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1.
Eur J Neurosci ; 60(1): 3597-3613, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38703054

RESUMO

Early disruptions to social communication development, including delays in joint attention and language, are among the earliest markers of autism spectrum disorder (autism, henceforth). Although social communication differences are a core feature of autism, there is marked heterogeneity in social communication-related development among infants and toddlers exhibiting autism symptoms. Neural markers of individual differences in joint attention and language abilities may provide important insight into heterogeneity in autism symptom expression during infancy and toddlerhood. This study examined patterns of spontaneous electroencephalography (EEG) activity associated with joint attention and language skills in 70 community-referred 12- to 23-month-olds with autism symptoms and elevated scores on an autism diagnostic instrument. Data-driven cluster-based permutation analyses revealed significant positive associations between relative alpha power (6-9 Hz) and concurrent response to joint attention skills, receptive language, and expressive language abilities. Exploratory analyses also revealed significant negative associations between relative alpha power and measures of core autism features (i.e., social communication difficulties and restricted/repetitive behaviors). These findings shed light on the neural mechanisms underlying typical and atypical social communication development in emerging autism and provide a foundation for future work examining neural predictors of social communication growth and markers of intervention response.


Assuntos
Comunicação , Humanos , Masculino , Lactente , Feminino , Transtorno do Espectro Autista/fisiopatologia , Eletroencefalografia/métodos , Atenção/fisiologia , Transtorno Autístico/fisiopatologia , Transtorno Autístico/psicologia , Comportamento Social , Encéfalo/fisiopatologia , Desenvolvimento da Linguagem
2.
Stat Med ; 43(17): 3239-3263, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38822707

RESUMO

Autism spectrum disorder (autism) is a prevalent neurodevelopmental condition characterized by early emerging impairments in social behavior and communication. EEG represents a powerful and non-invasive tool for examining functional brain differences in autism. Recent EEG evidence suggests that greater intra-individual trial-to-trial variability across EEG responses in stimulus-related tasks may characterize brain differences in autism. Traditional analysis of EEG data largely focuses on mean trends of the trial-averaged data, where trial-level analysis is rarely performed due to low neural signal to noise ratio. We propose to use nonlinear (shape-invariant) mixed effects (NLME) models to study intra-individual inter-trial EEG response variability using trial-level EEG data. By providing more precise metrics of response variability, this approach could enrich our understanding of neural disparities in autism and potentially aid the identification of objective markers. The proposed multilevel NLME models quantify variability in the signal's interpretable and widely recognized features (e.g., latency and amplitude) while also regularizing estimation based on noisy trial-level data. Even though NLME models have been studied for more than three decades, existing methods cannot scale up to large data sets. We propose computationally feasible estimation and inference methods via the use of a novel minorization-maximization (MM) algorithm. Extensive simulations are conducted to show the efficacy of the proposed procedures. Applications to data from a large national consortium find that children with autism have larger intra-individual inter-trial variability in P1 latency in a visual evoked potential (VEP) task, compared to their neurotypical peers.


Assuntos
Transtorno do Espectro Autista , Eletroencefalografia , Humanos , Transtorno do Espectro Autista/fisiopatologia , Transtorno Autístico/fisiopatologia , Modelos Estatísticos , Simulação por Computador , Dinâmica não Linear , Encéfalo/fisiopatologia
3.
J Surg Res ; 301: 455-460, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39033596

RESUMO

INTRODUCTION: Laparoscopy has demonstrated improved outcomes in abdominal surgery; however, its use in trauma has been less compelling. In this study, we hypothesize that laparoscopy may be observed to have lower costs and complications with similar operative times compared to open exploration in appropriately selected patients. METHODS: We retrospectively reviewed adult patients undergoing abdominal exploration after blunt and penetrating trauma at our level 1 center from 2008 to 2020. Data included mechanism, operative time, length of stay (LOS), hospital charges, and complications. Patients were grouped as follows: therapeutic and nontherapeutic diagnostic laparoscopy and celiotomy. Therapeutic procedures included suture repair of hollow viscus organs or diaphragm, evacuation of hematoma, and hemorrhage control of solid organ or mesenteric injury. Unstable patients, repair of major vascular injuries or resection of an organ or bowel were excluded. RESULTS: Two hundred ninety-six patients were included with comparable demographics. Diagnostic laparoscopy had shorter operative times, LOS, and lower hospital charges compared to diagnostic celiotomy controls. Similarly, therapeutic laparoscopy had shorter LOS and lower hospital costs compared to therapeutic celiotomy. The operative time was not statistically different in this comparison. Patients in the celiotomy groups had more postoperative complications. The differences in operative time, LOS and hospital charges were not statistically significant in the diagnostic laparoscopy compared to diagnostic laparoscopy converted to diagnostic celiotomy group, nor in the therapeutic laparoscopy compared to the diagnostic laparoscopy converted to therapeutic laparoscopy group. CONCLUSIONS: Laparoscopy can be used safely in penetrating and blunt abdominal trauma. In this cohort, laparoscopy was observed to have shorter operative times and LOS with lower hospital charges and fewer complications.


Assuntos
Traumatismos Abdominais , Análise Custo-Benefício , Laparoscopia , Tempo de Internação , Duração da Cirurgia , Humanos , Laparoscopia/economia , Laparoscopia/efeitos adversos , Laparoscopia/estatística & dados numéricos , Estudos Retrospectivos , Feminino , Masculino , Adulto , Tempo de Internação/estatística & dados numéricos , Tempo de Internação/economia , Pessoa de Meia-Idade , Traumatismos Abdominais/cirurgia , Traumatismos Abdominais/economia , Traumatismos Abdominais/diagnóstico , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Preços Hospitalares/estatística & dados numéricos , Ferimentos não Penetrantes/cirurgia , Ferimentos não Penetrantes/economia , Ferimentos não Penetrantes/diagnóstico , Ferimentos Penetrantes/cirurgia , Ferimentos Penetrantes/economia , Ferimentos Penetrantes/diagnóstico , Custos Hospitalares/estatística & dados numéricos , Adulto Jovem
4.
Artigo em Inglês | MEDLINE | ID: mdl-39324030

RESUMO

Mixed membership models are an extension of finite mixture models, where each observation can partially belong to more than one mixture component. A probabilistic framework for mixed membership models of high-dimensional continuous data is proposed with a focus on scalability and interpretability. The novel probabilistic representation of mixed membership is based on convex combinations of dependent multivariate Gaussian random vectors. In this setting, scalability is ensured through approximations of a tensor covariance structure through multivariate eigen-approximations with adaptive regularization imposed through shrinkage priors. Conditional weak posterior consistency is established on an unconstrained model, allowing for a simple posterior sampling scheme while keeping many of the desired theoretical properties of our model. The model is motivated by two biomedical case studies: a case study on functional brain imaging of children with autism spectrum disorder (ASD) and a case study on gene expression data from breast cancer tissue. These applications highlight how the typical assumption made in cluster analysis, that each observation comes from one homogeneous subgroup, may often be restrictive in several applications, leading to unnatural interpretations of data features.

5.
Eur J Neurosci ; 53(5): 1621-1637, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33043498

RESUMO

Auditory statistical learning (ASL) plays a role in language development and may lay a foundation for later social communication impairment. As part of a longitudinal study of infant siblings, we asked whether electroencephalography (EEG) measures of connectivity during ASL at 3 months of age-differentiated infants who showed signs of autism spectrum disorder (ASD) at age 18 months. We measured spectral power and phase coherence in the theta (4-6 Hz) and alpha (6-12 Hz) frequency bands within putative language networks. Infants were divided into ASD-concern (n = 14) and No-ASD-concern (n = 49) outcome groups based on their ASD symptoms at 18 months, measured using the Autism Diagnostic Observation Scale Toddler Module. Using permutation testing, we identified a trend toward reduced left fronto-central phase coherence at the electrode pair F9-C3 in both theta and alpha frequency bands in infants who later showed ASD symptoms at 18 months. Across outcome groups, alpha coherence at 3 months correlated with greater word production at 18 months on the MacArthur-Bates Communicative Development Inventory. This study introduces signal processing and analytic tools that account for the challenges inherent in infant EEG studies, such as short duration of recordings, considerable movement artifact, and variable volume conduction. Our results indicate that connectivity, as measured by phase coherence during 2.5 min of ASL, can be quantified as early as 3 months and suggest that early alternations in connectivity may serve as markers of resilience for neurodevelopmental impairments.


Assuntos
Transtorno do Espectro Autista , Encéfalo , Eletroencefalografia , Predisposição Genética para Doença , Humanos , Lactente , Estudos Longitudinais
6.
Dev Psychobiol ; 62(6): 858-870, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32215919

RESUMO

Visual statistical learning (VSL) refers to the ability to extract associations and conditional probabilities within the visual environment. It may serve as a precursor to cognitive and social communication development. Quantifying VSL in infants at familial risk (FR) for Autism Spectrum Disorder (ASD) provides opportunities to understand how genetic predisposition can influence early learning processes which may, in turn, lay a foundation for cognitive and social communication delays. We examined electroencephalography (EEG) signatures of VSL in 3-month-old infants, examining whether EEG correlates of VSL differentiated FR from low-risk (LR) infants. In an exploratory analysis, we then examined whether EEG correlates of VSL at 3 months relate to cognitive function and ASD symptoms at 18 months. Infants were exposed to a continuous stream of looming shape pairs with varying probability that the shapes would occur in sequence (high probability-deterministic condition; low probability-probabilistic condition). EEG was time-locked to shapes based on their transitional probabilities. EEG analysis examined group-level characteristics underlying specific components, including the late frontal positivity (LFP) and N700 responses. FR infants demonstrated increased LFP and N700 response to the probabilistic condition, whereas LR infants demonstrated increased LFP and N700 response to the deterministic condition. LFP at 3 months predicted 18-month visual reception skills and not ASD symptoms. Our findings thus provide evidence for distinct VSL processes in FR and LR infants as early as 3 months. Atypical pattern learning in FR infants may lay a foundation for later delays in higher level, nonverbal cognitive skills, and predict ASD symptoms well before an ASD diagnosis is made.


Assuntos
Transtorno do Espectro Autista/fisiopatologia , Córtex Cerebral/fisiopatologia , Percepção de Forma/fisiologia , Reconhecimento Visual de Modelos/fisiologia , Aprendizagem por Probabilidade , Eletroencefalografia , Feminino , Seguimentos , Predisposição Genética para Doença , Humanos , Lactente , Masculino , Risco
7.
Stat Med ; 38(30): 5587-5602, 2019 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-31659786

RESUMO

Electroencephalography (EEG) studies produce region-referenced functional data in the form of EEG signals recorded across electrodes on the scalp. It is of clinical interest to relate the highly structured EEG data to scalar outcomes such as diagnostic status. In our motivating study, resting-state EEG is collected on both typically developing (TD) children and children with autism spectrum disorder (ASD) aged 2 to 12 years old. The peak alpha frequency (PAF), defined as the location of a prominent peak in the alpha frequency band of the spectral density, is an important biomarker linked to neurodevelopment and is known to shift from lower to higher frequencies as children age. To retain the most amount of information from the data, we consider the oscillations in the spectral density within the alpha band, rather than just the peak location, as a functional predictor of diagnostic status (TD vs ASD), adjusted for chronological age. A covariate-adjusted region-referenced generalized functional linear model is proposed for modeling scalar outcomes from region-referenced functional predictors, which utilizes a tensor basis formed from one-dimensional discrete and continuous bases to estimate functional effects across a discrete regional domain while simultaneously adjusting for additional nonfunctional covariates, such as age. The proposed methodology provides novel insights into differences in neural development of TD and ASD children. The efficacy of the proposed methodology is investigated through extensive simulation studies.


Assuntos
Transtorno do Espectro Autista/diagnóstico , Eletroencefalografia/estatística & dados numéricos , Ritmo alfa/fisiologia , Transtorno do Espectro Autista/fisiopatologia , Bioestatística , Estudos de Casos e Controles , Criança , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Simulação por Computador , Humanos , Modelos Lineares , Modelos Neurológicos , Método de Monte Carlo
8.
Eur J Neurosci ; 47(6): 643-651, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28700096

RESUMO

Cognitive function varies substantially and serves as a key predictor of outcome and response to intervention in autism spectrum disorder (ASD), yet we know little about the neurobiological mechanisms that underlie cognitive function in children with ASD. The dynamics of neuronal oscillations in the alpha range (6-12 Hz) are associated with cognition in typical development. Peak alpha frequency is also highly sensitive to developmental changes in neural networks, which underlie cognitive function, and therefore, it holds promise as a developmentally sensitive neural marker of cognitive function in ASD. Here, we measured peak alpha band frequency under a task-free condition in a heterogeneous sample of children with ASD (N = 59) and age-matched typically developing (TD) children (N = 38). At a group level, peak alpha frequency was decreased in ASD compared to TD children. Moreover, within the ASD group, peak alpha frequency correlated strongly with non-verbal cognition. As peak alpha frequency reflects the integrity of neural networks, our results suggest that deviations in network development may underlie cognitive function in individuals with ASD. By shedding light on the neurobiological correlates of cognitive function in ASD, our findings lay the groundwork for considering peak alpha frequency as a useful biomarker of cognitive function within this population which, in turn, will facilitate investigations of early markers of cognitive impairment and predictors of outcome in high risk infants.


Assuntos
Ritmo alfa/fisiologia , Transtorno do Espectro Autista/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Rede Nervosa/crescimento & desenvolvimento , Rede Nervosa/fisiopatologia , Transtorno do Espectro Autista/complicações , Biomarcadores , Criança , Pré-Escolar , Disfunção Cognitiva/etiologia , Feminino , Humanos , Masculino
9.
Eur J Neurosci ; 41(8): 1095-101, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25858292

RESUMO

Individual differences in orientation discrimination threshold are related to both visually-induced peak gamma frequency and the presence of autistic traits. The relationship between peak gamma frequency and orientation discrimination thresholds may be due to both of these factors being mediated by levels of neural inhibition. No study has previously measured the relationship between peak gamma frequency and levels of autistic traits. Thus, this was the aim of the present study. We measured orientation discrimination thresholds and autistic traits in a neurotypical human sample (N = 33), and separately recorded electroencephalography to measure visually induced gamma activity. In line with our prediction, we found a significant relationship between peak gamma frequency and level of autistic traits. Consistent with previous work we also found significant relationships between orientation discrimination thresholds and level of autistic traits and between orientation discrimination thresholds and peak gamma frequency. Our results demonstrate that individuals with individuals with higher levels of autistic personality traits have a higher peak-gamma frequency and are better at discriminating between visual stimuli based on orientation. As both higher peak gamma frequency and lower orientation discrimination thresholds have been linked to higher levels of neural inhibition, this suggests that autistic traits co-occur with increased neural inhibition. This discovery is significant as it challenges the currently-held view that autism spectrum conditions are associated with increased neural excitation.


Assuntos
Transtorno do Espectro Autista/fisiopatologia , Córtex Cerebral/fisiologia , Ritmo Gama , Percepção Visual/fisiologia , Adolescente , Adulto , Discriminação Psicológica/fisiologia , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Personalidade , Limiar Sensorial , Adulto Jovem
10.
Clin Neurophysiol ; 165: 55-63, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38959536

RESUMO

OBJECTIVE: Electroencephalography (EEG) measures of visual evoked potentials (VEPs) provide a targeted approach for investigating neural circuit dynamics. This study separately analyses phase-locked (evoked) and non-phase-locked (induced) gamma responses within the VEP to comprehensively investigate circuit differences in autism. METHODS: We analyzed VEP data from 237 autistic and 114 typically developing (TD) children aged 6-11, collected through the Autism Biomarkers Consortium for Clinical Trials (ABC-CT). Evoked and induced gamma (30-90 Hz) responses were separately quantified using a wavelet-based time-frequency analysis, and group differences were evaluated using a permutation-based clustering procedure. RESULTS: Autistic children exhibited reduced evoked gamma power but increased induced gamma power compared to TD peers. Group differences in induced responses showed the most prominent effect size and remained statistically significant after excluding outliers. CONCLUSIONS: Our study corroborates recent research indicating diminished evoked gamma responses in children with autism. Additionally, we observed a pronounced increase in induced power. Building upon existing ABC-CT findings, these results highlight the potential to detect variations in gamma-related neural activity, despite the absence of significant group differences in time-domain VEP components. SIGNIFICANCE: The contrasting patterns of decreased evoked and increased induced gamma activity in autistic children suggest that a combination of different EEG metrics may provide a clearer characterization of autism-related circuitry than individual markers alone.


Assuntos
Transtorno Autístico , Eletroencefalografia , Potenciais Evocados Visuais , Ritmo Gama , Humanos , Potenciais Evocados Visuais/fisiologia , Masculino , Criança , Feminino , Ritmo Gama/fisiologia , Transtorno Autístico/fisiopatologia , Eletroencefalografia/métodos , Estimulação Luminosa/métodos
11.
Dev Cogn Neurosci ; 69: 101425, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39163782

RESUMO

Brain differences linked to autism spectrum disorder (ASD) can manifest before observable symptoms. Studying these early neural precursors in larger and more diverse cohorts is crucial for advancing our understanding of developmental pathways and potentially facilitating earlier identification. EEG is an ideal tool for investigating early neural differences in ASD, given its scalability and high tolerability in infant populations. In this context, we integrated EEG into an existing multi-site MRI study of infants with a higher familial likelihood of developing ASD. This paper describes the comprehensive protocol established to collect longitudinal, high-density EEG data from infants across five sites as part of the Infant Brain Imaging Study (IBIS) Network and reports interim feasibility and data quality results. We evaluated feasibility by measuring the percentage of infants from whom we successfully collected each EEG paradigm. The quality of task-free data was assessed based on the duration of EEG recordings remaining after artifact removal. Preliminary analyses revealed low data loss, with average in-session loss rates at 4.16 % and quality control loss rates at 11.66 %. Overall, the task-free data retention rate, accounting for both in-session issues and quality control, was 84.16 %, with high consistency across sites. The insights gained from this preliminary analysis highlight key sources of data attrition and provide practical considerations to guide similar research endeavors.


Assuntos
Transtorno do Espectro Autista , Encéfalo , Eletroencefalografia , Imageamento por Ressonância Magnética , Humanos , Eletroencefalografia/métodos , Lactente , Masculino , Feminino , Transtorno do Espectro Autista/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Confiabilidade dos Dados , Estudos Longitudinais , Estudos de Viabilidade , Artefatos
12.
J Data Sci ; 21(4): 715-734, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38883309

RESUMO

Bayesian methods provide direct inference in functional data analysis applications without reliance on bootstrap techniques. A major tool in functional data applications is the functional principal component analysis which decomposes the data around a common mean function and identifies leading directions of variation. Bayesian functional principal components analysis (BFPCA) provides uncertainty quantification on the estimated functional model components via the posterior samples obtained. We propose central posterior envelopes (CPEs) for BFPCA based on functional depth as a descriptive visualization tool to summarize variation in the posterior samples of the estimated functional model components, contributing to uncertainty quantification in BFPCA. The proposed BFPCA relies on a latent factor model and targets model parameters within a mixed effects modeling framework using modified multiplicative gamma process shrinkage priors on the variance components. Functional depth provides a center-outward order to a sample of functions. We utilize modified band depth and modified volume depth for ordering of a sample of functions and surfaces, respectively, to derive at CPEs of the mean and eigenfunctions within the BFPCA framework. The proposed CPEs are showcased in extensive simulations. Finally, the proposed CPEs are applied to the analysis of a sample of power spectral densities (PSD) from resting state electroencephalography (EEG) where they lead to novel insights on diagnostic group differences among children diagnosed with autism spectrum disorder and their typically developing peers across age.

13.
Cortex ; 148: 139-151, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35176551

RESUMO

Recent evidence suggests that structural and functional brain aging is atypical in adults with autism spectrum disorder (ASD). However, it remains unclear if oscillatory slowing, a key marker of neurophysiological aging, follows an atypical trajectory in this population. This study examines patterns of age-related oscillatory slowing in adults with ASD, captured by reductions in the brain's peak alpha frequency (PAF). Resting-state electroencephalography (EEG) data from adults (18-70 years) with ASD (N = 93) and non-ASD controls (N = 87) were pooled from three independent datasets. A robust curve-fitting procedure quantified the peak frequency of alpha oscillations (7-13 Hz) across all brain regions. Associations between PAF and age were assessed and compared between groups. Consistent with characteristic patterns of oscillatory slowing, PAF was negatively associated with age across the entire sample (p < .0001). A significant group-by-age interaction revealed that this relationship was more pronounced in adults with ASD (p < .01). These findings invite further longitudinal investigations of PAF in adults with ASD to confirm if age-related oscillatory slowing is accelerated.


Assuntos
Transtorno do Espectro Autista , Adulto , Envelhecimento , Encéfalo , Eletroencefalografia/métodos , Humanos
14.
Stat Interface ; 15(2): 209-223, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35664510

RESUMO

Electroencephalography (EEG) studies produce region-referenced functional data via EEG signals recorded across scalp electrodes. The high-dimensional data can be used to contrast neurodevelopmental trajectories between diagnostic groups, for example between typically developing (TD) children and children with autism spectrum disorder (ASD). Valid inference requires characterization of the complex EEG dependency structure as well as covariate-dependent heteroscedasticity, such as changes in variation over developmental age. In our motivating study, EEG data is collected on TD and ASD children aged two to twelve years old. The peak alpha frequency, a prominent peak in the alpha spectrum, is a biomarker linked to neurodevelopment that shifts as children age. To retain information, we model patterns of alpha spectral variation, rather than just the peak location, regionally across the scalp and chronologically across development. We propose a covariate-adjusted hybrid principal components analysis (CA-HPCA) for EEG data, which utilizes both vector and functional principal components analysis while simultaneously adjusting for covariate-dependent heteroscedasticity. CA-HPCA assumes the covariance process is weakly separable conditional on observed covariates, allowing for covariate-adjustments to be made on the marginal covariances rather than the full covariance leading to stable and computationally efficient estimation. The proposed methodology provides novel insights into neurodevelopmental differences between TD and ASD children.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32798139

RESUMO

BACKGROUND: Functional brain connectivity is altered in children and adults with autism spectrum disorder (ASD). Functional disruption during infancy could provide earlier markers of ASD, thus providing a crucial opportunity to improve developmental outcomes. Using a whole-brain multivariate approach, we asked whether electroencephalography measures of neural connectivity at 3 months of age predict autism symptoms at 18 months. METHODS: Spontaneous electroencephalography data were collected from 65 infants with and without familial risk for ASD at 3 months of age. Neural connectivity patterns were quantified using phase coherence in the alpha range (6-12 Hz). Support vector regression analysis was used to predict ASD symptoms at age 18 months, with ASD symptoms quantified by the Toddler Module of the Autism Diagnostic Observation Schedule, Second Edition. RESULTS: Autism Diagnostic Observation Schedule scores predicted by support vector regression algorithms trained on 3-month electroencephalography data correlated highly with Autism Diagnostic Observation Schedule scores measured at 18 months (r = .76, p = .02, root-mean-square error = 2.38). Specifically, lower frontal connectivity and higher right temporoparietal connectivity at 3 months predicted higher ASD symptoms at 18 months. The support vector regression model did not predict cognitive abilities at 18 months (r = .15, p = .36), suggesting specificity of these brain patterns to ASD. CONCLUSIONS: Using a data-driven, unbiased analytic approach, neural connectivity across frontal and temporoparietal regions at 3 months predicted ASD symptoms at 18 months. Identifying early neural differences that precede an ASD diagnosis could promote closer monitoring of infants who show signs of neural risk and provide a crucial opportunity to mediate outcomes through early intervention.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Adulto , Transtorno do Espectro Autista/diagnóstico , Biomarcadores , Encéfalo , Eletroencefalografia , Humanos , Lactente
16.
Autism Res ; 13(7): 1102-1110, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32282133

RESUMO

Motor impairments occur frequently in genetic syndromes highly penetrant for autism spectrum disorder (syndromic ASD) and in individuals with ASD without a genetic diagnosis (nonsyndromic ASD). In particular, abnormalities in gait in ASD have been linked to language delay, ASD severity, and likelihood of having a genetic disorder. Quantitative measures of motor function can improve our ability to evaluate motor differences in individuals with syndromic and nonsyndromic ASD with varying levels of intellectual disability and adaptive skills. To evaluate this methodology, we chose to use quantitative gait analysis to study duplication 15q syndrome (dup15q syndrome), a genetic disorder highly penetrant for motor delays, intellectual disability, and ASD. We evaluated quantitative gait variables in individuals with dup15q syndrome (n = 39) and nonsyndromic ASD (n = 21) and compared these data to a reference typically developing cohort. We found a gait pattern of slow pace, poor postural control, and large gait variability in dup15q syndrome. Our findings improve characterization of motor function in dup15q syndrome and nonsyndromic ASD. Quantitative gait analysis can be used as a translational method and can improve our identification of clinical endpoints to be used in treatment trials for these syndromes. Autism Res 2020, 13: 1102-1110. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Motor impairments, particularly abnormalities in walking, occur frequently in genetic syndromes highly penetrant for autism spectrum disorder (syndromic ASD). Here, using quantitative gait analysis, we find that individuals with duplication 15q syndrome have an atypical gait pattern that differentiates them from typically developing and nonsyndromic ASD individuals. Our findings improve motor characterization in dup15q syndrome and nonsyndromic ASD.


Assuntos
Transtorno do Espectro Autista , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/genética , Cromossomos Humanos Par 15 , Feminino , Análise da Marcha , Humanos , Masculino , Síndrome , Trissomia
18.
Res Autism Spectr Disord ; 57: 132-144, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31223334

RESUMO

BACKGROUND: Electroencephalography can elucidate neurobiological mechanisms underlying heterogeneity in ASD. Studying the full range of children with ASD introduces methodological challenges stemming from participants' difficulties tolerating the data collection process, leading to diminished EEGdataretentionandincreasedvariabilityin participant 'state' during the recording. Quantifying state will improve data collection methods and aide in interpreting results. OBJECTIVES: Observationally quantify participant state during the EEG recording; examine its relationship to child characteristics, data retention and spectral power. METHODS: Participants included 5-11 year-old children with D (N=39) and age-matched TD children (N=16). Participants were acclimated to the EEG environment using behavioral strategies. EEG was recorded while participants watched a video of bubbles. Participant 'state' was rated using a Likert scale (Perceived State Rating: PSR). RESULTS: Participants with ASD had more elevated PSR than TD participants. Less EEG data were retained in participants with higher PSR scores, but this was not related to age or IQ. TD participants had higher alpha power compared with the ASD group. Within the ASD group, participants with high PSR had decreased frontal alpha power. CONCLUSIONS: Given supportive strategies, EEG data was collected from children with ASD across cognitive levels. Participant state influenced both EEG data retention and alpha spectral power. Alpha suppression is linked to attention and vigilance, suggesting that these participants were less 'at rest'. This highlights the importance of considering state when conducting EEG studies with challenging participants, both to increase data retention rates and to quantify the influence of state on EEG variables.

19.
Autism Res ; 12(12): 1758-1773, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31419043

RESUMO

Tuberous sclerosis complex (TSC) is a rare genetic disorder that confers a high risk for autism spectrum disorders (ASD), with behavioral predictors of ASD emerging early in life. Deviations in structural and functional neural connectivity are highly implicated in both TSC and ASD. For the first time, we explore whether electroencephalographic (EEG) measures of neural network function precede or predict the emergence of ASD in TSC. We determine whether altered brain function (a) is present in infancy in TSC, (b) differentiates infants with TSC based on ASD diagnostic status, and (c) is associated with later cognitive function. We studied 35 infants with TSC (N = 35), and a group of typically developing infants (N = 20) at 12 and 24 months of age. Infants with TSC were later subdivided into ASD and non-ASD groups based on clinical evaluation. We measured features of spontaneous alpha oscillations (6-12 Hz) that are closely associated with neural network development: alpha power, alpha phase coherence (APC), and peak alpha frequency (PAF). Infants with TSC demonstrated reduced interhemispheric APC compared to controls at 12 months of age, and these differences were found to be most pronounced at 24 months in the infants who later developed ASD. Across all infants, PAF at 24 months was associated with verbal and nonverbal cognition at 36 months. Associations between early network function and later neurodevelopmental and cognitive outcomes highlight the potential utility of early scalable EEG markers to identify infants with TSC requiring additional targeted intervention initiated very early in life. Autism Res 2019, 12: 1758-1773. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Approximately half of infants with tuberous sclerosis complex (TSC) develop autism. Here, using EEG, we find that there is a reduction in communication between brain regions during infancy in TSC, and that the infants who show the largest reductions are those who later develop autism. Being able to identify infants who show early signs of disrupted brain development may improve the timing of early prediction and interventions in TSC, and also help us to understand how early brain changes lead to autism.


Assuntos
Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/fisiopatologia , Encéfalo/fisiopatologia , Desenvolvimento Infantil , Esclerose Tuberosa/complicações , Esclerose Tuberosa/fisiopatologia , Pré-Escolar , Eletroencefalografia/métodos , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino
20.
Neuropsychologia ; 111: 369-376, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29458075

RESUMO

Circuit level brain dysfunction has been suggested as a common mechanism through which diverse genetic risk factors and neurobiological sequelae lead to the core features of autism spectrum disorder (Geschwind 2009; Port et al. 2014). An important mediator of circuit level brain activity is lateral inhibition, and a number of authors have suggested that lateral inhibition may be atypical in ASD. However, evidence regarding putative atypical lateral connections in ASD is mixed. Here we employed a steady state visual evoked potential (SSVEP) paradigm to further investigate lateral connections within a group of high functioning adults with ASD. At a group level, we found no evidence of altered lateral interactions in ASD. Exploratory analyses reveal that greater ASD symptom severity (increased ADOS score) is associated with increased short range lateral inhibition. These results suggest that lateral interactions are not altered in ASD at a group-level, but that subtle alterations in such neurobiological processes may underlie the heterogeneity seen in the autism spectrum in terms of sensory perception and behavioral phenotype.


Assuntos
Transtorno do Espectro Autista/fisiopatologia , Inibição Neural , Córtex Visual/fisiopatologia , Percepção Visual/fisiologia , Adolescente , Adulto , Idoso , Eletroencefalografia , Potenciais Somatossensoriais Evocados , Potenciais Evocados Visuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estimulação Luminosa , Psicofísica , Adulto Jovem
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