Schizophrenia and autism as contrasting minds: neural evidence for the hypo-hyper-intentionality hypothesis

Abstract

Both schizophrenia (SCZ) and autism spectrum disorder (ASD) are characterized by mentalizing problems and associated neural dysfunction of the social brain. However, the deficits in mental state attribution are somehow opposed: Whereas patients with SCZ tend to over-attribute intentions to agents and physical events ("hyper-intentionality"), patients with autism treat people as devoid of intentions ("hypo-intentionality"). Here we aimed to investigate whether this hypo-hyper-intentionality hypothesis can be supported by neural evidence during a mentalizing task. Using functional magnetic resonance imaging (fMRI), we investigated the neural responses and functional connectivity during reading others intention. Scanning was performed in 23 individuals with ASD, 18 with paranoid SCZ and 23 gender and IQ matched control subjects. Both clinical groups showed reduced brain activation compared to controls for the contrast intentional vs physical information processing in left posterior superior temporal sulcus (pSTS) and ventral medial prefrontal cortex (vMPFC) for SCZ, and right pSTS in ASD. As predicted, these effects were caused in a group specific way: Relative increased activation for physical information processing in SCZ that was also correlated with positive PANNS score and relative decreased activation for intentional information processing in ASD. Additionally, we could demonstrate opposed connectivity patterns between the right pSTS and vMPFC in the clinical groups, ie, increased for SCZ, decreased for ASD. These findings represent opposed neural signatures in key regions of the social brain as predicted by the hyper-hypo-intentionality hypothesis.

Keywords: MPFC; autism; intention; mentalising; pSTS; schizophrenia.

Fig. 1.

A schematic illustration of predicted neural signatures for the hyper-hypo-intentionality hypothesis. The plots represent a priori predicted patterns of activations in mind-reading relevant regions according to the hypo-hyper-intentionality thesis. For TD we predict increased significant activation for the intention condition compared to the control condition. For both patient groups we predict opposed dysfunctional activations: Relatively reduced activation for the intention condition in ASD (hypo-intentional) and relatively increased activation for the control condition in SCZ (hyper-intentional).

Fig. 2.

Interaction of mentalizing (CInt>PhC) for TD>SCZ (A), TD>ASD (B), and ASD>SCZ (C). (A) Bar plots indicate effect sizes at the peak voxel in MPFC and left pSTS for all conditions in TD and SCZ. The amount of MPFC activation for PhC in the SCZ correlated positively with the total positive PANSS score (r = 0.73, P = .001). (B) Bar plots indicate effect sizes at the peak voxel in right pSTS for all conditions in TD and ASD. (C) Bar plots indicate effect sizes at the peak voxel in dMPFC for all conditions in ASD and SCZ. ROI analysis P < .05 FWE corrected (k > 15). Dashed rectangles indicate the beta parameters for PhC and CInt. Blue: TD; Red: ASD; and Green: SCZ.

Fig. 3.

Group × connectivity interaction. Connectivity was calculated using the right pSTS as a seed region (ANOVA second-level for CInt>PhC, P = .001 uncorrected, k > 15). (A) Group differences in connectivity strength for TD (blue) versus SCZ (green) for PhC. (B) Group differences in connectivity strength between TD (blue) vs ASD (red) for CInt.