Altered Maturation of Spontaneous Synchronous Neural Activity in the Social Brain of New-Born Infants with Risk Factors for ASD

Background:

Specific brain regions (such as the cingulate and fusiform gyri) play a key role in social cognitive processing. Although several studies have reported altered functional connectivity within these regions in individuals with ASD, it is unknown when such atypicalities emerge. Converging evidence from animal models of ASD indicates that genetic or environmental risk factors for ASD disrupt the maturation of ‘spontaneous synchronous’ brain activity in functional networks in early postnatal life. However, no-one has examined whether synchronous activity in social brain regions (e. g. fusiform gyrus and posterior cingulate) is altered in the first few weeks of life in human infants at-risk of ASD.

Objectives:

Here, we used Regional Homogeneity (ReHo) to quantify synchronous neural activity at ‘rest’ (fMRI) in neonates with (R+) and without (R-) an established risk factor for ASD (such as a sibling with a diagnosis). We hypothesized that there would be a group difference in synchronous activity and how it changes with age in the social brain.

Methods:

High temporal resolution fMRI during natural sleep was acquired in a Philips 3T Scanner from 24 R+ and 19 R- neonates within the first 4 weeks of life [R+ median age 42.85 weeks post-menstrual age (PMA); R- median age 42.71 weeks PMA]. Data pre-processing was implemented in FSL (www.fmrib.ox.ac.uk/fsl), with non-linear spatial normalization into an age-appropriate template space (http://brain-development.org/brain-atlases/multi-structural-neonatal-brain-atlas/). The pre-selected social regions-of-interest were based on the social brain atlas (https://neurovault.org/collections/2462/) and comprised the superior temporal gyrus, the fusiform gyrus, the posterior and the anterior cingulate and the insula, defined using the same neonatal atlas that was used as a template. Voxel-wise regional homogeneity (ReHo) values were extracted using AFNI 3dReHo for 27 nearest neighbors per voxel. Unpaired t-tests with permutation testing were used to compare the interaction between age and regional homogeneity maps in the regions of interest between groups with false discovery rate (FDR) correction for multiple comparisons.

Results:

We found a main effect of group; R+ neonates had significantly higher ReHo in all regions except the fusiform and the right insula. In addition, ReHo increased with age in the R- group, but decreased with age in the R+ group in every region-of-interest apart from the fusiform. This was most prominent in the bilateral posterior cingulate and left insula cortices where the ReHo-age interaction was significant (see figure 1).

Conclusions:

Our data indicates that atypical maturation of networks which support social behaviour happens from birth in infants at risk of ASD.