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Study objectives: To develop a non-invasive and practical wearable method for long-term tracking of infants' sleep. Methods: An infant wearable, NAPping PAnts (NAPPA), was constructed by combining a diaper cover and a movement sensor (triaxial accelerometer and gyroscope), allowing either real-time data streaming to mobile devices or offline feature computation stored in the sensor memory. A sleep state classifier (wake, N1/REM, N2/N3) was trained and tested for NAPPA recordings (N = 16649 epochs of 30 s), using hypnograms from co-registered polysomnography (PSG) as a training target in 33 infants (age 2 weeks to 18 months; Mean = 4). User experience was assessed from an additional group of 16 parents. Results: Overnight NAPPA recordings were successfully performed in all infants. The sleep state classifier showed good overall accuracy (78 %; Range 74-83 %) when using a combination of five features related to movement and respiration. Sleep depth trends were generated from the classifier outputs to visualise sleep state fluctuations, which closely aligned with PSG-derived hypnograms in all infants. Consistently positive parental feedback affirmed the effectiveness of the NAPPA-design. Conclusions: NAPPA offers a practical and feasible method for out-of-hospital assessment of infants' sleep behaviour. It can directly support large-scale quantitative studies and development of new paradigms in scientific research and infant healthcare. Moreover, NAPPA provides accurate and informative computational measures for body positions, respiration rates, and activity levels, each with their respective clinical and behavioural value.
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BACKGROUND: The ability to determine severity of encephalopathy is crucial for early neuroprotective therapies and for predicting neurodevelopmental outcome. The objective of this study was to assess a novel brain state of newborn (BSN) trend to distinguish newborns with presence of hypoxic ischemic encephalopathy (HIE) within hours after birth and predict neurodevelopmental outcomes at 2 years of age. METHOD: This is a prospective cohort study of newborns at 36 weeks' gestation or later with and without HIE at birth. The Total Sanart Score (TSS) was calculated based on a modified Sarnat exam within 6 h of life. BSN was calculated from electroencephalogram (EEG) measurements initiated after birth. The primary outcome at 2 year of age was a diagnosis of death or disability using the Bayley Scales of Infant Development III. RESULTS: BSN differentiated between normal and abnormal neurodevelopmental outcomes throughout the entire recording period from 6 h of life. Additionally, infants with lower BSN values had higher odds of neurodevelopmental impairment and HIE. BSN distinguished between normal (n = 86) and HIE (n = 46) and showed a significant correlation with the concomitant TSS. CONCLUSION: BSN is a sensitive real-time marker for monitoring dynamic progression of encephalopathy and predicting neurodevelopmental impairment. IMPACT: This is a prospective cohort study to investigate the ability of brain state of newborn (BSN) trend to predict neurodevelopmental outcome within the first day of life and identify severity of encephalopathy. BSN predicts neurodevelopmental outcomes at 2 years of age and the severity of encephalopathy severity. It also correlates with the Total Sarnat Score from the modified Sarnat exam. BSN could serve as a promising bedside trend aiding in accurate assessment and identification of newborns who may benefit from additional neuroprotection therapies.
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Developing objective and quantitative methods of early gross motor assessment is essential to better understand neurodevelopment and to support early therapeutic interventions. Here, we present a method to quantify gross motor performance using a multisensor wearable, MAIJU (Motility Assessment of Infants with a JUmpsuit), which offers an automated, scalable, quantitative, and objective assessment using a fully automated cloud-based pipeline. This wearable suit is equipped with four movement sensors that record synchronized data to a mobile phone utilizing a low-energy Bluetooth connection. An offline analysis in the cloud server generates fully analyzed results within minutes for each recording. These results include a graphical report of the recording session and a detailed result matrix that gives second-by-second classifications for posture, movement, infant carrying, and free playtime. Our recent results show the virtue of such quantified motor assessment providing a potentially effective method for distinguishing variations in the infant's gross motor development.
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Dispositivos Eletrônicos Vestíveis , Humanos , Lactente , Destreza Motora/fisiologia , Desenvolvimento Infantil/fisiologiaRESUMO
[This corrects the article DOI: 10.3389/fnhum.2021.675154.].
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The third trimester is a critical period for the development of functional networks that support the lifelong neurocognitive performance, yet the emergence of neuronal coupling in these networks is poorly understood. Here, we used longitudinal high-density electroencephalographic recordings from preterm infants during the period from 33 to 45â weeks of conceptional age (CA) to characterize early spatiotemporal patterns in the development of local cortical function and the intrinsic coupling modes [ICMs; phase-phase (PPCs), amplitude-amplitude (AACs), and phase-amplitude correlations (PACs)]. Absolute local power showed a robust increase with CA across the full frequency spectrum, while local PACs showed sleep state-specific, biphasic development that peaked a few weeks before normal birth. AACs and distant PACs decreased globally at nearly all frequencies. In contrast, the PPCs showed frequency- and region-selective development, with an increase of coupling strength with CA between frontal, central, and occipital regions at low-delta and alpha frequencies together with a wider-spread decrease at other frequencies. Our findings together present the spectrally and spatially differential development of the distinct ICMs during the neonatal period and provide their developmental templates for future basic and clinical research.
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Córtex Cerebral , Eletroencefalografia , Rede Nervosa , Humanos , Recém-Nascido , Eletroencefalografia/métodos , Feminino , Córtex Cerebral/fisiologia , Córtex Cerebral/crescimento & desenvolvimento , Masculino , Rede Nervosa/fisiologia , Rede Nervosa/crescimento & desenvolvimento , Recém-Nascido Prematuro/fisiologia , Neurônios/fisiologiaRESUMO
OBJECTIVE: To assess whether computational electroencephalogram (EEG) measures during the first day of life correlate to clinical outcomes in infants with perinatal asphyxia with or without hypoxic-ischemic encephalopathy (HIE). METHODS: We analyzed four-channel EEG monitoring data from 91 newborn infants after perinatal asphyxia. Altogether 42 automatically computed amplitude- and synchrony-related EEG features were extracted as 2-hourly average at very early (6 h) and early (24 h) postnatal age; they were correlated to the severity of HIE in all infants, and to four clinical outcomes available in a subcohort of 40 newborns: time to full oral feeding (nasogastric tube NGT), neonatal brain MRI, Hammersmith Infant Neurological Examination (HINE) at three months, and Griffiths Scales at two years. RESULTS: At 6 h, altogether 14 (33%) EEG features correlated significantly to the HIE grade ([r]= 0.39-0.61, p < 0.05), and one feature correlated to NGT ([r]= 0.50). At 24 h, altogether 13 (31%) EEG features correlated significantly to the HIE grade ([r]= 0.39-0.56), six features correlated to NGT ([r]= 0.36-0.49) and HINE ([r]= 0.39-0.61), while no features correlated to MRI or Griffiths Scales. CONCLUSIONS: Our results show that the automatically computed measures of early cortical activity may provide outcome biomarkers for clinical and research purposes. IMPACT: The early EEG background and its recovery after perinatal asphyxia reflect initial severity of encephalopathy and its clinical recovery, respectively. Computational EEG features from the early hours of life show robust correlations to HIE grades and to early clinical outcomes. Computational EEG features may have potential to be used as cortical activity biomarkers in early hours after perinatal asphyxia.
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OBJECTIVE: To evaluate the utility of a fully automated deep learning -based quantitative measure of EEG background, Brain State of the Newborn (BSN), for early prediction of clinical outcome at four years of age. METHODS: The EEG monitoring data from eighty consecutive newborns was analyzed using the automatically computed BSN trend. BSN levels during the first days of life (a of total 5427 hours) were compared to four clinical outcome categories: favorable, cerebral palsy (CP), CP with epilepsy, and death. The time dependent changes in BSN-based prediction for different outcomes were assessed by positive/negative predictive value (PPV/NPV) and by estimating the area under the receiver operating characteristic curve (AUC). RESULTS: The BSN values were closely aligned with four visually determined EEG categories (p < 0·001), as well as with respect to clinical milestones of EEG recovery in perinatal Hypoxic Ischemic Encephalopathy (HIE; p < 0·003). Favorable outcome was related to a rapid recovery of the BSN trend, while worse outcomes related to a slow BSN recovery. Outcome predictions with BSN were accurate from 6 to 48 hours of age: For the favorable outcome, the AUC ranged from 95 to 99% (peak at 12 hours), and for the poor outcome the AUC ranged from 96 to 99% (peak at 12 hours). The optimal BSN levels for each PPV/NPV estimate changed substantially during the first 48 hours, ranging from 20 to 80. CONCLUSIONS: We show that the BSN provides an automated, objective, and continuous measure of brain activity in newborns. SIGNIFICANCE: The BSN trend discloses the dynamic nature that exists in both cerebral recovery and outcome prediction, supports individualized patient care, rapid stratification and early prognosis.
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Asfixia Neonatal , Encéfalo , Eletroencefalografia , Humanos , Recém-Nascido , Eletroencefalografia/métodos , Eletroencefalografia/tendências , Asfixia Neonatal/fisiopatologia , Asfixia Neonatal/diagnóstico , Masculino , Feminino , Encéfalo/fisiopatologia , Hipóxia-Isquemia Encefálica/fisiopatologia , Hipóxia-Isquemia Encefálica/diagnóstico , Paralisia Cerebral/fisiopatologia , Paralisia Cerebral/diagnóstico , Valor Preditivo dos Testes , Pré-Escolar , Aprendizado Profundo , PrognósticoRESUMO
BACKGROUND: In children, objective, quantitative tools that determine functional neurodevelopment are scarce and rarely scalable for clinical use. Direct recordings of cortical activity using routinely acquired electroencephalography (EEG) offer reliable measures of brain function. METHODS: We developed and validated a measure of functional brain age (FBA) using a residual neural network-based interpretation of the paediatric EEG. In this cross-sectional study, we included 1056 children with typical development ranging in age from 1 month to 18 years. We analysed a 10- to 15-min segment of 18-channel EEG recorded during light sleep (N1 and N2 states). FINDINGS: The FBA had a weighted mean absolute error (wMAE) of 0.85 years (95% CI: 0.69-1.02; n = 1056). A two-channel version of the FBA had a wMAE of 1.51 years (95% CI: 1.30-1.73; n = 1056) and was validated on an independent set of EEG recordings (wMAE = 2.27 years, 95% CI: 1.90-2.65; n = 723). Group-level maturational delays were also detected in a small cohort of children with Trisomy 21 (Cohen's d = 0.36, p = 0.028). INTERPRETATION: A FBA, based on EEG, is an accurate, practical and scalable automated tool to track brain function maturation throughout childhood with accuracy comparable to widely used physical growth charts. FUNDING: This research was supported by the National Health and Medical Research Council, Australia, Helsinki University Diagnostic Center Research Funds, Finnish Academy, Finnish Paediatric Foundation, and Sigrid Juselius Foundation.
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Encéfalo , Gráficos de Crescimento , Humanos , Criança , Adolescente , Estudos Transversais , Redes Neurais de Computação , EletroencefalografiaRESUMO
Assessing infant carrying and holding (C/H), or physical infant-caregiver interaction, is important for a wide range of contexts in development research. An automated detection and quantification of infant C/H is particularly needed in long term at-home studies where development of infants' neurobehavior is measured using wearable devices. Here, we first developed a phenomenological categorization for physical infant-caregiver interactions to support five different definitions of C/H behaviors. Then, we trained and assessed deep learning-based classifiers for their automatic detection from multi-sensor wearable recordings that were originally used for mobile assessment of infants' motor development. Our results show that an automated C/H detection is feasible at few-second temporal accuracy. With the best C/H definition, the automated detector shows 96% accuracy and 0.56 kappa, which is slightly less than the video-based inter-rater agreement between trained human experts (98% accuracy, 0.77 kappa). The classifier performance varies with C/H definition reflecting the extent to which infants' movements are present in each C/H variant. A systematic benchmarking experiment shows that the widely used actigraphy-based method ignores the normally occurring C/H behaviors. Finally, we show proof-of-concept for the utility of the novel classifier in studying C/H behavior across infant development. Particularly, we show that matching the C/H detections to individuals' gross motor ability discloses novel insights to infant-parent interaction.
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Movimento , Dispositivos Eletrônicos Vestíveis , Lactente , Criança , Humanos , Desenvolvimento Infantil , Actigrafia , PaisRESUMO
The higher brain functions arise from coordinated neural activity between distinct brain regions, but the spatial, temporal, and spectral complexity of these functional connectivity networks (FCNs) has challenged the identification of correlates with neurobehavioral phenotypes. Characterizing behavioral correlates of early life FCNs is important to understand the activity dependent emergence of neurodevelopmental performance and for improving health outcomes. Here, we develop an analysis pipeline for identifying multiplex dynamic FCNs that combine spectral and spatiotemporal characteristics of the newborn cortical activity. This data-driven approach automatically uncovers latent networks that show robust neurobehavioral correlations and consistent effects by in utero drug exposure. Altogether, the proposed pipeline provides a robust end-to-end solution for an objective assessment and quantitation of neurobehaviorally meaningful network constellations in the highly dynamic cortical functions.
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Encéfalo , Imageamento por Ressonância Magnética , Recém-Nascido , Humanos , Encéfalo/diagnóstico por imagem , Mapeamento EncefálicoRESUMO
BACKGROUND: Despite therapeutic hypothermia (TH) and neonatal intensive care, 45-50% of children affected by moderate-to-severe neonatal hypoxic-ischemic encephalopathy (HIE) die or suffer from long-term neurodevelopmental impairment. Additional neuroprotective therapies are sought, besides TH, to further improve the outcome of affected infants. Allopurinol - a xanthine oxidase inhibitor - reduced the production of oxygen radicals and subsequent brain damage in pre-clinical and preliminary human studies of cerebral ischemia and reperfusion, if administered before or early after the insult. This ALBINO trial aims to evaluate the efficacy and safety of allopurinol administered immediately after birth to (near-)term infants with early signs of HIE. METHODS/DESIGN: The ALBINO trial is an investigator-initiated, randomized, placebo-controlled, double-blinded, multi-national parallel group comparison for superiority investigating the effect of allopurinol in (near-)term infants with neonatal HIE. Primary endpoint is long-term outcome determined as survival with neurodevelopmental impairment versus death versus non-impaired survival at 2 years. RESULTS: The primary analysis with three mutually exclusive responses (healthy, death, composite outcome for impairment) will be on the intention-to-treat (ITT) population by a generalized logits model according to Bishop, Fienberg, Holland (Bishop YF, Discrete Multivariate Analysis: Therory and Practice, 1975) and ."will be stratified for the two treatment groups. DISCUSSION: The statistical analysis for the ALBINO study was defined in detail in the study protocol and implemented in this statistical analysis plan published prior to any data analysis. This is in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT03162653. Registered on 22 May 2017.
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Lesões Encefálicas , Hipotermia Induzida , Hipóxia-Isquemia Encefálica , Criança , Lactente , Recém-Nascido , Humanos , Hipóxia-Isquemia Encefálica/diagnóstico , Hipóxia-Isquemia Encefálica/terapia , Alopurinol/efeitos adversos , Grupos Controle , Hipotermia Induzida/efeitos adversosRESUMO
INTRODUCTION: The substantial compression of the dural sac and the subsequent cranial shift of cerebrospinal fluid caused by a high-volume caudal block has been shown to significantly but transiently reduce cerebral blood flow. The aim of the present study was to determine whether this reduction in cerebral perfusion is significant enough to alter brain function, as assessed by electroencephalography (EEG). METHODS: Following ethics approval and parental informed consent, 11 infants (0-3 months) scheduled to undergo inguinal hernia repair were included in the study. EEG electrodes (using nine electrodes according to the 10-20 standard) were applied following anesthesia induction. Following a 5 min baseline period, a caudal block was performed (1.5 mL/kg), whereafter the EEG, hemodynamic, and cerebral near-infrared spectroscopy responses were followed during a 20 min observation period that was divided into four 5 min segments. Special attention was given to alterations in delta power activity since this may indicate cerebral ischemia. RESULTS: All 11 infants displayed transient EEG changes, mainly represented by increased relative delta power, during the initial 5-10 min postinjection. The observed changes had returned close to baseline values 15 min postinjection. Heart rate and blood pressure remained stable throughout the study. CONCLUSION: A high-volume caudal block appears to increase intracranial pressure, thereby reducing cerebral blood flow, to the extent that it transiently will affect cerebral function as assessed by EEG (increased delta power activity) in approximately 90% of small infants. TRIAL REGISTRATION NUMBER: ACTRN12620000420943.
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Anestesia Caudal , Eletroencefalografia , Lactente , Humanos , Hemodinâmica , Anestesia Geral , Pressão SanguíneaRESUMO
BACKGROUND: Automated computational measures of EEG have the potential for large-scale application. We hypothesised that a predefined measure of early EEG-burst shape (increased burst sharpness) could predict neurodevelopmental impairment (NDI) and mental developmental index (MDI) at 2 years of age over-and-above that of brain ultrasound. METHODS: We carried out a secondary analysis of data from extremely preterm infants collected for an RCT (SafeBoosC-II). Two hours of single-channel cross-brain EEG was used to analyse burst sharpness with an automated algorithm. The co-primary outcomes were moderate-or-severe NDI and MDI. Complete data were available from 58 infants. A predefined statistical analysis was adjusted for GA, sex and no, mild-moderate, and severe brain injury as detected by cranial ultrasound. RESULTS: Nine infants had moderate-or-severe NDI and the mean MDI was 87 ± 17.3 SD. The typical burst sharpness was low (negative values) and varied relatively little (mean -0.81 ± 0.11 SD), but the odds ratio for NDI was increased by 3.8 (p = 0.008) and the MDI was reduced by -3.2 points (p = 0.14) per 0.1 burst sharpness units increase (+1 SD) in the adjusted analysis. CONCLUSION: This study confirms the association between EEG-burst measures in preterm infants and neurodevelopment in childhood. Importantly, this was by a priori defined analysis. IMPACT: A fully automated, computational measure of EEG in the first week of life was predictive of neurodevelopmental impairment at 2 years of age. This confirms many previous studies using expert reading of EEG. Only single-channel EEG data were used, adding to the applicability. EEG was recorded by several different devices thus this measure appears to be robust to differences in electrodes, amplifiers and filters. The likelihood ratio of a positive EEG test, however, was only about 2, suggesting little immediate clinical value.
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Encéfalo , Lactente Extremamente Prematuro , Lactente , Humanos , Recém-Nascido , Encéfalo/diagnóstico por imagem , Ecoencefalografia , Ultrassonografia , EletroencefalografiaRESUMO
BACKGROUND: Perinatal asphyxia often leads to hypoxic-ischemic encephalopathy (HIE) with a high risk of neurodevelopmental consequences. While moderate and severe HIE link to high morbidity, less is known about brain effects of perinatal asphyxia with no or only mild HIE. Here, we test the hypothesis that cortical activity networks in the newborn infants show a dose-response to asphyxia. METHODS: We performed EEG recordings for infants with perinatal asphyxia/HIE of varying severity (n = 52) and controls (n = 53) and examined well-established computational metrics of cortical network activity. RESULTS: We found graded alterations in cortical activity networks according to severity of asphyxia/HIE. Furthermore, our findings correlated with early clinical recovery measured by the time to attain full oral feeding. CONCLUSION: We show that both local and large-scale correlated cortical activity are affected by increasing severity of HIE after perinatal asphyxia, suggesting that HIE and perinatal asphyxia are better represented as a continuum rather than the currently used discreet categories. These findings imply that automated computational measures of cortical function may be useful in characterizing the dose effects of adversity in the neonatal brain; such metrics hold promise for benchmarking clinical trials via patient stratification or as early outcome measures. IMPACT: Perinatal asphyxia causes every fourth neonatal death worldwide and provides a diagnostic and prognostic challenge for the clinician. We report that infants with perinatal asphyxia show specific graded responses in cortical networks according to severity of asphyxia and ensuing hypoxic-ischaemic encephalopathy. Early EEG recording and automated computational measures of brain function have potential to help in clinical evaluation of infants with perinatal asphyxia.
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Asfixia Neonatal , Córtex Cerebral , Eletroencefalografia , Hipóxia-Isquemia Encefálica , Humanos , Recém-Nascido , Asfixia Neonatal/fisiopatologia , Asfixia Neonatal/complicações , Hipóxia-Isquemia Encefálica/fisiopatologia , Feminino , Masculino , Córtex Cerebral/fisiopatologia , Estudos de Casos e Controles , Rede Nervosa/fisiopatologia , Índice de Gravidade de DoençaRESUMO
Functional brain age measures in children, derived from the electroencephalogram (EEG), offer direct and objective measures in assessing neurodevelopmental status. Here we explored the effectiveness of 32 preselected 'handcrafted' EEG features in predicting brain age in children. These features were benchmarked against a large library of highly comparative multivariate time series features (>7000 features). Results showed that age predictors based on handcrafted EEG features consistently outperformed a generic set of time series features. These findings suggest that optimization of brain age estimation in children benefits from careful preselection of EEG features that are related to age and neurodevelopmental trajectory. This approach shows potential for clinical translation in the future.Clinical Relevance-Handcrafted EEG features provide an accurate functional neurodevelopmental biomarker that tracks brain function maturity in children.
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Encéfalo , Eletroencefalografia , Criança , Humanos , Fatores de Tempo , Eletroencefalografia/métodos , BenchmarkingRESUMO
The recently-developed infant wearable MAIJU provides a means to automatically evaluate infants' motor performance in an objective and scalable manner in out-of-hospital settings. This information could be used for developmental research and to support clinical decision-making, such as detection of developmental problems and guiding of their therapeutic interventions. MAIJU-based analyses rely fully on the classification of infant's posture and movement; it is hence essential to study ways to increase the accuracy of such classifications, aiming to increase the reliability and robustness of the automated analysis. Here, we investigated how self-supervised pre-training improves performance of the classifiers used for analyzing MAIJU recordings, and we studied whether performance of the classifier models is affected by context-selective quality-screening of pre-training data to exclude periods of little infant movement or with missing sensors. Our experiments show that i) pre-training the classifier with unlabeled data leads to a robust accuracy increase of subsequent classification models, and ii) selecting context-relevant pre-training data leads to substantial further improvements in the classifier performance.Clinical relevance- This study showcases that self-supervised learning can be used to increase the accuracy of out-of-hospital evaluation of infants' motor abilities via smart wearables.
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Movimento , Dispositivos Eletrônicos Vestíveis , Lactente , Humanos , Reprodutibilidade dos Testes , PosturaRESUMO
The measurement of heart rate variability (HRV) in preterm infants provides important information on function to clinicians. Measuring the underlying electrocardiogram (ECG) in the neonatal intensive care unit is a challenge and there is a trade off between extracting accurate measurements of the HRV and the amount of ECG processed due to contamination. Knowledge on the effects of 1) quantization in the time domain and 2) missing data on the calculation of HRV features will inform clinical implementation. In this paper, we studied multiple 5 minute epochs from 148 ECG recordings on 56 extremely preterm infants. We found that temporal adjustment of NN peaks improves the estimate of the NN interval resulting in HRV features (m = 9) that are better correlated with age (median percentage increase in correlation of individual features: 0.2%, IQR: 0.0 to 5.6%; correlation with age predictor and age from 0.721 to 0.787). Improved (sub-sample) quantization of the NN intervals (via interpolation) reduced the overall value of HRV features (median percentage reduction in feature value: -1.3%, IQR: -18.8 to 0.0; m = 9), primarily through a reduction in the energy of high-frequency oscillations. HRV features were also robust to missing data, with measures such as mean NN, fractal dimension and the smoothed nonlinear energy operator (SNEO) less susceptible to missing data than features such as VLF, LF, and HF. Furthermore, age predictions derived from a combination of HRV measures were more robust to missing data than individual HRV measures.Clinical Relevance-Poor quantization in time when estimating the NN peak and the presence of missing data confound HRV measures, particularly spectral measures.
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Eletrocardiografia , Lactente Extremamente Prematuro , Lactente , Humanos , Recém-Nascido , Frequência Cardíaca/fisiologia , FractaisRESUMO
Early neurodevelopment is critically dependent on the structure and dynamics of spontaneous neuronal activity; however, the natural organization of newborn cortical networks is poorly understood. Recent adult studies suggest that spontaneous cortical activity exhibits discrete network states with physiological correlates. Here, we studied newborn cortical activity during sleep using hidden Markov modeling to determine the presence of such discrete neonatal cortical states (NCS) in 107 newborn infants, with 47 of them presenting with a perinatal brain injury. Our results show that neonatal cortical activity organizes into four discrete NCSs that are present in both cardinal sleep states of a newborn infant, active and quiet sleep, respectively. These NCSs exhibit state-specific spectral and functional network characteristics. The sleep states exhibit different NCS dynamics, with quiet sleep presenting higher fronto-temporal activity and a stronger brain-wide neuronal coupling. Brain injury was associated with prolonged lifetimes of the transient NCSs, suggesting lowered dynamics, or flexibility, in the cortical networks. Taken together, the findings suggest that spontaneously occurring transient network states are already present at birth, with significant physiological and pathological correlates; this NCS analysis framework can be fully automatized, and it holds promise for offering an objective, global level measure of early brain function for benchmarking neurodevelopmental or clinical research.
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Lesões Encefálicas , Sono de Ondas Lentas , Zinostatina , Adulto , Recém-Nascido , Lactente , Feminino , Gravidez , Humanos , Lesões Encefálicas/diagnóstico por imagem , Encéfalo , Sono , BenchmarkingRESUMO
Cortical activity depends upon a continuous supply of oxygen and other metabolic resources. Perinatal disruption of oxygen availability is a common clinical scenario in neonatal intensive care units, and a leading cause of lifelong disability. Pathological patterns of brain activity including burst suppression and seizures are a hallmark of the recovery period, yet the mechanisms by which these patterns arise remain poorly understood. Here, we use computational modeling of coupled metabolic-neuronal activity to explore the mechanisms by which oxygen depletion generates pathological brain activity. We find that restricting oxygen supply drives transitions from normal activity to several pathological activity patterns (isoelectric, burst suppression, and seizures), depending on the potassium supply. Trajectories through parameter space track key features of clinical electrophysiology recordings and reveal how infants with good recovery outcomes track toward normal parameter values, whereas the parameter values for infants with poor outcomes dwell around the pathological values. These findings open avenues for studying and monitoring the metabolically challenged infant brain, and deepen our understanding of the link between neuronal and metabolic activity.