Bartel, L. P. | bioRxiv Science

bioRxiv2021

The road not taken: disconnection of a human-unique cortical pathway in schizophrenia and its effects on naturalistic social cognition

BackgroundEfficient processing of complex and dynamic social scenes relies on intact connectivity of many underlying cortical areas and networks, but how connectivity deficits affect this functioning in social cognition remains unknown. Here we measure these relationships using functionally based localization of social cognition areas, resting-state functional connectivity, and movie-watching data. MethodsIn 42 schizophrenia participants (SzP) and 41 healthy controls (HC), we measured the functional connectivity of areas localized by face-emotion processing, theory-of-mind, and attention tasks. We quantified the weighted shortest path length between visual and medial prefrontal theory-of-mind areas in both populations to assess the impact of functional connectivity deficits on network structure. We then correlated connectivity along the shortest path in each group with movie-evoked activity in a key node of the theory-of-mind network (TPJp). ResultsSzP had pronounced connectivity deficits in temporoparietal junction/posterior superior temporal sulcus (TPJ-pSTS) areas involved in face-emotion processing (t(81)=4.4, p=0.00002). In HC the shortest path connecting visual and medial prefrontal theory-of-mind areas passed through TPJ-pSTS, whereas in SzP the shortest path passed through prefrontal cortex (PFC). While movie-evoked TPJp activity correlated with connectivity along the TPJ-pSTS pathway in both groups (r=0.43, p=0.002), it additionally correlated with connectivity along the PFC pathway only in SzP (rSzP=0.56, p=0.003). ConclusionsConnectivity along the human-unique TPJ-pSTS pathway affects both the network architecture and functioning of areas involved in processing complex dynamic social scenes. These results demonstrate how focal deficits can have widespread impacts across cortex.

neuroscience↗

bioRxiv2019

Failure to engage the TPJ-pSTS during naturalistic scene processing in schizophrenia

The ability to search for and detect social cues, such as facial expressions of emotion, is critical to the understanding of complex dynamic social situations. This ability involves the coordinated actions of multiple cognitive domains, including face-emotion processing, mentalization, and visual attention. Individuals with schizophrenia are generally impaired in social cognition, and have been shown to have deficits in all of these domains. However, the whether the neural substrates of these impairments are shared or separate remains unclear. One candidate region for a shared substrate is the right temporoparietal junction/posterior superior temporal sulcus (TPJ-pSTS), which contains areas belonging to all of the cortical networks underlying these domains. Here we use functional MRI to examine differences in cortical activity evoked by a naturalistic movie, and link these results to impaired visual scanning and social cognition. 27 schizophrenia participants and 21 healthy controls watched a 15-minute clip of the movie \"The Good, the Bad, and the Ugly\" while high resolution multiband BOLD-fMRI activity was recorded. Inter-subject correlation was used to measure the evoked activity. BOLD-fMRI activity was also correlated with motion content in the movie, with the average activity in other cortical areas, and with frequency of saccades made during the movie. Visual scanning performance was measured in a separate behavioral experiment, and social cognition measured by The Awareness of Social Inference Test (TASIT). Contrasting the groups revealed that the TPJ-pSTS has the largest engagement deficit in both cortical hemispheres in schizophrenia patients versus healthy controls. Follow-up analyses find that brain activity in this region is less correlated with the motion content of the movie, that this region is abnormally synchronized to the other cortical areas involved in the cognitive domains underlying visual scanning of social scenes, and that activity this region is less correlated with the saccades made during the movie. Lastly, schizophrenia participant visual scanning performance of this clip was impaired compared to healthy controls, and correlated across the two groups with social cognition. These results indicate that the TPJ-pSTS plays less of an integral role in the coordination of face-emotion processing, mentalization, and visual attention in schizophrenia participants versus healthy controls. This functional deficit then impacts the visual scanning of a complex dynamic visual scenes, which in turn affects the comprehension of that scene. These findings indicating that the TPJ-pSTS is potentially the shared substrate for all of these deficits will lead to new treatments targeting this region to improve social cognition in individuals with schizophrenia.

neuroscience↗