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1.
Physiol Res ; 73(2): 205-216, 2024 Apr 30.
Article En | MEDLINE | ID: mdl-38710050

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.


Attention Deficit Disorder with Hyperactivity , Memory Disorders , Attention Deficit Disorder with Hyperactivity/psychology , Attention Deficit Disorder with Hyperactivity/genetics , Humans , Animals , Memory Disorders/psychology , Memory Disorders/etiology , Learning , Disease Models, Animal , Learning Disabilities/psychology , Learning Disabilities/etiology , Memory
2.
Neurosci Biobehav Rev ; 161: 105688, 2024 Jun.
Article En | MEDLINE | ID: mdl-38670298

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.


Learning Disabilities , Humans , Animals , Learning Disabilities/physiopathology , Learning Disabilities/etiology , Pyramidal Cells/physiology , Fetal Alcohol Spectrum Disorders/physiopathology , Neurodevelopmental Disorders/physiopathology , Down Syndrome/physiopathology , Fragile X Syndrome/physiopathology
3.
J Neurooncol ; 167(2): 315-322, 2024 Apr.
Article En | MEDLINE | ID: mdl-38409461

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.


Learning Disabilities , Neurofibromatoses , Adult , Humans , Quality of Life , Neurofibromatoses/psychology , Relaxation Therapy , Learning Disabilities/etiology , Learning Disabilities/therapy , Health Education
4.
PLoS One ; 18(10): e0293067, 2023.
Article En | MEDLINE | ID: mdl-37862316

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.


Learning Disabilities , Parturition , Pregnancy , Female , Humans , Child , Systematic Reviews as Topic , Learning , Learning Disabilities/etiology , Hypoxia , Review Literature as Topic
5.
JAMA Pediatr ; 177(10): 1039-1046, 2023 10 01.
Article En | MEDLINE | ID: mdl-37603356

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.


Child Development , Communication Disorders , Developmental Disabilities , Screen Time , Child, Preschool , Female , Humans , Infant , Male , Pregnancy , Cohort Studies , Communication , Japan , Developmental Disabilities/etiology , Communication Disorders/etiology , Problem Solving , Learning Disabilities/etiology
7.
J Neural Transm (Vienna) ; 130(3): 409-424, 2023 03.
Article En | MEDLINE | ID: mdl-36547695

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.


Attention Deficit and Disruptive Behavior Disorders , Child Development , Learning Disabilities , Vision Disorders , Visual Cortex , Visual Perception , Vision, Ocular , Cognition , Humans , Child , Vision Disorders/complications , Vision Disorders/congenital , Learning Disabilities/etiology , Attention Deficit and Disruptive Behavior Disorders/etiology , Visual Cortex/abnormalities
8.
Child Neuropsychol ; 29(5): 808-824, 2023 07.
Article En | MEDLINE | ID: mdl-36278854

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.


Attention Deficit Disorder with Hyperactivity , Brain Concussion , Brain Injuries, Traumatic , Brain Injuries , Learning Disabilities , Child , Humans , Adult , Young Adult , Attention Deficit Disorder with Hyperactivity/complications , Attention Deficit Disorder with Hyperactivity/epidemiology , Incidence , Cohort Studies , Birth Cohort , Brain Injuries, Traumatic/complications , Brain Injuries, Traumatic/epidemiology , Learning Disabilities/epidemiology , Learning Disabilities/etiology , Brain Injuries/complications , Brain Concussion/complications
9.
AJNR Am J Neuroradiol ; 43(7): 1042-1047, 2022 07.
Article En | MEDLINE | ID: mdl-35680160

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.


Learning Disabilities , White Matter , Anisotropy , Child , Diffusion Tensor Imaging , Humans , Learning Disabilities/diagnostic imaging , Learning Disabilities/etiology , Learning Disabilities/pathology , Memory Disorders/diagnostic imaging , Memory Disorders/etiology , Memory Disorders/pathology , Uncinate Fasciculus , White Matter/diagnostic imaging , White Matter/pathology
10.
Distúrb. comun ; 34(1): e52385, mar. 2022. ilus, tab
Article Pt | LILACS | ID: biblio-1396516

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.


Humans , Male , Female , Child , Reading , Phonetics , Multilingualism , Learning Disabilities/etiology , Underachievement , Education, Primary and Secondary , Language Disorders/etiology
11.
BMJ Case Rep ; 15(2)2022 Feb 10.
Article En | MEDLINE | ID: mdl-35144960

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.


Arthroplasty, Replacement, Hip , Femoral Fractures , Femoral Neck Fractures , Learning Disabilities , Adult , Femoral Fractures/complications , Femoral Fractures/diagnostic imaging , Femoral Fractures/surgery , Femoral Neck Fractures/diagnostic imaging , Femoral Neck Fractures/surgery , Fracture Fixation, Internal , Humans , Learning Disabilities/etiology , Treatment Outcome
12.
Child Care Health Dev ; 48(1): 55-67, 2022 01.
Article En | MEDLINE | ID: mdl-34331711

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.


Learning Disabilities , Problem Behavior , Child , Child, Preschool , Educational Status , Emotions , Female , Humans , Learning Disabilities/epidemiology , Learning Disabilities/etiology , Pregnancy , Surveys and Questionnaires
13.
Arch Dis Child Fetal Neonatal Ed ; 107(1): 98-104, 2022 Jan.
Article En | MEDLINE | ID: mdl-33597225

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.


Developmental Disabilities/etiology , Neonatal Abstinence Syndrome/complications , Opioid-Related Disorders/complications , Opioid-Related Disorders/therapy , Pregnancy Complications/therapy , Brain/growth & development , Electrophysiology , Female , Heroin Dependence/complications , Heroin Dependence/therapy , Humans , Infant, Newborn , Learning Disabilities/etiology , Morphine Dependence/complications , Morphine Dependence/therapy , Neonatal Abstinence Syndrome/diagnosis , Neonatal Abstinence Syndrome/physiopathology , Neonatal Abstinence Syndrome/therapy , Neuroimaging , Pregnancy , Prognosis
14.
Int J Mol Sci ; 22(23)2021 Nov 30.
Article En | MEDLINE | ID: mdl-34884752

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.


Anesthesia, General/adverse effects , GABAergic Neurons/physiology , gamma-Aminobutyric Acid/physiology , Anesthesia, General/methods , Animals , Animals, Newborn , Apoptosis , Brain/cytology , Brain/growth & development , Brain/physiology , Child Behavior Disorders/etiology , Child, Preschool , Electrophysiological Phenomena , Humans , Infant , Infant, Newborn , Interneurons/physiology , Learning Disabilities/etiology , Models, Neurological , Neuroimaging , Neurotoxicity Syndromes/etiology
15.
Proc Natl Acad Sci U S A ; 118(45)2021 11 09.
Article En | MEDLINE | ID: mdl-34732576

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.


Cognition Disorders/etiology , Diabetes Mellitus/psychology , Epilepsy/psychology , Hippocampus/metabolism , Infant, Newborn, Diseases/psychology , KATP Channels/genetics , Motor Disorders/etiology , Psychomotor Disorders/psychology , Animals , Diabetes Mellitus/etiology , Diabetes Mellitus/metabolism , Disease Models, Animal , Epilepsy/etiology , Epilepsy/metabolism , Female , Gain of Function Mutation , Infant, Newborn, Diseases/etiology , Infant, Newborn, Diseases/metabolism , Learning Disabilities/drug therapy , Learning Disabilities/etiology , Long-Term Potentiation , Male , Memory Disorders/drug therapy , Memory Disorders/etiology , Mice, Transgenic , Psychomotor Disorders/etiology , Psychomotor Disorders/metabolism , Sulfonylurea Compounds/therapeutic use
16.
Proc Natl Acad Sci U S A ; 118(42)2021 10 19.
Article En | MEDLINE | ID: mdl-34654742

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.


Dopaminergic Neurons/metabolism , Learning Disabilities/etiology , Memory Disorders/etiology , Stress, Physiological , Animals , Chronic Disease , Depression/etiology , Drosophila melanogaster , Smell/physiology
17.
Sci Rep ; 11(1): 16220, 2021 08 10.
Article En | MEDLINE | ID: mdl-34376777

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.


Feeding Behavior , Larva/physiology , Learning Disabilities/pathology , Malnutrition/complications , Memory Disorders/pathology , Wasps/physiology , Animals , Learning Disabilities/etiology , Memory Disorders/etiology
18.
Eur J Pediatr ; 180(12): 3499-3507, 2021 Dec.
Article En | MEDLINE | ID: mdl-34115168

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.


Hirschsprung Disease , Learning Disabilities , Adult , Child , Cross-Sectional Studies , Hirschsprung Disease/complications , Humans , Learning Disabilities/epidemiology , Learning Disabilities/etiology , Quality of Life , Surveys and Questionnaires
19.
Dev Neuropsychol ; 46(3): 232-248, 2021.
Article En | MEDLINE | ID: mdl-33900858

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.


Learning Disabilities , Spatial Navigation , Child , Executive Function , Humans , Learning Disabilities/diagnosis , Learning Disabilities/etiology , Mathematics , Memory, Short-Term
20.
CBE Life Sci Educ ; 20(2): ar17, 2021 06.
Article En | MEDLINE | ID: mdl-33769838

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.


Attention Deficit Disorder with Hyperactivity , Learning Disabilities , Humans , Learning Disabilities/etiology , Mathematics , Students , Technology
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