A prospective, observational, single-center study of the effects of illness and nutrition on growth and cognition in AGA VLBW preterm infants
Sara Ramel, MD (Department of Pediatrics)
Ellen Demerath, PhD (Department of Epidemiology and Community Health), Michael Georgieff, MD (Department of Pediatrics), Bridget Davern (Department of Pediatrics), Neely Miller (Department of Pediatrics), Heather Gray (Department of Maternal Fetal Medicine)
The objectives of this study are: 1) to investigate the relationship between linear growth and fat-free body mass (FFM), and subsequent cognitive function, and 2) to identify modifiable nutritional and non-nutritional factors that influence FFM accretion (and potentially cognition) during and after initial hospitalization in very low birth weight (VLBW) preterm infants. This study will test the following novel hypotheses: 1) cognitive function in VLBW preterm infants is a function of linear growth and FFM accretion; 2) both modifiable nutritional and non-nutritional factors influence FFM accretion during and after initial hospitalization in VLBW preterm infants and that these factors affect cognitive status at 24 months of age corrected for the degree of prematurity (CA); and 3) alterations in the growth hormone axis and increased pro-inflammatory cytokines mediate the relationship of slower length growth and FFM accretion to cognitive outcomes.
Emotion regulation in the transition to adolescence
Shreya Lakhan-Pal, Graduate Student (Institute of Child Development)
Kathleen Thomas, PhD (Institute of Child Development)
The capacity to regulate one’s emotions is a critical skill that develops into adulthood. Adolescence is a period of emotional vulnerability and hypersensitivity, and is marked by a rise in the onset of affective disorders like depression and anxiety. Problems with emotion regulation (ER) are implicated in most forms of psychopathology and in decreased socioemotional health, suggesting that successful ER may be a key protective factor during adolescence. Despite its significance in psychopathology and emotional development, little is known about changes in ER in this time.
While social regulation plays an important role throughout the lifespan, evidence suggests that it becomes less effective during adolescence. Social structures and expectations are in dramatic flux, and emotions are more volatile. During stressful situations, neither parent nor friend presence effectively regulates stress hormones or emotion-related neural activity,and neural networks for self-regulation are still developing. Thus, it seems likely that there is a period of emotional vulnerability when social regulation wanes while self-regulation is still maturing. In the proposed study, I aim to address this gap by jointly examining social and self-regulation efficacy during the transition to adolescence, and by determining how the two are associated with caregiver emotional styles.
Enhanced early nutrition for preterm infants to improve neurodevelopment and minimize metabolic risk
Sara Ramel, MD (Department of Pediatrics)
Ellen Demerath, Ph.D. (Department of Public Health)
Preterm infants undergo early growth failure while in the Neonatal Intensive Care Unit (NICU) that persists for years after discharge home. This growth failure is occurring at a time of rapid brain development, and has been associated with negative long-term neurodevelopmental outcomes. In addition, early growth failure is often followed by rapid catch-up growth in childhood, which is associated with later metabolic (obesity/diabetes/hypertension) risk. Enhanced early nutrition has been associated with improved weight gain and neurodevelopment in several small observational studies, but is not routinely provided due to hesitancy surrounding possible intolerance and concern that increased nutrition will lead to increased adiposity. Lack of randomized controlled trials on this question create concern that the observed benefit of enhanced early nutrition is actually the result of confounding, whereby healthier babies are from the start inadvertently more likely to receive better nutrition, and also exhibit faster growth and better health outcomes.The overall objective of the proposal is to demonstrate the feasibility of providing increased calories and protein in the first week of life to VLBW preterm infants, and to generate pilot data on the effects of this intervention on growth and neurodevelopmental outcomes.
Event-related potentials for early detection of the cerebral form of X-linked adrenoleukodystrophy: a feasibility study
Rene Pierpont, Ph.D., L.P. (Department of Pediatrics)
Julie Eisengart, Ph.D. (Department of Pediatrics), Weston Miller, MD (Department of Pediatrics), Paul Orchard, MD (Department of Pediatrics), Michael Georgieff, MD (Department of Pediatrics)
Adrenoleukodystrophy (ALD) is a devastating childhood neurodegenerative disease for which the onset of central nervous system (CNS) involvement is unpredictable, although previous research has shown that thirty-five percent of affected boys develop clinically evident cerebral involvement (cALD) between 4-10 years of age (1). The disease is characterized by progressive cerebral demyelination and inflammation. Devastating neurological and cognitive decline is associated with cALD, with death occurring a few years following the onset of clinically-evident disease. Patients with cALD have a fairly predictable, consistent pattern of white matter disease progression. Previous studies in other at-risk populations have demonstrated the ability of scalp-recorded event-related potentials (ERPs) to detect brain functional abnormalities prior to the onset of behavioral symptomatology. Early detection of the cerebral form of ALD would revolutionize treatment outcomes for patients with this condition. Given the fairly consistent pattern of cerebral disease progression within white matter tracts, and the fact that latency of ERP components are sensitive to changes in myelination and synaptic efficiency, we hypothesize that ERPs may enable more reliable prediction of disease onset than traditional behavioral measures, for which performance may be vulnerable to non-disease influences such as fatigue or anxiety.
Impact of the intestinal microbiome on infant neurodevelopment
Ellen Demerath, Ph.D. (Department of Epidemiology and Community Health)
Today the majority of pregnant women in the United States are either overweight or obese at conception with their offspring having greater adiposity at birth, a 2-fold greater risk of later obesity, and neonatal insulin resistance. Animal models indicate that maternal obesity may have deleterious effects on brain development in offspring. Preliminary data from our laboratory suggest that infants born to mothers with high pre-gravid BMI have altered cognitive processing of visual and audio stimuli compared to infants born to mothers with normal BMIs. Maternal obesity can also cause changes in the intestinal microbiome of offspring, both pre- and postnatally. Intestinal microbial communities are thought to affect the development immunity, metabolism, and brain function, with effects that extend across an individual’s lifespan. Our main objective is to determine how variations in microbiome signatures early in life correlate with variations in hippocampal development as indexed by ERPs. The specific aims are to 1) Examine the variation in the infant biome at one month and six months of age; and 2) Determine whether these variations are associated with poorer hippocampal-based electrophysiology outcomes and behavior, and slower myelination-dependent speed of processing not only at in the neonatal period but six months later as well.
Longitudinal assessment of asymptomatic congenital CMV infection in Minnesota infants identified by universal screening: what is risk of sequelae?
Mark Schleiss, MD (Department of Pediatrics)
Jed Elison, PhD (Institute of Child Development), Igor Nestrasil, MD, PhD (Department of Pediatrics), Erin Osterholm, MD (Department of Pediatrics)
Symptomatic congenital CMV (cCMV) infections are commonly encountered in clinical practice, affecting approximately 0.65% of all newborns. Such infections - in symptomatic newborns - carry a substantial risk for long-term neurodevelopmental sequelae including developmental delay, mental retardation, seizure disorders, cerebral palsy, and sensorineural hearing loss. Nucleoside antiviral therapy is associated with only modest improvements in audiological and neurodevelopmental outcomes. It is much less clear how to manage infants identified with asymptomatic cCMV infection. These infants have in the past essentially escaped clinical recognition, precisely because these children are asymptomatic at birth, and there is no universal newborn cCMV screen. However, the landscape of cCMV screening is rapidly evolving, and there is increasing interest in implementation of universal cCMV screening programs. In spite of recent progress, universal newborn screening for congenital CMV in many ways remains an area of scientific uncertainty. The optimal screening methodology remains uncertain. We don’t know if asymptomatic infants should undergo full laboratory and neuroimaging evaluations, or whether treatment of infants with asymptomatic congenital CMV with antivirals should be considered. Our proposal will conduct neurocognitive and neuroimaging studies in asymptomatic infants identified with congenital CMV infection in the context of a universal screening program to address these important areas of knowledge deficit.
Perinatal Stroke: Understanding Brain Reorganization through Infant Neuroimaging and Neuromodulation
Bernadette Gillick, PhD, MSPT, PT (Department of Rehabilitation Medicine)
Michael Georgieff, MD (Department of Neonatology), Raghavendra Rao, MD (Department of Neonatology)
The purpose of this study is to use MRI/DTI TMS and electroencephalography (EEG) to comprehensively examine both the CST integrity and cortical excitability in infants following perinatal stroke, and to identify association with sensorimotor outcome as evaluated by clinical behavioral assessments of infants. The results of this study will provide fundamental information as to the feasibility and safety of applying non-sedative/natural sleeping MRI/DTI scanning and TMS in infants. This study will also investigate the relationship between modeled electric field and measured motor threshold across hemispheres. This may help identify anatomical markers that can predict electric field strength and thus could be used for dosing considerations for future neuromodulation interventions. Additionally, sensory stimulation evoked event related potential amplitude will be compared between infants with stroke and typical development to identify whether infants with stroke demonstrate early sensory processing differences compared to typically developing peers.
Quantifying eye tracking and EEG metrics of social perception during infancy
Charisse Pickron, PhD (Institute of Child Development)
Jed Elison, PhD (Institute of Child Development)
The healthy development of key neurocognitive functions, such as face recognition and social cognitive function, is essential for learning to navigate one’s environment. Individual differences in these functions predict important developmental outcomes including successful social communication skills, school readiness, and interpersonal relationships. Several recent investigations have focused on understanding how early perceptual experience influences the behavioral and neural specificity of face processing during the first year of life. Research in this area has revealed several perceptual biases arising within the first year of life, including the other-race effect. These findings indicate that infants’ ability to readily differentiate among face identities is narrowed to the race and gender groups that they have the most experience with.
This indicates that being able to attend to and possibly learn from faces is influenced by familiarity with facial features such as race and gender. Attentional biases for social information may be relevant to these changes in face processing capabilities. The ability to characterize the microarchitecture of looking patterns and neural activity responses during passive viewing of social and non-social stimuli has markedly advanced the study of infant cognition and social cognition.
To date, very few studies have recorded electrical brain activity while simultaneously recording looking patterns in developmental populations. Thus more research is needed to better characterize the relation between looking patterns and electrical responses measured from the brain. Together these methods will provide clearer characterization of changes in infants’ attentional and perceptual capabilities during the first years of life. Additionally, the current project will provide evidence for potential underlying neural and attentional mechanisms which drive changes in social information processing during the first year of life.
Rett Syndrome: health and behavioral analyses
Frank Symons, PhD (Department of Educational Psychology)
Most widely available assessments of sensory processing and cognitive functioning rely on the participant’s ability to respond verbally or motorically to instructions or sensory stimuli. Individuals with Rett syndrome, as well as some other genetic syndromes, present with verbal and motoric deficits that make the administration of such assessments difficult or even impossible. Therefore, the development of novel or adapted methods for assessing cognitive functioning in this population is necessary. The primary aim of this protocol is to develop and test a modified Mullen Scales of Early Learning (MSEL) developmental test for populations with language and motor limitations. We will do so by implementing an adapted administration protocol and incorporating eye-tracking technology. The preservation of visual attention and eye gaze communication in individuals with Rett syndrome makes this population amenable to study using eye tracking paradigms. Integration of an eye tracker with a 128-channel EEG system, permits co-registration of eye position with the moment-by-moment transactions that take place in the brain, allowing for a passive assessment of cortical function.