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.
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.
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.
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).