Failure to engage the temporoparietal junction/posterior superior temporal sulcus predicts impaired naturalistic social cognition in schizophrenia

Abstract

Schizophrenia is associated with marked impairments in social cognition. However, the neural correlates of these deficits remain unclear. Here we use naturalistic stimuli to examine the role of the right temporoparietal junction/posterior superior temporal sulcus (TPJ-pSTS)-an integrative hub for the cortical networks pertinent to the understanding complex social situations-in social inference, a key component of social cognition, in schizophrenia. Twenty-seven schizophrenia participants and 21 healthy control subjects watched a clip of the film The Good, the Bad and the Ugly while high resolution multiband functional MRI images were collected. We used inter-subject correlation to measure the evoked activity, which we then compared to social cognition as measured by The Awareness of Social Inference Test (TASIT). We also compared between groups the TPJ-pSTS blood oxygen level-dependent activity (i) relationship with the motion content in the film; (ii) synchronization with other cortical areas involved in the viewing of the movie; and (iii) relationship with the frequency of saccades made during the movie. Activation deficits were greatest in middle TPJ (TPJm) and correlated significantly with impaired TASIT performance across groups. Follow-up analyses of the TPJ-pSTS revealed decreased synchronization with other cortical areas, decreased correlation with the motion content of the movie, and decreased correlation with the saccades made during the movie. The functional impairment of the TPJm, a hub area in the middle of the TPJ-pSTS, predicts deficits in social inference in schizophrenia participants by disrupting the integration of visual motion processing into the TPJ. This disrupted integration then affects the use of the TPJ to guide saccades during the visual scanning of the movie clip. These findings suggest that the TPJ may be a treatment target for improving deficits in a key component of social cognition in schizophrenia participants.

Keywords: attention; biological motion; functional MRI; hubs; visual scanning.

Figure 1

Greyordinate comparison of ISC reveals focal TPJ-pSTS deficits. (A and B) Right hemisphere views of healthy control (HC) (A) and schizophrenia participants (SzP) (B) ISC maps demonstrate strong engagement of occipitotemporal visual, dorsal attention, pSTS, and prefrontal areas. (C) The contrast map reveals a focal deficit that is the only cluster to survive multiple-comparisons correction. No cluster survives correction in the left hemisphere. White frame in C outlines region shown in cropped images in Figs 2 and 3.

Figure 2

Localizer task activations and region of interest definitions. (A) Activation by moving faces in static/moving emotional faces localizer. (B) Activation by motion in from motion localizer. Compared to moving emotional faces in A, pSTS subdivisions are largely not activated by non-biological motion. (C) Activation by static faces in static/moving emotional faces localizer. (D) Contrast of moving and static faces in static/moving emotional faces localizer. Purple borders for pSTS subdivisions defined on this contrast. (E) Activation by target detection during attention localizer. (F) Activation/deactivation by visual search (RSVP stream processing) during attention localizer. TPJa (green border) defined by conjunction of detection activation (E) and deactivation during visual search (F) and assigned to the ventral attention network.^, pSTG (cyan border) defined by activation focus on the posterior STG during visual search (activation similar to the motion localizer in B) and assigned to the dorsal attention network.^, (G) Activation by mentalizing localizer. Whereas activation by moving emotion faces in A covers the pSTS, activation by mentalizing is limited to the TPJ, mostly on the angular gyrus (TPJp, yellow border) but also extending to the TPJa. TPJm (red border) defined as cortical zone not included in any of the other regions of interest. (H) TPJ-pSTS subdivisions in comparison to the ‘hubs’ map from . The TPJm boundary outlines one of these hub zones. (I) Comparison of activation by moving emotional faces (purple), target detection (green), and mentalizing (yellow) within the TPJ and pSTS regions of interest. The tasks each evoke a complex pattern of activity (dotted lines mark activation significance threshold) (P < 0.05). The localizer task activations separate first between the TPJ and pSTS [TPJ-pSTS × task: F(1,70) = 9.7, P = 0.002]. Within the TPJ, there was a significant difference in activation of each region of interest by each task [region of interest × task: F(1,106): 3.9, P = 0.05]. This interaction was driven by TPJp primarily being activated by mentalization, TPJa primarily being activated by detection/reorienting, and TPJm (red box) being activated by both moving facial expressions and detection/reorienting.

Figure 3

Activation of the TPJ-pSTS subdivisions measured by ISC. (A) Healthy controls (HC). (B) Schizophrenia participants (SzP). (C) Contrast of the two groups. Focal ISC deficit falls mostly within TPJm. (D) Region of interest × region of interest group comparison of ISC in the TPJ-pSTS. In the violin plots, the envelope represents the full distribution of the data, the open circle marks the median, and the solid horizontal line the mean. *P < 0.05, **P < 0.01.

Figure 4

TPJm activation (measured by ISC) correlates with TASIT performance across both groups. Partial correlation shown after accounting for correlation of group membership with TASIT performance. SzP = schizophrenia participants.

Figure 5

Differences in TPJ synchronization with other regions of interest. (A and B) Greyordinate synchronization maps of average healthy control (HC) MT activity (seed location shown by green filled circle) demonstrating robust correlations in both populations with occipitotemporal visual, dorsal attention, pSTS, and prefrontal areas. (C) Greyordinate contrast reveals strong deficit spread across all TPJ regions of interest. (D) MT → TPJ region of interest synchronization deficits in schizophrenia participants. (E and F) Similar deficits for FFA and FEF. (G–I) Increased synchronization or decreased anticorrelation of medial and lateral prefrontal areas with the TPJ. In the violin plots, the envelope represents the full distribution of the data, the open circle marks the median, and the solid horizontal line the mean. See Supplementary Fig. 2 for greyordinate synchronization maps for areas shown in E–I. *P < 0.05, **P < 0.01, ***P < 0.001. amPFC = anteromedial prefrontal cortex; aMFG = anterior middle frontal gyrus; dACC = dorsal anterior cingulate cortex; L = left; R = right.

Figure 6

Motion and saccade frequency correlations with BOLD activity time course. (A and B) Right lateral views of motion correlation maps in healthy controls (HC) (A) and schizophrenia participants (SzP) (B) shows consistent correlations with occipital, ventral temporal, and frontoparietal areas. (C) Greyordinate contrast reveals focal deficit within TPJ. (D) Motion correlation deficits by TPJ region of interest showing strongest deficits in TPJm. (E and F) Right lateral views of saccade frequency correlation maps in healthy controls (E) and schizophrenia participants (F) demonstrates robust correlation with occipitotemporal visual, dorsal attention, pSTS, and prefrontal areas. (G) Greyordinate contrast reveals focal deficit within TPJ. (H) Saccade correlations by region of interest showing strongest deficits in TPJp. In the violin plots, the envelope represents the full distribution of the data, the open circle marks the median, and the solid horizontal line the mean. *P < 0.05, **P < 0.01.

Figure 7

Pseudo-anatomic layout (A) and schematic (B) of the interactions between networks involved in visual scanning of social scenes at the TPJ-pSTS, modified from Patel et al. In healthy controls (blue line), the TPJ-pSTS serves as a third pathway linking visual areas to the prefrontal cortex and dorsal attention areas that control attention and saccade planning/visual scanning. Information about moving facial expressions from MT and FFA converges on the pSTS. This information is conveyed to TPJp and TPJa via TPJm. These TPJ areas are modulated by prefrontal mentalization areas, such as those in mPFC, and prefrontal cognitive control (cingulo-opercular/salience) areas, such as aIns and dACC. Based on these various inputs, the TPJp determines whether additional visual scanning is needed to update the ongoing mentalization operations. If visual scanning is needed, the TPJa is activated, which then triggers saccade planning in the dorsal attention areas through prefrontal cortex. In schizophrenia participants (red line) this third pathway is disrupted in the TPJ-pSTS, preventing its use in the guidance of visual scanning of social scenes. aIns = anterior insula; dACC = dorsal anterior cingulate cortex; mPFC = medial prefrontal cortex; MT = middle temporal; PFC = prefrontal cortex.