Early cognitive, social and neural mechanisms that precede clinical onset of ASD in a community sample

Over the last few years, there has been an increasing interest in the
investigation of early cognitive and neural biomarkers that precede the
clinical onset of autism spectrum disorder (ASD) to promote an earlier
detection and intervention, and thus, improved long-term outcomes. Indeed, ASD
is a neurodevelopmental disorder associated with a heterogeneous set of
deficits. For this reason, a clinical diagnosis is rarely made before three or
four years of age as the expression of ASD is subtle and not captured
consistently through behavioural measures. However, the majority of these
studies has been focusing on prospective longitudinal studies of infants at
high familial risk for ASD (HR-sibs), that is, infants who have an older
sibling with a clinical ASD diagnosis.
Prospective longitudinal HR-sibs studies have provided unique and valuable
insights regarding the early ASD phenotype. However, it remains unclear whether
these studies are representative of all children with ASD. In fact, this
population may not be representative, hampering generalization for the
estimated 89% children from community settings who cannot be identified based
on known genetic risk factors (such as having an older sibling with ASD). Thus,
it is important to determine the suitability of using HR*siblings as a
reference group for the development of ASD, as well as to further inform
possible etiologic heterogeneity. In the proposed study, we aim to investigate
the neural and cognitive correlates (through eye-tracking, EEG/ERP and
cognitive measures) in a community sample of infants at heightened non-familial
risk for ASD (HR) and in age and gender matched low-risk controls (LR).
Moreover, we aim to explore whether early social abnormalities in children
identified as high-risk from community settings (HR) are associated with
atypicalities in early cognitive and neural markers of ASD in HR-sibling
designs.

Objectives: 1) Assess neural and cognitive biomarkers (through eye-tracking,
EEG/ERP and cognitive measures) in a community sample of infants at heightened
non-familial risk for ASD and in age and gender matched low-risk controls. The
HR group is defined as at *risk* based on the display of early social
abnormalities. 2) Explore whether atypicalities in biomarkers in a community
high-risk sample are associated with atypicalities in early cognitive and
neural markers of ASD as found in familial high-risk designs. 3) Assess the ASD
diagnostic status of both groups of infants at 36 months.

A non-invasive explorative longitudinal study which will make use of
eye-tracking, electroencephalography and behavioural measures. Measures will be
taken at ages 18-24 months. At 36 months, we will determine the ASD diagnostic
status of both groups of infants with the administration of the ADOS-2.

The proposed research concerns the early cognitive and neural markers of
infants from a community sample at risk for ASD and controls. Investigating
early ASD markers has the potential of improving our understanding of
underlying mechanisms of ASD, further validating previous findings from HR-sibs
literature. The identification of early cognitive and neural markers that
precede the onset of ASD symptoms is of great scientific and clinical relevance
for an earlier intervention and, thus, improved long-term outcomes.
Autism is a developmental disorder which is characterized by its onset in early
childhood. As our aim is to identify biomarkers of early ASD, the main research
question of the current project cannot be answered by testing older children,
adolescents and adult participants. EEG and eye-tracking are techniques that do
not pose any risk to the subjects.There are no invasive measures, the risks
associated with these measurements are negligible, no adverse events are
expected, and the burden for the participants is considered to be minimal. The
research team has extensive experience with high-risk and control infants of
similar or even younger age, and thus, has ample experience working with
infants and training researchers. Moreover, this means that the our age group
is relatively easily accessible by our research team, since recruitment is
supported by the SCOPE project (NL65479.091.18) and the Well-Baby Offices for
the high-risk children and by the Baby & Child Research Center (Radboud
University, Nijmegen) for the low-risk children. Our study will require a visit
to the Donders Center for Cognitive Neuroimaging (DCCN) with a time investment
of about 2 to hours, including breaks in between, and another visit at 36
months for assessing diagnostic outcome.