Aberrant Cerebellar-Cerebro Functional Connectivity in Children and Adolescents with Autism Spectrum Disorder

Background:

The cerebellum is one of the brain regions most consistently reported to have neuropathological findings in patients with autism spectrum disorder (ASD). Previous resting state functional connectivity (rsFC) studies in healthy adults have reported that the cerebellum forms widespread functional networks with the cerebral cortices and contributes to various cognitive functions (Buckner et al., 2011). However, studies on cerebellar-cerebro rsFCs in patients with ASD were very sparse.

Objectives:

Aim of this study was to investigate cerebellar-cerebro FC in children and adolescents with ASD using resting state functional magnetic resonance imaging (MRI) and to know whether its abnormalities are related to executive and socio-communicative deficits in children and adolescents with ASD.

Methods:

Echo planar imaging functional volume and T₁-weighted images of 16 subjects with ASD (all males; age: 11.1 ± 2.0 years) and 20 typically developing (TD) subjects (all males; age: 10.5 ± 2.5 years) were acquired on a 3 tesla MRI scanner. Furthermore, we added 130 male subjects extracted from the Autism Brain Imaging Data Exchange (ABIDE) II (ASD = 42, age: 10.7 ± 1.8 years; TD = 88, age: 10.3 ± 1.7 years). Final sample included 58 subjects with ASD (all males; mean age: 10.8 ± 1.9 years) and 108 TD subjects (all males; mean age: 10.3 ± 1.8 years). Seed-based rsFC analysis was performed using the CONN toolbox (http://www.nitrc.Org/projects/conn/). Cerebellar ROIs were created using the probabilistic MR Atlas of the human cerebellum (Diedrichsen, 2009). Group differences in FCs were examined using two sample t-tests, covarying for full-scale intelligence quotient (FSIQ) and mean frame wise displacement (FD) scores, and imaging sites. Correlation analyses were performed between FC values showing significant group differences and scores in the Social Responsiveness Scale (SRS), the Behavior Rating Inventory of Executive Function (BRIEF), and the Autism Diagnostic Observation Schedule (ADOS) in the ASD group.

Results:

The ASD group showed aberrant cerebellar-cerebro FCs relative to TD children. Findings of aberrant FCs with the cerebral regions converged mainly on the posterior lateral hemisphere and vermis of the cerebellum. The increased FCs between several posterior cerebellar subregions and left insula, left middle frontal gyrus, and right supramarginal gyrus were found. In addition, the decreased FCs between right dentate nucleus and several cerebral regions were found. In the ASD group, connectivity between right Crus II and left insula was negatively related to the Global Executive Composite (GEC) score in the BRIEF (r = −0.408, p = 0.002) and connectivity between vermis X and left angular gyrus was positively related to the total score in the ADOS-G (r = 0.408, p = 0.034) .

Conclusions:

Findings of aberrant FCs converged mainly on the posterior lateral hemisphere, the right dentate nucleus, and the posterior inferior vermis of the cerebellum. These results were consistent with those of previous studies reporting structural and neuropathological abnormalities in the cerebellum (D'Mello et al., 2015; Riva et al., 2013; Wegiel et al., 2014). Our findings may help to provide effective therapeutic interventions in children and adolescents with ASD.