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BACKGROUND: Consumption of alcohol during pregnancy impacts fetal development and may lead to a variety of physical, cognitive, and behavioral abnormalities in childhood collectively known as fetal alcohol spectrum disorder (FASD). The FASD spectrum includes children with fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (pFAS), and alcohol-related neurodevelopmental disorder (ARND). Children with a FASD or prenatal alcohol exposure (PAE) have impaired white matter, reduced structural volumes, impaired resting-state functional connectivity when measured with fMRI, and spectral hypersynchrony as infants. Magnetoencephalography (MEG) provides high temporal resolution and good spatial precision for examining spectral power and connectivity patterns unique from fMRI. The impact of PAE on MEG resting-state spectral power in children remains unknown. METHODS: We collected 2 minutes of eyes-open and eyes-closed resting-state data in 51 children (8 to 12 years of age) with 3 subgroups included: 10 ARND/PAE, 15 FAS/pFAS, and 26 controls (TDC). MEG data were collected on the Elekta Neuromag system. The following spectral metrics were compared between subgroups: power, normalized power, half power, 95% power, and Shannon spectral entropy (SSE). MEG spectral data were correlated with behavioral measures. RESULTS: Our results indicate children with FAS/pFAS had reduced spectral power and normalized power, particularly within the alpha frequency band in sensor parietal and source superior parietal and lateral occipital regions, along with elevated half power, 95% power, and SSE. We also found select hemisphere specific effects further indicating reduced corpus callosum connectivity in children with a FASD. Interestingly, while the ARND/PAE subgroup had significant differences from the FAS/pFAS subgroup, in many cases spectral data were not significantly different from TDC. CONCLUSIONS: Our results were consistent with previous studies and provide new insight into resting-state oscillatory differences both between children with FAS and TDC, and within FASD subgroups. Further understanding of these resting-state variations and their impact on cognitive function may help provide early targets for intervention and enhance outcomes for individuals with a FASD.
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Atenção/fisiologia , Encéfalo/fisiopatologia , Comportamento Infantil/fisiologia , Transtornos do Espectro Alcoólico Fetal/fisiopatologia , Magnetoencefalografia , Estudos de Casos e Controles , Criança , Feminino , Humanos , MasculinoRESUMO
BACKGROUND: Rapid automatised naming (RAN) and rapid alternating stimulus (RAS) are reliable predictors of reading disability. The underlying biology of reading disability is poorly understood. However, the high correlation among RAN, RAS and reading could be attributable to shared genetic factors that contribute to common biological mechanisms. OBJECTIVE: To identify shared genetic factors that contribute to RAN and RAS performance using a multivariate approach. METHODS: We conducted a multivariate genome-wide association analysis of RAN Objects, RAN Letters and RAS Letters/Numbers in a sample of 1331 Hispanic American and African-American youth. Follow-up neuroimaging genetic analysis of cortical regions associated with reading ability in an independent sample and epigenetic examination of extant data predicting tissue-specific functionality in the brain were also conducted. RESULTS: Genome-wide significant effects were observed at rs1555839 (p=4.03×10-8) and replicated in an independent sample of 318 children of European ancestry. Epigenetic analysis and chromatin state models of the implicated 70 kb region of 10q23.31 support active transcription of the gene RNLS in the brain, which encodes a catecholamine metabolising protein. Chromatin contact maps of adult hippocampal tissue indicate a potential enhancer-promoter interaction regulating RNLS expression. Neuroimaging genetic analysis in an independent, multiethnic sample (n=690) showed that rs1555839 is associated with structural variation in the right inferior parietal lobule. CONCLUSION: This study provides support for a novel trait locus at chromosome 10q23.31 and proposes a potential gene-brain-behaviour relationship for targeted future functional analysis to understand underlying biological mechanisms for reading disability.
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Negro ou Afro-Americano/genética , Dislexia/genética , Genoma Humano , Estudo de Associação Genômica Ampla , Genômica , Hispânico ou Latino/genética , Alelos , Biologia Computacional/métodos , Dislexia/diagnóstico , Epigênese Genética , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Genômica/métodos , Humanos , Desequilíbrio de Ligação , Masculino , Metanálise como Assunto , Neuroimagem , Polimorfismo de Nucleotídeo Único , Característica Quantitativa HerdávelRESUMO
The cortical responses to auditory stimuli undergo rapid and dramatic changes during the first 3 years of life in normally developing (ND) children, with decreases in latency and changes in amplitude in the primary peaks. However, most previous studies have focused on children >3 years of age. The analysis of data from the early stages of development is challenging because the temporal pattern of the evoked responses changes with age (e.g., additional peaks emerge with increasing age) and peak latency decreases with age. This study used the topography of the auditory evoked magnetic field (AEF) to identify the auditory components in ND children between 6 and 68 months (n = 48). The latencies of the peaks in the AEF produced by a tone burst (ISI 2 ± 0.2 s) during sleep decreased with age, consistent with previous reports in awake children. The peak latencies of the AEFs in ND children and children with autism spectrum disorder (ASD) were compared. Previous studies indicate that the latencies of the initial components of the auditory evoked potential (AEP) and the AEF are delayed in children with ASD when compared to age-matched ND children >4 years of age. We speculated whether the AEF latencies decrease with age in children diagnosed with ASD as in ND children, but with uniformly longer latencies before the age of about 4 years. Contrary to this hypothesis, the peak latencies did not decrease with age in the ASD group (24-62 months, n = 16) during sleep (unlike in the age-matched controls), although the mean latencies were longer in the ASD group as in previous studies. These results are consistent with previous studies indicating delays in auditory latencies, and they indicate a different maturational pattern in ASD children and ND children. Longitudinal studies are needed to confirm whether the AEF latencies diverge with age, starting at around 3 years, in these 2 groups of children.
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Córtex Auditivo/fisiopatologia , Transtorno do Espectro Autista/fisiopatologia , Mapeamento Encefálico , Potenciais Evocados Auditivos/fisiologia , Estimulação Acústica/métodos , Transtorno do Espectro Autista/diagnóstico , Criança , Pré-Escolar , Eletroencefalografia/métodos , Feminino , Humanos , Lactente , Magnetoencefalografia/métodos , MasculinoRESUMO
At rest children with prenatal alcohol exposure (PAE) exhibit impaired static and dynamic functional connectivity, along with decreased alpha oscillations. Sex-specific information regarding the impact of PAE on whole-brain resting-state gamma spectral power remains unknown. Eyes-closed and eyes-open MEG resting-state data were examined in 83 children, ages 6-13 years of age. Using a matched design, the sample consisted of 42 typically developing children (TDC) (22 males/20 females) and 41 children with PAE and/or a fetal alcohol spectrum disorders (FASD) diagnosis (21 males/20 females). Whole-brain source resting-state spectral power was examined to determine group and sex specific relationships. Within gamma, we found sex and group specific changes such that female participants with PAE/FASD had increased gamma power when compared to female TDC and male participants with PAE/FASD. These differences were detected in most source regions analyzed during both resting-states, and were observed across the age spectrum examined. Within delta, we found sex and group specific changes such that female participants with PAE/FASD had decreased delta power when compared to female TDC and male participants with PAE/FASD. The reduced delta oscillations in female participants with PAE/FASD were detected in several source regions during eyes-closed rest and were evident at younger ages. These results indicate PAE alters neural oscillations during rest in a sex-specific manner, with females with PAE/FASD showing the largest perturbations. These results further demonstrate PAE has global effects on resting-state spectral power and connectivity, creating long-term consequences by potentially disrupting the excitation/inhibition balance in the brain, interrupting normative neurodevelopment.
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Transtornos do Espectro Alcoólico Fetal , Efeitos Tardios da Exposição Pré-Natal , Criança , Humanos , Masculino , Feminino , Gravidez , Encéfalo , Caracteres SexuaisRESUMO
BACKGROUND: Prenatal alcohol exposure (PAE) can result in harmful and long-lasting neurodevelopmental changes. Children with PAE or a fetal alcohol spectrum disorder (FASD) have decreased white matter volume and resting-state spectral power compared to typically developing controls (TDC) and impaired resting-state static functional connectivity. The impact of PAE on resting-state dynamic functional network connectivity (dFNC) is unknown. METHODS: Using eyes-closed and eyes-open magnetoencephalography (MEG) resting-state data, global dFNC statistics and meta-states were examined in 89 children aged 6-16 years (51 TDC, 38 with FASD). Source analyzed MEG data were used as input to group spatial independent component analysis to derive functional networks from which the dFNC was calculated. RESULTS: During eyes-closed, relative to TDC, participants with FASD spent a significantly longer time in state 2, typified by anticorrelation (i.e., decreased connectivity) within and between default mode network (DMN) and visual network (VN), and state 4, typified by stronger internetwork correlation. The FASD group exhibited greater dynamic fluidity and dynamic range (i.e., entered more states, changed from one meta-state to another more often, and traveled greater distances) than TDC. During eyes-open, TDC spent significantly more time in state 1, typified by positive intra- and interdomain connectivity with modest correlation within the frontal network (FN), while participants with FASD spent a larger fraction of time in state 2, typified by anticorrelation within and between DMN and VN and strong correlation within and between FN, attention network, and sensorimotor network. CONCLUSIONS: There are important resting-state dFNC differences between children with FASD and TDC. Participants with FASD exhibited greater dynamic fluidity and dynamic range and spent more time in states typified by anticorrelation within and between DMN and VN, and more time in a state typified by high internetwork connectivity. Taken together, these network aberrations indicate that prenatal alcohol exposure has a global effect on resting-state connectivity.
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Transtornos do Espectro Alcoólico Fetal , Efeitos Tardios da Exposição Pré-Natal , Criança , Humanos , Feminino , Gravidez , Encéfalo , Mapeamento Encefálico , Transtornos do Espectro Alcoólico Fetal/diagnóstico por imagem , Imageamento por Ressonância Magnética , Vias Neurais/diagnóstico por imagem , Efeitos Tardios da Exposição Pré-Natal/diagnóstico por imagemRESUMO
Introduction: The teratogenic effects of prenatal alcohol exposure (PAE) have been examined in animal models and humans. The current study extends the prior literature by quantifying differences in brain structure for individuals with a fetal alcohol spectrum disorder (FASD) compared to typically developing controls, as well as examining FASD subtypes. We hypothesized the FASD group would reveal smaller brain volume, reduced cortical thickness, and reduced surface area compared to controls, with the partial fetal alcohol syndrome (pFAS)/fetal alcohol syndrome (FAS) subtypes showing the largest effects and the PAE/alcohol-related neurodevelopmental disorder (ARND) subtype revealing intermediate effects. Methods: The sample consisted of 123 children and adolescents recruited from a single site including children with a diagnosis of FASD/PAE (26 males, 29 females) and controls (34 males, 34 females). Structural T1-weighted MRI scans were obtained on a 3T Trio TIM scanner and FreeSurfer v7.2 was used to quantify brain volume, cortical thickness, and surface area. Analyses examined effects by subgroup: pFAS/FAS (N = 32, Mage = 10.7 years, SEage = 0.79), PAE/ARND (N = 23, Mage = 10.8, SEage = 0.94), and controls (N = 68, Mage = 11.1, SEage = 0.54). Results: Total brain volume in children with an FASD was smaller relative to controls, but subtype analysis revealed only the pFAS/FAS group differed significantly from controls. Regional analyses similarly revealed reduced brain volume in frontal and temporal regions for children with pFAS/FAS, yet children diagnosed with PAE/ARND generally had similar volumes as controls. Notable differences to this pattern occurred in the cerebellum, caudate, and pallidum where children with pFAS/FAS and PAE/ARND revealed lower volume relative to controls. In the subset of participants who had neuropsychological testing, correlations between volume and IQ scores were observed. Goodness-of-Fit analysis by age revealed differences in developmental patterns (linear vs. quadratic) between groups in some cases. Discussion: This study confirmed prior results indicating decreased brain volume in children with an FASD and extended the results by demonstrating differential effects by structure for FASD subtypes. It provides further evidence for a complex role of PAE in structural brain development that is likely related to the cognitive and behavioral effects experienced by children with an FASD.
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Children with prenatal alcohol exposure (PAE) often suffer from cognitive and neurobehavioral dysfunction throughout their lives, which may rise to a level of concern such that children receive a diagnosis under the fetal alcohol spectrum disorders (FASD) umbrella. Magnetoencephalography (MEG) contributes direct insight into neural processing and functional connectivity measures with temporal precision to understand cortical processing disorders that manifest during development. The impairment of perception may become more consequential among school-aged children with an FASD in the process of intellectual functioning and behavioral maturation. Fifty participants with the age range of 8-13 years participated in our study following parental informed consent and child assent. For each participant, visual responses were recorded using magnetoencephalography (MEG) while performing a prosaccade task with central stimuli (fovea centralis) and peripheral stimuli (left and right of central) presented on a screen, requiring participants to shift their gaze to the stimuli. After source analysis using minimum norm estimation (MNE), we investigated visual responses from each participant by measuring the latency and amplitude of visual evoked fields. Delayed peak latency of the visual response was identified in the primary visual area (calcarine fissure) and visual association areas (v2, v3) in young children with an FASD for both stimulus types (central and peripheral). But the difference in visual response latency was only statistically significant (p ≤ 0.01) for the peripheral (right) stimulus. We also observed reduced amplitude (p ≤ 0.006) of visual evoked response in children with an FASD for the central stimulus type in both primary and visual association areas. Multiple visual areas show impairment in children with an FASD, with visual delay and conduction disturbance more prominent in response to peripheral stimuli. Children with an FASD also exhibit significantly reduced amplitude of neural activation to central stimuli. These sensory deficits may lead to slow cognitive processing speed through continued intra-cortical network disturbance in children with an FASD.
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Transtornos do Espectro Alcoólico Fetal , Efeitos Tardios da Exposição Pré-Natal , Adolescente , Criança , Pré-Escolar , Potenciais Evocados Visuais , Feminino , Transtornos do Espectro Alcoólico Fetal/psicologia , Humanos , Magnetoencefalografia , Gravidez , Tempo de Reação/fisiologiaRESUMO
Prenatal alcohol exposure (PAE) can result in long-lasting changes to physical, behavioral, and cognitive functioning in children. PAE might result in decreased white matter integrity, corticothalamic tract integrity, and alpha cortical oscillations. Previous investigations of alpha oscillations in PAE/fetal alcohol spectrum disorder (FASD) have focused on average spectral power at specific ages; therefore, little is known about alpha peak frequency (APF) or its developmental trajectory making this research novel. Using resting-state MEG data, APF was determined from parietal/occipital regions in participants with PAE/FASD or typically developing controls (TDC). In total, MEG data from 157 infants, children, and adolescents ranging in age from 6 months to 17 years were used, including 17 individuals with PAE, 61 individuals with an FASD and 84 TDC. In line with our hypothesis, we found that individuals with PAE/FASD had significantly reduced APF relative to TDC. Both age and group were significantly related to APF with differences between TDC and PAE/FASD persisting throughout development. We did not find evidence that sex or socioeconomic status had additional impact on APF. Reduced APF in individuals with an FASD/PAE may represent a long-term deficit and demonstrates the detrimental impact prenatal alcohol exposure can have on neurophysiological processes.
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Relationships between repetitive behaviors (RBs) and associated clinical features (i.e., cognitive and adaptive functioning levels, sleep problems, medication use, and other behavioral problems) were examined in two groups (High nonverbal IQ > or = 97 versus Low nonverbal IQ < or = 56) of children with autism spectrum disorders (n = 14; mean age = 10 years, 7 months). For the group as a whole, nonverbal cognitive ability (NVIQ) (as measured by the Leiter-R), adaptive functioning level, the presence of sleep problems, and three scales of the Aberrant Behavior Checklist (ABC) (Irritability, Lethargy, and Hyperactivity) were highly correlated with total RB scores on the Repetitive Behavior Scale-Revised (RBS-R). After controlling for NVIQ, adaptive level, sleep problems, and two scales of the ABC (Irritability and Lethargy) were not significantly associated with RB scores. However, there remained a significant positive correlation between the presence of RBs and the Hyperactivity scale of the ABC. Parent ratings of their stress levels and the presence of RBs in their children were highly correlated. The relationship between RBs and associated clinical features in autism is complex and future studies should control for cognitive ability when examining the direct and indirect relationships of these variables with RBs.
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Transtorno Autístico/patologia , Transtorno Autístico/psicologia , Comportamento Estereotipado/classificação , Adaptação Psicológica , Criança , Cognição , Feminino , Humanos , Masculino , Índice de Gravidade de Doença , Transtornos do Sono-VigíliaRESUMO
OBJECTIVE: To investigate neurometabolite concentrations in right prefrontal white matter in children with attention-deficit/hyperactivity disorder (ADHD) and relations of neurometabolites with attention skill and frontal anatomy. METHOD: Single voxel proton magnetic resonance spectroscopy ( H-MRS), quantitative morphometric analysis of left and right dorsolateral frontal volumes, and assessment of attentional problems with the Conners Continuous Performance Test were undertaken in 23 children (17 male) with ADHD (with no comorbid learning disabilities) and 24 matched controls (16 male). RESULTS: No overall group differences were found for any neurometabolite. However, a group by sex interaction was noted for -acetylaspartate, such that girls with ADHD had especially low concentrations. Morphological analyses revealed smaller right (but not left) dorsolateral volumes in children with ADHD, and in the ADHD group this volume correlated with neurometabolite concentrations. In the ADHD group Continuous Performance Test performance was related to both dorsolateral volume and the creatine-phosphocreatine peak from H-MRS. CONCLUSIONS: These results add to a growing body of evidence suggesting sex-specific neurobiological differences in ADHD and draw attention to relationships between neurochemistry, neuroanatomy, and performance in children with ADHD. Study limitations include small sample size and clinical heterogeneity among the children with ADHD.
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Ácido Aspártico/análogos & derivados , Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Lobo Frontal/metabolismo , Lateralidade Funcional/fisiologia , Espectroscopia de Ressonância Magnética , Prótons , Ácido Aspártico/metabolismo , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Criança , Feminino , Humanos , Masculino , Testes NeuropsicológicosRESUMO
This study compared magnetic resonance imaging size differences in several brain regions and neurocognitive function in a group of male and female children with attention-deficit/hyperactivity disorder (ADHD) with no comorbid learning disorders with a normal control group of children. The ADHD group demonstrated smaller total brain, superior prefrontal, and right superior prefrontal volumes, as well as significantly smaller areas for cerebellar lobules I-V and VIII-X, total corpus callosum area, and splenium. No group differences were observed for the inferior prefrontal, caudate, or cerebellar volumes, or for the area of cerebellar lobules VI-VII. In the ADHD group but not in the control group, greater right superior prefrontal volume predicted poorer performance on a test of sustained attention. Patterns of brain abnormality did not differ in male and female children with ADHD.
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Transtorno do Deficit de Atenção com Hiperatividade/patologia , Encéfalo/patologia , Imageamento por Ressonância Magnética , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Estudos de Casos e Controles , Criança , Transtornos Cognitivos/patologia , Feminino , Humanos , Masculino , Fatores SexuaisRESUMO
Whereas the model of Jellinek [Q. J. Stud. Alcohol 7 (1952) 673] of a predictable progression of alcoholism is generally supported, there have been few published studies regarding the natural history of illicit drug disorders. Identification of the development of drug abuse and/or dependence can inform clinicians and researchers on issues, such as diagnosis, prognosis, assessment, and prevention. This study employed a new measure adapted from the 46 events described in Jellinek's progression of alcoholism. Nine licit and illicit substances were also included within the cardsort. Fifty-two individuals motivated to enter drug treatment by a loved one were assessed pretreatment. The drug initiation sequence reported by this sample was as follows: alcohol, tobacco, inhalants, marijuana, and then other drugs. Spearman rank correlation coefficients were conducted between the drug sample and that of Jellinek yielding a modest correlation (r=.35, P=.019). These results suggest that Jellinek's model of progression of alcoholism may also apply to the development of drug disorders. However, important differences found between the alcohol and drug progressions are discussed.
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Transtornos Relacionados ao Uso de Substâncias/psicologia , Adolescente , Adulto , Transtornos Relacionados ao Uso de Álcool/psicologia , Alcoolismo/psicologia , Transtornos Relacionados ao Uso de Cocaína/psicologia , Feminino , Alucinógenos , Dependência de Heroína/psicologia , Humanos , Hipnóticos e Sedativos , Drogas Ilícitas , Masculino , Abuso de Maconha/psicologia , Pessoa de Meia-Idade , Modelos Psicológicos , Tabagismo/psicologiaRESUMO
While the reliability of assessment instruments designed for use with adults is well established, much less is known about the adequacy of these instruments for adolescent substance abusers. As part of a comprehensive intake evaluation, the Inventory of Drug Use Consequences (InDUC) was administered both to forty adolescents assigned to a probationary substance abuse treatment program and to one of their parents. The correlation was statistically significant between Parent and Adolescent InDUC score(s), but the interrater reliability was relatively low. IQ scores and level of substance use were considered as moderator variables, but neither showed a significant effect. History of head injury, however, significantly moderated this relationship; those adolescents reporting no history of head injury showed little correspondence with Parent InDUC Score(s), whereas those adolescents with a history of head injury showed significant correlations with parent InDUC scores. This suggests that a history of head injury may affect the way in which adolescents perceive substance-related consequences.
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BACKGROUND: Long-term survivors of acute lymphoblastic leukemia (ALL) are reported to have post-treatment neurological changes as well as neuropsychological changes. Few studies have investigated the relationship between magnetic resonance imaging (MRI) volumetric measurements of brain regions of interest and cognitive functioning. This study examined the relationship between hippocampal volumes and long-term memory abilities in survivors of ALL. PROCEDURE: Ten survivors of ALL and ten matched controls underwent MRI acquisition. The participants completed a battery of tests measuring both visual and verbal long-term memory. Volumetric measurements of the hippocampus were obtained by consecutive manual tracing using the NIH Image 1.52 program. Estimates of whole brain volume were also obtained. RESULTS: No significant group differences were found in right or left hippocampi. Nor were there significant differences between the two groups on measures of long-term memory. Correlations between volumetric measurements of the hippocampus and measures of long-term memory were non-significant. CONCLUSIONS: Our hypothesis of deficits in both long-term memory and its neural substrates was not supported. It was concluded that the hippocampus, as an early developing structure, may be less vulnerable to chemotherapy treatment. Children surviving ALL are able to retain and retrieve once learned information comparable with peers.