Moreover, those with learning disabilities failed to sustain statistically significant gains in Psychological QoL at 12-months, while those without learning disabilities sustained all gains., Conclusion: Adults with NF and learning disabilities have lower Psychological and Environmental QoL. While interventions show promise in improving QoL regardless of learning disabilities, additional measures may bolster clinical benefit and sustainability among those with learning disabilities., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The extent to which performance validity (PVT) and symptom validity (SVT) tests measure separate constructs is unclear. Prior research using the Minnesota Multiphasic Personality Inventory (MMPI-2 & RF) suggested that PVTs and SVTs are separate but related constructs. However, the relationship between Personality Assessment Inventory (PAI) SVTs and PVTs has not been explored. This study aimed to replicate previous MMPI research using the PAI, exploring the relationship between PVTs and overreporting SVTs across three subsamples, neurodevelopmental (attention deficit-hyperactivity disorder (ADHD)/learning disorder), psychiatric, and mild traumatic brain injury (mTBI)., Methods: Participants included 561 consecutive referrals who completed the Test of Memory Malingering (TOMM) and the PAI. Three subgroups were created based on referral question. The relationship between PAI SVTs and the PVT was evaluated through multiple regression analysis., Results: The results demonstrated the relationship between PAI symptom overreporting SVTs, including Negative Impression Management (NIM), Malingering Index (MAL), and Cognitive Bias Scale (CBS), and PVTs varied by referral subgroup. Specifically, overreporting on CBS but not NIM and MAL significantly predicted poorer PVT performance in the full sample and the mTBI sample. In contrast, none of the overreporting SVTs significantly predicted PVT performance in the ADHD/learning disorder sample but conversely, all SVTs predicted PVT performance in the psychiatric sample., Conclusions: The results partially replicated prior research comparing SVTs and PVTs and suggested that constructs measured by SVTs and PVTs vary depending upon population. The results support the necessity of both PVTs and SVTs in clinical neuropsychological practice.

Background: Strokes frequently result in long-term motor deficits, imposing significant personal and economic burdens. However, our understanding of the underlying neural mechanisms governing motor learning in stroke survivors remains limited - a fact that poses significant challenges to the development and optimisation of therapeutic strategies., Objective: This study investigates the diversity in motor learning aptitude and its associated neurological mechanisms. We hypothesised that stroke patients exhibit compromised overall motor learning capacity, which is associated with altered activity and connectivity patterns in the motor- and default-mode-network in the brain., Methods: We assessed a cohort of 40 chronic-stage, mildly impaired stroke survivors and 39 age-matched healthy controls using functional Magnetic Resonance Imaging (fMRI) and connectivity analyses. We focused on neural activity and connectivity patterns during an unilateral motor sequence learning task performed with the unimpaired or non-dominant hand. Primary outcome measures included task-induced changes in neural activity and network connectivity., Results: Compared to controls, stroke patients showed significantly reduced motor learning capacity, associated with diminished cerebral lateralization. Task induced activity modulation was reduced in the motor network but increased in the default mode network. The modulated activation strength was associated with an opposing trend in task-induced functional connectivity, with increased connectivity in the motor network and decreased connectivity in the DMN., Conclusions: Stroke patients demonstrate altered neural activity and connectivity patterns during motor learning with their unaffected hand, potentially contributing to globally impaired motor learning skills. The reduced ability to lateralize cerebral activation, along with the enhanced connectivity between the right and left motor cortices in these patients, may signify maladaptive neural processes that impede motor adaptation, possibly affecting long-term rehabilitation post-stroke. The contrasting pattern of activity modulation and connectivity alteration in the default mode network suggests a nuanced role of this network in post-stroke motor learning. These insights could have significant implications for the development of customised rehabilitation strategies for stroke patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Developmental learning disorder (DLD) belongs to neurodevelopmental disorders because it results from the developmental neurodiversity of the brain. The main causes of DLD are genetics, but environmental factors, like inadequate supply of oxygen during pregnancy or labor, are considered., Methods: Our search strategy will consist of electronic databases (PubMed, PsycINFO, Web of Science, EMBASE, and Cochrane Library) and hand searching. The observational studies including cohort and case-control studies will be included. The primary outcome will be (DLD). Screening and eligibility will be done independently by two reviewers based on pre-specified eligibility criteria. Data extraction will be based on a pre-pilot data extraction form, and conducted by two authors independently. Study quality will be assessed by two authors independently. Any discrepancies identified at any stage of the review will be resolved by discussion or/and consultation with another reviewer. We plan a narrative and tabular summary of the findings., Discussion: This systematic review of aetiology follows the traditional approach to evidence-based healthcare. This secondary research will assess the association between hypoxia and DLD by assessing the relationship of health-related event and outcome and examining the association between them. This review can provide information for healthcare professionals and policymakers indicating whether taking into account information about hypoxia should be permanently included in the diagnostic ontogenetic interview in the process of diagnosing neurodevelopmental disorders., Systematic Review Registration: PROSPERO: CRD42022371387., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Radtke et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: Whether some domains of child development are specifically associated with screen time and whether the association continues with age remain unknown., Objective: To examine the association between screen time exposure among children aged 1 year and 5 domains of developmental delay (communication, gross motor, fine motor, problem-solving, and personal and social skills) at age 2 and 4 years., Design, Participants, and Setting: This cohort study was conducted under the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study. Pregnant women at 50 obstetric clinics and hospitals in the Miyagi and Iwate prefectures in Japan were recruited into the study between July 2013 and March 2017. The information was collected prospectively, and 7097 mother-child pairs were included in the analysis. Data analysis was performed on March 20, 2023., Exposure: Four categories of screen time exposure were identified for children aged 1 year (<1, 1 to <2, 2 to <4, or ≥4 h/d)., Main Outcomes and Measures: Developmental delays in the 5 domains for children aged 2 and 4 years were assessed using the Japanese version of the Ages & Stages Questionnaires, Third Edition. Each domain ranged from 0 to 60 points. Developmental delay was defined if the total score for each domain was less than 2 SDs from its mean score., Results: Of the 7097 children in this study, 3674 were boys (51.8%) and 3423 were girls (48.2%). With regard to screen time exposure per day, 3440 children (48.5%) had less than 1 hour, 2095 (29.5%) had 1 to less than 2 hours, 1272 (17.9%) had 2 to less than 4 hours, and 290 (4.1%) had 4 or more hours. Children's screen time was associated with a higher risk of developmental delay at age 2 years in the communication (odds ratio [OR], 1.61 [95% CI, 1.23-2.10] for 1 to <2 h/d; 2.04 [1.52-2.74] for 2 to <4 h/d; 4.78 [3.24-7.06] for ≥4 vs <1 h/d), fine motor (1.74 [1.09-2.79] for ≥4 vs <1 h/d), problem-solving (1.40 [1.02-1.92] for 2 to <4 h/d; 2.67 [1.72-4.14] for ≥4 vs <1 h/d), and personal and social skills (2.10 [1.39-3.18] for ≥4 vs <1 h/d) domains. Regarding risk of developmental delay at age 4 years, associations were identified in the communication (OR, 1.64 [95% CI, 1.20-2.25] for 2 to <4 h/d; 2.68 [1.68-4.27] for ≥4 vs <1 h/d) and problem-solving (1.91 [1.17-3.14] for ≥4 vs <1 h/d) domains., Conclusions and Relevance: In this study, greater screen time for children aged 1 year was associated with developmental delays in communication and problem-solving at ages 2 and 4 years. These findings suggest that domains of developmental delay should be considered separately in future discussions on screen time and child development.

The aim of this study was to understand the risk of developing attention-deficit/hyperactivity disorder (ADHD) or learning disability (LD) after childhood traumatic brain injury (TBI) in a population-based birth cohort. Cases of TBI for children from birth to 10 years were confirmed and stratified by severity of injury. For each TBI case, two age-matched and sex-matched referents without TBI were identified from the same birth cohort. Presence of ADHD and LD before age 19 were confirmed using medical and/or school records. Associations between TBI exposure and subsequent ADHD or LD were assessed in multivariable Cox regression models, adjusting for maternal age, education, and race. The incidence rate of TBI before age 10 was 1,156 per 100,000 person-years. Children who had a TBI before age 10 were more likely to have met the research criteria for ADHD (hazard ratio [HR], 1.68; 95% CI, 1.15-2.45) or LD (HR, 1.29; 95% CI, 1.00-1.68) by age 19. No statistically significant associations were shown between TBI and ADHD or LD when restricted to definite and probable TBI cases (consistent with moderate to severe and mild TBI, respectively) and their referents. Significant associations were shown when the analysis was confined to possible TBI cases (consistent with concussive TBI) and their referents (ADHD: HR, 2.05; 95% CI, 1.31-3.20; and LD: HR, 1.42; 95% CI, 1.05-1.91). Increased risk for developing ADHD and LD by adulthood was shown particularly for children with the least-severe injuries, indicating that factors other than trauma-related altered brain function likely contribute to this risk.

Vision has a crucial role to play in human development and functioning. It is, therefore, not surprising that vision plays a fundamental role in the development of the child. As a consequence, an alteration in visual function is, therefore, likely to hinder the child's development. Although ocular disorders are well known, diagnosed and taken into account, cerebral visual impairments (CVI) resulting from post-chiasmatic damage are largely underdiagnosed. However, among the disorders resulting from an episode of perinatal asphyxia and/or associated with prematurity, or neonatal hypoglycaemia, CVIs are prominent. In this article, we focus on the role of the possible effects of CVI on a child's learning abilities, leading to major difficulty in disentangling the consequences of CVI from other neurodevelopmental disorders (NDD) such as dyslexia, dyscalculia, dysgraphia, attention-deficit/hyperactivity disorder (ADHD), developmental coordination disorder (DCD) and autism spectrum disorders (ASD). Although we focus here on the possible overlap between children with CVI and children with other NDD, De Witt et al. (Wit et al. Ear Hear 39:1-19, 2018) have raised exactly the same question regarding children with auditory processing disorders (the equivalent of CVI in the auditory modality). We underline how motor, social and cognitive development as well as academic success can be impaired by CVI and raise the question of the need for systematic evaluation for disorders of vision, visual perception and cognition in all children presenting with a NDD and/or previously born under adverse neurological conditions., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background and Purpose: Verbal declarative memory performance relies on frontotemporal connectivity. The uncinate fasciculus is a major association tract connecting the frontal and temporal lobes. Hemispheric asymmetries contribute to various cognitive and neurobehavioral abilities. Here we investigated microstructural alterations and hemispheric asymmetry of the uncinate fasciculus and their possible correlation to memory performance of children with learning disorders attributed to verbal memory deficits., Materials and Methods: Two groups of right-handed children with learning disorders attributed to verbal memory deficits and typically developing children ( n = 20 and 22, respectively) underwent DTI on a 1.5T scanner. Tractography of the uncinate fasciculus in both hemispheres was performed, and fractional anisotropy and diffusivity indices (radial diffusivity, axial diffusivity, and trace) were obtained. The asymmetry index was calculated. Verbal memory was assessed using subsets of the Stanford Binet Intelligence Scale, 4th edition, a dyslexia assessment test, and the Illinois test of Psycholinguistic Abilities. Correlation between diffusion metrics and verbal memory performance was investigated in the learning disorders group. Also, hemispheric differences in each group were tested, and between-group comparisons were performed., Results: Children with learning disorders showed absence of the normal left-greater-than-right asymmetry of fractional anisotropy and the normal right-greater-than-left asymmetry of radial diffusivity seen in typically developing children. Correlation with verbal memory subsets revealed that the higher the fractional anisotropy and asymmetry index, the better the rapid naming performance ( P <.05) was., Conclusions: These findings demonstrated microstructural aberrations with reduction of hemispheric asymmetry of the uncinate fasciculus, which could disrupt the normal frontotemporal connectivity in children with learning disorders attributed to verbal memory deficits. This outcome gives more understanding of pathologic mechanisms underlying this disorder., (© 2022 by American Journal of Neuroradiology.)

Neck of femur fractures (NOFF) are one of the major health concerns, with their incidence and the cost of care rising each year. Though a plethora of literature remains available on NOFF and its management, we found very little evidence for management of NOFF in patients with short stature and learning disability. Because of this unique combination of conditions in our patient, we had to deviate from the standard practice in terms of the implant choice. The usage of cemented Asian C stem AMT with a 36 mm metallic head which is normally reserved for total hip replacements, helped us obtain the desired hip joint stability. This was supplemented by early involvement of the learning disability physiotherapy team and eventually the patient had a satisfactory outcome at 8 months of follow-up. This rare amalgamation of NOFF, short stature and learning disability deserves more attention which our case report hopes to achieve., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The study aims to investigate the social, emotional, and behavioral challenges in children with a specific learning disability (SLD) and to identify the factors that accompany these problems by screening with the Strengths and Difficulties Questionnaire (SDQ)., Methods: The descriptive study was conducted on 278 children with SLD. Strengths and difficulties in children were evaluated by the SDQ applied to their mothers. The percentage of cases above the cut-off limits of the SDQ was calculated. Chi-square test and multiple logistic regression analysis were used for analysis., Results: The mean (SD) total SDQ score was 15.8 (6.5). The percentage of scores of abnormal total difficulties in SLD was 47.8%. Multivariate analysis revealed that cases exposed to antenatal smoking had higher odds ratio of abnormal emotional symptoms and abnormal total difficulties; cases with poor familial income and the presence of a history of antenatal smoking exposure showed considerably higher odds ratio of conduct problems; cases with younger age at the diagnosis of SLD, dyscalculia, extreme duration of preschool screen time (≥4 h), and history of hospitalization had significantly higher odds ratio for hyperactivity-inattention problems; and cases having shorter breastfeeding duration had higher odds ratio of peer problems compared to counterparts., Conclusion: Children with SLD have a high score on the SDQ. Practitioners could especially give guidance and support to families with financial problems and those having a child with an early age at diagnosis, exposure to antenatal smoking, short breastfeeding period, early age of the first screen use, and long screen exposure duration during the preschool period., (© 2021 John Wiley & Sons Ltd.)

Illicit use of opioids is a global health crisis with major implications for women and children. Strategies for managing opioid use disorder (OUD) in pregnancy have been tested over the past 40 years, but studies have focused on maternal and pregnancy outcomes, with less attention given to long-term follow-up of exposed children. Here, we provide a narrative review of recent advances in the assessment and management of neonatal opioid withdrawal syndrome (NOWS), and we summarise evidence from multiple domains-neuroimaging, electrophysiology, visual development and function, neurodevelopment, behaviour, cognition and education-which suggests that prenatal opioid exposure modifies child development. Further studies are required to determine the optimal management of pregnant women with OUD and babies with NOWS. We identify knowledge gaps and suggest that future study designs should evaluate childhood outcomes, including infant brain development and long-term neurocognitive and visual function., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

This study describes functional and health-related quality of life (HRQoL) outcomes in patients with Hirschsprung's disease (HSCR) with associated learning disability or neurodevelopmental delay (LD), completing a core outcome set for HSCR. This was a cross-sectional study from a tertiary pediatric surgery center. Patients treated between 1977 and 2013 were prospectively contacted to complete an outcomes survey. Children under 12 and older patients with LD were assisted to complete these by a proxy. Bowel and urologic function were assessed (Rintala's BFS and modified DanPSS) along with HRQoL (PedsQL/GIQLI/SF-36). Thirty-two patients with LD were compared to 186 patients with normal cognition. Patients with LD had 76% survival over the follow-up period, compared to 99% in the remainder of the cohort. Poor functional outcomes were common in the patients with LD, considerably higher than cognitively normal patients: with weekly issues withholding stool, soiling and fecal accidents in over half of patients surveyed (44-60%), and urinary incontinence in 46%. Use of permanent stoma was significantly higher (22% vs. 4%; p = 0.001). HRQoL was worse in domains of physical functioning in adults and children but not for social or emotional domains in adults. Subgroup analysis of patients with Down syndrome suggested similar functional results but better QoL. Multivariate analysis demonstrated a dramatically higher incidence of poor continence outcomes in patients with LD (adjusted OR 9.6 [4.0-23]).Conclusions: We provide LD-specific outcomes showing inferior function but similar HRQoL to other patients with HSCR, this is much needed in the counselling of families of these children. What is Known: • Hirschsprung's disease is commonly associated with syndromes or other anomalies with resultant cognitive impairments. • The outcomes for these patients specifically have been poorly described in the literature. What is New: • Objective functional and quality of life surveys demonstrate significant differences from patients without cognitive impairment. • Patients with learning disability Patients with associated LD were almost ten times more likely to have an associated poor functional outcome, with very little impact on proxy-reported quality of life., (© 2021. The Author(s).)

Human and animal studies have elucidated the apparent neurodevelopmental effects resulting from neonatal anesthesia. Observations of learning and behavioral deficits in children, who were exposed to anesthesia early in development, have instigated a flurry of studies that have predominantly utilized animal models to further interrogate the mechanisms of neonatal anesthesia-induced neurotoxicity. Specifically, while neonatal anesthesia has demonstrated its propensity to affect multiple cell types in the brain, it has shown to have a particularly detrimental effect on the gamma aminobutyric acid (GABA)ergic system, which contributes to the observed learning and behavioral deficits. The damage to GABAergic neurons, resulting from neonatal anesthesia, seems to involve structure-specific changes in excitatory-inhibitory balance and neurovascular coupling, which manifest following a significant interval after neonatal anesthesia exposure. Thus, to better understand how neonatal anesthesia affects the GABAergic system, we first review the early development of the GABAergic system in various structures that have been the focus of neonatal anesthesia research. This is followed by an explanation that, due to the prolonged developmental curve of the GABAergic system, the entirety of the negative effects of neonatal anesthesia on learning and behavior in children are not immediately evident, but instead take a substantial amount of time (years) to fully develop. In order to address these concerns going forward, we subsequently offer a variety of in vivo methods which can be used to record these delayed effects.

ATP-sensitive potassium (K ATP ) gain-of-function (GOF) mutations cause neonatal diabetes, with some individuals exhibiting developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome. Mice expressing K ATP -GOF mutations pan-neuronally (nK ATP -GOF) demonstrated sensorimotor and cognitive deficits, whereas hippocampus-specific hK ATP -GOF mice exhibited mostly learning and memory deficiencies. Both nK ATP -GOF and hK ATP -GOF mice showed altered neuronal excitability and reduced hippocampal long-term potentiation (LTP). Sulfonylurea therapy, which inhibits K ATP , mildly improved sensorimotor but not cognitive deficits in K ATP -GOF mice. Mice expressing K ATP -GOF mutations in pancreatic β-cells developed severe diabetes but did not show learning and memory deficits, suggesting neuronal K ATP -GOF as promoting these features. These findings suggest a possible origin of cognitive dysfunction in DEND and the need for novel drugs to treat neurological features induced by neuronal K ATP -GOF., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Chronic stress could induce severe cognitive impairments. Despite extensive investigations in mammalian models, the underlying mechanisms remain obscure. Here, we show that chronic stress could induce dramatic learning and memory deficits in Drosophila melanogaster The chronic stress-induced learning deficit (CSLD) is long lasting and associated with other depression-like behaviors. We demonstrated that excessive dopaminergic activity provokes susceptibility to CSLD. Remarkably, a pair of PPL1-γ1pedc dopaminergic neurons that project to the mushroom body (MB) γ1pedc compartment play a key role in regulating susceptibility to CSLD so that stress-induced PPL1-γ1pedc hyperactivity facilitates the development of CSLD. Consistently, the mushroom body output neurons (MBON) of the γ1pedc compartment, MBON-γ1pedc>α/β neurons, are important for modulating susceptibility to CSLD. Imaging studies showed that dopaminergic activity is necessary to provoke the development of chronic stress-induced maladaptations in the MB network. Together, our data support that PPL1-γ1pedc mediates chronic stress signals to drive allostatic maladaptations in the MB network that lead to CSLD., Competing Interests: The authors declare no competing interest.

Animals have evolved cognitive abilities whose impairment can incur dramatic fitness costs. While malnutrition is known to impact brain development and cognitive functions in vertebrates, little is known in insects whose small brain appears particularly vulnerable to environmental stressors. Here, we investigated the influence of diet quality on learning and memory in the parasitoid wasp Venturia canescens. Newly emerged adults were exposed for 24 h to either honey, 20% sucrose solution, 10% sucrose solution, or water, before being conditioned in an olfactory associative learning task in which an odor was associated to a host larvae (reward). Honey fed wasps showed 3.5 times higher learning performances and 1.5 times longer memory retention than wasps fed sucrose solutions or water. Poor diets also reduced longevity and fecundity. Our results demonstrate the importance of early adult nutrition for optimal cognitive function in these parasitoid wasps that must quickly develop long-term olfactory memories for searching suitable hosts for their progeny., (© 2021. The Author(s).)

Objective: This study aimed to examine the predictors of cognitive performance in patients with pediatric mild traumatic brain injury (pmTBI) and to determine whether group differences in cognitive performance on a computerized test battery could be observed between pmTBI patients and healthy controls (HC) in the sub-acute (SA) and the early chronic (EC) phases of injury., Method: 203 pmTBI patients recruited from emergency settings and 159 age- and sex-matched HC aged 8-18 rated their ongoing post-concussive symptoms (PCS) on the Post-Concussion Symptom Inventory and completed the Cogstate brief battery in the SA (1-11 days) phase of injury. A subset (156 pmTBI patients; 144 HC) completed testing in the EC (~4 months) phase., Results: Within the SA phase, a group difference was only observed for the visual learning task (One-Card Learning), with pmTBI patients being less accurate relative to HC. Follow-up analyses indicated higher ongoing PCS and higher 5P clinical risk scores were significant predictors of lower One-Card Learning accuracy within SA phase, while premorbid variables (estimates of intellectual functioning, parental education, and presence of learning disabilities or attention-deficit/hyperactivity disorder) were not., Conclusions: The absence of group differences at EC phase is supportive of cognitive recovery by 4 months post-injury. While the severity of ongoing PCS and the 5P score were better overall predictors of cognitive performance on the Cogstate at SA relative to premorbid variables, the full regression model explained only 4.1% of the variance, highlighting the need for future work on predictors of cognitive outcomes.

Vestibular and ocular motor assessment has gained popularity as a tool for sport-related concussion among healthcare professionals. With awareness of premorbid risk factors, such as attentional problems, it is imperative to understand their effects at baseline. The purpose of this study was to examine the effects of attention deficit/hyperactivity disorder (ADHD) and diagnosed learning disability (LD) on vestibular and oculomotor baseline concussion assessment in pediatrics. Pediatric athletes between the ages of 8 and 14 years with ADHD/LD ( n  = 30) and match controls without ADHD/LD ( n  = 30) completed baseline concussion testing, consisting of symptom provocation on the Vestibular/Ocular Motor Screening (VOMS) and oculomotor performance on near point of convergence (NPC) and King-Devick (K-D) tools. Those diagnosed with ADHD/LD performed worse on baseline saccades ( p range = .02-.10), convergence ( p  = .04), vestibular ocular reflex (VOR) ( p  = .03) and visual motion sensitivity (VMS) ( p  = .04) of the VOMS. Base rate analyses revealed that 26% of athletes in the ADHD/LD group had ≥1 and 13.3% had ≥2 VOMS domains over clinical cutoff levels, compared to 3.3% (≥1 domain) and 0 (≥2 domains) of controls. Individuals with ADHD/LD also performed worse on K-D assessment ( p  = .005). However, no differences were reported on NPC distance ( p  = .19). These findings suggest worse baseline concussion assessment scores on vestibular/ocular motor assessment domains in pediatric athletes diagnosed with ADHD/LD. Additional research is needed on assessment outcomes to determine if special consideration to those diagnosed with ADHD/LD is warranted.

Importance: Literacy has been described as an important social determinant of health. Its components emerge in infancy and are dependent on genetic, medical, and environmental factors. The American Academy of Pediatrics advocates a substantial role for pediatricians in literacy promotion, developmental surveillance, and school readiness to promote cognitive, relational, and brain development. Many children, especially those from minority and underserved households, enter kindergarten unprepared to learn to read and subsequently have difficulty in school., Observations: Emergent literacy is a developmental process beginning in infancy. Component skills are supported by brain regions that must be adequately stimulated and integrated to form a functional reading network. Trajectories are associated with genetic, medical, and environmental factors, notably the home literacy environment, which is defined as resources, motivation, and stimulation that encourage the literacy development process. Eco-biodevelopmental models are advocated by the American Academy of Pediatrics, and these models offer insights into the neurobiological processes associated with environmental factors and the ways in which these processes may be addressed to improve outcomes. Emergent literacy is well suited for such a model, particularly because the mechanisms underlying component skills are elucidated. In addition to cognitive-behavioral benefits, the association of home literacy environment with the developing brain before kindergarten has recently been described via neuroimaging. Rather than a passive approach, which may subject the child to stress and engender negative attitudes, early literacy screening and interventions that are administered by pediatric practitioners can help identify potential reading difficulties, address risk factors during a period when neural plasticity is high, and improve outcomes., Conclusions and Relevance: Neuroimaging and behavioral evidence inform an eco-biodevelopmental model of emergent literacy that is associated with genetic, medical, and home literacy environmental factors before kindergarten, a time of rapid brain development. This framework is consistent with recommendations from the American Academy of Pediatrics and provides insights to help identify risk factors and signs of potential reading difficulties, tailor guidance, and provide direction for future research.

Self-advocacy is linked to the success and retention of students with disabilities in college. Self-advocacy is defined as communicating individual wants, needs, and rights to determine and pursue required accommodations. While self-advocacy is linked to academic success, little is known about how students with disabilities in science, technology, engineering, and mathematics (STEM) practice self-advocacy. We previously developed a model of self-advocacy for STEM students with attention-deficit/hyperactivity disorder (ADHD) and/or specific learning disabilities (SLD). Here, we use this model to examine what factors support or hinder self-advocacy in undergraduate STEM courses. We conducted semistructured interviews with 25 STEM majors with ADHD and/or SLD and used qualitative approaches to analyze our data. We found internal factors, or factors within a participant, and external factors, the situations and people, described by our participants, that influenced self-advocacy. These factors often interacted and functioned as a support or barrier, depending on the individuals and their unique experiences. We developed a model to understand how factors supported or hindered self-advocacy in STEM. Supporting factors contributed to a sense of comfort and security for our participants and informed their perceptions that accommodation use was accepted in a STEM course. We share implications for research and teaching based on our results.

Objective: The Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) is commonly used to assist with post-concussion return-to-play decisions for athletes. Additional investigation is needed to determine whether embedded indicators used to determine the validity of scores are influenced by the presence of neurodevelopmental disorders (NDs)., Method: This study examined standard and novel ImPACT validity indicators in a large sample of high school athletes (n = 33,772) with or without self-reported ND., Results: Overall, 7.1% of athletes' baselines were judged invalid based on standard ImPACT validity criteria. When analyzed by group (healthy, ND), there were significantly more invalid ImPACT baselines for athletes with an ND diagnosis or special education history (between 9.7% and 54.3% for standard and novel embedded validity criteria) when compared to athletes without NDs. ND history was a significant predictor of invalid baseline performance above and beyond other demographic characteristics (i.e., age, sex, and sport), although it accounted for only a small percentage of variance. Multivariate base rates are presented stratified for age, sex, and ND., Conclusions: These data provide evidence of higher than normal rates of invalid baselines in athletes who report ND (based on both the standard and novel embedded validity indicators). Although ND accounted for a small percentage of variance in the prediction of invalid performance, negative consequences (e.g., extended time out of sports) of incorrect decision-making should be considered for those with neurodevelopmental conditions. Also, reasons for the overall increase noted here, such as decreased motivation, "sandbagging", or disability-related cognitive deficit, require additional investigation.

Rare heritable syndromes may affect educational attainment. Here, we study education in neurofibromatosis 1 (NF1) that is associated with multifaceted medical, social and cognitive consequences. Educational attainment in the Finnish population-based cohort of 1408 individuals with verified NF1 was compared with matched controls using Cox proportional hazards model with delayed entry and competing risk for death. Moreover, models accounting for the effects of cancer at age 15-30 years, parental NF1 and developmental disorders were constructed. Overall, the attainment of secondary education was reduced in individuals with NF1 compared to controls (hazard ratio 0.83, 95%CI 0.74-0.92). History of cancer and developmental disorders were major predictors of lack of secondary education. Individuals with NF1 obtained vocational secondary education more often than general upper secondary education. Consequently, NF1 decreased the attainment of Bachelor's and Master's degrees by 46%-49% and 64%-74%, respectively. Surprisingly, the non-NF1 siblings of individuals with NF1 also had lower educational attainment than controls, irrespective of parental NF1. In conclusion, NF1 is associated with reduced educational attainment and tendency for affected individuals to obtain vocational instead of academic education. Individuals living with NF1, especially those with cancer, developmental disorders or familial NF1, need effective student counseling and learning assistance., (© 2020 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)

In a few situations, the consequences secondary to a carcinological pathology require an assessment of damages for compensatory purposes. This is particularly the case when liable parties have been found to be at cause of the disease: occupational pathologies in the case of inexcusable employer's fault, exposure to a radioactive risk, for example in the context of full compensation for damages suffered by the victims of nuclear experiments performed by France, or lastly, in the after-effects of late diagnosis. This article does not discuss the imputability of cancer pathologies to an event, but it proposes an adaptation of methods for assessing damages, in an attempt to provide full compensation for damages., (Copyright © 2021 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Mathematics Learning Disorder (MLD) has been found to be related to impairments in cognitive functions. Spatial ability (SA), which is made up of eight single but unified elements can be assumed to have a leading part in different areas of math skills. The first objective of this study was to explore differences in SA factors in 128 school children of third to sixth grade with and without MLD. The Flexibility of Closure, Closure Speed, Perceptual Speed, Visualization, Spatial Relation, Spatial Orientation, Spatial Temporal, and Wayfinding were measured through eight tasks. The second objective of the study was to explore the SA factors' ability to predict the performance of MLD participants in three executive functions. The results revealed that participants with MLD had poorer performance in all the SA tasks and it took longer to finish the visualization, spatial relation, and spatial orientation tasks compared to children with typical development (TD). Regression analysis indicated that some of the SA factors could predict working memory and cognitive flexibility, but they were unable to predict response inhibition. Regarding these results, applying SA factors in cognitive rehabilitation programs of children with MLD seems necessary.

It is hypothesized that perinatal cerebellar injury leads to long-term functional deficits due to circuit dysmaturation. Using a novel integration of GCaMP6f fiber photometry with automated measurement of cerebellar behavior using the ErasmusLadder, we causally link cerebellar injury to altered Purkinje cell responses during maladaptive behavior. Chemogenetic inhibition of neonatal Purkinje cells is sufficient to phenocopy the effects of perinatal cerebellar injury. Our results uncover a direct link between perinatal cerebellar injury and activity-dependent maturation of cerebellar cortex., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

RAB7, a member of RAS oncogene family-like 1 (RAB7L1), is a GTPase belonging to the Rab family and acts as an upstream regulator to regulate the kinase activity of leucine-rich repeat kinase 2 (LRRK2). Although LRRK2 has been shown to aggravate secondary brain injury (SBI) after intracerebral hemorrhage (ICH), it is unknown whether RAB7L1 is also involved in this process. The purpose of the present study was to investigate the role of RAB7L1 in ICH-induced SBI in vivo. Autologous blood was injected into adult male Sprague-Dawley rats to induce an ICH model in vivo. The results showed that the protein levels of RAB7L1 increased after ICH. Overexpression of RAB7L1 induced neuronal apoptosis and damage, as demonstrated by TUNEL-positive and FJB-positive cells, and exacerbated ICH-induced learning and cognitive dysfunctions; in contrast, downregulation of RAB7L1 via RNA interference yielded comparatively opposite changes in these parameters. In summary, this study demonstrates that RAB7L1 promotes SBI after ICH and may represent a potential target for ICH therapy.

This study was designed to test whether the Cronobacter sakazakii infection-impaired contextual learning and memory are mediated by the activation of the complement system; subsequent activation of inflammatory signals leads to alternations in serotonin transporter (SERT). To test this, rat pups (postnatal day, PND 15) were treated with either C. sakazakii (10 7  CFU) or Escherichia coli OP50 (10 7  CFU) or Luria bertani broth (100 μL) through oral gavage and allowed to stay with their mothers until PND 24. Experimental groups' rats were allowed to explore (PNDs 31-35) and then trained in contextual learning task (PNDs 36-43). Five days after training, individuals were tested for memory retention (PNDs 49-56). Observed behavioural data showed that C. sakazakii infection impaired contextual-associative learning and memory. Furthermore, our analysis showed that C. sakazakii infection activates complement system complement anaphylatoxin (C5a) (a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS1)) and mitogen-activated protein kinase kinase1 (MEKK1). Subsequently, MEKK1 induces pro-inflammatory signals possibly through apoptosis signal-regulating kinase-1 (ASK-1), c-Jun N-terminal kinase (JNK1/3) and protein kinase B gamma (AKT-3). In parallel, activated nuclear factor kappa-light-chain-enhancer B cells (NF-κB) induces interleukin-6 (IL-6) and IFNα-1, which may alter the level of serotonin transporter (SERT). Observed results suggest that impaired contextual learning and memory could be correlated with C5a-mediated NF-κβ and ASK1 pathways.

The basal ganglia are important for movement and executive function, but its contribution to language is less understood. This study explored language outcomes associated with childhood basal ganglia stroke. A detailed language coding scheme, which examined expressive and receptive language, verbal fluency, narrative discourse, pragmatic/applied language, and academics, was developed from qualitative and quantitative data acquired from neuropsychological testing and reports. Overall intellectual functioning and verbal comprehension was in the average range. Twelve participants had psychological diagnoses, including Learning Disorder. No one had a Language Disorder diagnosis. Among the 18 children who did not receive a diagnosis, many exhibited language issues in the mild to severe range according to our coding scheme. These children had higher-order language difficulties in verbal fluency, narrative, and pragmatic language rather than overt expressive difficulties noted in Diagnostic and Statistical Manual (DSM) diagnostic criteria. There was an association between infarct size and ESL/immersion education, math performance, and presence of a psychological diagnosis. Psychological diagnosis was also associated with literacy skills. The results highlight that language issues following basal ganglia stroke may not be fully captured by standardized neuropsychological tests and psychological diagnoses. Findings reinforce the need to integrate quantitative and qualitative findings when examining language functioning.

The hippocampus is known to play a critical role in a variety of complex abilities, including visual-spatial reasoning, social functioning, and math. Nonverbal learning disability (NVLD) is a neurodevelopmental disorder characterized by deficits in visual-spatial reasoning that are accompanied by impairment in social function or mathematics, as well as motor or executive function skills. Despite the overlap between behaviors supported by the hippocampus and impairments in NVLD, the structure and function of the hippocampus in NVLD has not been studied. To address this gap in the literature, we first compared hippocampal volume and resting-state functional connectivity in children with NVLD (n = 24) and typically developing (TD) children (n = 20). We then explored associations between hippocampal structure, connectivity, and performance on measures of spatial, social, and mathematical ability. Relative to TD children, those with NVLD showed significant reductions in left hippocampal volume and greater hippocampal-cerebellar connectivity. In children with NVLD, reduced hippocampal volume associated with worse mathematical problem solving. Although children with NVLD exhibited more social problems (social responsiveness scale [SRS]) and higher hippocampal-cerebellar connectivity relative to TD children, greater connectivity was associated with fewer social problems among children with NVLD but not TD children. Such an effect may suggest a compensatory mechanism. These structural and functional alterations of the hippocampus may disrupt its putative role in organizing conceptual frameworks through cognitive mapping, thus contributing to the cross-domain difficulties that characterize NVLD., (© 2020 Wiley Periodicals LLC.)

Background: Deficits in visual statistical learning and predictive processing could in principle explain the key characteristics of inattention and distractibility in attention deficit hyperactivity disorder (ADHD). Specifically, from a Bayesian perspective, ADHD may be associated with flatter likelihoods (increased sensory processing noise), and/or difficulties in generating or using predictions. To our knowledge, such hypotheses have never been directly tested., Methods: We here test these hypotheses by evaluating whether adults diagnosed with ADHD (n = 17) differed from a control group (n = 30) in implicitly learning and using low-level perceptual priors to guide sensory processing. We used a visual statistical learning task in which participants had to estimate the direction of a cloud of coherently moving dots. Unbeknown to the participants, two of the directions were more frequently presented than the others, creating an implicit bias (prior) towards those directions. This task had previously revealed differences in other neurodevelopmental disorders, such as autistic spectrum disorder and schizophrenia., Results: We found that both groups acquired the prior expectation for the most frequent directions and that these expectations substantially influenced task performance. Overall, there were no group differences in how much the priors influenced performance. However, subtle group differences were found in the influence of the prior over time., Conclusion: Our findings suggest that the symptoms of inattention and hyperactivity in ADHD do not stem from broad difficulties in developing and/or using low-level perceptual priors., Competing Interests: The authors have declared that no competing interests exist. As stated above, SML reports receiving, in the past three years, personal fees from Janssen, Otsuka and Sunovion, and research funding from Janssen and Lundbeck. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Light exerts critical non-visual effects on a multitude of physiological processes and behaviors, including sleep-wake behavior and cognitive function. In this study, we investigated the effects of continued exposure to different colors of light on cognitive function after sepsis in old mice. We found that exposure to red light, but not green light, exaggerated learning impairments and anxiety-like behaviors after sepsis. Red light also induced remarkable splenomegaly and altered the diversity and composition of the fecal microbiota. Pseudo germ-free mice transplanted with fecal bacteria from septic mice exposed to red light developed the same behavioral defects and splenomegaly as their donors. Intriguingly, splenectomy and subdiaphragmatic vagotomy reversed the learning impairments and anxiety-like behaviors resulting from red light exposure after sepsis. After subdiaphragmatic vagotomy, no differences in behavior or spleen size were observed among pseudo germ-free mice transplanted with fecal bacteria from septic mice exposed to different colors of light. Our results suggested that red light exposure after sepsis in old mice causes gut microbiota dysfunction, thus stimulating signaling through the subdiaphragmatic vagus nerve that induces splenomegaly and aggravates learning impairments and anxiety-like behaviors.

Hypothyroidism-associated learning and memory impairment is reported to be connected to oxidative stress and reduced levels of brain-derived neurotrophic factor (BDNF). The effects of neuronal nitric oxide inhibitor 7-nitroindazole (7NI) on brain tissues oxidative damage, nitric oxide (NO), BDNF and memory impairments in hypothyroid juvenile rats were investigated. Male Wistar juvenile rats (20 days old) were divided into five groups, including Martinez et al. (J Neurochem 78 (5):1054-1063, 2001). Control in which vehicle was injected instead of 7NI, (Jackson in Thyroid 8 (10):951-956, 1998) Propylthiouracil (PTU) where 0.05% PTU was added in drinking water and vehicle was injected instead of 7NI, (Gong et al. in BMC Neurosci 11 (1):50, 2010; Alva-Sánchez et al. in Brain Res 1271:27-35, 2009; Anaeigoudari et al. in Pharmacol Rep 68 (2): 243-249, 2016) PTU-7NI 5, PTU-7NI 10 and PTU-7NI 20 in which 5, 10, or 20 mg/kg7NI was injected intraperitoneally (i.p.). Following 6 weeks, Morris water maze (MMW) and passive avoidance learning (PAL) tests were used to evaluate the memory. Finally, the hippocampus and the cortex of the rats were removed after anesthesia by urethane to be used for future analysis. The escape latency and traveled path in MWM test was increased in PTU group (P < 0.001). PTU also reduced the latency to enter the dark box of PAL and the time spent and the distance in the target quadrant in MWM test (P < 0.001 and P < 0.01). Treatment with 7NI attenuated all adverse effects of PTU (P < 0.05 to P < 0.001). PTU lowered BDNF and thiol content and superoxide dismutase (SOD) and catalase (CAT) activities in the brain but increased malondialdehyde (MDA) and nitric oxide (NO) metabolites. In addition, 7NI improved thiol, SOD, CAT, thiol, and BDNF but attenuated MDA and NO metabolites. The results of the current study showed that 7NI improvement in the learning and memory of the hypothyroid juvenile rats, which was accompanied with improving of BDNF and attenuation of NO and brain tissues oxidative damage.

Objective: To assess the Global School Adaptation (GSA) questionnaire of children's abilities and classroom behavior administered to teachers of very preterm children at 5 years of age as a predictor of the need for educational support (grade retention, special class, learning support) at age 7., Study Design: We assessed 858 very preterm children (<33 weeks of gestation) at 5 years of age using the GSA and again at 7 years to determine the use of educational support. We examined the association between the GSA score and educational support at 7 years and performed a receiver operating characteristic curve analysis., Results: At 7 years of age, 130 children had educational support (15.2%). Children with a nonoptimal GSA score (<45) at 5 years required educational support more often (57.7%) than children with a GSA score of 45 or greater (15.4%) (OR, 7.5; 95% CI, 5.02-11.21). The need for educational support was associated with male sex; a low parent socioeconomic level; lower birth weight, birth head circumference, or gestational age (28-30 weeks of gestation); severe neurologic complications; patent ductus arteriosus ligation; and the use of therapy services at 5 years of age. After adjustment, only the GSA score was associated with educational support at 7 years of age (OR, 0.86; 95% CI, 0.84-0.88). A receiver operating characteristic curve analysis of the GSA performance revealed an optimal cut-off at 48, with a sensitivity of 70.8%, a specificity of 73.5%, and an area under the curve of 0.79., Conclusions: Using a cut-off score of 48, the GSA at 5 years of age may be a useful tool to identify children born preterm at risk of school-based learning difficulties., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Brain injury resulting from repeated mild traumatic insult is associated with cognitive dysfunction and other chronic co-morbidities. The current study tested the effects of aberrant neurogenesis in a mouse model of repeated mild traumatic brain injury (rmTBI). Using Barnes Maze analysis, we found a significant reduction in spatial learning and memory at 24 days post-rmTBI compared to repeated sham (rSham) injury. Cell fate analysis showed a greater number of BrdU-labeled cells which co-expressed Prox-1 in the DG of rmTBI-injured mice which coincided with enhanced cFos expression for neuronal activity. We then selectively ablated dividing neural progenitor cells using a 7-day continuous infusion of Ara-C prior to rSham or rmTBI. This resulted in attenuation of cFos and BrdU-labeled cell changes and prevented associated learning and memory deficits. We further showed this phenotype was ameliorated in EphA4f. /f /Tie2-Cre knockout compared to EphA4f. /f wild type mice, which coincided with altered mRNA transcript levels of MCP-1, Cx43 and TGFβ. These findings demonstrate that cognitive decline is associated with an increased presence of immature neurons and gene expression changes in the DG following rmTBI. Our data also suggests that vascular EphA4-mediated neurogenic remodeling adversely affects learning and memory behavior in response to repeated insult.

Pediatric obstructive sleep apnea affects a large number of children and has multiple end-organ sequelae. Although many of these have been demonstrated to be reversible, the effects on some of the organ systems, including the brain, have not shown easy reversibility. Progress in this area has been hampered by lack of a preclinical model to study the disease. Therefore, perioperative and sleep physicians are tasked with making a number of difficult decisions, including optimal surgical timing to prevent disease evolution, but also to keep the perioperative morbidity in a safe range for these patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: The medial olivocochlear system (MOCS) is composed of fibres projecting directly onto outer hair cells and plays a role in improving the signal-to-noise ratio. The MOCS can be evaluated by measuring suppression of the otoacoustic emissions evoked by contralateral acoustic stimulation. Dyslexic children present an increased probability of auditory processing disorder (APD). These children may present paradoxical MOCS dysfunction., Case Report: We report the case of a dyslexic child with APD, who was severely disabled in a noisy environment. Audiometric tests were normal, and the central auditory assessment showed labile MOCS functioning that was not only ineffective, but also potentially deleterious, possibly accounting for this child's hearing impairment in a noisy environment., Discussion: This case illustrates the importance of audiological assessment and objective investigation of MOCS function in children with a learning disability, especially with hearing difficulties in the presence of noise, in whom auditory training can be beneficial., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Millions of children undergo general anesthesia each year, and animal and human studies have indicated that exposure to anesthesia at an early age can impact neuronal development, leading to behavioral and learning impairments that manifest later in childhood and adolescence. Here, we examined the effects of isoflurane, a commonly-used general anesthetic, which was delivered to newborn rabbits. Trace eyeblink classical conditioning was used to assess the impact of neonatal anesthesia exposure on behavioral learning in adolescent subjects, and a variety of MRI techniques including fMRI, MR volumetry, spectroscopy and DTI captured functional, metabolic, and structural changes in key regions of the learning and sensory systems associated with anesthesia-induced learning impairment. Our results demonstrated a wide array of changes that were specific to anesthesia-exposed subjects, which supports previous studies that have pointed to a link between early anesthesia exposure and the development of learning and behavioral deficiencies. These findings point to the need for caution in avoiding excessive use of general anesthesia in young children and neonates.

Introduction: Exposure to noise stress during early life may permanently affect the structure and function of the central nervous system. The aim of this study was to evaluate the effects of prenatal exposure to urban traffic noise on the spatial learning and memory of the rats' offspring and the expression of glucocorticoid receptors (GRs) in their hippocampi., Methods: Three g\roups of pregnant rats were exposed to recorded urban traffic noise for 1, 2 or 4 h/day during the last week of pregnancy. At the age of 45 days, their male offspring were introduced to the Morris water maze (MWM) for assessment of spatial learning and memory. The corticosterone levels were measured in the offspring's sera by radioimmunoassay, and the relative expression of glucocorticoid and mineralocorticoid receptors (MRs) in their hippocampi was evaluated via RT-PCR., Results: Facing urban traffic noise for 2 and 4 h/day during the third trimester of pregnancy caused the offspring to spend more time and to travel a larger distance than the controls to find the target platform. Analogously, these two groups were inferior to their control counterparts in the probe test. Also, prenatal noise stress elevated the corticosterone concentration in the sera of the rats' offspring and dose-dependently decreased the relative expression of the mRNA of both GRs and MRs in their hippocampi., Conclusions: Urban traffic noise exposure during the last trimester of pregnancy impairs spatial learning and memory of rat offspring and reduces GRs and MRs gene expression in the hippocampus.

Purpose This systematic review synthesized a set of peer-reviewed studies published between 1985 and 2019 and addressed the effectiveness of existing narrative and expository discourse interventions for late elementary- and middle school-aged students with language-related learning disabilities. Method A methodical search of the literature for interventions targeting expository or narrative discourse structure for students aged 9-14 years with group experimental designs identified 33 studies, seven of which met specific criteria to be included in this review. Results An 8-point critical appraisal scale was applied to analyze the quality of the study design, and effect sizes were calculated for six of the seven studies; equivocal to small effects of far-transfer outcomes (i.e., generalizability to other settings) and equivocal to moderate near-transfer outcomes (i.e., within the treatment setting) were identified. The most effective intervention studies provided explicit instruction of expository texts with visual supports and student-generated learning materials (e.g., notes or graphic organizers) with moderate dosage (i.e., 180-300 min across 6-8 weeks) in a one-on-one or paired group setting. Greater intervention effects were also seen in children with reading and/or language disorders, compared to children with overall academic performance difficulties. Conclusions A number of expository discourse interventions showed promise for student use of learned skills within the treatment setting (i.e., near-transfer outcomes) but had limited generalization of skills (i.e., far-transfer outcomes). Supplemental Material https://doi.org/10.23641/asha.12449258.

Stress affects cognitive function. Whether stress enhances or impairs cognitive function depends on several factors, including the 1) type, intensity, and duration of the stressor; 2) type of cognitive function under study; and 3) timing of the stressor in relation to learning or executing the cognitive task. Furthermore, sex differences among the effects of stress on cognitive function have been widely documented. Described here is an adaptation of an automated operant strategy shifting paradigm to assess how variations in stress affect cognitive flexibility in male and female Sprague Dawley rats. Specifically, restraint stress is used before or after training in this operant-based task to examine how stress affects cognitive performance in both sexes. Particular brain areas associated with each task in this automated paradigm have been well-established (i.e., the medial prefrontal cortex and orbitofrontal cortex). This allows for targeted manipulations during the experiment or the assessment of particular genes and proteins in these regions upon completion of the paradigm. This paradigm also allows for the detection of different types of performance errors that occur after stress, each of which has defined neural substrates. Also identified are distinct sex differences in perseverative errors after a repeated restraint stress paradigm. The use of these techniques in a preclinical model may reveal how stress affects the brain and impairs cognition in psychiatric disorders, such as post-traumatic stress disorder (PTSD) and major depressive disorder (MDD), which display marked sex differences in prevalence.