Neurale Netzwerke der Selbst- und Fremdrepräsentation und deren Integrität bei Schizophrenie

Successfully taking part in social interactions is of great importance for survival of human beings. Hence, we have a need for constant screening of social contexts and meaning as well as for accurately attributing the agency of observed actions. Therefore, our brain should be well adapted to these processes. However, impaired social functioning is a core characteristic in schizophrenia. In the context of this thesis, three functional magnetic resonance imaging (fMRI) studies were performed investigating the neural processes underlying social cognition abilities in the brain of patients with schizophrenia, as well as in the non-pathologic brain. We focused on three particular social abilities, namely (1) perception of cooperation (Study #1), (2) perception of self-generated and observed actions (Study #2), and (3) inferring agency of observed actions (Study #3). Until now cooperation is a form of social interaction that has received little attention in research on schizophrenia – although it is known that patients show altered cooperation behavior (e.g., Wischniewski et al., 2009). Additionally, patients with paranoid schizophrenia suffer from persecutory delusions, accompanied by feelings of being watched or followed (M. Startup & S. Startup, 2005) caused by false inferences regarding the intentions of others (Frith & Frith, 1999). To date, more empirical research is needed to further investigate the possible relation between social interaction deficits and delusions (Freeman, 2007). For this purpose, we constructed an fMRI paradigm: participants watched video stimuli in which two actors manipulate objects together – or as in the control condition – one actor manipulates the object alone. We studied a possible relation of brain activity in response to the stimuli and psychopathology (Study #1). Additionally, social cognition deficits are often explained by alterations of the observation-execution matching system i.e., the mirror neuron system (MNS). This system is activated when subjects view or perform grasping movements (e.g., Iacoboni et al., 2005). Surprisingly, just a few studies focus on the functionality of this system in schizophrenia. A simple task was used to probe the integrity of the MNS: participants observed an actor while grasping an object and periodically performed a similar action in the scanner (Study #2). Besides evaluating activation differences between groups, connectivity analyses were performed. If self and other actions are comparably processed within the MNS, there is a need for a control mechanism that still enables an accurate distinction between self and non-self for agency attributions (Leube et al., 2012). Patients with schizophrenia often suffer from delusions of influence, which suggests that their sense of self is disturbed. It is assumed that a failure of the efference copy mechanism, which compares efferent with reafferent signals and attenuates the sensory consequences of self-produced movements, causes passivity phenomena (e.g., Ford & Mathalon, 2004). To test this hypothesis, participants performed both intentional and unintentional continuous hand-movements. We periodically manipulated visual feedback of their action by introducing a temporal delay to create a sensory-motor discrepancy – simulating “non-self” feedback (Study #3). We have shown in Study #1 that the network for perception of cooperative and non-cooperative behavior is altered in a mirror-inverted way in paranoid schizophrenia. More precisely, in schizophrenic patients parts of the cooperation-network showed attenuation in response to the cooperative context, but were significantly increased in the non-cooperative context compared to controls. Furthermore, the latter finding was associated with persecutory delusions in patients. Showing this pattern of results, we provide novel experimental evidence for the idea of an overactivated Theory of mind (ToM) network in patients, which might reflect overmentalizing (Abu-Akel & Bailey, 2000). This could be attributed to ambiguous perception of the non-cooperative scenes resulting from a constantly hyperactive intention detector (Walter et al., 2009) and the patients’ abnormal threat perception (Fear et al., 1996). Moreover, results of Study #1 support the assumption that the ToM network plays an important role in the formation of delusions. The findings of Study #2 suggest that a broader MNS dysconnectivity may be responsible for the social deficit in schizophrenia that reduces social functioning because it might disturb an essential sensory feedback exchange within the MNS. In Study #2, it is discussed that this newly observed MNS dysconnectivity might be a major contributor to social cognitive aberrances in schizophrenia - e.g., imitation, mentalizing, and empathizing deficits, as well as attributional style. In Study #3 we identified the inferior frontal gyrus (IFG) as a potential candidate for a control entity that enables a distinction between self and non-self within the MNS with shared neural representations for “self” and “other”. However, in patients the sensory mismatch detection was altered, suggesting that the IFG is the neural correlate of the failure of the efference mechanism in schizophrenia. More specifically, due to dysconnectivity of the IFG to other parts of the mismatch network, signal exchange between perceptual and motor areas (which is necessary for the efference mechanism) seems to be affected. Moreover, alterations in this network were related to passivity symptom-ratings. This defective network might cause self-monitoring deficits in patients, which contributes to clinical core symptoms of schizophrenia i.e. the emergence of disorders of the self (see Farrer & Franck, 2007).