Autism & Development Disabilites

Quantifying the Brain Developmental Trajectory of Autism-Associated Brain Overgrowth Using 3D Cellular Resolution Imaging Award: $39,069 We aim to develop high throughput computational tools for 3D light-sheet microscopy images to quantify the brain developmental trajectory of autism-associated brain overgrowth. The computational tools developed in this project will be used to study cortical development in the mouse brain, including how typical development is altered by an autism-associated genetic mutation. Need/Problem: Alterations in brain development are associated with a variety of neuropsychiatric disorders, including autism spectrum disorder (ASD). Many studies demonstrate that mouse models re-capitulate a core human phenotype, brain overgrowth, associated with an increase in the neural progenitor pool and that this brain overgrowth shows a regionally specific pattern. However, we do not know the cell-types that are driving the effect. And due to the limited temporal resolution of previous [...]

Cellular and Molecular Mechanisms Leading to Early Brain Overgrowth Need/Problem: Autism spectrum disorder (ASD) is an etiologically heterogeneous disorder that affects 1 in 68 individuals, and confers a lifelong burden to most affected individuals and their families. ASD has been consistently characterized by early brain overgrowth in neuroimaging studies. Grant Summary: We will generate and study neural cells from individuals with ASD and matched controls who have been profiled with behavioral assessments and neuroimaging since infancy in order to identify cellular and molecular mechanisms leading to early brain overgrowth. Goals and Projected Outcomes: Insight into these mechanisms will further understanding of disease pathogenesis, delineate convergent biological pathways within a heterogeneous disorder, and will inform targeted early therapeutic intervention. Heather Hazlett Jason Stein Grant Details: Induced pluripotent stem cells (iPSCs) are an excellent model system [...]

Early Brain Development via Deep Learning of DNA Award: $39,742 Need/Problem: Innovative methodological strategies are urgently needed to predict short-term and long-term cognitive outcome at early life so that early intervention can be implemented before any cognitive delay appears. Grant Summary: This grant is to develop deep convolutional neural networks to build a predictive model for early brain development through genome-wide DNA markers and developmental trajectories of cortical thickness and surface area. Goals and Projected Outcomes: The goal of this study is to develop the first deep learning procedure to predict early brain development using data from two well-characterized population cohorts studied from birth through 2 years of age. The success of this study will present strong proof that deep learning predicting neurodevelopment and cognitive functions is effective and powerful using genome-wide DNA markers, while none of other competing [...]

Prospective Identification of Individuals with a Brain Overgrowth Form of Autism Award: $40,000 This grant will take a first step towards developing a polygenic risk score for brain overgrowth in a large sample of human neural progenitor cells. Understanding the genetic basis of brain overgrowth will enable the development of this important tool for identification of infants at increased risk for the overgrowth form of autism in the general population. Joseph Piven, M.D., with Mark Zylka, Ph.D. and Jason Stein, Ph.D. Need/Problem: Early (pre-symptomatic) brain overgrowth has emerged as a primary mechanism underlying the development of later autism in a subset of infants at high familial risk for this disorder.  Understanding the genetic basis of brain overgrowth will enable the development of a genetic tool (genetic risk score for brain overgrowth) for [...]

Identifying Key Metabolites in the Microbiome-Gut-Brain Axis During Infancy Award: $64,881 The human gastrointestinal system contains a vastly complex system of microbes. We know that the composition and interactions of these microbial communities impact our neurodevelopment, cognition, and emotional behavior, but how is still largely unclear. Researchers will study the interactions between gut bacteria, bacterial gene expression, the presence of stress hormones, and a number of other chemical and behavioral factors, in infants. If a pattern exists, the data could help identify risk factors for psychiatric illness, and lead to preventive therapies and treatments. Rebecca Knickmeyer Santelli, Ph.D. and John Gilmore, M.D. Need/Problem: The composition of the gut microbiome (the trillions of microbes inhabiting the intestinal tract) impacts neurodevelopment, cognition, and stress-related behaviors relevant to a wide range of psychiatric illnesses, but [...]

Excitation-inhibition imbalance in autistic auditory cortex and its effects on spectro-temporal sound integration Award: $100,000 Recent studies on autistic patients have accumulated rich knowledge on these diseases at both genetic and behavioral levels. However, we still know little about the neuronal circuit mechanisms that connect the gene mutations to the behavioral deficits. Researchers will study how disturbed interplay between excitatory and inhibitory neurons leads to auditory processing deficits in autistic brains. The circuit-level knowledge obtained in this study will help identifying the novel therapeutic entry points for developing future treatments. Hiroyuki Kato, Ph.D. Need/Problem: In social species like humans, hearing is of particular importance for vocal communication among conspecifics. In this research, we aim to understand the neuronal circuit mechanisms that lead to disturbed auditory processing in autistic brains. Grant Summary: Using [...]