The Role of the Medial Prefontal Cortex in Self-Agency in Schizophrenia.

Schizophrenia is a disorder of the self. In particular, patients show cardinal deficits in self-agency (i.e., the experience and awareness of being the agent of one's own thoughts and actions) that directly contribute to positive psychotic symptoms of hallucinations and delusions and distort reality monitoring (defined as distinguishing self-generated information from externally-derived information). Predictive coding models suggest that the experience of self-agency results from a minimal prediction error between the predicted sensory consequence of a self-generated action and the actual outcome. In other words, the experience of self-agency is thought to be driven by making reliable predictions about the expected outcomes of one's own actions. Most of the agency literature has focused on the motor system; here we present a novel viewpoint that examines agency from a different lens using distinct tasks of reality monitoring and speech monitoring. The self-prediction mechanism that leads to self-agency is necessary for reality monitoring in that self-predictions represent a critical precursor for the successful encoding and memory retrieval of one's own thoughts and actions during reality monitoring to enable accurate self-agency judgments (i.e., accurate identification of self-generated information). This self-prediction mechanism is also critical for speech monitoring where we continually compare auditory feedback (i.e., what we hear ourselves say) with what we expect to hear. Prior research has shown that the medial prefrontal cortex (mPFC) may represent one potential neural substrate of this self-prediction mechanism. Unfortunately, patients with schizophrenia (SZ) show mPFC hypoactivity associated with self-agency impairments on reality and speech monitoring tasks, as well as aberrant mPFC functional connectivity during intrinsic measures of agency during resting states that predicted worsening psychotic symptoms. Causal neurostimulation and neurofeedback techniques can move the frontiers of schizophrenia research into a new era where we implement techniques to manipulate excitability in key neural regions, such as the mPFC, to modulate patients' reliance on self-prediction mechanisms on distinct tasks of reality and speech monitoring. We hypothesize these findings will show that mPFC provides a unitary basis for self-agency, driven by reliance on self-prediction mechanisms, which will facilitate the development of new targeted treatments in patients with schizophrenia.