ABSTRACT
Autism Spectrum Disorder (ASD) and other neurodevelopmental conditions are currently classified according to
behavioral criteria. This clinical diagnostic framework does not take into account underlying pathophysiology and
is often insufficient to predict outcomes. The long-term goal is to develop biomarkers that will help cluster
individuals with ASD and related conditions into biologically distinct groups (“biotypes”) and provide the means
to understand the underlying neural mechanisms. Developing biomarkers for use in children is particularly
important so that they can be used from the time symptoms are first recognized. Objective measurement of
sensory processing via electroencephalography (EEG) is a non-invasive and scientifically translatable method
to measure function of neural circuits. The proposed project tests the central hypothesis that EEG measures of
sensory processing predict behavioral phenotype (i.e., they are relevant to functional outcome) but also inform
the reclassification of neurodevelopmental conditions by neural circuit pathophysiology to complement
behavioral phenotype. This project uses EEG to measure sensory/neural circuit function in 3-4 year old children
with ASD (n=150), typical development (TD; n=75), and children who do not have ASD but whose caregivers
have concerns about how they process sensory information (Sensory Processing Concerns (SPC) group;
n=150). Aim 1: Determine how circuit-level brain activity, measured in response to sensory stimuli, is altered in
children with ASD vs. SPC vs. TD. Aim 2: Test if sensory EEG endophenotypes predict behavioral phenotype
(e.g., anxiety, attention, irritability, social skills) within and across groups (ASD, TD, SPC). Aim 3: Delineate
neurobiologically-informed subtypes of neural circuit activity in individuals. Rather than relying on behavioral
phenotype as the gold standard, this exploratory aim takes a data-driven approach to cluster individuals in ASD
(and potentially SPC) into biologically distinct subgroups (biotypes) defined by EEG measures of neural circuit
activity to sensory inputs. The proposed project is conceptually innovative because it uses the paradoxical co-
occurrence of sensory hyper- and hypo-reactivity within individuals as the nidus for developing biomarkers that
reflect the granular neurobiological principles underlying sensory processing and ASD. The proposed project is
technically innovative because many of the proposed EEG measures are novel or have never been used to
study ASD. The project is significant because it moves the field from developing biomarkers that reflect
behavioral understanding of ASD towards biomarkers that provide neurobiological understanding of ASD.
Ultimately, this will allow development of diagnostic and stratification biomarkers that guide biologically targeted,
personalized treatments in children with ASD and other neurodevelopmental conditions.
