Functional Connectivity Abnormalities during Self-Referential Cognitive Processing in Autism Spectrum Conditions

Background: Individuals with autism spectrum conditions (ASC) have broad impairments in self-referential cognition (Lombardo et al., 2007, PLoS One). The underlying neural mechanism for these impairments appears to be localized in the ventral medial prefrontal cortex (vMPFC). We explored the distributed neural circuit in which vMPFC participates (via functional connectivity methods) during self-referential judgments.

Objectives: To assess functional connectivity patterns from vMPFC during self-referential judgments, in people with and without ASC.

Methods: 30 adult males (18-45 years old) with a diagnosis of Asperger Syndrome and 33 age-, sex-, and IQ-matched neurotypical adults were scanned at 3T during fMRI while making mentalizing or physical judgments about themselves or a non-close other. Functional connectivity analyses were implemented with psychophysiological interaction (PPI) analyses in SPM5.

Results: Neurotypical adults exhibited a clear pattern of functional connectivity from vMPFC during Self>Other judgments. This pattern of increased functional connectivity during self-referential judgments extended into anterior insula (AI), ventral premotor cortex (PMv), somatosensory cortex (SI/SII), and middle cingulate cortex (MCC). This functional connectivity pattern was absent among the ASC group. Group differences between Controls>ASC illuminated this absence of significant functional connectivity in the ASC group. When exploring the Self-Mentalizing>Self-Physical contrast, the ASC group showed more vMPFC functional connectivity than neurotypicals within areas associated with the default mode network, such as posterior cingulate/precuneus (PCC) and temporo-parietal junction (TPJ).

Conclusions: These results demonstrate that the underlying computations occurring during self-referential cognitive processes in ASC are severely limited in their implementation throughout the brain. Individuals with ASC do not show the normative pattern of vMPFC engagement during self-referential judgments. Futhermore, the normative functional connectivity pattern that arises from recruitment of vMPFC is absent in the ASC group. Thus, not only is processing atypical in vMPFC, but distributed neural processing across an entire neural circuit important for self-referential cognitive processes also appears to be abnormally organized. These results are also important because they highlight that normative vMPFC functioning during self-referential cognitive processing relies on the interactions between other areas associated with embodied representations such as anterior insula, somatosensory cortex, ventral premotor cortex, and middle cingulate cortex. What is most striking is that individuals with ASC do not recruit these regions in tandem with processing in vMPFC. Such an observation goes further into describing the neural mechanisms underlying the atypical organization of self-referential cognitive processes in ASC. Finally, the observation of increased vMPFC functional connectivity with the default mode network during Self-Mentalizing judgments may signal that the deficit in self-mentalizing arises from the vMPFC being unable to disengage its interactions with the default mode of functional brain organization and shift into task-specific processing for the mentalizing task at hand.