Theory of Mind: The Importance of the Right Connections

Background: Evidence from post mortem and neuroimaging studies suggests that autism spectrum disorder (ASD) may be a disorder of connectivity (e.g. Bailey et al., 1998; Courchesne & Pierce, 2005; Just et al., 2004). The potential impact of disordered connectivity on cognitive function is yet to be fully established. In typically developing (TD) individuals, several brain regions have been associated with Theory of Mind (ToM), including the medial prefrontal cortex, temporoparietal junction, and superior temporal regions. It has been suggested that these distinct regions may comprise a ToM network. ToM is a core deficit of ASD (e.g. Baron-Cohen et al., 1985; Perner et al., 1991) and functional neuroimaging studies have indicated abnormal activity within (Happé et al., 1996; Baron-Cohen et al., 1999) and functional connectivity between (Castelli et al., 2002) areas typically associated with ToM. Furthermore, diffusion tensor imaging has revealed abnormalities in the connective white matter tissue between ToM regions in ASD (Barnea-Goraley et al., 2004).

Objectives: 1) to investigate the ToM network in TD individuals; 2) to determine whether disruption to connections between network components might contribute to the ToM deficit in ASD. 

Methods: Behavioural and functional MRI data from eighteen males with ASD and eighteen TD males are reported. ToM was assessed using a comic strip paradigm based on the task devised by Sarfati et al. (1997). DTI data were acquired and tract-based spatial statistics conducted on measures of fractional anisotropy (FA) to assess white matter (WM) integrity.

Results: The pattern of activity evoked by ToM comics in TD individuals is largely consistent with results from previous studies. Moreover, the same comics evoked a different pattern of activity in individuals with ASD, particularly in medial prefrontal regions. Analysis of the diffusion data revealed several regions of altered white matter integrity (FA) in the individuals with ASD. Interestingly, there is evidence of both increased and decreased FA relative to the TD group.

Conclusions: The pattern of activity evoked by the ToM cartoons in TD is consistent with previous evidence that several distinct brain regions are involved in ToM. Furthermore, the different pattern of activity in ASD suggests that there may be differences in the way that this network is organised and functions in ASD. The potential relationship between altered FA and anomalous ToM-related activity in ASD will be discussed.