The Neural Correlates of Emotional Lability in Children with Autism Spectrum Disorder

Abstract

Autism spectrum disorder (ASD) is exceptionally heterogeneous in both clinical and physiopathological presentations. Clinical variability applies to ASD-specific symptoms and frequent comorbid psychopathology such as emotional lability (EL). To date, the physiopathological underpinnings of the co-occurrence of EL and ASD are unknown. As a first step, we examined within-ASD inter-individual variability of EL and its neuronal correlates using resting-state functional magnetic resonance imaging (R-fMRI). We analyzed R-fMRI data from 58 children diagnosed with ASD (5-12 years) in relation to the Conners' Parent Rating Scale EL index. We performed both an a priori amygdala region-of-interest (ROI) analysis, and a multivariate unbiased whole-brain data-driven approach. While no significant brain-behavior relationships were identified regarding amygdala intrinsic functional connectivity (iFC), multivariate whole-brain analyses revealed an extended functional circuitry centered on two regions: middle frontal gyrus (MFG) and posterior insula (PI). Follow-up parametric and nonparametric ROI-analyses of these regions revealed relationships between EL and MFG- and PI-iFC with default, salience, and visual networks suggesting that higher-order cognitive and somatosensory processes are critical for emotion regulation in ASD. We did not detect evidence of amygdala iFC underpinning EL in ASD. However, exploratory whole-brain analyses identified large-scale networks that have been previously reported abnormal in ASD. Future studies should consider EL as a potential source of neuronal heterogeneity in ASD and focus on multinetwork interactions.

Keywords: CWAS; autism; emotion dysregulation; emotional lability.

FIG. 1.

Parametric and nonparametric analyses surface maps show regions whose iFC with middle frontal gyrus (a) and posterior insula (b) significantly correlated with parent-rated EL in children with ASD. Clusters whose iFC positively correlated with EL are shown in red, and those negatively correlated are shown in blue. Results from parametric and nonparametric statistical analyses are shown in the top and the bottom panel, respectively. ASD, autism spectrum disorder; EL, emotional lability; iFC, intrinsic functional connectivity. Color images available online at www.liebertpub.com/brain