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Nelson, Charles

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Nelson, Charles

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Now showing 1 - 10 of 77
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    Lateralization of ERPs to speech and handedness in the early development of Autism Spectrum Disorder
    (BioMed Central, 2017) Finch, Kayla H.; Seery, Anne M.; Talbott, Meagan R.; Nelson, Charles; Tager-Flusberg, Helen
    Background: Language is a highly lateralized function, with typically developing individuals showing left hemispheric specialization. Individuals with autism spectrum disorder (ASD) often show reduced or reversed hemispheric lateralization in response to language. However, it is unclear when this difference emerges and whether or not it can serve as an early ASD biomarker. Additionally, atypical language lateralization is not specific to ASD as it is also seen more frequently in individuals with mixed- and left-handedness. Here, we examined early asymmetry patterns measured through neural responses to speech sounds at 12 months and behavioral observations of handedness at 36 months in children with and without ASD. Methods: Three different groups of children participated in the study: low-risk controls (LRC), high risk for ASD (HRA; infants with older sibling with ASD) without ASD, and HRA infants who later receive a diagnosis of ASD (ASD). Event-related potentials (ERPs) to speech sounds were recorded at 12 months. Utilizing a novel observational approach, handedness was measured by hand preference on a variety of behaviors at 36 months. Results: At 12 months, lateralization patterns of ERPs to speech stimuli differed across the groups with the ASD group showing reversed lateralization compared to the LRC group. At 36 months, factor analysis of behavioral observations of hand preferences indicated a one-factor model with medium to high factor loadings. A composite handedness score was derived; no group differences were observed. There was no association between lateralization to speech at 12 months and handedness at 36 months in the LRC and HRA groups. However, children with ASD did show an association such that infants with lateralization patterns more similar to the LRC group at 12 months were stronger right-handers at 36 months. Conclusions: These results highlight early developmental patterns that might be specific to ASD, including a potential early biomarker of reversed lateralization to speech stimuli at 12 months, and a relation between behavioral and neural asymmetries. Future investigations of early asymmetry patterns, especially atypical hemispheric specialization, may be informative in the early identification of ASD.
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    Early Life Inflammation and Neurodevelopmental Outcome in Bangladeshi Infants Growing Up in Adversity
    (The American Society of Tropical Medicine and Hygiene, 2017) Jiang, Nona M.; Tofail, Fahmida; Ma, Jennie Z.; Haque, Rashidul; Kirkpatrick, Beth; Nelson, Charles; Petri, William A.
    Abstract. Exposure to profound adversity can negatively affect the neurodevelopment of children, but biologic mechanisms that underlie this association remain unknown. We sought to determine whether elevated levels of the inflammatory markers C-reactive protein (CRP) and soluble CD14 (sCD14) are associated with neurodevelopmental outcomes in Bangladeshi children. A total of 422 infant–mother pairs from an urban slum in Dhaka, Bangladesh were enrolled at birth and followed prospectively. Inflammation was measured with sCD14, interleukin (IL)-1β, and IL-6 at 18 weeks, and CRP at 6, 18, 40, and 53 weeks. Psychologists assessed cognitive, language, motor, and social emotional development using the Bayley Scales of Infant and Toddler Development at 78 and 104 weeks of age. We tested for the association of inflammatory markers with developmental outcomes, independent of previously identified associations such as malnutrition, family income, and maternal education. Every 10 pg/mL increase in sCD14 was associated with a 1.1–2.0 decrement in cognitive and motor scores at 78 weeks and in all domains at 104 weeks. The cumulative number of CRP elevations that a child experienced in the first year of life, as well as IL-1β and IL-6 at 18 weeks of age, were also negatively associated with Bayley Scales results. CRP, sCD14, IL-1β, and IL-6 were associated with lower neurodevelopmental outcomes. Our findings implicate a role of inflammation in the neurodevelopment of children growing up in adversity.
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    EEG power at 3 months in infants at high familial risk for autism
    (BioMed Central, 2017) Levin, April; Varcin, Kandice J.; O’Leary, Heather M.; Tager-Flusberg, Helen; Nelson, Charles
    Background: Alterations in brain development during infancy may precede the behavioral manifestation of developmental disorders. Infants at increased risk for autism are also at increased risk for other developmental disorders, including, quite commonly, language disorders. Here we assess the extent to which electroencephalographic (EEG) differences in infants at high versus low familial risk for autism are present by 3 months of age, and elucidate the functional significance of EEG power at 3 months in predicting later development. Methods: EEG data were acquired at 3 months in infant siblings of children with autism (high risk; n = 29) and infant siblings of typically developing children (low risk; n = 19) as part of a prospective, longitudinal investigation. Development across multiple domains was assessed at 6, 9, 12, 18, 24, and 36 months. Diagnosis of autism was determined at 18–36 months. We assessed relationships between 3-month-olds’ frontal EEG power and autism risk, autism outcome, language development, and development in other domains. Results: Infants at high familial risk for autism had reduced frontal power at 3 months compared to infants at low familial risk for autism, across several frequency bands. Reduced frontal high-alpha power at 3 months was robustly associated with poorer expressive language at 12 months. Conclusions: Reduced frontal power at 3 months may indicate increased risk for reduced expressive language skills at 12 months. This finding aligns with prior studies suggesting reduced power is a marker for atypical brain function, and infants at familial risk for autism are also at increased risk for altered developmental functioning in non-autism-specific domains.
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    Role of maternal health and infant inflammation in nutritional and neurodevelopmental outcomes of two-year-old Bangladeshi children
    (Public Library of Science, 2018) Donowitz, Jeffrey R.; Cook, Heather; Alam, Masud; Tofail, Fahmida; Kabir, Mamun; Colgate, E. Ross; Carmolli, Marya P.; Kirkpatrick, Beth D.; Nelson, Charles; Ma, Jennie Z.; Haque, Rashidul; Petri, William A.
    Background: Previous studies have shown maternal, inflammatory, and socioeconomic variables to be associated with growth and neurodevelopment in children from low-income countries. However, these outcomes are multifactorial and work describing which predictors most strongly influence them is lacking. Methodology/Principal findings We conducted a longitudinal study of Bangladeshi children from birth to two years to assess oral vaccine efficacy. Variables pertaining to maternal and perinatal health, socioeconomic status, early childhood enteric and systemic inflammation, and anthropometry were collected. Bayley-III neurodevelopmental assessment was conducted at two years. As a secondary analysis, we employed hierarchical cluster and random forests techniques to identify and rank which variables predicted growth and neurodevelopment. Cluster analysis demonstrated three distinct groups of predictors. Mother’s weight and length-for-age Z score (LAZ) at enrollment were the strongest predictors of LAZ at two years. Cognitive score on Bayley-III was strongly predicted by weight-for-age (WAZ) at enrollment, income, and LAZ at enrollment. Top predictors of language included Rotavirus vaccination, plasma IL 5, sCD14, TNFα, mother’s weight, and male gender. Motor function was best predicted by fecal calprotectin, WAZ at enrollment, fecal neopterin, and plasma CRP index. The strongest predictors for social-emotional score included plasma sCD14, income, WAZ at enrollment, and LAZ at enrollment. Based on the random forests’ predictions, the estimated percentage of variation explained was 35.4% for LAZ at two years, 34.3% for ΔLAZ, 42.7% for cognitive score, 28.1% for language, 40.8% for motor, and 37.9% for social-emotional score. Conclusions/Significance: Birth anthropometry and maternal weight were strong predictors of growth while enteric and systemic inflammation had stronger associations with neurodevelopment. Birth anthropometry was a powerful predictor for all outcomes. These data suggest that further study of stunting in low-income settings should include variables relating to maternal and prenatal health, while investigations focusing on neurodevelopmental outcomes should additionally target causes of systemic and enteric inflammation.
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    Early deprivation disruption of associative learning is a developmental pathway to depression and social problems
    (Nature Publishing Group UK, 2018) Sheridan, Margaret A.; McLaughlin, Katie A.; Winter, Warren; Fox, Nathan; Zeanah, Charles; Nelson, Charles
    Exposure to psychosocial deprivation is associated with elevations in numerous forms of impairment throughout the life-course. Disruptions in associative learning may be a key mechanism through which adversity, particularly psychosocial deprivation, increases risk for impairment. Existing data consistent with this claim come entirely from correlational studies. Here, we present the first experimental evidence relating psychosocial deprivation and disruptions in multiple forms of associative learning. Using data from the Bucharest Early Intervention Project, we demonstrate that randomized placement into a family caregiving environment during the infant/toddler period as compared to prolonged institutional care normalizes two forms of associative learning in early adolescence: reward responsivity and implicit motor learning. These forms of associative learning significantly mediate the effect of institutional rearing on depressive symptoms and peer relationships. In sum, we provide evidence for a novel pathway linking early experience to psychopathology and peer relationships through basic associative learning mechanisms.
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    Biological embedding of childhood adversity: from physiological mechanisms to clinical implications
    (BioMed Central, 2017) Berens, Anne E.; Jensen, Sarah; Nelson, Charles
    Background: Adverse psychosocial exposures in early life, namely experiences such as child maltreatment, caregiver stress or depression, and domestic or community violence, have been associated in epidemiological studies with increased lifetime risk of adverse outcomes, including diabetes, heart disease, cancers, and psychiatric illnesses. Additional work has shed light on the potential molecular mechanisms by which early adversity becomes “biologically embedded” in altered physiology across body systems. This review surveys evidence on such mechanisms and calls on researchers, clinicians, policymakers, and other practitioners to act upon evidence. Observations Childhood psychosocial adversity has wide-ranging effects on neural, endocrine, immune, and metabolic physiology. Molecular mechanisms broadly implicate disruption of central neural networks, neuroendocrine stress dysregulation, and chronic inflammation, among other changes. Physiological disruption predisposes individuals to common diseases across the life course. Conclusions: Reviewed evidence has important implications for clinical practice, biomedical research, and work across other sectors relevant to public health and child wellbeing. Warranted changes include increased clinical screening for exposures among children and adults, scale-up of effective interventions, policy advocacy, and ongoing research to develop new evidence-based response strategies.
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    Motion correction for infant functional near-infrared spectroscopy with an application to live interaction data
    (SPIE-Intl Soc Optical Eng, 2018-02-13) Behrendt, Hannah F.; Firk, Christine; Nelson, Charles; Perdue, Katherine L.
    Correcting for motion is an important consideration in infant functional near-infrared spectroscopy studies. We tested the performance of conventional motion correction methods and compared probe motion and data quality metrics for data collected at different infant ages (5, 7, and 12 months) and during different methods of stimulus presentation (video versus live). While 5-month-olds had slower maximum head speed than 7- or 12-month-olds, data quality metrics and hemodynamic response recovery errors were similar across ages. Data quality was also similar between video and live stimulus presentation. Motion correction algorithms, such as wavelet filtering and targeted principal component analysis, performed well for infant data using infant-specific parameters, and parameters may be used without fine-tuning for infant age or method of stimulus presentation. We recommend using wavelet filtering with iqr=0.5; however, a range of parameters seemed acceptable. We do not recommend using trial rejection alone, because it did not improve hemodynamic response recovery as compared to no correction at all. Data quality metrics calculated from uncorrected data were associated with hemodynamic response recovery error, indicating that full simulation studies may not be necessary to assess motion correction performance.
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    Dynamic Eye Tracking Based Metrics for Infant Gaze Patterns in the Face-Distractor Competition Paradigm
    (Public Library of Science, 2014) Ahtola, Eero; Stjerna, Susanna; Yrttiaho, Santeri; Nelson, Charles; Leppänen, Jukka M.; Vanhatalo, Sampsa
    Objective: To develop new standardized eye tracking based measures and metrics for infants’ gaze dynamics in the face-distractor competition paradigm. Method Eye tracking data were collected from two samples of healthy 7-month-old (total n = 45), as well as one sample of 5-month-old infants (n = 22) in a paradigm with a picture of a face or a non-face pattern as a central stimulus, and a geometric shape as a lateral stimulus. The data were analyzed by using conventional measures of infants’ initial disengagement from the central to the lateral stimulus (i.e., saccadic reaction time and probability) and, additionally, novel measures reflecting infants gaze dynamics after the initial disengagement (i.e., cumulative allocation of attention to the central vs. peripheral stimulus). Results: The results showed that the initial saccade away from the centrally presented stimulus is followed by a rapid re-engagement of attention with the central stimulus, leading to cumulative preference for the central stimulus over the lateral stimulus over time. This pattern tended to be stronger for salient facial expressions as compared to non-face patterns, was replicable across two independent samples of 7-month-old infants, and differentiated between 7 and 5 month-old infants. Conclusion: The results suggest that eye tracking based assessments of infants’ cumulative preference for faces over time can be readily parameterized and standardized, and may provide valuable techniques for future studies examining normative developmental changes in preference for social signals. Significance Standardized measures of early developing face preferences may have potential to become surrogate biomarkers of neurocognitive and social development.
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    Visual Event-Related Brain Potentials in 4-Month-Old Infants at Risk for Neurodevelopmental Impairments
    (Wiley, 1997) deRegnier, Raye-Ann O.; Georgieff, Michael K.; Nelson, Charles
    The recording of event-related potentials (ERPs) is an electrophysiologic technique that has been used to evaluate the functional maturation of neural pathways responsible for recognition memory systems in infants and children. The purpose of this study was to evaluate ERP correlates of visual recognition memory in 4-month-old infants at risk for later cognitive impairments. We compared ERPs using a test of shape recognition at 4 months of age (adjusted for prematurity) in 16 high-risk, neonatal intensive care unit (NICU) survivors and 16 healthy full-term infants. ERPs were recorded while infants were familiarized with one stimulus (a red cross, 15 trials), then tested with 60 trials of this familiar stimulus and a novel stimulus (a red corkscrew). Both the NICU and control groups' ERPs demonstrated evidence of differential processing of the two stimuli, but the NICU groups' ERP patterns were distinctly different from those of the control group. In the NICU group, the novel stimulus elicited parietal positivity at 1000-1700 ms poststimulus, whereas in the control group the novel stimulus elicited occipital and frontal negativity at 500-1700 ms poststimulus. The ERP pattern demonstrated by the NICU group was atypical as it has not been previously described in healthy infants. The results of the study indicate that the ERP technique can be used to demonstrate altered patterns of neural activity during tasks of visual recognition memory in high-risk infants. We speculate that the atypical ERP patterns described in this study may indicate that patterns of synaptic organization were altered by neonatal events
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    Functional connectivity in the first year of life in infants at-risk for autism: a preliminary near-infrared spectroscopy study
    (Frontiers Media S.A., 2013) Keehn, Brandon; Wagner, Jennifer B.; Tager-Flusberg, Helen; Nelson, Charles
    Background: Autism spectrum disorder (ASD) has been called a “developmental disconnection syndrome,” however the majority of the research examining connectivity in ASD has been conducted exclusively with older children and adults. Yet, prior ASD research suggests that perturbations in neurodevelopmental trajectories begin as early as the first year of life. Prospective longitudinal studies of infants at risk for ASD may provide a window into the emergence of these aberrant patterns of connectivity. The current study employed functional connectivity near-infrared spectroscopy (NIRS) in order to examine the development of intra- and inter-hemispheric functional connectivity in high- and low-risk infants across the first year of life. Methods: NIRS data were collected from 27 infants at high risk for autism (HRA) and 37 low-risk comparison (LRC) infants who contributed a total of 116 data sets at 3-, 6-, 9-, and 12-months. At each time point, HRA and LRC groups were matched on age, sex, head circumference, and Mullen Scales of Early Learning scores. Regions of interest (ROI) were selected from anterior and posterior locations of each hemisphere. The average time course for each ROI was calculated and correlations for each ROI pair were computed. Differences in functional connectivity were examined in a cross-sectional manner. Results: At 3-months, HRA infants showed increased overall functional connectivity compared to LRC infants. This was the result of increased connectivity for intra- and inter-hemispheric ROI pairs. No significant differences were found between HRA and LRC infants at 6- and 9-months. However, by 12-months, HRA infants showed decreased connectivity relative to LRC infants. Conclusions: Our preliminary results suggest that atypical functional connectivity may exist within the first year of life in HRA infants, providing support to the growing body of evidence that aberrant patterns of connectivity may be a potential endophenotype for ASD.