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

Patel, G. H.; Gruskin, D. C.; Arkin, S. C.; Jamerson, E. C.; Ruiz-Betancourt, D. R.; Klim, C. C.; Sanchez-Pena, J. P.; Bartel, L. P.; Lee, J. K.; Grinband, J.; Martinez, A.; Berman, R. A.; Ochsner, K. N.; Leopold, D. A.; Javitt, D. C.

doi:10.1101/2021.08.04.455137

bioRxiv · 10.1101/2021.08.04.455137

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

Patel, G. H.·Gruskin, D. C.·Arkin, S. C.·Jamerson, E. C.·Ruiz-Betancourt, D. R.·Klim, C. C.·Sanchez-Pena, J. P.·Bartel, L. P.·Lee, J. K.·Grinband, J.·Martinez, A.·Berman, R. A.·Ochsner, K. N.·Leopold, D. A.·Javitt, D. C.

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Abstract

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.

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Patel, G. H., Gruskin, D. C., Arkin, S. C., Jamerson, E. C., Ruiz-Betancourt, D. R., Klim, C. C., Sanchez-Pena, J. P., Bartel, L. P., Lee, J. K., Grinband, J., Martinez, A., Berman, R. A., Ochsner, K. N., Leopold, D. A., Javitt, D. C.. 2021-08-05. The road not taken: disconnection of a human-unique cortical pathway in schizophrenia and its effects on naturalistic social cognition. https://doi.org/10.1101/2021.08.04.455137

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