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ABSTRACTChildren HIV-exposed, uninfected (CHEU) are at risk for compromised developmental outcomes. Attention is important for behavioural, cognitive and academic skills, yet has not been thoroughly investigated compared to children HIV-unexposed uninfected (CHUU). Fifty-five CHEU and 51 CHUU children were recruited at 5.5 years of age. Measures of inattention (IA), hyperactivity/impulsivity (HI) and total scores were collected using the parent-reported ADHD-Rating-Scale-IV. Measures of intelligence, visuomotor skills, academics and adaptive functioning were obtained. Analyses of between-group differences were performed as were correlational and multiple regression models, accounting for maternal education, employment and delivery type. Few children met clinical cut-offs for probable ADHD (3.6% CHEU, 2.0% CHUU), and no group differences in measures of IA, HI and combined scores were found. CHEU scored significantly lower than CHUU on intelligence, visuomotor function, academic skills and aspects of adaptive behaviour, though within age expectations. Lower Full-Scale IQ and Processing Speed were associated with higher IA in CHEU and lower adaptive functioning with higher IA in CHUU. Across both groups, children of unemployed mothers had more HI symptoms. CHEU were not at increased risk for attention difficulties at 5.5 years of age. Maternal employment status highlights the contribution of sociodemographic factors in shaping behaviour and neurodevelopment.
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Infecções por HIV , Criança , Humanos , Pré-Escolar , HIV , Inteligência , Cognição , Adaptação PsicológicaRESUMO
Those born very preterm (VPT; <32 weeks gestational age) have an increased risk in developing a wide range of cognitive deficits. In early-to-late childhood, brain structure has been shown to be altered in VPT compared to full-term (FT) children; however, the results are inconsistent. The current study examined subcortical volumes, cortical thickness, and surface area in a large cohort of VPT and FT children aged 4-12 years. Structural magnetic resonance imaging (MRI) was obtained on 120 VPT and 146 FT children who returned up to three times, resulting in 176 VPT and 173 FT unique data points. For each participant, Corticometric Iterative Vertex-based Estimation of Thickness was used to obtain global measurements of total brain, cortical grey and cortical white matter volumes, along with surface-based measurements of cortical thickness and surface area, and Multiple Automatically Generated Templates (MAGeT) brain segmentation tool was used to segment the subcortical structures. To examine group differences and group-age interactions, mixed-effects models were used (controlling for whole-brain volume). We found few differences between the two groups in subcortical volumes. The VPT children showed increased cortical thickness in frontal, occipital and fusiform gyri and inferior pre-post-central areas, while thinning occurred in the midcingulate. Cortical thickness in occipital regions showed more rapid decreases with age in the VPT compared to the FT children. VPT children also showed both regional increases, particularly in the temporal lobe, and decreases in surface area. Our results indicate a delayed maturational trajectory in those born VPT.
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Córtex Cerebral/anatomia & histologia , Desenvolvimento Infantil , Substância Cinzenta/anatomia & histologia , Lactente Extremamente Prematuro , Substância Branca/anatomia & histologia , Córtex Cerebral/diagnóstico por imagem , Córtex Cerebral/crescimento & desenvolvimento , Criança , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/crescimento & desenvolvimento , Humanos , Lactente Extremamente Prematuro/fisiologia , Recém-Nascido , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Substância Branca/diagnóstico por imagem , Substância Branca/crescimento & desenvolvimentoRESUMO
Identifying trajectories of early white matter development is important for understanding atypical brain development and impaired functional outcomes in children born very preterm (<32 weeks gestational age [GA]). In this study, 161 diffusion images were acquired in children born very preterm (median GA: 29 weeks) shortly following birth (75), term-equivalent (39), 2 years (18), and 4 years of age (29). Diffusion tensors were computed to obtain measures of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), which were aligned and averaged. A paediatric atlas was applied to obtain diffusion metrics within 12 white matter tracts. Developmental trajectories across time points demonstrated age-related changes which plateaued between term-equivalent and 2 years of age in the majority of posterior tracts and between 2 and 4 years of age in anterior tracts. Between preterm and term-equivalent scans, FA rates of change were slower in anterior than posterior tracts. Partial least squares analyses revealed associations between slower MD and RD rates of change within the external and internal capsule with lower intelligence quotients and language scores at 4 years of age. These results uniquely demonstrate early white matter development and its linkage to cognitive functions.
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Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Lactente Extremamente Prematuro/crescimento & desenvolvimento , Substância Branca/diagnóstico por imagem , Substância Branca/crescimento & desenvolvimento , Atlas como Assunto , Pré-Escolar , Imagem de Difusão por Ressonância Magnética , Imagem de Tensor de Difusão , Feminino , Humanos , Recém-Nascido , Inteligência , Idioma , Estudos Longitudinais , Masculino , Testes Neuropsicológicos , Fatores SexuaisRESUMO
Despite antibiotic treatment, up to 40% of patients have impaired fertility after epididymitis due to serovars of Escherichia coli, a frequent pathogen. The reasons for infertility are unclear, but it may result from epididymal duct obstruction. To determine whether E. coli infection of the epididymis causes obstruction due to fibrosis, and to identify the key mediators, tissues from patients with epididymitis were assessed. Additionally, epididymitis was induced with uropathogenic E. coli (UPEC) or commensal serovars in wild-type and MyD88(-/-) mice, which are relatively unresponsive to bacterial pathogens. Epididymal organ cultures were treated with activin A and bacteria and their histology and levels of cytokines and fibrosis markers were analysed. Patients with epididymitis showed severe fibrosis of the epididymal duct. In mice, UPEC infection also caused fibrosis and ductal obstruction in the cauda epididymis. Levels of mRNA for fibrotic markers (α-smooth muscle actin, fibronectin) and cytokines (activin A, TNFα, IL-1α, IL-1ß, IL-6) and total collagen levels were significantly elevated. This fibrotic response was blunted by the loss of MyD88. Activin A induced fibrosis in cultured epididymis, which was inhibited by the activin-binding protein follistatin. In summary, bacterial epididymitis causes fibrosis and obstruction. The milder tissue damage in Myd88(-/-) UPEC epididymitis highlights the importance of the host response to infection in causing epididymal damage. Elevated levels of activin A in vivo and fibrotic remodelling elicited by activin A in vitro indicate that this cytokine is a potential target for supplementary treatment to antibiotic therapy. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Epididimo/microbiologia , Epididimite/microbiologia , Infecções por Escherichia coli/patologia , Músculo Liso/microbiologia , Escherichia coli Uropatogênica , Actinas/metabolismo , Idoso , Animais , Colágeno/metabolismo , Citocinas/metabolismo , Epididimo/metabolismo , Epididimo/patologia , Epididimite/metabolismo , Epididimite/patologia , Infecções por Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Fibronectinas/metabolismo , Fibrose/metabolismo , Fibrose/microbiologia , Fibrose/patologia , Humanos , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Músculo Liso/metabolismo , Músculo Liso/patologia , Fator 88 de Diferenciação Mieloide/genética , Fator 88 de Diferenciação Mieloide/metabolismoRESUMO
OBJECTIVE: To identify perinatal risk factors associated with long-term neurocognitive and behavioral impairments in children born very preterm using a multivariate, partial least squares approach. STUDY DESIGN: Twenty-seven perinatal clinical and magnetic resonance imaging measures were collected at birth and during the neonatal intensive care stay for 105 neonates born very preterm (≤ 32 weeks gestational age). One-half of the children returned for neuropsychological assessments at 2 and 4 years of age. Parent-reported behavioral measures were also obtained at 4 years of age. Three partial least squares analyses were performed to determine associations between clinical and radiologic measures with cognitive outcomes at 2 and 4 years of age, as well as with behavioral measures at 4 years of age. RESULTS: Within the first components of each analysis, only intrauterine growth restriction, male sex, and absence of antenatal corticosteroid use were associated with poorer cognitive and language ability at 2 and 4 years of age, accounting for 79.6% and 71.4% of the total variance, respectively. In addition, white matter injury at term-equivalent age contributed to more problematic internalizing behaviors, behavioral symptoms, and impaired executive function at 4 years of age, accounting for 67.9% of the total variance. CONCLUSIONS: Using this data-driven multivariate approach, specific measures in prenatal and early postnatal life are shown to be selectively and significantly associated with cognitive and behavioral outcomes in children born very preterm. Early detection of risk factors can help inform prognoses of children at greatest risk of long-term impairments.
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Encéfalo/patologia , Desenvolvimento Infantil , Deficiências do Desenvolvimento/patologia , Lactente Extremamente Prematuro , Imageamento por Ressonância Magnética/métodos , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Masculino , Testes Neuropsicológicos , Gravidez , Nascimento Prematuro/fisiopatologia , Fatores de RiscoRESUMO
PURPOSE: To measure cerebellar growth in a longitudinal cohort of very preterm infants to identify early predictors of subsequent brain growth. Although the cerebellum grows rapidly during late gestation, the rate and variability of growth following premature birth, and the effects of associated injury, are largely unknown. MATERIALS AND METHODS: In all, 105 very-preterm born infants (24-32 weeks GA) were imaged using magnetic resonance imaging (MRI) at birth, term-equivalent, 2, and 4 years of age. Cerebellar and total cerebral volumes were estimated from 1 mm isotropic T1 -weighted scans acquired at 1.5T and 3T, using an atlas-based approach. Linear models were used to analyze cerebellar volume as cross-sectional and longitudinal functions of age, clinical, and radiological correlates. Linear models were also used to test for associations between volume and cognitive outcome. RESULTS: Cerebellar volume increased rapidly with age-at-scan during both the preterm (0.7 mL/wk, P < 0.001) and term periods (1.8 mL/wk, P < 0.001). Infants with grade 3 or 4 germinal matrix hemorrhage (GMH) had smaller cerebellar volumes as a percentage of total brain volume starting at birth and continuing to 4 years of age (-0.43%, -0.57%, -1.09% at preterm, term, and 4 years, respectively, P < 0.01). Irrespective of age-at-scan, early cerebellar volume was predictive of volume at 4 years of age (slope = 1.3, P < 0.001). Cerebellar volumes were not found to predict cognitive outcome at 4 years of age; P < 0.2. CONCLUSION: High-grade GMH and small perinatal cerebellar size is predictive of cerebellar development up to 4 years of age. These findings suggest that it is possible to identify individuals at high risk of reduced cerebellar volumes at an early age. J. Magn. Reson. Imaging 2016;43:1462-1473.
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Envelhecimento/fisiologia , Cerebelo/diagnóstico por imagem , Cerebelo/crescimento & desenvolvimento , Interpretação de Imagem Assistida por Computador/métodos , Lactente Extremamente Prematuro/crescimento & desenvolvimento , Imageamento por Ressonância Magnética/métodos , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Técnica de SubtraçãoRESUMO
INTRODUCTION: The purpose of this study was to assess the impact of brain injury on white matter development and long-term outcomes in very preterm (VPT) neonates. METHODS: Eighty-five VPT neonates (born <32/40 weeks gestational age (GA)) scanned within 2 weeks of birth were divided into three groups based on the presence of perinatal cerebral injury: (i) no injury, (ii) mild/moderate injury and (iii) severe injury. Diffusion tensor imaging (DTI) was acquired for each neonate and fractional anisotropy (FA), and diffusivity measures were calculated in the posterior limb of the internal capsule (PLIC) and optic radiation (OR). At 2 and 4 years of age, 41 and 44 children were assessed for motor and visual-motor abilities. Analyses determined the relation between GA and DTI measures, injury groups and DTI measures as well as developmental assessments. RESULTS: GA was related to all DTI measures within the PLIC bilaterally, FA in the OR bilaterally and AD in the left OR. The severely injured group had significantly different DTI measures in the left PLIC compared to the other two groups, independent of lateralization of lesions. Group differences in the left OR were also found, due to higher incidence of the white matter injury in the left hemisphere. No differences were found between groups and outcome measures at 2 and 4 years, with the exception of destructive periventricular venous haemorrhagic infarction (PVHI). CONCLUSIONS: DTI measures of the PLIC and OR were affected by injury in VPT neonates. These findings seen shortly after birth did not always translate into long-term motor and visual-motor impairments suggesting compensatory mechanisms.
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Lesões Encefálicas/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Transtornos Motores/diagnóstico , Transtornos da Visão/diagnóstico , Substância Branca/diagnóstico por imagem , Substância Branca/lesões , Lesões Encefálicas/patologia , Vias Eferentes/diagnóstico por imagem , Vias Eferentes/lesões , Vias Eferentes/patologia , Feminino , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Masculino , Sensibilidade e Especificidade , Vias Visuais/diagnóstico por imagem , Vias Visuais/lesões , Vias Visuais/patologia , Substância Branca/patologiaRESUMO
We evaluated whether the volume and growth rate of critical brain structures measured by MRI in the first weeks of life following very preterm (<32/40 weeks) birth could predict subsequent neurodevelopmental outcomes at 4 years of age. A significant proportion of children born very prematurely have cognitive deficits, but these problems are often only detected at early school age. Structural T2-weighted magnetic resonance images were acquired in 96 very preterm neonates scanned within 2 weeks of birth and 70 of these at term-equivalent age. An automated 3D image analysis procedure was used to measure the volume of selected brain structures across all scans and time points. At 4 years of age, 53 children returned for neuropsychological assessments evaluating IQ, language and visual motor integration. Associations with maternal education and perinatal measures were also explored. Multiple regression analyses revealed that growth of the caudate and globus pallidus between preterm birth and term-equivalent age predicted visual motor integration scores after controlling for sex and gestational age. Further associations were found between caudate and putamen growth with IQ and language scores. Analyses at either preterm or term-equivalent age only found associations between normalized deep grey matter growth and visual motor integration scores at term-equivalent age. Maternal education levels were associated with measures of IQ and language, but not visual motor integration. Thalamic growth was additionally linked with perinatal measures and presence of white matter lesions. These results highlight deep grey matter growth rates as promising biomarkers of long-term outcomes following very preterm birth, and contribute to our understanding of the brain-behaviour relations in these children.
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Gânglios da Base/crescimento & desenvolvimento , Desenvolvimento Infantil/fisiologia , Substância Cinzenta/crescimento & desenvolvimento , Lactente Extremamente Prematuro/crescimento & desenvolvimento , Inteligência/fisiologia , Idioma , Desempenho Psicomotor/fisiologia , Tálamo/crescimento & desenvolvimento , Biomarcadores , Pré-Escolar , Feminino , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , MasculinoRESUMO
Objective: In patients with epilepsy, the insula has been increasingly recognized as a common site of seizures. There is growing interest in understanding the cognitive and psychological consequences of insular epilepsy to help provide clinical recommendations to support patient's cognitive and psychosocial functioning, and to help identify candidates for epilepsy resective surgery. The aim of this scoping review was to describe the cognitive and behavioural characteristics associated with insular epilepsy in children and adults. Method: A systematic search was completed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis -Extension for Scoping Reviews guidelines. Eligible studies reported on a neuropsychological or behavioural outcome, using standardized or research-based psychological measures, in individuals with insular epilepsy, (i.e. the seizure focus and/or surgical resection included the insula), and a comparison group. After duplicates were removed, 2,423 citations were identified from the search, and 39 studies were included in the scoping review. Results: Across the included studies, intellectual/global cognitive functioning and language were most often evaluated. Lower functioning was found across multiple cognitive and behavioural processes in pediatric and adult patients with insular epilepsy. Following resective surgery involving the insula, behavioural and cognitive outcomes are general stable. Conclusions: The results of this scoping review further neuropsychologists' knowledge of the cognitive and behavioural outcomes of insular seizures prior to and following surgical treatment. These results can aid in counselling patients of the potential cognitive dysfunctions, and aid with treatment planning.
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Concussions present with a myriad of symptomatic and cognitive concerns; however, the relationship between these functional disruptions and the underlying changes in the brain are not yet well understood. Hubs, or brain regions that are connected to many different functional networks, may be specifically disrupted after concussion. Given the implications in concussion research, we quantified hub disruption within the default mode network (DMN) and between the DMN and other brain networks. We collected resting-state functional magnetic resonance imaging data from collegiate student-athletes (n = 44) at three time points: baseline (before beginning their athletic season), acute post-injury (approximately 48h after a diagnosed concussion), and recovery (after starting return-to-play progression, but before returning to contact). We used self-reported symptoms and computerized cognitive assessments collected across similar time points to link these functional connectivity changes to clinical outcomes. Concussion resulted in increased connectivity between regions within the DMN compared with baseline and recovery, and this post-injury connectivity was more positively related to symptoms and more negatively related to visual memory performance compared with baseline and recovery. Further, concussion led to decreased connectivity between DMN hubs and visual network non-hubs relative to baseline and recovery, and this post-injury connectivity was more negatively related to somatic symptoms and more positively related to visual memory performance compared with baseline and recovery. Relationships between functional connectivity, symptoms, and cognition were not significantly different at baseline versus recovery. These results highlight a unique relationship between self-reported symptoms, visual memory performance, and acute functional connectivity changes involving DMN hubs after concussion in athletes. This may provide evidence for a disrupted balance of within- and between-network communication highlighting possible network inefficiencies after concussion. These results aid in our understanding of the pathophysiological disruptions after concussion and inform our understanding of the associations between disruptions in brain connectivity and specific clinical presentations acutely post-injury.
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Concussão Encefálica , Rede de Modo Padrão , Humanos , Concussão Encefálica/diagnóstico por imagem , Cognição , Encéfalo/diagnóstico por imagem , AtletasRESUMO
HIV-exposed uninfected (HEU) children during the preschool and early school ages may be at-risk for neurodevelopmental challenges due to in utero and perinatal exposure to HIV and/or antiretroviral (ARV) medications. HEU children and HIV-unexposed uninfected (HUU) children from the community were recruited and tested at 3 to 4 and 5 to 6 years of age. Demographic information, HIV/ARV exposure and measures of intelligence, visuomotor skills, and adaptive functioning were obtained. Nonparametric tests assessed group differences and multiple regression analyses adjusted for demographic variables. Additional multiple regression analyses were performed within the HEU group to investigate associations between neurodevelopmental measures and variables of HIV/ARV exposure. At 3 to 4 years, 211 HEU children and 31 HUU children were assessed, and 144 HEU children and 58 HUU children were assessed at 5 to 6 years of age. At 3 to 4 years of age, HEU children scored significantly lower on measures of Full-Scale IQ, Performance IQ, visual motor integration, and adaptive functioning. At 5 to 6 years of age, HEU children scored significantly lower on all neurodevelopmental measures. At both ages, children who were female and those with mothers who were employed achieved higher scores on measures intellectual ability and/or adaptive functioning. Within the HEU group, no consistent associations were found between neurodevelopmental measures and HIV/ARV specific variables. HEU children demonstrated significantly lower scores on neurodevelopmental measures than HUU children during early childhood. Gaps in verbal intellectual abilities were identified with age, highlighting the importance of monitoring neurodevelopment in this population over time. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
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Infecções por HIV , Complicações Infecciosas na Gravidez , Criança , Desenvolvimento Infantil , Pré-Escolar , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Inteligência , Testes de Inteligência , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológicoRESUMO
Very preterm (VPT: ≤32 weeks of gestational age) birth poses an increased risk for social and cognitive morbidities that persist throughout life. Resting-state functional network connectivity studies provide information about the intrinsic capacity for cognitive processing. We studied the following four social-cognitive resting-state networks: the default mode, salience, frontal-parietal and language networks. We examined functional connectivity using magnetoencephalography with individual head localization using each participant's MRI at 6 (n = 40) and 8 (n = 40) years of age compared to age- and sex-matched full-term (FT) born children (n = 38 at 6 years and n = 43 at 8 years). VPT children showed increased connectivity compared to FT children in the gamma band (30-80 Hz) at 6 years within the default mode network (DMN), and between the DMN and the salience, frontal-parietal and language networks, pointing to more diffuse, less segregated processing across networks at this age. At 8 years, VPT children had more social and academic difficulties. Increased DMN connectivity at 6 years was associated with social and working memory difficulties at 8 years. Therefore, we suggest that increased DMN connectivity contributes to the observed emerging social and cognitive morbidities in school age.
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Encéfalo , Lactente Extremamente Prematuro , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Criança , Cognição , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , MagnetoencefalografiaRESUMO
OBJECTIVE: Direct injury to the corpus callosum (CC) due to neurosurgical interventions in infants with posthemorrhagic ventricular dilatation (PHVD) has not been reported in the literature. The authors observed a subset of infants who had suffered penetrating CC injury after neurosurgical interventions for PHVD and hypothesized that this pattern of injury may result in suboptimal CC maturation and neurodevelopmental impairment. METHODS: In this multicenter, retrospective, observational study, 100 preterm and 17 full-term infants with PHVD were included and compared with 23 preterm controls. Both neonatal and postneonatal brain MRI scans were assessed for injury, and measurements were performed on postneonatal MRI scans at 2 years' corrected age. Neurodevelopmental outcome was assessed at 2 years' corrected age. RESULTS: A total of 269 brain MRI scans of 140 infants were included. Of infants with PHVD, 48 (41%) had penetrating CC injury following neurosurgical interventions. The median (IQR) CC midsagittal surface area was smaller in infants with CC injury when compared with infants with PHVD who had intact CC and controls (190 mm2 [149-262 mm2] vs 268 mm2 [206-318 mm2] vs 289 mm2 [246-320 mm2], respectively; p < 0.001). In the univariate analysis, the area of the CC was associated with cognitive Z score (coefficient 0.009 [95% CI 0.005-0.012], p < 0.001) and motor Z score (coefficient 0.009 [95% CI 0.006-0.012], p < 0.001). In the multivariable model, CC injury was not independently associated with cognitive and motor Z score after adjusting for gestational age and presence of periventricular hemorrhagic infarction (coefficient 0.04 [95% CI -0.36 to 0.46] and -0.37 [95% CI -0.83 to 0.09], p = 0.7 and 0.1, respectively). CONCLUSIONS: CC injury was not uncommon following neurosurgical interventions for PHVD in both preterm and full-term infants. At the age of 2 years, the CC midsagittal surface area was smaller in infants with injury, but CC injury was not independently associated with cognitive and motor outcomes at 2 years' corrected age.
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BACKGROUND AND OBJECTIVES: Neurocognitive outcomes after surgery for temporal lobe epilepsy in childhood are variable. Postoperative changes are not directly predicted by seizure freedom, and associations between epilepsy, neuropsychological function, and developing neural networks are poorly understood. Here, we leveraged whole-brain connectomic profiling in magnetoencephalography (MEG) to retrospectively study associations between brain connectivity and neuropsychological function in children with temporal lobe epilepsy undergoing resective surgery. METHODS: Clinical and MEG data were retrospectively analyzed for children who underwent temporal lobe epilepsy surgery at the Hospital for Sick Children from 2000 to 2021. Resting-state connectomes were constructed from neuromagnetic oscillations via the weighted-phase lag index. Using a partial least-squares (PLS) approach, we assessed multidimensional associations between patient connectomes, neuropsychological scores, and clinical covariates. Bootstrap resampling statistics were performed to assess statistical significance. RESULTS: A total of 133 medical records were reviewed, and 5 PLS analyses were performed. Each PLS analysis probed a particular neuropsychological domain and the associations between its baseline and postoperative scores and the connectomic data. In each PLS analysis, a significant latent variable was identified, representing a specific percentage of the variance in the data and relating neural networks to clinical covariates, which included changes in rote verbal memory (n = 41, p = 0.01, σ2 = 0.38), narrative/verbal memory (n = 57, p = 0.00, σ2 = 0.52), visual memory (n = 51, p = 0.00, σ2 = 0.43), working memory (n = 44, p = 0.00, σ2 = 0.52), and overall intellectual function (n = 59, p = 0.00, σ2 = 0.55). Children with more diffuse, bilateral intrinsic connectivity across several frequency bands showed lower scores on all neuropsychological assessments but demonstrated a greater propensity for gains after resective surgery. DISCUSSION: Here, we report that connectomes characterized by diffuse connectivity, reminiscent of developmentally immature networks, are associated with lower preoperative cognition and postoperative cognitive improvement. These findings provide a potential means to understand neurocognitive function in children with temporal lobe epilepsy and expected changes postoperatively.
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Conectoma , Epilepsia do Lobo Temporal , Epilepsia , Criança , Cognição , Epilepsia/cirurgia , Epilepsia do Lobo Temporal/cirurgia , Humanos , Testes Neuropsicológicos , Estudos RetrospectivosRESUMO
HIV-exposed uninfected (HEU) children may be at-risk for poorer academic achievement compared to HIV-unexposed uninfected (HUU) children due to in utero and perinatal exposure to HIV and/or anti-retroviral (ARV) medication. Understanding the risk factors for academic underachievement is important for implementing timely intervention and academic supports. HEU (N = 110, mean (SD) age 5.59 (0.22) years) and HUU (N = 43, mean (SD) age 5.73 (0.64) years) children completed assessments of general intelligence (WPPSI-III) and academic achievement (WRAT-4). Parent interviews and medical record reviews were used to obtain sociodemographic and maternal health data. HUU children scored significantly higher than HEU children on single word reading (p = 0.006), math calculation skills (p = 0.003), Verbal IQ, Performance IQ, Full Scale IQ, and Processing Speed (all WPPSI-III measures p < 0.001). Verbal IQ at 3-4 years predicted academic achievement at 5-6 years of age, yet sociodemographic and medical factors did not. These findings demonstrate that HEU children obtained significantly lower scores of intellectual, reading, and math abilities during early childhood. Addressing these early gaps before HEU children enter primary school will be critical for optimizing their learning and academic potential.
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Sucesso Acadêmico , Infecções por HIV/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Estudos de Casos e Controles , Pré-Escolar , Cognição/fisiologia , Feminino , Humanos , Masculino , Transtornos do Neurodesenvolvimento/epidemiologia , Gravidez , Fatores de Risco , Escalas de WechslerRESUMO
Working memory (WM) deficits are pervasive co-morbidities of epilepsy. Although the pathophysiological mechanisms underpinning these impairments remain elusive, it is thought that WM depends on oscillatory interactions within and between nodes of large-scale functional networks. These include the hippocampus and default mode network as well as the prefrontal cortex and frontoparietal central executive network. Here, we review the functional roles of neural oscillations in subserving WM and the putative mechanisms by which epilepsy disrupts normative activity, leading to aberrant oscillatory signatures. We highlight the particular role of interictal epileptic activity, including interictal epileptiform discharges and high frequency oscillations (HFOs) in WM deficits. We also discuss the translational opportunities presented by greater understanding of the oscillatory basis of WM function and dysfunction in epilepsy, including potential targets for neuromodulation.
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Anophthalmia, characterized by the absence of an eye(s), is a rare major birth defect with a relatively unexplored neuroanatomy. Longitudinal comparison of white matter development in an anophthalmic (AC) very preterm (VPT) child with both binocular VPT and full-term (FT) children provides unique insights into early neurodevelopment of the visual system. VPT-born neonates (<32wks gestational age), including the infant with unilateral anophthalmia, underwent neuroimaging every two years from birth until 8 years. DTI images (N = 168) of the optic radiation (OR) and a control track, the posterior limb of the internal capsule (PLIC), were analysed. The diameter of the optic nerves (ON) were analysed using T1-weighted images. Significant group differences in FA and AD were found bilaterally in the OR and PLIC. This extends the literature on altered white matter development in VPT children, being the first longitudinal study showing stable group differences across the 4, 6 and 8 year timepoints. AC showed greater deficits in FA and AD bilaterally, but recovered towards VPT group means from 4 to 8 years-of-age. Complete lack of binocular input would be responsible for these early deficits; compensatory mechanisms may facilitate structural improvement over time. AC's ON exhibited significant atrophy ipsilateral to the anophthalmic eye. Functionally, AC displayed normal visual acuity and form perception, but naso-temporal bias in motion perception. Following these groups and AC longitudinally enabled novel understanding of the joint influence of monocular vision and VPT birth on neurodevelopment.
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Anoftalmia , Lactente Extremamente Prematuro , Substância Branca , Encéfalo , Criança , Pré-Escolar , Imagem de Tensor de Difusão , Feminino , Humanos , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Substância Branca/diagnóstico por imagemRESUMO
Children born very preterm (VPT) are at high-risk for altered brain development and impaired neurodevelopmental outcomes but are not well-studied before school-age. We investigated 64 four-year-olds: 37 VPT children [<32 weeks gestational age [GA]; 22 males; mean GA: 28.8 weeks ± 1.6], 25 full-term (FT) children (12 males), plus two VPT cases with ventriculomegaly and exceptionally resilient outcomes. All children underwent high-resolution structural magnetic resonance imaging and developmental assessments. Measures of brain volume, cortical thickness, and surface area were obtained. Children born VPT demonstrated reduced cerebral and cerebellar white matter volumes yet increased cerebral gray matter, temporal lobe, occipital lobe and ventricle volumes after adjusting for total brain volume. Cortical thickness was greater in the VPT children compared to FT children across all lobes. On developmental assessments, the VPT children scored lower on average than FT children while the two cases had intact cognitive abilities. In addition to larger ventricle volumes, the two cases had white matter and gray matter volumes within the ranges of the FT children. The VPT children displayed distinct differences in structural brain volumes at 4 years of age, consistent with delayed maturation. The cases with persistent ventriculomegaly and good cognitive outcomes displayed typical gray matter and increased white matter volumes, indicating a potential protective developmental phenomenon contributing to their intact cognitive abilities.
RESUMO
Children born very preterm (VPT; <32â¯weeks gestational age [GA]) are at greater risk for a range of cognitive deficits that typically manifest at school age. Here we examine the hypothesis that these children have altered myelin maturational that can be detected by myelin sensitive MRI measures prior to school age. We included 33 four-year old children born VPT (mean GA; 28.7â¯weeks) and 23 four-year old full term (FT) children and completed magnetization transfer (MT), T1-weighted (T1-w) and T2-weighted (T1-w) magnetic resonance imaging as well as developmental assessments. Both MT ratio (MTR) and T1-w/T2-w ratio images were calculated, and group differences were probed using tract-based spatial statistics (TBSS) in white matter, and region of interest (ROI) analysis in white, subcortical gray and cortical gray matter. The relations between MTR and T1-w/T2-w ratio, as well as with developmental assessments, were investigated in all three brain divisions. In children born VPT, TBSS and ROI analysis revealed that both MTR and T1-w/T2-w ratio were significantly reduced in white matter compared to children born FT. ROI analysis showed reductions in T1-w/T2-w ratio in VPT children compared to FT children in the thalamus, putamen and amygdala, as well as in the occipital and temporal lobes. Across the VPT and FT children, T1-w/T2-w ratio and MTR were highly correlated across white, subcortical gray and cortical gray matter. Both measures correlated positively with developmental assessments in individual white matter tracts and cortical and subcortical ROIs, suggesting that higher MTR and T1-w/T2-w ratio is related to better cognitive performance. Together these findings are consistent with delayed myelination in VPT born children.
Assuntos
Encéfalo/diagnóstico por imagem , Encéfalo/crescimento & desenvolvimento , Desenvolvimento Infantil/fisiologia , Imagem de Tensor de Difusão , Lactente Extremamente Prematuro/crescimento & desenvolvimento , Bainha de Mielina/fisiologia , Pré-Escolar , Imagem de Tensor de Difusão/métodos , Feminino , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética/métodos , MasculinoRESUMO
INTRODUCTION: The underlying microstructural properties of white matter differences in children born very preterm (<32â¯weeks gestational age) can be investigated in depth using multi-shell diffusion imaging. The present study compared white matter across the whole brain using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) metrics in children born very preterm and full-term children at six years of age. We also investigated associations between white matter microstructure with early brain injury and developmental outcomes. METHOD: Multi-shell diffusion imaging, T1-weighted anatomical MR images and developmental assessments were acquired in 23 children born very preterm (16 males; mean scan age: 6.57⯱â¯0.34â¯years) and 24 full-term controls (10 males, mean scan age: 6.62⯱â¯0.37â¯years). DTI metrics were obtained and neurite orientation dispersion index (ODI) and density index (NDI) were estimated using the NODDI diffusion model. FSL's tract-based spatial statistics were performed on traditional DTI metrics and NODDI metrics. Voxel-wise comparisons were performed to test between-group differences and within-group associations with developmental outcomes (intelligence and visual motor abilities) as well as early white matter injury and germinal matrix/intraventricular haemorrhage (GMH/IVH). RESULTS: In comparison to term-born children, the children born very preterm exhibited lower fractional anisotropy (FA) across many white matter regions as well as higher mean diffusivity (MD), radial diffusivity (RD), and ODI. Within-group analyses of the children born very preterm revealed associations between higher FA and NDI with higher IQ and VMI. Lower ODI was found within the corona radiata in those with a history of white matter injury. Within the full-term group, associations were found between higher NDI and ODI with lower IQ. CONCLUSION: Children born very preterm exhibit lower FA and higher ODI than full-term children. NODDI metrics provide more biologically specific information beyond DTI metrics as well as additional information of the impact of prematurity and white matter microstructure on cognitive outcomes at six years of age.