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.
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-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).
SPARK: Simons Foundation powering autism research for knowledge, a national cohort of individuals and families affected by autism spectrum disorder protocol
Suma Jacob, MD, PhD (Department of Psychiatry)
Amy Esler, PhD (Department of Pediatrics)
The purpose of SPARK : Simons Foundation Powering Autism Research for Knowledge (hereinafter referred to as SPARK) is to recruit, engage, and retain a community of 50,000 individuals with ASD along with their family members in the United States to identify the causes of ASD, accelerate clinical research by providing the autism research community with a genotyped cohort of consented participants, and establish a research cohort of individuals and families with ASD. The data generated will facilitate identification of additional genes that contribute strongly to ASD and define their corresponding genotype-phenotype relationships. Data from this cohort will also help identify additional non-genetic causes of ASD. A long term goal of SPARK is to enable genotype-driven clinical research in ASD, which may translate into genotype-driven therapeutics and treatment of ASD. This type of ‘precision medicine’ approach is an emerging strategy for disease treatment and prevention that takes into account individual genetic variability, environment, and lifestyle. Noteworthy advances in precision medicine have been made for specific cancers, but the methodology is not currently available for most diseases. Many researchers are working towards precision medicine, and SPARK is one such project. A limited data set from this study will be made available to qualified researchers, so that scientific and treatment advances can be made as rapidly as possible.
The development of attentional orienting to semantic salience in infancy: Concurrent associations between visual orienting and white matter development
Jed Elison, PhD (Institute of Child Development)
Robin Sifre, Graduate Student (Institute of Child Development)
While a large body of work has charted the emergence of selective attention, less is known about the role that orienting to semantic salience plays in selective attention. Specifically, to what extent can experience with a stimulus modify its semantic salience, and how does the developing brain integrate these modifications into attentional biases? We intend to assess the extent to which reward-modulated semantic salience captures attention in infancy, and how structural brain development supports these abilities. We will focus on 7 to 9 months for two reasons: First, this period marks an important transition toward more sophisticated selective attention; thus, there should be high variability in orienting to semantic salience during this transition. Structural variability in neural circuitry could function as one source of this variance. Second, there is growing evidence suggesting that the social deficits observed in individuals with autism spectrum disorder (ASD) may be traced back to early differences in attention orienting and its relation to white matter microstructure at this age. This project will provide the first normative developmental trajectory of 1) infants’ attentional orienting to semantic salience, and 2) the white matter fiber bundles supporting this orienting ability, as a key first step toward studying this construct in infants considered at high-risk for ASD.
Toddler and Parent Play Study
Megan Gunnar, PhD (Institute of Child Development)
Emily Reilly, PhD candidate (Institute of Child Development)
Sensitive caregiving in the first years of life helps children manage their own emotions and arousal, promoting healthy development and a decreased risk of psychopathology-related symptoms later in childhood. This sensitive care can be derailed by parent trauma histories and depression, which is why sensitivity has become a target of many parenting interventions. Still, these interventions are not successful with some parents, challenging researchers to instead focus on the capacities necessary for sensitive responding. Compassion, we argue, is a principal capacity for sensitivity.
Compassion involves both an understanding of another’s distress and the motivation to act on this understanding to help alleviate their distress — abilities necessary to enact a sensitive response to a child. Encouragingly, compassion is malleable and can be induced with loving kindness meditations, which involve sending thoughts of loving kindness to yourself and a series of people. Biological measures, such as respiratory sinus arrhythmia (RSA), can be used to capture compassionate responding because another’s distress activates our physiological arousal. Employing heart rate variability methods provides an opportunity to measure effects of an LKM intervention at the biological level. Intervening to improve sensitivity by targeting compassion with an LKM could provide a cost-effective, efficient, and possibly more successful method for empowering parents to respond sensitively to their child, thereby preventing the development of mental illness in the next generation. However, it is first necessary to ensure the association between compassion and sensitivity.
Utilizing eye-tracking to study the normative trajectory of social information processing
Suma Jacob, M.D., Ph.D. (Department of Psychiatry)
Sunday Francis, PhD (Department of Psychiatry), Amy Esler, PhD (Department of Pediatrics)
Social information processing includes many behaviors, deficits in some of these behaviors have been observed in autism spectrum disorder (ASD) individuals through behavioral and neuroimaging studies. These impairments emerge early in development and persist over time, and may in part be related to atypical eye movements during assessment of visual stimuli containing social information.
We propose to examine the normal distribution of social information processing and how these capacities differ in our existing cohort of ASD individuals. The developmental trajectories of social information processing change over time, and need to be thoroughly characterized across a broad age of NTs and ASD individuals. Our clinical research team is currently studying novel drug treatments that improve social functioning throughout development. However, treatment outcome measures that reliability document changes in social information processing are limited in ASD. Studies of novel pharmacological and non-pharmacological interventions would benefit from a non-invasive, easily measured, and accessible outcome measure that would provide a measurement of treatment efficacy. By collecting eye tracking and physiological data in typically developing individuals as they perform electronic visual tasks we aim to map the trajectory of social information processing in NTs. Improved characterization of the distribution of social information processing capacities in a neuro-typical cohort will provide a unique platform with which to compare individuals with neurodevelopmental disorders (NDDs).