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

Abstract

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.

Stria terminalis, amygdala, and temporoparietal junction networks facilitate efficient emotion processing under expectations

“…In psychosis, for example, there is a deficit in recognising threatening emotions (Behere, 2015;Mandal, Pandey, & Prasad, 1998;van't Wout et al, 2007) and also misattribution of threat (Premkumar et al, 2008). These abnormalities in threat processing have strong links to neurobiological factors; specifically, abnormal activation and connectivity in similar brain regions as those identified in the current study (i.e., amygdala, temporoparietal junction, BNST, ACC, and hippocampus) (Bitsch, Berger, Nagels, Falkenberg, & Straube, 2018;Bryant et al, 2008;Buff et al, 2017;Felmingham et al, 2008;Rabellino et al, 2015;Rabellino et al, 2018;Underwood, Kumari, & Peters, 2016;Underwood, Peters, & Kumari, 2015). These abnormalities in threat processing have strong links to neurobiological factors; specifically, abnormal activation and connectivity in similar brain regions as those identified in the current study (i.e., amygdala, temporoparietal junction, BNST, ACC, and hippocampus) (Bitsch, Berger, Nagels, Falkenberg, & Straube, 2018;Bryant et al, 2008;Buff et al, 2017;Felmingham et al, 2008;Rabellino et al, 2015;Rabellino et al, 2018;Underwood, Kumari, & Peters, 2016;Underwood, Peters, & Kumari, 2015).…”

“…In contrast, in anxiety and post-traumatic stress disorder, there is an abnormal anticipation of threat (Gross & Hen, 2004). These abnormalities in threat processing have strong links to neurobiological factors; specifically, abnormal activation and connectivity in similar brain regions as those identified in the current study (i.e., amygdala, temporoparietal junction, BNST, ACC, and hippocampus) (Bitsch, Berger, Nagels, Falkenberg, & Straube, 2018;Bryant et al, 2008;Buff et al, 2017;Felmingham et al, 2008;Rabellino et al, 2015;Rabellino et al, 2018;Underwood, Kumari, & Peters, 2016;Underwood, Peters, & Kumari, 2015). In contrast to disorders of threat processing, depression has been consistently linked with impaired perception of happiness (Bourke, Douglas, & Porter, 2010) and reduced activity in the limbic network (Lawrence et al, 2004), with antidepressant treatment associated with increased amygdala activation to happy faces (Norbury et al, 2009).…”

Nonsocial and social cognition in schizophrenia: current evidence and future directions

“…For example, compared to controls, schizophrenia patients showed reduced functional connectivity involving the limbic structures (including amygdala) during facial affect processing. During a mentalizing task, schizophrenia patients showed reduced connectivity between temporoparietal junction and temporal lobe regions (including hippocampus and middle temporal gyrus) compared to controls.…”

<p>Impaired Cognitive Abilities in Siblings of Patients with Temporal Lobe Epilepsy</p>

“…47 Patients with right TLE also showed less extensive structural damage compared to left TLE patients. 50 The right temporal lobe is more closely related to emotional recognition 57,58 and social cognition, [59][60][61][62] which we did not evaluate. In our study, right TLE patients had higher scores in certain neuropsychological tests than left TLE patients, and their siblings did not demonstrate cognitive deficits, is in accord with previous researches.…”