Amelioration of social impairments in autism: Possible role of vagal afferent stimulation in modification of the prefrontal-amygdala connectivity

Impairment in social interactions is a prominent feature of autism spectrum disorder (ASD). The present hypothesis explains the possible role of vagal afferent stimulation in the modification of prefrontal-amygdala connectivity in the amelioration of social impairments in ASD. Currently, there is no definitive treatment for ASD. However, there is documented evidence showing that interventions that increase vagal tone lead to the improvement of autism-related social symptoms. However, the exact mechanism that explains the correlation between the elevation of vagal tone and the amelioration of autism-related symptoms has not been elucidated. In the present hypothesis, it is proposed that the increase in vagal tone affects the nucleus tractus solitarius (NTS) in the brainstem. The NTS has strong connections with other brainstem nuclei, such as the locus coeruleus and dorsal raphe nucleus. The aforementioned nuclei are the main sources of norepinephrine and serotonin, with extensive projections to various brain areas, especially the prefrontal cortex (PFC) and amygdala. PFC-amygdala functional connectivity plays an important role in social behavior and emotion regulation. Therefore, visceral stimulation, which subsequently increases the vagal tone, possibly leads to the improvement of autistic social deficits through the enhancement of PFC-amygdala functional connectivity. Further investigations are needed to evaluate the function of the mentioned neural pathways during visceral stimulation in individuals with ASD.