摘要
Autism is a neurodevelopmental disorder in which affected individuals exhibit atypical behaviors in social interaction and communication, and have restricted or stereotyped patterns of behaviors (Baron-Cohen & Belmonte, 2005; Behrmann, Thomas, & Humphreys, 2006; Frith & Happe, 2005). Consistent with the fact that multiple cognitive and affective behaviors are implicated in autism (Williams, Goldstein, & Minshew, 2006), neuroanatomical studies have reported widespread changes in cerebral grey and white matter in, among other regions, the amygdala, hippocampus, caudate nucleus and cerebellum (Amaral, Schumann, & Nordahl, 2008; Bachevalier & Loveland, 2006; Belmonte, et al., 2004; Herbert, 2005; Herbert, et al., 2004; McAlonan, et al., 2005). Additionally, recent neuroimaging studies have revealed disruptions in the structural and functional connectivity within and between cortical regions in individuals with autism during the execution of predefined tasks as well as during resting state conditions (Barnea-Goraly, et al., 2004; Hrdlicka, 2008; Kennedy, Redcay, & Courchesne, 2006; Kleinhans, et al., 2008; Vandenbroucke, Scholte, Engeland, Lamme, & Kemner, 2008). What remains unknown is how these neural disruptions manifest under real-life circumstances, and to what extent they have functional consequences for the individual's behavioral and cognitive profile.
To characterize the cortical response under conditions approximating real-life circumstances, we used fMRI to map the whole-brain activation profile in adults with autism during free-viewing of an engaging movie and we compared this profile to that evinced by typical participants. The carefully orchestrated audio-visual movie sequence is well-suited for driving reliable activation simultaneously in multiple brain areas (Hanson, Gagliardi, & Hanson, 2008; Hasson, Furman, Clark, Dudai, & Davachi, 2008; Hasson, Nir, Levy, Fuhrmann, & Malach, 2004; Hasson, Yang, Vallines, Heeger, & Rubin, 2008a; Jaaskelainen, et al., 2008; Wilson, Molnar-Szakacs, & Iacoboni, 2008). The data were analyzed by comparing the evoked fMRI response time courses across different subjects (inter-subject correlation, henceforth inter-SC; (Hasson, et al., 2004), and by comparing response time courses elicited by repeated presentations of the same stimulus within the same individual (intra-subject correlation, henceforth intra-SC; (Golland, et al., 2007). Computing the inter-SC within the typical individuals (typical-typical), on a voxel-by-voxel basis, quantifies the reliability of the response time courses in each brain area in the typical group. Using this analysis, we demonstrated that, across typical observers, approximately 30%–65% of the cerebrum evinces similar shared response time courses under free viewing of complex naturalistic stimuli (Hasson, Furman, et al., 2008; Hasson, et al., 2004; Hasson, Yang, Vallines, Heeger, & Rubin, 2008b). Moreover, these reliable responses, although widespread, are nonetheless selective (i.e., the response time courses differ from one brain area to another; (Hasson, Malach, & Heeger, submitted).
Here, we compare the cortical responses of individuals with autism against this typical response benchmark. Computing the inter-SC between the typical and the autism groups (typical-autism) provides a measure of similarity in the functional response in each brain area across the two groups. Low inter-SC between the typical-autism groups in conjunction with high inter-SC within the typical group would indicate that the response time course in a given brain area is markedly different in individuals with autism. Moreover, high inter-SC within the autism group (autism-autism) in conjunction with low inter-SC between the typical-autism groups can identify reliable response time courses, which are unique to the autism group and are not observed in the typical subjects. Finally, computing the intra-SC within each autistic individual across repeated presentations can reveal the unique set of response time courses, which, although possibly variable across the group, are nonetheless reliable within an individual. Critically, this type of functional analysis does not make any a priori assumptions about affected regions. Rather, the within- and between-groups inter-SC and within-individual intra-SC analyses permit an unbiased exploration of the entire cortex in the quest for differences in the patterns of brain responses between members of the two groups.