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Principal Investigator: Lauren Kupis
Organization: UNIVERSITY OF CALIFORNIA LOS ANGELES
Fiscal Year: 2024
Award: $40,967
Funding agency: National Institute of Mental Health
Abstract
Autism spectrum disorder (ASD) affects one in 44 children.
1 Early diagnosis is critical for optimizing
outcomes, yet children are not typically diagnosed until 4 years of age.2 In concert with early behavioral signs,
early neural markers could identify toddlers at risk of developing ASD to aid earlier diagnosis and targeted
interventions. Neuroimaging studies have primarily examined structural brain abnormalities in toddlers at high
risk of developing ASD3. A growing body of work provides evidence for functional brain network connectivity
alterations in older children with ASD (7-12 years of age).4 While innovative dynamic functional magnetic
resonance imaging (fMRI) methods reveal candidate brain networks of dysfunction underlying the heterogeneity
of the disorder and symptom severity in older children with ASD,567,8no study to date has evaluated the relationship
between brain network dynamics and behavioral outcomes in toddlers with ASD. Restricted and repetitive
behaviors (RRBs), core symptoms of ASD,9 are particularly understudied. The goal of this project is to identify
early functional brain biomarkers of ASD and brain-behavior relationships with RRB outcomes across mixed
clinical and typically developing (TD) groups. This study will utilize a dataset previously collected by the UCSD
ACE Center comprised of toddlers (12-36 months, n = 231) who were identified as either TD or at-risk for a
developmental disability using an early screening form (Communication and Symbolic Behavior Scales
Developmental Profile; CSBS-DP).10Some toddlers were later diagnosed with ASD (n = 89), TD (n = 70), other
diagnosis (n = 72; Language Delay, Developmental Delay, and Autism Features). Since the sample includes
multiple diagnostic groups, this dataset offers a unique opportunity to examine early brain biomarkers for ASD
and RRBs across diagnostic categories, as envisioned by the Research Domain Criteria (RDoC) approach.11
Early behavioral indicators alone do not always clearly indicate which children will go onto to develop ASD.12 The
results from this study may lead to the development of reliable biomarkers to identify children at risk for ASD in
concert with overt behavioral signs of the disorder. Neural biomarkers of ASD and RRBs will in turn lead to earlier
and more efficient diagnosis and treatments. This work builds upon the applicant’s previous research experience
at the UCSD ACE Center collecting neuroimaging data from toddlers.13 The applicant has previously examined
dynamic brain biomarkers of RRB symptoms in older children with ASD (8-12 yo),7,14–16 reviewed the brain
biomarker literature in toddlers with ASD,3analyzed large lifespan neuroimaging datasets (n = 601), and gained
a foundation in statistics and clinical neuroscience. Through formal coursework and individual meetings, the
applicant plans to engage in four major areas of training: (1) cutting-edge analyses to assess brain dynamics
using functional neuroimaging data, (2) sophisticated statistical approaches for modelling longitudinal data, (3)
considerations for conducting research with young children at risk for autism, and (4) career development.
Terms: <0-11 years old><12 year old><12 years of age><4 year old><4 years of age><ASD><Affect><Area><Autism><Autism Diagnosis><Autistic Disorder><Behavior><Behavioral><Biological><Biological Markers><Brain><Brain Nervous System><Care Givers><Caregivers><Categories><Child><Child Development Disorders><Child Youth><Children (0-21)><Clinical><Cognition><Cognitive><Communication><Data><Data Analyses><Data Analysis><Data Set><Development><Developmental Delay><Developmental Delay Disorders><Developmental Disabilities><Diagnosis><Diagnostic><Dimensions><Disease><Disorder><Distress><Early Diagnosis><Early Infantile Autism><Early identification><Encephalon><Family><Foundations><Functional MRI><Functional Magnetic Resonance Imaging><Goals><Heterogeneity><Impairment><Individual><Infantile Autism><Intervention><Intervention Strategies><Kanner's Syndrome><Language Delays><Lateral><Learning><Life><Literature><Machine Learning><Maps><Measures><Medial><Methods><Modeling><Neurosciences><Outcome><RDoC><Reporting><Research><Research Domain Criteria><Research Methodology><Research Methods><Rest><Risk><Sampling><Seminal><Severities><Sleep><Social Adjustment><Social Development><Specific Child Development Disorders><Symptoms><Techniques><Testing><Time><Toddler><Training><Work><age 12 years><age 4 years><autism attributes><autism biomarker><autism diagnostic observation schedule><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 children><autistic features><autistic spectrum disorder><autistic symptoms><autistic traits><autistic-like symptoms><behavior outcome><behavior prediction><behavioral outcome><behavioral prediction><bio-markers><biologic><biologic marker><biomarker><brain abnormalities><brain based><brain behavior><career><career development><children on the autism spectrum><children with ASD><children with autism><children with autism spectrum disorder><cognitive development><critical period><daily functioning><data interpretation><developmental><early detection><early screening><experience><fMRI><flexibility><flexible><four year old><four years of age><high risk><image-based method><imaging method><imaging modality><improved><innovate><innovation><innovative><interventional strategy><kids><life span><lifespan><machine based learning><meeting><meetings><network dysfunction><neural><neural correlate><neural imaging><neuro-imaging><neuroimaging><neurological imaging><novel><prospective><psychologic><psychological><repetitive behavior><research and methods><skills><social adaptation><social communication><statistics><targeted drug therapy><targeted drug treatments><targeted therapeutic><targeted therapeutic agents><targeted therapy><targeted treatment><twelve year old><twelve years of age><youngster>