Charles Nelson

Charles Nelson
Harvard Medical School | HMS · Department of Pediatrics

PhD

About

749
Publications
272,131
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
49,978
Citations

Publications

Publications (749)
Article
Full-text available
Background Tuberous Sclerosis Complex (TSC) is a rare genetic condition caused by mutation to TSC1 or TSC2 genes, with a population prevalence of 1/7000 births. TSC manifests behaviorally with features of autism, epilepsy, and intellectual disability. Resting state electroencephalography (EEG) offers a window into neural oscillatory activity and ma...
Article
Full-text available
Background Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental outcome among children with a history of early institutional care. Prior research on institutionalized children suggested that accelerated physical growth in childhood is a risk factor for ADHD outcomes. Methods The current study examined physical and neuroph...
Article
Full-text available
Deaths of parents and grandparent caregivers threaten child well-being owing to losses of care, financial support, safety and family stability, but are relatively unrecognized as a public health crisis. Here we used cause-specific vital statistics death registrations in a modeling approach to estimate the full magnitude of orphanhood incidence and...
Article
The aperiodic “slope” of the EEG power spectrum (i.e., aperiodic exponent, commonly represented as a slope in log–log space) is hypothesized to index the cortical excitatory‐inhibitory balance. Slope has been associated with various neurodevelopmental outcomes in older children and adults, as well as with family history of ADHD in infants. Here, we...
Article
Full-text available
Exposure to stressful events is linked to anxiety symptoms in children, although research examining this association in the first five years of life is limited. We sought to examine the role of various aspects of family stressful experiences such as the total accumulation, impact, and type (measured longitudinally in the first five years of life) o...
Article
Full-text available
Introduction Maternal undernutrition and inflammation in utero may significantly impact the neurodevelopmental potential of offspring. However, few studies have investigated the effects of pregnancy interventions on long-term child growth and development. This study will examine the effects of prenatal nutrition and infection management interventio...
Article
Tuberous sclerosis complex (TSC) is a genetic condition characterized by both medical and neuropsychiatric diagnoses that emerge across the lifespan. As part of a clinical trial, caregivers of children with TSC were interviewed about their experiences navigating medical, school, and social services. Semistructured interviews (N = 20) with caregiver...
Preprint
Full-text available
Delays in language often co-occur among toddlers diagnosed with autism. Despite the high prevalence of language delays, the neurobiology underlying such language challenges remains unclear. Prior research has shown reduced EEG power across multiple frequency bands in 3-to-6-month-old infants with an autistic sibling, followed by accelerated increas...
Article
Children’s neural responses to emotions may play a role in the intergenerational transmission of anxiety. In a prospective longitudinal study of a community sample of N = 464 mother–child dyads, we examined relations among maternal anxiety symptoms when children were infants and age 5 years, child neural responses to emotional faces (angry, fearful...
Article
Full-text available
Background Over a third of children globally do not meet their developmental potential, and children living in low and middle-income countries (LMICs) are most vulnerable. Understanding the contextual factors that influence cognitive development for children in LMICs is crucial to inform and develop interventions. We sought to characterize developm...
Article
Full-text available
Mental health disorders are associated with decreased quality of life, economic productivity loss, and increased mortality. The association between stressful experiences and psychopathology is well documented. However, studies are needed to understand the impact of timing of stressful events, types of traumatic experiences, and of family resilience...
Article
Full-text available
Over three hundred million children live in environments of extreme poverty, and the biological and psychosocial hazards endemic to these environments often expose these children to infection, disease, and inflammatory responses. Chronic inflammation in early childhood has been associated with diminished cognitive outcomes, and despite this establi...
Article
Anxiety disorders are among the most prevalent of all mental health disorders, often originating in early childhood and extending into later childhood, adolescence, and adulthood. Determining salient risk factors that precede their development is important for prevention and intervention efforts. Towards this end, we examined the role of temperamen...
Preprint
Restricted and repetitive behaviors (RRBs) are an early-emerging and defining feature of autism spectrum disorder (ASD). This longitudinal study examined developmental trajectories of RRBs as measured by the Repetitive Behavior Scale-Revised (RBS-R) in 12-36-month-old infants (n = 207), including those with elevated likelihood of ASD due to familia...
Preprint
Background Anxiety and depression are highly prevalent in youth and can cause significant distress and functional impairment. The presence of maternal anxiety and depression are well-established risk factors for child internalizing psychopathology, yet the responsible mechanisms linking the two remain unclear. Methods We examined the potential med...
Preprint
Background Emerging evidence suggests that aperiodic EEG activity may follow a nonlinear growth trajectory in childhood. However, existing studies are limited by small assessment windows and cross-sectional samples that are unable to fully capture these patterns. The current study aimed to characterize the developmental trajectories of aperiodic ac...
Preprint
Malnutrition, particularly undernutrition, is a critical global health challenge, contributing to nearly half of all deaths among children under 5 and severely impacting physical and mental health, along with neural and cognitive development. Prior research by Xie et al. (2019a) linked growth faltering to altered EEG functional connectivity (FC) at...
Article
Full-text available
Aperiodic activity is a background arrhythmic component of electroencephalogram (EEG) that is present in the power spectrum and characterized by an aperiodic offset and an aperiodic exponent. These components have been proposed as a marker of brain maturation, reflecting alterations in excitatory–inhibitory (E:I) balance and exhibiting developmenta...
Article
Full-text available
Auditory statistical learning, or the ability to detect statistical regularities in continuously presented stimuli, is thought to be one element that underlies language acquisition. Prior studies have uncovered behavioral and neural correlates of statistical learning, yet additional work is needed from low- and middle-income countries to explore wh...
Article
Adversity within low‐ and middle‐income countries (LMICs) poses severe threats to neurocognitive development, which can be partially mitigated by high‐quality early family experiences. Specifically, maternal scaffolding and home stimulation can buffer cognitive development in LMIC, possibly by protecting underlying neural functioning. However, the...
Article
Full-text available
The development of neural circuits has long-lasting effects on brain function, yet our understanding of early circuit development in humans remains limited. Here, periodic EEG power features and aperiodic components were examined from longitudinal EEGs collected from 592 healthy 2–44 month-old infants, revealing age-dependent nonlinear changes sugg...
Article
It has now been extensively documented that parental mental health has deteriorated since the beginning of the COVID‐19 pandemic. Although pandemic‐related stress has been widespread, parents faced the unique challenge of navigating remote schooling. Parental oversight of children's education, loss of access to school supportive resources, and the...
Preprint
Full-text available
Background: Tuberous Sclerosis Complex (TSC) manifests behaviorally with features of autism, epilepsy, and intellectual disability. Resting state electroencephalography (EEG) offers a window into neural oscillatory activity and may serve as an intermediate biomarker between gene expression and behavioral manifestations. Such a biomarker could be us...
Preprint
Full-text available
The infant brain undergoes rapid and significant developmental changes in the first three years of life. Understanding these changes through the prediction of chronological age using neuroimaging data can provide insights into typical and atypical brain devel- opment. We utilized longitudinal resting-state EEG data from 457 typically developing inf...
Article
Objective This study was undertaken to characterize quantitative electroencephalographic (EEG) features in participants from the Natural history study of RTT and Related Disorders and to assess the potential for these features to act as objective measures of cortical function for Rett syndrome (RTT). Methods EEG amplitude and power features were d...
Article
There is no relationship more vital than the one a child shares with their primary caregivers early in development. Yet many children worldwide are raised in settings that lack the warmth, connection, and stimulation provided by a responsive primary caregiver. In this study, we used data from the Bucharest Early Intervention Project (BEIP), a longi...
Article
Full-text available
Irritability reflects a propensity for frustration and anger, and is a transdiagnostic symptom of both externalizing and internalizing psychopathology. While early adverse experiences are associated with higher levels of irritability, experiences of early psychosocial deprivation and whether family-based placements can mitigate the impact on subseq...
Article
Full-text available
Previous research links resting frontal gamma power to key developmental outcomes in young neurotypical (NT) children and infants at risk for language impairment. However, it remains unclear whether gamma power is specifically associated with language or with more general cognitive abilities among young children diagnosed with autism spectrum disor...
Article
Background: There are limited data on the impact of perinatal inflammation on child neurodevelopment in low-middle income countries and among growth-restricted infants. Methods: Population-based, prospective birth cohort study of 288 infants from July 2016-March 2017 in Sylhet, Bangladesh. Umbilical cord blood was analyzed for interleukin(IL)-1α...
Preprint
Full-text available
Importance: Deaths of parents and grandparent caregivers linked to social and health crises threaten child wellbeing due to losses of nurturance, financial support, physical safety, family stability, and care. Little is known about the full burden of all-causes and leading cause-specific orphanhood and caregiver death beyond estimates from select c...
Preprint
Full-text available
Importance: Deaths of parents and grandparent caregivers linked to social and health crises threaten child wellbeing due to losses of nurturance, financial support, physical safety, family stability, and care. Little is known about the full burden of all-causes and leading cause-specific orphanhood and caregiver death beyond estimates from select c...
Article
Full-text available
Studies from high‐income populations have shown that stimulating, supportive communicative input from parents promote children's cognitive and language development. However, fewer studies have identified specific features of input supporting the healthy development of children growing up in low‐ or middle‐income countries. The current study propose...
Article
Full-text available
Introduction Reversing malnutrition-induced impairment of cognition and emotional regulation is a critical global gap. We hypothesize that brain-targeted micronutrient supplemented nutritional rehabilitation in children with moderate acute malnutrition, followed by 2 years micronutrient supplementation will impact on the cognition and emotion regul...
Article
Individual differences in sensitivity to context are posited to emerge early in development and to influence the effects of environmental exposures on a range of developmental outcomes. The goal of the current study was to examine the hypothesis that temperament characteristics and biological sex confer differential vulnerability to the effects of...
Article
Background and objectives Neighborhood socioeconomic disadvantage is associated with lower neurocognitive scores and differences in brain structure among school-age children. Associations between positive neighborhood characteristics, infant brain activity, and cognitive development are underexplored. We examined direct and indirect associations be...
Preprint
Exposure to psychosocial adversity (PA) is associated with poor behavioral, physical, and mental health outcomes in adulthood. Growing evidence suggests that deficits in executive functions may in part moderate these outcomes, with inhibitory control as an example of such a putative moderator. However, much of the literature examining the developme...
Article
Full-text available
Shortly after birth, human infants demonstrate behavioral selectivity to social stimuli. However, the neural underpinnings of this selectivity are largely unknown. Here, we examine patterns of functional connectivity to determine how regions of the brain interact while processing social stimuli and how these interactions change during the first 2 y...
Preprint
Full-text available
Background: Restricted and repetitive behaviors (RRB) are among the primary characteristics of autism spectrum disorder (ASD). Despite the potential impact on later developmental outcomes, our understanding of the neural underpinnings of RRBs is limited. Alterations in EEG alpha activity have been observed in ASD and implicated in RRBs, however, de...
Article
Full-text available
Early childhood adversity increases risk for negative lifelong impacts on health and wellbeing. Identifying the risk factors and the associated biological adaptations early in life is critical to develop scalable early screening tools and interventions. Currently, there are limited, reliable early childhood adversity measures that can be deployed p...
Article
Inhibition (a temperamental profile characterized by elevated levels of avoidance behaviors) is associated with increased likelihood for developing anxiety and depression, whereas exuberance (a temperamental profile characterized by elevated levels of approach behaviors) is associated with increased likelihood for developing externalizing condition...
Preprint
Full-text available
Introduction Reversing malnutrition-induced impairment of cognition and emotional regulation is a critical global gap. We hypothesize that brain-targeted micronutrient supplemented nutritional rehabilitation in children with moderate acute malnutrition, followed by 2 years micronutrient supplementation will impact on the cognition and emotion regul...
Article
Understanding the impact that early psychosocial neglect has on the course of human development has implications for the millions of children around the world who are living in contexts of adversity. In the United States, approximately 76% of cases reported to child protective services involve neglect; worldwide, there are more than 150 million orp...
Article
Full-text available
There is growing interest in telomere length as an indicator of current and future health. Although early childhood is a period of rapid telomere attrition, little is known about the factors that influence telomere biology during this time. Adult research suggests that telomere length is influenced by psychological characteristics. This study’s goa...
Article
Full-text available
Children raised in institutions display deficits in error monitoring and increased psychopathology. Deficits in error monitoring might be a pathway for the emergence of psychopathology in previously institutionalized adolescents. Here we investigate the impact of early psychosocial deprivation and a foster care intervention on error monitoring and...
Preprint
Full-text available
The development of neural circuits over the first years of life has long-lasting effects on brain function, yet our understanding of early circuit development in humans remains limited. Here, aperiodic and periodic EEG power features were examined from longitudinal EEGs collected from 592 healthy 2–44 month-old infants, revealing age-dependent nonl...
Preprint
Full-text available
The time-course of developing brain circuits plays a fundamental role in brain maturation and later cognitive functioning, but thus far has been poorly characterized in humans. Here, aperiodic and periodic EEG power features were examined from longitudinal EEGs collected from 592 healthy 2-44 month-old infants, revealing age-dependent nonlinear cha...
Article
Full-text available
Introduction Anxiety is the most common manifestation of psychopathology in youth, negatively affecting academic, social, and adaptive functioning and increasing risk for mental health problems into adulthood. Anxiety disorders are diagnosed only after clinical symptoms emerge, potentially missing opportunities to intervene during critical early pr...
Article
Full-text available
The overarching goal of this paper is to examine the efficacy of early intervention when viewed through the lens of developmental neuroscience. We begin by briefly summarizing neural development from conception through the first few postnatal years. We emphasize the role of experience during the postnatal period, and consistent with decades of rese...
Article
Full-text available
Objective Research on bifactor models of psychopathology in early childhood is limited to community samples with little longitudinal follow-up. We examined general and specific forms of psychopathology within 2 independent samples of preschool-aged Romanian children. Within a sample with children exposed to psychosocial deprivation, we also examine...
Article
Full-text available
Resting brain activity has been widely used as an index of brain development in neuroscience and clinical research. However, it remains unclear whether early differences in resting brain activity have meaningful implications for predicting long-term cognitive outcomes. Using data from the Bucharest Early Intervention Project (Zeanah et al., 2003),...
Article
Background: Therapeutic hypothermia (TH) is standard of care for moderate to severe neonatal hypoxic ischemic encephalopathy (HIE) but many survivors still suffer lifelong disabilities and benefits of TH for mild HIE are under active debate. Development of objective diagnostics, with sensitivity to mild HIE, are needed to select, guide, and assess...
Article
Objective: The Bucharest Early Intervention Project is the first randomized controlled trial of foster care as an alternative to institutional care. The authors synthesized data from nearly 20 years of assessments of the trial to determine the overall intervention effect size across time points and developmental domains. The goal was to quantify t...
Article
Intergenerational transmission of internalizing disorders (anxiety and depression) is well documented, but the responsible pathways are underspecified. One possible mechanism is via programming of the child's parasympathetic nervous system (PNS). For example, maternal depression and anxiety, via multiple pathways, may heighten child PNS reactivity,...
Article
Full-text available
We sought to characterize developmental trajectories of EEG spectral power over the first 2 years after birth and examine whether family income or maternal education alter those trajectories. We analyzed EEGs (n = 161 infants, 534 EEGs) collected longitudinally between 2 and 24 months of age, and calculated frontal absolute power across 7 canonical...
Article
Full-text available
Open science practices work to increase methodological rigor, transparency, and replicability of published findings. We aim to reflect on what the functional near-infrared spectroscopy (fNIRS) community has done to promote open science practices in fNIRS research and set goals to accomplish over the next 10 years.
Preprint
Improving the geographic and economic inclusiveness of developmental neuroscience is an urgent concern, and functional near-infrared spectroscopy (fNIRS) is one tool extending the reach of neuroimaging beyond the communities closest to university laboratories. Where structural imaging facilities are unavailable, however, comparing fNIRS data across...
Article
Clinical trials in autism spectrum disorder (ASD) often rely on clinician rating scales and parent surveys to measure autism-related features and social behaviors. To aid in the selection of these assessments for future clinical trials, the Autism Biomarkers Consortium for Clinical Trials (ABC-CT) directly compared eight common instruments with res...
Article
During the first year of life, infants become increasingly attuned to facial emotion, with heightened sensitivity to faces conveying threat observed by age seven months as illustrated through attentional biases (e.g., slower shifting away from fearful faces). Individual differences in these cognitive attentional biases have been discussed in relati...
Preprint
Shortly after birth, human infants demonstrate behavioural selectivity to social stimuli. However, the neural underpinnings of this selectivity are largely unknown. Here we examine patterns of functional connectivity to determine how regions of the brain interact while processing social stimuli and how these interactions change during the first two...
Article
Full-text available
Background Developing biomarkers is a priority for drug development for all conditions, but vital in the rare neurodevelopmental disorders where sensitive outcome measures are lacking. We have previously demonstrated the feasibility and tracking of evoked potentials to disease severity in Rett syndrome and CDKL5 deficiency disorder. The aim of the...
Article
Full-text available
Importance Research evidence is mounting for the association between infant screen use and negative cognitive outcomes related to attention and executive functions. The nature, timing, and persistence of screen time exposure on neural functions are currently unknown. Electroencephalography (EEG) permits elucidation of the neural correlates associat...
Article
Full-text available
Background Although investigations have begun to differentiate biological and neurobiological responses to a variety of adversities, studies considering both endocrine and immune function in the same datasets are limited. Methods Associations between proximal (family functioning, caregiver depression, and anxiety) and distal (SES-D; socioeconomic...
Preprint
In this study we sought to characterize developmental trajectories of EEG spectral power over the first 2 years after birth and examine whether family income or maternal education alter those trajectories. EEGs (n=161 infants, 534 EEGs) collected longitudinally between 2 and 24 months of age were analyzed. Absolute frontal power across 7 canonical...
Conference Paper
Functional near infrared spectroscopy relies on consistent and precise optode location and scalp morphology for accurate analyses. Herein, we present a scalp surface-based parcellation that compensates for variations in optode location and scalp morphology.
Article
Full-text available
Abstract Background Differences in face processing in individuals with ASD is hypothesized to impact the development of social communication skills. This study aimed to characterize the neural correlates of face processing in 12-month-old infants at familial risk of developing ASD by (1) comparing face-sensitive event-related potentials (ERP) (Nc,...
Article
Full-text available
Background Fragile X syndrome (FXS) is the most prevalent form of inherited intellectual disability and is commonly associated with autism. Previous studies have linked the structural and functional alterations in FXS with impaired sensory processing and sensory hypersensitivity, which may hinder the early development of cognitive functions such as...
Article
Frontal asymmetry (FA), the difference in brain activity between the left versus right frontal areas, is thought to reflect approach versus avoidance motivation. This study (2012–2021) used functional near‐infrared spectroscopy to investigate if infant (Mage = 7.63 months; N = 90; n = 48 male; n = 75 White) FA in the dorsolateral prefrontal cortex...