Amygdala Connectivity with Frontal Mirror Neuron Areas Relates to Empathic Traits In Typically Developing Children and Children with Autism

Background: Deficits in emotional processing and empathy have commonly been observed in individuals with Autism Spectrum Disorders (ASD). The amygdala plays a central role in emotional processing and many studies have reported altered amygdala structure and function in ASD. The mirror neuron system (MNS) is believed to be connected to the amygdala via the anterior insula, allowing for an intuitive understanding of others emotions (Carr et al., 2003). In fact, empathic behavior has been related to activity in both amygdala and MNS while processing emotional (Pfeifer et al., 2008) and non-emotional facial stimuli (Schulte-Ruther et al. 2007). Both altered amygdala and MNS activity (Dapretto et al, 2006), as well as functional connectivity (Rudie et al., under review), have previously been reported in children and adolescents with ASD during an emotional facial processing task.

Objectives: Here we sought to examine how the degree of functional connectivity between amygdala and MNS areas might be related to individual differences in empathic behavior in both typically-developing (TD) and ASD children and adolescents.

Methods: Seventeen children with ASD and 23 TD children (matched by age, gender, IQ and head motion) passively observed faces displaying different emotions (angry, fearful, happy, sad, and neutral) while undergoing functional Magnetic Resonance Imaging (fMRI). Using a jittered event-related design, faces were presented every 3 seconds according to an optimized random sequence, with each face being displayed for 2 sec. Each subject filled out the Interpersonal Reactivity Index (IRI), a multidimensional measure of empathy. The amygdala, as defined from the Harvard-Oxford probabilistic atlas (25% probability), was used as a seed region in a whole brain functional connectivity analysis. Covarying for age and IQ, scores from the IRI (total and subscales) were then used in multiple regression analyses using the amygdala connectivity maps.

Results: A significant relationship between amygdala-MNS connectivity and empathic behavior was observed for the empathic concern subscale, irrespective of diagnosis (z > 2.3, corrected for multiple comparisons at the cluster level). Specifically, individuals who rated themselves as having higher empathic concern, as measured by the IRI, displayed stronger connectivity between the amygdala and the right pars opercularis. This relationship was evident in both TD and ASD groups.

Conclusions: The present findings are consistent with a simulation model of affective empathy (Carr et al., 2003) whereby mirror neurons simulate the observed facial expressions and send signals to limbic areas, evoking neural activity that allows the observer to feel what others are feeling. Although empathic behavior, as well as MNS activity and connectivity, have been shown to be reduced in ASD as compared to neurotypical individuals, our findings indicate that the degree of coupling between limbic and MNS circuitry predict individual differences in empathic behavior in both typical and atypical development.