Abstract

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.

Highlights

  • Self-agency is defined as the experience and awareness of being the agent of one’s own thoughts, actions and action outcomes, and provides the founding basis for our interactions with the world [1,2,3,4,5]

  • In our reality monitoring task, in which subjects distinguish self-generated from externally-derived information, healthy controls (HC) showed increased medial prefrontal cortex (mPFC) activity, shown in beta power suppression, that was observed within a specific time window preceding the successful encoding and retrieval of self-generated information, which correlated with accurate judgments of self-agency, indicating mPFC represents one neural correlate of the self-prediction mechanisms that leads to self-agency [6,21]

  • In our current work, we examine if mPFC modulates the reliance on selfprediction signals in SZ, in which case repetitive transcranial magnetic stimulation (rTMS)-induced increased mPFC activation will induce smaller corrective responses during speech monitoring that will correlate with improved self-agency judgments during reality monitoring and improved positive symptoms in SZ

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Summary

Introduction

Self-agency is defined as the experience and awareness of being the agent of one’s own thoughts, actions and action outcomes, and provides the founding basis for our interactions with the world (i.e., reality monitoring) [1,2,3,4,5]. Hallucinations are thought to result from the misattribution of patients’ internal thoughts as external voices; and delusions of influence in schizophrenia occur when patients feel their own actions are no longer controlled by themselves [10]. These psychotic symptoms of hallucinations and delusions are thought to result from impaired self-predictions about the expected outcome of one’s own actions [3,10,11]. The psychopathology of hallucinations and delusions suggest patients show reduced reliance on self-predictions about their own action outcomes, misattributing them as being externally-produced, which is thought to result in patients’ lost sense of self-agency and break from reality (i.e., impaired reality-monitoring) [3,11].

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