It is important to understand the neural mechanisms underlying the link of anxiety and amygdala dysfunction in ASD. Here, we combined explicit and implicit (backwardly masked) perception of fearful faces to elicit amygdala reactivity in controls and participants with ASD, who varied in autistic trait and self-reported anxiety. The results showed that, as compared to the controls, amygdala reactivity was significantly lower towards explicit fear, but was comparable to implicit fear in ASD. The correlations of amygdala reactivity with the AQ and STAI-S were dissociated between explicit and implicit fear. Furthermore, in ASD relative to controls, the amygdala exhibited an aberrant and more negative functional connectivity with the superior parietal cortex, fusiform gyrus, and hippocampus in explicit fear, whereas a more positive connectivity with the medial prefrontal cortex, temporal pole, and hippocampus during implicit fear. On one hand, the existing over-reactivity to neutral faces, along with stronger negative couplings in both dorsal and ventral neural pathways during explicit threat, may explain why the failure to compensate the preexisting hyperarousal –even with the extra cost of energy consumption– in ASD would lead to a higher level of anxiety and more severe autistic traits . On the other hand, during implicit threat, the stronger positive connectivity along the ventral neural pathways indicates consciousness-dependent transmission of socially relevant information in ASD [26, 37].
ASD shows weaker amygdala reactivity towards explicit fear, although its activity appears to be comparable to the controls during implicit fear. One preliminary study in adults with ASD uncovered heightened amygdala activation, but this research was limited to a backward masking paradigm with subthreshold presentations of fearful faces . The present findings extend the existing scientific literature by demonstrating a significant dissociation dependent on explicit and implicit threat. Such a dissociation appears parallel to the empathy imbalance hypothesis of autism in regards to the surplus of emotional empathy in people with ASD . Compelling evidence concerning this excess in emotional empathy characteristic of autism comes from self-report questionnaires, facial electromyography, and event-related potentials. As shown by the Interpersonal Reactivity Index, which includes items designed to tap each facet of empathy, people with Asperger syndrome scored significantly higher than the controls on the personal distress scale . These findings indicate that people with Asperger's syndrome might have a tendency to be anxious, and that this may contribute to a particular susceptibility towards empathic overarousal. As indicated by facial electromyography, which measures automatic mimicry of subtle emotional responses, youths with ASD showed significantly heightened electromyographic responsiveness when being presented with pictures of happy and fearful faces, and instructed to judge the gender of each face . This result contrasts with those of another study that found deficits in the automatic mimicry of emotional faces . The crucial difference between the two studies lies on whether the subjects were set to an active task requiring careful attention to the faces or not. Deficits in eye contact, as indicated by aberrant visual attention, have been a hallmark of autism . In parallel, as shown by the event-related potentials for pain empathy, an early automatic component (N2) indexing empathic arousal, was heightened in individuals with ASD . These findings are consistent with the hypothesis that the underlying capacity for emotional empathy in autism is not just intact, but excessive. People with autism may not actively attend to socioemotional information in order to minimize empathic hyperarousal.
The correlation between AQ and amygdala reactivity is dissociated, as it is dependent on whether threat is explicit or implicit. Among the variety of screening tools developed to quantify autistic traits, the most commonly used is probably the Autism-Spectrum Quotient (AQ). The AQ has been used to screen clinical samples  and to predict performance on cognitive tasks , social cognition , facial mimicry , gaze preference to social stimuli , and speech perception . In the same line, more severe autistic traits, as assessed by the AQ, were coupled with weaker mismatch negativity (MMN) . Not until recently was the MMN, a component of the event-related potentials to an odd stimulus in a sequence of stimuli, utilized as an index for pre-attentive salience detection of emotional voice processing [50–52]. The unexpected presence of emotional spoken syllables embedded in a passive oddball paradigm were able to activate the amygdala, which was associated with individual differences in social orientation . The amygdala reactivity to explicit and implicit fearful faces exhibited opposite associations with MMN . Thus, it is no surprise to see a dissociation regarding the coupling between AQ and amygdala reactivity dependent on explicit and implicit threat.
The amygdala-centered functional connectivity between explicit and implicit threat is dissociated in ASD. Although many studies have reported that individuals with ASD have atypical brain connectivity patterns, the results of more recent studies do not support unanimously the traditional view where individuals with ASD are described as having lower connectivity between distal brain regions and increased connectivity within proximal brain regions . For instance, literature reviews observed a general trend supporting the hypothesis of long-range functional under-connectivity, however, the status of local connectivity remains unclear . Thus, further investigations of connectivity with respect to behavior are needed to probe the underlying brain networks implicated in core deficits of ASD. In the same vein, thalamocortical disconnectivity could account for sensorimotor symptoms in ASD . Restricted interest and repetitive behaviors could be determined via inter- and intra-hemispheric functional disconnectivity . Here, this study reidentifies the dorsal and ventral networks as showing shared activity, and more importantly, demonstrates the existence of attention dissociated amygdala-centered pathways, towards threat [58, 59]. ASD showed significantly stronger negative signal couplings in both dorsal and ventral neural pathways during explicit threat processing whereas stronger positive correlation along the ventral neural pathways during implicit threat processing.
Some limitation of this study must be acknowledged. First, regarding sample homogeneity, the generalizability of the results may be limited because people with low-functioning ASD were not included. Second, the relatively wide age range of subjects here might interact with developmental brain changes. Accordingly, based on the same theorems as previous work , we have conducted the imaging processing with DARTEL, as well as the correlation analysis with age and the inclusion of age as a covariate of no interest, as well as DARTEL corrections. This may not be the optimal design, and future studies are warranted with a larger sample size.