Learning difficulties often not documented in newly diagnosed focal epilepsy.

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.

Learning and Memory Impairments With Attention-Deficit/Hyperactivity Disorder.

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.

Connecting the dots: Motor and default mode network crossroads in post-stroke motor learning deficits.

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.

Dysfunctions of cellular context-sensitivity in neurodevelopmental learning disabilities.

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.

Diverse learners: learning disabilities and quality of life following mind-body and health education interventions for adults with neurofibromatosis.

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.

Developmental learning disorders in children with prenatal/perinatal exposure to hypoxia: A systematic review protocol.

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.

Screen Time at Age 1 Year and Communication and Problem-Solving Developmental Delay at 2 and 4 Years.

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.

From vision to cognition: potential contributions of cerebral visual impairment to neurodevelopmental disorders.

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.

Incidence and risk of attention-deficit/hyperactivity disorder and learning disability by adulthood after traumatic brain injury in childhood: a population-based birth cohort study.

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.

Asymmetry Matters: Diffusion Tensor Tractography of the Uncinate Fasciculus in Children with Verbal Memory Deficits.

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.

Processamento fonológico e leitura em crianças com dificuldade de aprendizagem em escolas bilíngues português-inglês: relatos de casos / Phonological processing and reading in children with learning difficulties in Portuguese-English bilingual schools: case reports / Procesamiento y lectura fonológica en niños con dificultades de aprendizaje en escuelas bilingües portugués-inglés: reporte de casos

Introdução: Há influência positiva no desenvolvimento da linguagem, quando ocorre a exposição a um novo idioma. No entanto, quando se considera esse contexto em crianças com dificuldade de aprendizagem, o deficit apresentado na primeira língua pode ser transferido para o aprendizado da segunda. Objetivo: O objetivo do presente estudo é caracterizar o desempenho em processamento fonológico e leitura em três crianças com dificuldade de aprendizagem em escolas bilíngues português-inglês. Método: Os dados gerais sobre o desenvolvimento e desempenho nas habilidades de consciência fonológica, memória de trabalho fonológica, acesso ao léxico mental e leitura em três crianças de 8 a 9 anos de idade, cursando 2º e 3º ano do ensino fundamental foram descritos; todos com, ao menos, dois anos de exposição à escola bilíngue, especialmente na alfabetização. Na avaliação, foram aplicados os protocolos CONFIAS, Memória de Trabalho Fonológica, TENA, RAN e Protocolo de Avaliação da Compreensão Leitora de Textos Expositivos. Resultado: as crianças apresentaram desempenho aquém do esperado nas habilidades do processamento fonológico, na fluência da leitura oral, bem como na compreensão leitora. Conclusão: esses resultados podem contribuir tanto para a compreensão de aspectos da linguagem escrita na atuação do fonoaudiólogo com crianças bilíngues, quanto para as implicações clínicas e educacionais, haja vista a escassez de estudos nessa área, no Brasil.

Introduction: There is a positive influence on language development when there is exposure to a new language. However, when considering this context in children with learning difficulties, the deficits presented in the first language can be transferred to the learning of the second. Objective: The aim of the present study was to characterize the performance in phonological processing and reading in three children with learning difficulties from Brazilian-English bilingual schools. Method: General data on the development and performance in phonological awareness skills, phonological working memory, access to mental lexicon and reading in three children aged 8 to 9 years, attending the 2nd and 3rd year of elementary school were described; all with at least two years of exposure to bilingual school, especially in literacy. In the evaluation, the protocols CONFIAS, Phonological Working Memory, TENA, RAN and Protocol for Assessment of Reading Comprehension of Expository Texts were applied. Results: The children performed below expectations in terms of phonological processing skills, difficulties in oral reading fluency, as well as in reading comprehension. Conclusion: These results can contribute to the understanding of aspects of written language in the performance of speech therapists with bilingual children, regarding clinical and educational implications, given the scarcity of studies in this area in Brazil.;Introducción: Existe una influencia positiva en el desarrollo del lenguaje cuando hay exposición a un nuevo idioma. Sin embargo, al considerar este contexto en niños con dificultades de aprendizaje, los déficits presentados en el primer idioma se pueden trasladar al aprendizaje del segundo. Objetivo: El objetivo del presente estudio fue caracterizar el desempeño en procesamiento fonológico y lectura en tres niños con dificultades de aprendizaje de escuelas bilingües brasileño-inglés. Método: Se describieron datos generales sobre el desarrollo y desempeño en las habilidades de conciencia fonológica, memoria de trabajo fonológica, acceso al léxico mental y lectura en tres niños de 8 a 9 años de 2º y 3º de primaria; todos con al menos dos años de exposición a la escuela bilingüe, especialmente en alfabetización. En la evaluación se aplicaron los protocolos CONFIAS, Memoria Fonológica de Trabajo, TENA, RAN y Protocolo de Evaluación de la Comprensión Lectora de Textos Expositivos. Resultados: Los niños se desempeñaron por debajo de las expectativas en términos de habilidades de procesamiento fonológico, dificultades en la fluidez de la lectura oral, así como en la comprensión lectora. Conclusión: Estos resultados pueden contribuir a la comprensión de aspectos del lenguaje escrito en el desempeño de logopedas con niños bilingües, en cuanto a implicaciones clínicas y educativas, dada la escasez de estudios en esta área en Brasil.

Introduction: There is a positive influence on language development when there is exposure to a new language. However, when considering this context in children with learning difficulties, the deficits presented in the first language can be transferred to the learning of the second. Objective: The aim of the present study was to characterize the performance in phonological processing and reading in three children with learning difficulties from Brazilian-English bilingual schools. Method: General data on the development and performance in phonological awareness skills, phonological working memory, access to mental lexicon and reading in three children aged 8 to 9 years, attending the 2nd and 3rd year of elementary school were described; all with at least two years of exposure to bilingual school, especially in literacy. In the evaluation, the protocols CONFIAS, Phonological Working Memory, TENA, RAN and Protocol for Assessment of Reading Comprehension of Expository Texts were applied. Results: The children performed below expectations in terms of phonological processing skills, difficulties in oral reading fluency, as well as in reading comprehension. Conclusion: These results can contribute to the understanding of aspects of written language in the performance of speech therapists with bilingual children, regarding clinical and educational implications, given the scarcity of studies in this area in Brazil.;Introducción: Existe una influencia positiva en el desarrollo del lenguaje cuando hay exposición a un nuevo idioma. Sin embargo, al considerar este contexto en niños con dificultades de aprendizaje, los déficits presentados en el primer idioma se pueden trasladar al aprendizaje del segundo. Objetivo: El objetivo del presente estudio fue caracterizar el desempeño en procesamiento fonológico y lectura en tres niños con dificultades de aprendizaje de escuelas bilingües brasileño-inglés. Método: Se describieron datos generales sobre el desarrollo y desempeño en las habilidades de conciencia fonológica, memoria de trabajo fonológica, acceso al léxico mental y lectura en tres niños de 8 a 9 años de 2º y 3º de primaria; todos con al menos dos años de exposición a la escuela bilingüe, especialmente en alfabetización. En la evaluación se aplicaron los protocolos CONFIAS, Memoria Fonológica de Trabajo, TENA, RAN y Protocolo de Evaluación de la Comprensión Lectora de Textos Expositivos. Resultados: Los niños se desempeñaron por debajo de las expectativas en términos de habilidades de procesamiento fonológico, dificultades en la fluidez de la lectura oral, así como en la comprensión lectora. Conclusión: Estos resultados pueden contribuir a la comprensión de aspectos del lenguaje escrito en el desempeño de logopedas con niños bilingües, en cuanto a implicaciones clínicas y educativas, dada la escasez de estudios en esta área en Brasil.

Management of neck of femur fracture in an adult with short stature and learning disability.

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.

Strengths and difficulties in children with specific learning disabilities.

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.

Opioids and the developing brain: time to rethink perinatal care for infants of opioid-dependent mothers.

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.

Early Development of the GABAergic System and the Associated Risks of Neonatal Anesthesia.

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.

Cognitive deficits and impaired hippocampal long-term potentiation in KATP-induced DEND syndrome.

ATP-sensitive potassium (KATP) gain-of-function (GOF) mutations cause neonatal diabetes, with some individuals exhibiting developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome. Mice expressing KATP-GOF mutations pan-neuronally (nKATP-GOF) demonstrated sensorimotor and cognitive deficits, whereas hippocampus-specific hKATP-GOF mice exhibited mostly learning and memory deficiencies. Both nKATP-GOF and hKATP-GOF mice showed altered neuronal excitability and reduced hippocampal long-term potentiation (LTP). Sulfonylurea therapy, which inhibits KATP, mildly improved sensorimotor but not cognitive deficits in KATP-GOF mice. Mice expressing KATP-GOF mutations in pancreatic ß-cells developed severe diabetes but did not show learning and memory deficits, suggesting neuronal KATP-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 KATP-GOF.

A pair of dopamine neurons mediate chronic stress signals to induce learning deficit in Drosophila melanogaster.

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/ß 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.

Poor adult nutrition impairs learning and memory in a parasitoid wasp.

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.

Outcomes in Hirschsprung's disease with coexisting learning disability.

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.