Functional Connectivity in the Salience Network Differs Between Infants at High- and Low-Risk for ASD

Background: Autism spectrum disorders (ASD) are characterized by deficits in social communication and sensory processing. Disruptions in brain connectivity have been implicated in ASD (Geschwind & Levitt, 2007), which may result from altered prenatal neural development (Stoner et al., 2014). In particular, hyperconnectivity of the salience network (SN) has been associated with symptom severity in children with ASD (Uddin et al., 2013). The SN is involved in modulating attention to salient aspects in the internal and external environment. Social stimuli represent salient features of an infant’s environment (Johnson & Morton, 1991) and atypical attention allocation to social stimuli has been observed among infants who develop ASD (e.g., Shic, Macari, & Chawarska, 2104). This feature of ASD may stem from altered functional connectivity within the SN during infancy.

Objectives: Here we examine functional connectivity in the SN in 6-week-old infants at high- (HR) and low-risk (LR) for ASD in order to identify how early patterns of connectivity may relate to social cognitive development.  

Methods: An 8-minute rs-fcMRI scan was acquired during natural sleep in 6-week HR and LR infants on a 3T Trio Scanner. Risk status was determined by virtue of having one or more older siblings with a confirmed ASD diagnosis. The rs-fcMRI data were motion scrubbed and preprocessed using FSL. The SN was identified using the right insula region-of-interest from an infant atlas (Shi et al., 2011) as the seed. The Autism Observation Scale for Infants was administered 12 months.  

Results: HR and LR infants were matched on age (t(32) =.44, p =.65) and head motion (t(32) =.37, p = .71).Whole-brain correlation maps generated from the insula seed demonstrated that the SN was detectable in all infants (p<.05, cluster corrected). In comparison to LR infants, HR infants exhibited hyperconnectivity between the right insula and somatosensory areas; in comparison to HR infants, LR infants showed stronger connectivity between the right insula and frontal regions of the SN (p < 0.05, cluster corrected). Hyperconnectivity between the right insula and sensory cortices among HR infants was associated with the severity of early ASD symptomatology (r = -.83, p<0.001).  

Conclusions: These preliminary findings indicate that risk status is associated with significant differences in SN connectivity as early as 6 weeks of age. The right insula has been identified as the hub of the SN, which is involved in modulating attention to interoceptive and exteroceptive stimuli (e.g., Uddin & Menon, 2009). Hyperconnectivity between the right insula and somatosensory cortices in the HR group may cascade to altered developmental trajectories characterized by diminished attention to external social stimuli and increased attention to internal sensory perception (e.g., sensory over-responsivity—Green et al., 2013). Although diagnoses cannot be confirmed until 36 months, these findings suggest that disruptions in SN connectivity may provide early reliable biomarkers of ASD before observable social and cognitive symptoms are present.