Habituation to neutral faces; Language regression in ASD

The authors conducted a study designed to test the hypothesis that amygdala but not fusiform gyrus responses to neutral facial stimuli would fail to decrease from the first presentation to the second presentation in a group of adults with ASD compared with adult controls. The authors conducted the study because of previous observations of amygdala overarousal in autism in response to social stimuli. The authors used faces with neutral facial expressions because of their interpretation of the literature that the amygdala has a broader function in interpretation of socially salient features than only to detect emotional information. When the same stimulus leads to a diminished response (habituation, or increased response in the case of sensitization), it is one indication of neural plasticity and learning. Therefore, the authors proposed less habituation related to decreased plasticity in the amygdala. The important step of demonstrating equal performance in accuracy was established. There was a difference in reaction time with faster reaction time in the control group at time 1 but not time 2. This demonstrates a difference in processing efficiency independent of habituation. It is also interesting that the increase in reaction time from time 1 to time 2 was equivalent in the two groups, suggesting that the effect of increased reaction time related to decreased salience (importance or novelty) on second presentation was equivalent in the two groups. The authors found that the response to first presentation of faces was equivalent in the group with ASD compared with the adult controls. There was a reduction from the first presentation to the second presentation in both groups in fusiform fMRI activation. The most notable finding was that amygdala fMRI activation did not diminish in the adults with ASD, but did diminish (habituate) from the first to the second presentation in the adult controls. One question is why the behavioral response (reaction time, which did increase from first to second presentation) was dissociated from the amygdala response in the adults with ASD? It appears that the reaction time effect is more consistent with the finding of no difference in habituation between the groups in the fusiform gyrus fMRI response. There was a negative correlation between amygdala fMRI habituation and Autism Diagnostic Observation Schedule (ADOS) Social Domain scores, such that less habituation of amygdala fMRI response was related to greater social impairment. Discussion of a model in which early increased amygdala size and overactivation leading to excitotoxicity followed by atrophy is a speculative model in the literature with relatively little experimental support. It is equally or more likely that altered expression of key proteins involved in long-term development of the amygdala leads to altered plasticity. Another (related) possibility is that dysregulation of experience-dependent plasticity leads to an absence of full maturation of dendritic spines leading to a decreased effective size of synaptic fields. This is more consistent with neuropathological studies that did not indicate atrophy of the amygdala, but rather developmental immaturity, particularly in a reduction of dendritic arborization.