Unmasking Anxiety in Autism: Explicit and Implicit Threatening Faces Dissociate Amygdala-centered Functional Connectivity

Abstract Background: Anxiety is the most prevalent comorbidity in individuals diagnosed with autism spectrum disorder (ASD). Amygdala reactivity to explicit and implicit threat processing is predictive of anxiety-related symptomatology. The neural mechanisms underlying the link between anxiety and ASD remains elusive. Methods: In this fMRI study, we recruited young adults with ASD (N = 31) and matched them with controls, then proceeded to assess their autistic and anxiety traits by the use of the Autism-Spectrum Quotient (AQ) and the State-Trait Anxiety Inventory (STAI-S), respectively; and scanned their hemodynamic responses, including amygdala, in response to explicit and implicit (backwardly masked) perception of threatening faces. Results: As compared to controls, the amygdala reactivity in ASD subjects was significantly lower to explicit threat, but comparable for implicit threat. The correlations of the amygdala reactivity with the AQ and STAI-S were dissociated depending on threat processing (explicit or implicit). Furthermore, the amygdala in ASD relative to controls had a more negative functional connectivity with the superior parietal cortex, fusiform gyrus, and hippocampus for explicit threat, whereas a more positive connectivity with the medial prefrontal cortex, temporal pole, and hippocampus for implicit threat. Conclusion: In ASD, the transmission of socially relevant information along dorsal and ventral neural pathways centered on the amygdala is dissociated depending on explicit and implicit threat processing. This dissociation, ascribed to their failure to compromise pre-existing hyperarousal, might contribute to anxiety in ASD.