31778
Atypical Cortico-Cerebellar Connectivity in Newborn Infants at Risk of Developing ASD
While atypical functional connectivity in resting state networks has been widely reported in adults with ASD, little attention has been directed to functional activity in the cerebellum, which communicates with somatosensory, executive control network and salience networks (Habas, 2009). Discrepancies in the limited cortico-cerebellar connectivity studies in adults further call for a better understanding of possible atypical developmental of cortico-cerebellar connectivity (Crippa, 2016). Furthermore, adults with social anxiety disorder show decreased functional connectivity between the cerebellum and the executive control network (Yuan 2017), suggesting cortico-cerebellar connectivity might be involved in atypical social behavior observed in ASD.
Objectives:
Here, we used Regional Homogeneity (ReHo) and seed based correlation analysis to quantify functional connectivity in the cerebellum and the cortico-cerebellar connectivity at ‘rest’ (fMRI) in neonates with (R+) and without (R-) an established risk factor for ASD. We hypothesized that there would be a group difference on the maturation of intra-cerebellar and cortico-cerebellar functional connectivity.
Methods:
High temporal resolution fMRI during natural sleep was acquired in a Philips 3T Scanner from 18 R+ and 18 R- neonates within the first 4 weeks of life [R+ mean age 42.68 weeks post-menstrual age (PMA); R- mean age 42.24 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/). Voxel-wise regional homogeneity (ReHo) values were extracted using AFNI 3dReHo for 27 nearest neighbors per voxel. Unpaired t-tests with permutation testing was used to compare the interaction between age and regional homogeneity maps in the cerebellum between groups with false discovery rate (FDR) correction for multiple comparisons. Next, we calculated the correlation between the mean timeseries of the cerebellum with each cortical voxel for each subject and z-transformed it. The same permutation analysis applied for ReHo was used to compare the cortico-cerebellar z-maps between groups.
Results:
We found an interaction effect of ReHo and age in the cerebellum: ReHo increased with age in the R- group, but it did not in the R+ group (Figure 1). While strongest connectivity with the cerebellum was observed in the somatosensory motor regions, significant differences between groups were observed in the superior parietal and dorsolateral prefrontal cortex in the left hemisphere. R+ had higher functional connectivity between the cerebellum and regions involved in executive control network (Figure 2).
Conclusions:
Our results show infants at risk of developing ASD might be born with and proceed with an atypical maturation of cortico-cerebellar connectivity. Atypical connectivity might be particularly vulnerable in networks that have been previously associated to social anxiety.