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
Longitudinal studies in MPS disorders: a multicenter study of the lysosomal disease network, longitudinal studies of brain structure and function in MPS disorders
Chester B. Whitley, PhD, MD (Department of Pediatrics)
The purpose of this study is to examine the changes in the central nervous system over time in patients with MPS I, II, IV, VI, and VII in both structure and function. We have determined that localization in the brain of abnormal cognitive and behavioral attributes varies by the type of MPS disorder. We will be examining how changes in the brain over time reflects the natural course of the disease or the effects of past or currently administered treatment such as hematopoietic cell transplant, systemic enzyme replacement or intrathecal enzyme replacement.
We hypothesize that specific and localized neuroimaging, neuropsychological and neurobehavioral findings and their relationship will be distinct for each MPS disorder. Further, without appropriate treatment, functions will decline and structure will change over time specific to each disease and stage of disease. We hypothesize that treatments such as ERT, HCT, HCT+ERT, and palliative and rehabilitation therapies, will differentially affect brain structure, functions and quality of life. Finally, we hypothesize that for each MPS type, variables such as age at first treatment, severity of disease, medical events related and unrelated to the disease, mutation, family and environmental factors, sensory abnormalities, and sociodemographic variables will influence brain functional and structural outcomes as well as quality-of-life.
Mapping the Human Connectome During Typical Development
Kathleen Thomas, PhD (Institute of Child Development), Essa Yacoub, PhD (Center for Magnetic Resonance Imaging)
The major technological and analytical advances in adult human brain imaging achieved as part of the Human Connectome Projects (HCP) have allowed unprecedented examination of structural and functional brain connectivity at previously impossible levels of spatial and temporal resolution. While this information has proven crucial to our understanding of normative variation in adult brain connectivity, little is known about the developmental processes through which this variation arises. In this project, we apply the tools and analytical approaches developed by the HCP to understand how structural and functional wiring of the brain develops. This work is conducted through a consortium of five sites (Harvard University, University of California at Los Angeles, University of Minnesota, University of Oxford, Washington University in St. Louis), with extensive complimentary expertise in human brain imaging and neural development and including many of the investigators from the original adult and pilot lifespan HCPs. This group will acquire, analyze, and publicly share approximately 1500 high quality neuroimaging and associated behavioral datasets on healthy children and adolescents from 5–21 years of age. This unique protocol is designed to provide rich, multimodal data on several biological and cognitive constructs that are of critical importance to health and well-being across this age range and allow a wide range of investigators in the community to test a host of crucial hypotheses about brain development and connectivity.
Maternal obesity, breast milk composition and infant growth
Ellen Demerath, Ph.D. (Department of Epidemiology and Community Health)
Today, the majority of pregnant women in the US are either overweight or obese. Their offspring have a greater adiposity at birth, a greater risk of later obesity and neonatal insulin resistance. Breast feeding has many clear benefits that many include protection against obesity (its long term effects and sequelae). Recent evidence shows that breast milk is a highly complex fluid with significant variation both between and within lactating women. Little effort has been made to examine breast milk composition in obese women and its impact on infant metabolic status. The objective of this research study is to access whether or not variation in breast milk composition is related to both maternal adiposity and infant metabolic status.
Microstructural and functional MRI signatures of brain alterations in patients with mucopolysaccharidosis
Igor Nestrasil, MD, PhD (Department of Pediatrics)
Julie Eisengart, Phd, LP (Department of Pediatrics)
We intend to employ a non-invasive technique using brain magnetic resonance imaging (MRI) along with analysis of microstructural and functional MRI signatures of these regions to measure and determine the alterations and their impact on clinical variability in mucopolysaccharidosis (MPS) patients. The study aims to identify the neuronal and functional signatures in MPS patients who have been scanned longitudinally. To accomplish this aim, we have established MRI parameters for detection of abnormalities in myelin content, microstructural integrity, and functional connectivity in the brain of MPS patients. The study also aims to determine the role of myelin abnormalities in cognitive deterioration in MPS subjects by relating comprehensive neurocognitive assessments to their respective MRI outcomes.
Mindful breathing and neuromodulation for depression in young people
Kathryn Cullen, MD (Department of Psychiatry)
Bonnie Klimes-Dougan, PhD (Department of Psychology), Kelvin Lim, MD (Department of Psychiatry)
Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that can modulate neural activity. If paired with Mindful breating training (MBT), tDCS may be able to enhance learning and neural changes associated with MBT. This study will test the efficacy of a novel treatment comprised of MBT and tDCS in adolescent depression. We propose that for patients with depression, where the core feature is persistent negative mood, a training task that engages the DLPFC’s role in regulating emotion may optimally reduce symptoms of depression. Mindful breathing training may be a suitable task to down-regulate negative affect and prime the fronto-limbic circuit. Further, this work will advance our understanding the synergistic effects of combining MBT with tDCS to target the connections between the DLPFC with the default mode network (DMN) and limbic regions. If successful, this study will aid in the development of novel treatments for adolescent depression and improve the ability of neuromodulation to treat depression.
Modes of Cognition and Arousal
Daniel Berry, PhD (Institute of Child Development)
Developing the ability to regulate one’s thoughts and attention—or ‘executive functioning’ (EF)—is a central developmental milestone of early childhood. The benefits of EF development are well known. These abilities support children’s burgeoning academic and social skills and successful transition to formal schooling. As such, there is a reasonable tendency to equate stronger EF as being 'better’ for learning.
Notably, Life History models highlight the idea that many complex developmental phenomena are often more about adaptive trade-offs than they are about clear-cut deficits. From this perspective, ‘better’ learning is reframed as a relative question: ‘better,' to what end? For example, we know that EF deficits can undermine learning that requires organizing and integrating new and existing information —skills that are quite useful in stable, predictable contexts. Yet, there is increasing reason to suspect that such top-down control may also bias thinking toward known heuristics and, thus, away from richer sets of cognitive alternatives. As such, EF may provide an incredibly useful tool for efficiently building upon what we know, yet come at the cost of increasing inflexibility in our receptiveness to novel information and alternative ways of thinking. This latter 'cognitive receptiveness' is fundamental to inductive reasoning, creative thinking, and implicit/conventional learning—abilities that that are quite adaptive in unpredictable environments that require rapid, qualitative shifts in thinking.
Collectively, the aim of this study is to begin to test the trade-offs of EF in the context of different types of cognitive tasks.
NET-Works 2 at the U
Alicia Kunin-Batson, PhD, LP (Department of Pediatrics)
Lauren Crain, PhD (Health Partners Institute), Simone French, PhD (School of Public Health), Megan Gunner, PhD (Institute of Child Development), Aaron Kelly, PhD (Department of Pediatrics), Elyse Kharbanda, MD, MPH (Health Partners Institute), Nancy Sherwood, PhD (School of Public Health)
Heart disease accounts for 1 in 4 deaths in the US with obesity as a leading risk factor. While prior studies have linked early environmental stressors such as socioeconomic disadvantage to childhood obesity and later cardiovascular disease risk some youth will be resilient and will not develop disease despite risk exposure. Developing optimal interventions requires understanding the protective factors that foster resilience, the pathways through which early environmental stressors contribute to emerging dysregulation in cardiometabolic processes, and the timing during childhood when impacts are observed. There is a significant gap in our knowledge; specifically, a relative dearth of information on the pathways, timing, and risk and protective factors that translate early environmental stressors into emerging cardiometabolic risk during childhood. Prior studies have been hampered by limited assessment of environmental stressors, lack of assessment of biologically plausible pathways (e.g., activity of the hypothalamic-pituitary-adrenocortical (HPA) axis) and a lack of use of sufficiently sensitive measures to detect important cardiometabolic domains in childhood. Most importantly, prior studies have not rigorously examined parenting and child behavioral factors as moderators of the relationship between psychosocial stressors and cardiometabolic risk and resilience. Identification of these potentially modifiable protective factors is crucial for optimizing interventions to prevent the development of cardiovascular and metabolic diseases. The NET-Works 2 at the U study will address this knowledge gap using a unique cohort of racially/ethnically diverse, low income children who participated in a two-arm randomized controlled obesity prevention trial.
The goal of this prospective study and the next logical step in our work is to characterize the emergence of dysregulation in cardiometabolic processes in this high-risk cohort of children at 7-10 years of age, and identify the malleable factors that mitigate the deleterious impact of early environmental stressors on later cardiometabolic risk.
Neurobehavioral functioning in youth
Christine Conelea, PhD (Department of Psychiatry)
Suma Jacob, MD, PhD (Department of Psychiatry)
Despite the recognition of high comorbidity rates and overlapping features among neurodevelopmental disorders, studies assessing neurocognitive functioning have typically only included youth within one diagnostic category (e.g., compare ASD vs. healthy controls). The current study will use a transdiagnostic approach to examine patterns of neurocognitive functioning in a sample of youth with a variety of neurodevelopmental disorders (ASD, OCD, ADHD, and tic disorders (TDs)). Identifying patterns of neurobehavioral functioning in a diagnostically heterogeneous sample has the potential to improve our ability to match youth to appropriate treatments and to inform development of new treatments.
Neurobehavioral mechanisms in tic suppression
Christine Conelea, PhD (Department of Psychiatry)
Kathryn Cullen, MD (Department of Psychiatry), Kelvin Lim, MD (Department of Psychiatry)
The overall research objective of this project is to examine neurobehavioral mechanisms underlying tic suppression using an innovative methodology that integrates repetitive transcranial magnetic stimulation (rTMS) with an established behavioral tic suppression paradigm. TMS is a non-invasive procedure that temporarily increases or decreases cortical activity, which allows researchers to make inferences about the neurobiological underpinnings of a disorder. TMS has been used to examine the pathophysiology of tics by targeting the motor cortex node of the CSTC, which is involved in voluntary suppression of movement (primary motor cortex, M1) and involuntary urges to move (supplementary motor cortex, SMA). This work has primarily compared M1 and SMA functioning across discrete diagnostic categories (e.g., Tourette Syndrome (TS) vs. controls; TS vs. TS+ADHD) but has yet to focus on the relationship between motor cortex functioning and tics themselves. Direct examination of tics and urges after rTMS can be accomplished using an established behavioral paradigm developed to study the effects of context on tic suppression. The proposed study will examine the effect of 1hz active versus sham rTMS over SMA on tic frequency, suppressability, and urges in youth with chronic tics. Research linking this behavioral tic suppression paradigm with targeted examination of SMA activation will help clarify the neurobehavioral mechanisms underlying tic suppression.
Neurodevelopmental effects of fetal alcohol exposure (CIFASD)
Jeff Wozniak, Ph.D., L.P. (Department of Psychiatry)
Bryon Mueller, Ph.D. (Psychiatry), Christopher Boys, Ph.D. (Department of Pediatrics), Kelvin Lim, M.D. (Department of Psychiatry)
The long-term aims of this research are to understand the neurobiological abnormalities that underlie cognitive and behavioral deficits in children with prenatal alcohol exposure. Prior research has clearly demonstrated that children with Fetal Alcohol Syndrome (FAS) have characteristic abnormalities in both the structure and function of their brains. Individuals with FAS have lower intellectual functioning, attention deficits, problems with memory/learning, and difficulties with organization/planning. Much less is known about brain structure and function in children who have a less severe diagnosis within the category of Fetal Alcohol Spectrum Disorder (FASD). This is the diagnostic term applied to those who have been exposed to alcohol prenatally and show some cognitive deficits but do not show all of the classic physical features of FAS (such as delayed growth and unusual facial features). We will use Magnetic Resonance Imaging (MRI) and neurocognitive tests to assess brain abnormalities in children with FASD compared to control participants.