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Principal Investigator: Meghan H Puglia
Organization: UNIVERSITY OF VIRGINIA
Fiscal Year: 2024
Award: $207,919
Funding agency: National Institute of Mental Health
Project Summary
Current gold-standard diagnostic techniques for Autism Spectrum Disorder (ASD) rely on behavioral
observation, and diagnosis is often not conferred until after age 4. This delay is unfortunate, because early
intervention can drastically improve outcomes. Given the rapid and sweeping changes in neural architecture,
cognitive ability, and behavioral repertoire that occur within the first year of life, identifying early-emerging
neurobiological markers that can predict abnormal neurodevelopment before behavioral symptoms manifest is
a public health priority. Following the onset of behavioral signs and symptoms, there is great need for stratification
biomarkers that can dissect ASD heterogeneity, thereby informing individualized treatment plans. Such a
precision-medicine approach necessitates greater understanding of the longitudinal pathways of development
in domains. This will set the stage for biomarkers that are sensitive to, and predictive of, changes in behavior
resulting from effective interventions.
This proposal aims to identify and validate features of temperodynamic brain signal variability that can serve
as diagnostic, risk, and/or treatment response biomarkers of social dysfunction in ASD. Traditionally modeled
out of analyses as mere “noise”, measures of temperodynamic neural variability capture the inherently fluctuating
nature of the brain, which is increasingly understood to play a valuable functional role in the establishment of
neural networks and in the transfer of information throughout the brain. Temperodynamic neural variability has
been linked to cognitive performance, development, and autism.
The current proposal will capitalize and expand upon this promising neurobiological marker to 1) identify and
optimize metrics for assessing temperodynamic neural variability by conducting the most comprehensive
comparison of time-series analytics of any study to date, and 2) establish these metrics as biomarkers for
neurodevelopmental outcomes by leveraging large clinical and longitudinal data sets consisting of multilevel
genetic, neural, and behavioral data.
The proposed research extends the candidate’s prior work through new training in autism research,
translational developmental cognitive neuroscience, and timeseries and predictive analytics applied to large-
scale datasets necessary to advance biomarker development. These training goals will support the candidate’s
ultimate career goal of developing an independent research program dedicated to the use of interdisciplinary,
multidimensional, collaborative, and cutting-edge approaches to understanding the neurobiological and
developmental factors that contribute to individual differences in social behavior across the full continuum of
abilities – from healthy to disordered. The University of Virginia is committed to high caliber, collaborative
research and scientific preeminence in neuroscience, autism, and data science and will provide the ideal
environment for conducting this type of interdisciplinary, multidimensional child health-oriented project.
Terms: <0-11 years old><21+ years old><ASD><Adolescent><Adolescent Youth><Adult><Adult Human><Age><Age Months><Algorithms><Architecture><Autism><Autistic Disorder><Behavior><Behavioral><Behavioral Symptoms><Biological Markers><Brain><Brain Nervous System><Caliber><Cell Communication and Signaling><Cell Signaling><Child><Child Health><Child Youth><Children (0-21)><Classification><Clinical><Clinical Trials><Collaborations><Coupling><DNA Methylation><Data><Data Science><Data Set><Dedications><Development><Diagnosis><Diagnostic><Diagnostic Findings><Diagnostic Method><Diagnostic Procedure><Diagnostic Technique><Dimensions><Disease><Disorder><EEG><Early Infantile Autism><Early Intervention><Early identification><Electroencephalogram><Electroencephalography><Encephalon><Engineering / Architecture><Enrollment><Entropy><Environment><Epigenetic><Epigenetic Change><Epigenetic Mechanism><Epigenetic Process><Foundations><Genetic><Goals><Heterogeneity><Individual Differences><Infant><Infantile Autism><Intracellular Communication and Signaling><Kanner's Syndrome><Lead><Life><Link><Longitudinal Studies><Measures><Mentors><Modeling><Nature><Neural Development><Neurobiology><Neurocognitive><Neurosciences><Noise><Ocytocin><Outcome><Oxytocin><Oxytocin Receptor><Pathway interactions><Pb element><Play><Prediction of Response to Therapy><Predictive Analytics><Premature Infant><Receptor Gene><Recombinant Oxytocin><Research><Rest><Risk><Role><Sampling><Sensitivity and Specificity><Series><Signal Transduction><Signal Transduction Systems><Signaling><Signs and Symptoms><Social Behavior><Social Perception><Stratification><Systematics><Testing><Time><Training><Treatment outcome><Universities><Virginia><Work><adulthood><aged><ages><autism attributes><autism biomarker><autism indicator><autism marker><autism spectral disorder><autism spectrum disorder><autism spectrum disorder features><autism spectrum disorder indicator><autism spectrum disorder symptoms><autism symptomology><autism symptoms><autism-like symptoms><autism-related attributes><autistic><autistic behavior><autistic behaviour><autistic children><autistic features><autistic spectrum disorder><autistic symptoms><autistic traits><autistic-like behavior><autistic-like symptoms><behavior observation><behavioral observation><bio-markers><biologic marker><biological signal transduction><biomarker><biomarker development><biotypes><career><children on the autism spectrum><children with ASD><children with autism><children with autism spectrum disorder><cognitive ability><cognitive development><cognitive neuroscience><cognitive performance><cohort><customized therapy><customized treatment><developmental><effective intervention><enroll><epigenetic biomarker><epigenetic marker><epigenetically><epigenome><heavy metal Pb><heavy metal lead><improved outcome><individualized medicine><individualized patient treatment><individualized therapeutic strategy><individualized therapy><individualized treatment><infants born premature><infants born prematurely><juvenile><juvenile human><kids><large scale data><large scale data sets><large scale datasets><long-term study><longitudinal data set><longitudinal dataset><longitudinal outcome studies><longterm study><neural><neural network><neurobiological><neurodevelopment><neurophysiological><neurophysiology><new marker><novel biomarker><novel marker><pathway><patient specific therapies><patient specific treatment><precision medicine><precision-based medicine><predict therapeutic response><predict therapy response><premature baby><premature infant human><preterm baby><preterm infant><preterm infant human><programs><public health priorities><response biomarker><response markers><response to therapy><response to treatment><sex><social defects><social deficits><social disorders><social dysfunction><social role><sociobehavior><sociobehavioral><tailored medical treatment><tailored therapy><tailored treatment><therapeutic response><therapy prediction><therapy response><treatment planning><treatment prediction><treatment response><treatment response prediction><treatment responsiveness><unique treatment><youngster>