Causal role of medial superior frontal cortex on enhancing neural information flow and self-agency judgments in the self-agency network.

Self-agency is being aware of oneself as the agent of one's thoughts and actions. Self-agency is necessary for successful interactions with the outside world (reality-monitoring). Prior research has shown that the medial superior prefrontal gyri (mPFC/SFG) may represent one neural correlate underlying self-agency judgments. However, the causal relationship remains unknown. Here, we applied high-frequency 10 Hz repetitive transcranial magnetic stimulation (rTMS) to modulate the excitability of the mPFC/SFG site that we have previously shown to mediate self-agency. For the first time, we delineate causal neural mechanisms, revealing precisely how rTMS modulates SFG excitability and impacts directional neural information flow in the self-agency network by implementing innovative magnetoencephalography (MEG) phase-transfer entropy (PTE) metrics, measured from pre-to-post rTMS. We found that, compared to control rTMS, enhancing SFG excitability by rTMS induced significant increases in information flow between SFG and specific cingulate and paracentral regions in the self-agency network in delta-theta, alpha, and gamma bands, which predicted improved self-agency judgments. This is the first multimodal imaging study in which we implement MEG PTE metrics of 5D imaging of space, frequency and time, to provide cutting-edge analyses of the causal neural mechanisms of how rTMS enhances SFG excitability and improves neural information flow between distinct regions in the self-agency network to potentiate improved self-agency judgments. Our findings provide a novel perspective for investigating causal neural mechanisms underlying self-agency and create a path towards developing novel neuromodulation interventions to improve self-agency that will be particularly useful for patients with psychosis who exhibit severe impairments in self-agency.