Altered Anterior Insular Asymmetry in Pre-teen and Adolescent Youth with Autism Spectrum Disorder

Abstract

Autism Spectrum Disorder (ASD) is hallmarked by social-emotional reciprocity deficits. Social-emotional responding requires the clear recognition of social cues as well as the internal monitoring of emotional salience. Insular cortex is central to the salience network, and plays a key role in approach-avoidance emotional valuation. Consistent right anterior insular hypoactivity and variable volumetric differences of insular cortical volumes were shown previously. The current study analyzed anterior and posterior insular volume/asymmetry changes in ASD across age. Age was used as an additional grouping variable as previous studies indicated differential regional volume in ASD individuals before and after puberty onset. In the current sample, pre-teen ASD expressed left lateralized anterior insula, while adolescent ASD had right lateralization. Typically developing (TD) individuals expressed the opposite lateralization of anterior insula in both age-groups (right greater than left anterior insular volume among pre-teen TD and left greater than right anterior insular volume among adolescent TD). Social-emotional calibrated severity scores from the ADOS were positively correlated with leftward anterior insular asymmetry and negatively correlated with proportional right anterior insular volumes in ASD. Insular cortex has a lateralized role in autonomic nervous system regulation (parasympathetic control in the left, sympathetic control in the right). Atypical insular asymmetry in ASD may contribute to the development of networks with a diminished salience signal to human faces and voices, and may lead to more learned passive avoidant responses to such stimuli at younger ages, leading to more distressed responses in adolescence. Data here supports the use of early behavioral intervention to increase awareness of and reward for social-emotional cues.

Keywords: Asymmetry; Autism; Autonomic nervous system; Development; Insular cortex; Morphometry.

Figure 1:

Anterior Insular Asymmetry Quotient Group by Age Group Interaction. Mean AQs for anterior insular cortex by diagnostic group and age group (ASD Pre-teen (N=14), Adolescent (N=11); TD Pre-teen (N=9), Adolescent (N=8)). Positive AQs denote leftward asymmetry and negative AQs denote rightward asymmetry. There was a significant diagnosis-by-age group interaction for anterior insular AQ (F1,37=5.121, p=.029, η2=.12).

Figure 2:

ADOS Social Symptom Severity Correlation with Anterior Insula. Scatter plots of right anterior insular volume (p=.025), proportional to right hemispheric volume, and anterior insular AQ (p=.046) plotted against ADOS Social scores in ASD individuals (N=25). Positive AQs denote leftward asymmetry and negative AQs denote rightward asymmetry.