Current CNBD Research Studies
Below is a list of current CNBD research studies. Subject tags will link you to study listings by topic.
Perturbation: Substance Use, Nutrition, Genetic/Congenital/Developmental Condition, Prematurity, Social/Emotional Development, Behavioral Development, Cognitive Development, Institutional Neglect/Deprivation
Neuromodulation augmented cognitive remediation to improve executive dysfunction in fetal alcohol spectrum disorder
Jeffrey R. Wozniak, Ph.D., L.P. (Department of Psychiatry)
Christopher J. Boys, Ph.D. (Department of Pediatrics), Kelvin Lim, MD (Department of Psychiatry)
Prenatal alcohol exposure (PAE) has profound detrimental effects on brain development and, as a result, has permanent consequences for cognition, learning, and behavior. Individuals with Fetal Alcohol Spectrum Disorders (FASD) commonly have a range of neurocognitive impairments that directly lead to practical problems with learning, attention, working memory, task planning/execution, and decision making, among other areas of functioning. Despite the profound public health burden posed by FASD, there have been very few treatment studies of any sort in this population. Our group conducted the first randomized controlled trials of the nutrient choline as a neurodevelopmental intervention in 2-5 year old children with FASD, in which we demonstrated effects on sequential memory. For older children, a very different neurodevelopmental target is needed, and for this we have narrowed our focus to “plasticity” (the brain’s ability to adapt). We propose to conduct a novel pilot study to examine the effects of cognitive remediation training augmented with tDCS in children and adolescents with FASD. Functional magnetic resonance imaging will be collected to provide preliminary data of brain circuitry changes created by this intervention.
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.
Pilot study of administration of intravenous laronidase following allogeneic transplantation for Hurler Syndrome (MT2009-20)
Paul J. Orchard, M.D. (Department of Pediatrics)
Weston Miller, MD (Pediatric Blood and Marrow Transplantation), Lynda Polgreen, MD (Pediatric Endocrinology), Jakub Tolar, MD, PhD (Pediatric Blood and Marrow Transplantation)
Hurler Syndrome or mucopolysaccharidosis type I (MPS I), is a rare, genetic, storage disease of early childhood in which the affected individual cannot breakdown long chains of sugar molecules called mucopolysaccharides due to a lack of the enzyme (α-L-iduronidase). As a result, there is a build-up of these molecules, leading to cellular and organ failure. The effects of Hurler Syndrome are multi-systemic and the natural history of this disease culminates in death during early childhood. Currently, hematopoietic cell transplant (HCT) is used to slow or halt the progressive course of the disease; however, individuals often continue to struggle with orthopedic, sensory, growth, and cognitive difficulties as they age. Enzyme replacement therapy (ERT) has been found to be helpful in other types of the mucopolysaccharidoses (such as type II) as well as the less severe form of MPS I (Hurler-Scheie and Scheie Syndromes), but it has yet to be tried in individuals with Hurler Syndrome post-HCT. This is a single center pilot study in which recombinant α-L-iduronidase (Laronidase) will be given weekly for two years in 10 patients with Hurler syndrome who have previously been treated with HCT.
Pilot study of gait in mucopolysaccharidoses
Igor Nestrasil, PhD (Department of Pediatrics)
Elsa Shapiro, PhD (Department of Pediatrics), John Anderson, M.D., Ph.D. (Department of Otolaryngology), Christopher Fuller (Department of Otolaryngology), Lynda Polgreen. M.D. (Department of Pediatrics)
Preservation of mobility is an emerging clinical challenge and is the main primary endpoint evaluated perpetually in clinical trials. The ability to obtain objective outcome measures, which are accurate as well as responsive and relevant to change in disease burden, is a crucial condition for the evaluation of both disease severity and treatment efficacy. We plan to develop a gait evaluation technique, which will provide an efficient non-invasive gait assessment that is reliable, and accurate. In this project, we will be examining gait difficulties in mucopolysaccharidoses (MPS). MPS are group of lysosomal storage disorders (LSDs) caused by specific enzyme deficiency. Impaired mobility is a symptom very frequently seen in MPS and has a significant impact on quality of life and functional abilities. The 6 minute walk test, which has been historically used in other MPS studies, depends on endurance, and motivation. Kinematic gait analysis, which we plan to employ will not depend on either and will yield quantitative data. We will also collect control data from healthy pediatric population. It bears a tremendous potential for future applications of the method. We plan to establish reference values which can be readily used to evaluate gait impairment in other disorders, e.g. rheumatoid arthritis, cerebral palsy, and can be used in related clinical studies. We expect that kinematic gait analysis as a robust quantitative tool holds a strong potential to replace fatiguing, strenuous, and mostly endurance measuring walk tests in future clinical trials.
Pubertal stress recalibration hypothesis
Megan R Gunnar, Ph.D. (Institute of Child Development)
Bradley Miller, M.D./Ph.D. (Department of Pediatrics)
Youth with severely adverse early life histories are at double the risk of increased emotional problems as they transition from childhood into adolescence. This risk may reflect the calibration of stress-mediating systems to harsh conditions during sensitive periods early in life. Yet, not all youth with such histories are affected. The proposed study tests the novel pubertal stress recalibration hypothesis; specifically puberty opens a second sensitive period for calibration of stress-mediating systems to current life conditions at the approach of sexual maturity. For youth who experienced adverse early care, pubertal development allows a shifting of stress-system activity to that seen among youth without such histories if concurrent stressors are low and a hyper-sensitization of stress activity if current life conditions are stressful. Our target participants will be youth adopted internationally from orphanages (post-institutionalied, PI) youth, compared to youth reared in their families of origin (non-adopted,NA). We will follow 368 youth examining them annually over 3 time points (0, 1 and 2 yrs). The use of an accelerated longitudinal design (4 grps: 7-8, 9-10, 11-12, 13-14 yrs) and growth curve modeling allows examination of a broad range of the pubertal period (7 through 16 yrs). Annual measures will be made of the HPA axis (salivary cortisol), the ANS (salivary alpha amylase) for PI and NA youth in relation to current life stress (Youth Life Stress Interview completed annually) and pubertal stage (annual nurse-conducted Tanner Staging). Measures of stress-mediating systems activity will be obtained using the Trier Social Stress Test for Children and home assessment of the cortisol awakening response (CAR). Our prior research with PI youth showed a normalization of the CAR by Tanner stage 3-5, compared to same aged youth at stages 1-2. This proposal is a logical extension of that work that will also test the hypothesis that shifts in stress-system activity mediates the increase in emotional problem symptoms in adolescence. The results of this study should help determine whether the peripubertal period is a critical time to intervene with children exposed to early life adversity.
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.
Screening for profiles of risk associated with ASD and other emerging atypical phenotypes
Jed Elison, PhD (Institute of Child Development)
Suma Jacob, MD, PhD (Department of Psychiatry), Amy Esler, PhD, LP (Department of Pediatrics), Jason Wolff, PhD (Department of Educational Psychology)
There is a great need for improved screening approaches and improved implementation of screening procedures to identify children who will need early intervention for ASD. New screening approaches are needed to capture the heterogeneity of the disorder(s), which includes identifying children who are likely to access services in the community even though they may not meet strict research criteria for an autism spectrum diagnosis.
In the current application, we propose to test a new screening approach that we refer to as pheno-screening. We ask parents to complete online versions of standardized questionnaires that are designed to capture individual differences in highly dimensional traits relevant to the early emergence of clinically impairing behaviors that constitute ASD. We use data driven approaches to derive clusters or latent classes of children that represent a continuum of risk. Next, based on a given cluster’s profile, we invite children into the laboratory for direct phenotypic assessment that also includes measurement of biomarkers hypothesized to help us parse the heterogeneity of behavioral profiles encapsulated by an ASD diagnosis. Improved screening procedures promise to advance early identification, and improved characterization of biomarkers associated with risk promises to advance new interventions designed to target specific mechanisms associated with behavioral symptomatology.
Social Buffering over the Pubertal Transition
Megan Gunnar, PhD (Institute of Child Development), Kathleen Thomas, PhD (Institute of Child Development)
The effectiveness of social buffering in regulating stress appears to wane for a period with puberty at the same time that stress-reactivity increases and young adolescents become more vulnerable to stress-related affective pathology. However, there is a dearth of knowledge regarding the neural underpinnings of social buffering in children and the changes in neural responses to potential social buffers with puberty. In addition, to date, the loss of social buffering effectiveness with puberty has primarily been examined using activity of the hypothalamic-pituitary-adrenocortical (HPA) axis as the stress measure. Our proposed experiments will examine the pervasiveness of the effect by examining sympathetic and parasympathetic responses, in addition to salivary cortisol. They will determine whether the loss of social buffering also extends to threat stimuli as it does in adults and to situations in which two friends are both experiencing the stressful event together. Finally, they will explore whether puberty is associated with an emergence of sex differences in social buffering by parents and friends. Our prior research uncovered the waning of the effectiveness of parents to serve as social buffers of the HPA axis over the pubertal transition and the concomitant failure of friends to “step in” as stress buffers. The proposed experiments are the logical extension of this work. The results will have the potential to drive significant attention to the role of developmental disruptions in social stress buffering as possible contributing factors in the rise of affective problems in the early teen years.
Social-emotional development in children with neurofibromatosis type 1, Noonan Syndrome and unaffected siblings
Rene Pierpont, PhD (Department of Pediatrics)
Rebekah Hudock, PhD (Department of Pediatrics), Margaret Semrud-Clikeman, PhD (Department of Pediatrics), Christopher Moertel, MD (Department of Pediatrics)
Neurofibromatosis type 1 (NF1) and Noonan syndrome (NS) are genetic syndromes affecting multiple systems in the body. They are also called "RASopathies" because they are caused by mutations in the RAS-MAPK signaling pathway. Past research has shown that children with RASopathies are at risk for neuropsychological deficits, including problems with attention and other aspects of behavior. The purpose of the current study is to better understand social competencies of children with NF1 and NS and to identify risk factors for social difficulties. We hypothesize that children with NF1 and NS will demonstrate greater problems with social competency that their unaffected peers. We will examine the relationship between overall ratings of social competency and more specific risk factors (i.e., social anxiety, poor social communication, and poor social cognition).