Three things to remember if you are a functional magnetic resonance imaging researcher of face processing in autism spectrum disorders.

One’s brain engages in a remarkably complex series of processes when generating its pattern of neural responses to a picture of one’s mother. fMRI studies generally explicitly or implicitly measure the neural activity related to thought processes, such as attention, appraisal, manipulation of information, associations, and judgment. However, these thought processes are extremely difficult to assess independent of behavioral correlates. The dependence on behavior can be problematic as behavioral output may not fully capture the multiple dimensions of cognitive and emotional reactivity. To more fully characterize responses to particular sets of stimuli, it seems that one needs to monitor cognitive, affective, and behavioral processes simultaneously. After years of partitioning component processes, it seems that cognitive neuroscience is now engaged in trying to “piece Humpty Dumpty together again” (1). In fMRI research of face processing in autism spectrum disorders (ASD), a host of meaningful dimensions may actually matter in interpreting results and comparing findings across studies. Examples of such dimensions are whether face stimuli are static or dynamic; contrived or naturalistic; familiar or unfamiliar; personally significant or impersonal; presented for natural viewing or guided by conspicuous attentional cueing. It would be naive to disregard these factors by assuming that all faces are similar. Although a great deal can be learned by treating faces as a unique class of objects, we cannot forget that they are also the most ubiquitous generator of human interest and motivation, feelings and responses in our daily lives. And they are proxies to our life histories of experiences with people. This is a particularly important consideration in the work with individuals with neurodevelopmental disorders such as autism, whose mind and brain have been sculpted by years of abnormal social experiences dating back to infancy. A study in this issue of Biological Psychiatry details how Pierce and Redcay (2) measured brain activity (using fMRI) while 6- to 12-year-old children with ASD and typical controls viewed pictures of faces. Face stimuli consisted of pictures of a familiar adult, a familiar child, a stranger adult and a stranger child. Given the established role of the fusiform gyrus (FG) in face recognition, their analysis focused primarily on this structure, but it also included highly interconnected areas such as amygdala and anterior and posterior cingulate. Their results revealed normal FG activity in the children with ASD when viewing a face of their mother or other children. This is in contrast to a host of studies involving older individuals with ASD which have consistently revealed hypoactivation of the FG (see 3 for a review). However, most of these studies involved the faces of strangers. Indeed, consistent with this literature, Pierce and Redcay did find FG abnormalities when the children with ASD viewed faces of strangers. These results led them to conclude that FG abnormalities in ASD may (1) be the result of reduced attention and interest; and (2) be the result of abnormal modulation of the FG by other structures (e.g., hypoactivation of the posterior cingulate, which is postulated to be involved in internally focused tasks such as autobiographical memory). Although the relatively small number of subjects involved in this study prevents us from seeing these results as conclusive, they raise a number of important questions that every fMRI researcher of face processing in ASD should consider in their studies: