Impaired Right Temporoparietal Junction-Hippocampus Connectivity in Schizophrenia and Its Relevance for Generating Representations of Other Minds

Schizophrenia is associated with impaired and exaggerated Theory of Mind processes, pointing on alterations in generating a representation of another person's mind. Despite recent work on healthy subjects suggesting that a coupling between the right temporoparietal junction (rTPJ) and the hippocampus is relevant for building representations of others' intentions, the neural basis of related dysfunctions in patients with schizophrenia remains unclear. Therefore, we used structural and functional magnetic resonance imaging together with a modified prisoner's dilemma game to test the hypotheses, that patients show dysfunctional social updating on behavioral level accompanied by altered rTPJ-hippocampus coupling on a functional and a structural level. During the task, 31 patients with schizophrenia and 20 healthy controls interacted with 3 playing partners, who behaved according to stable strategies competitively, cooperatively, or randomly. Our data show that patients adapted their social behavior less flexibly to the playing partners than healthy controls, indicating differences in forming mental representations of the counterparts' intentions. Patients showed lower functional connectivity between the rTPJ and temporal lobe regions such as the hippocampus, the fusiform gyrus, and the middle temporal gyrus, indicating that in patients the rTPJ fails to integrate memory-informed processing streams during mental state inferences. Remarkably, the rTPJ-hippocampus coupling accounted for the participants' adaptive social behavior in the task, suggesting that a neural pathway relevant for updating social knowledge and forming forward predictions in social interactions is altered in schizophrenia.