# Causal Role of Medial Prefrontal Neural Activity in Self-Agency in Schizophrenia

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $808,199

## Abstract

Project Summary
Patients with schizophrenia (SZ) show severe deficits in self-agency (i.e., the experience of being the agent of
one's own thoughts and actions), that directly contribute to debilitating psychotic symptoms and distort reality
monitoring (i.e., defined as distinguishing self-generated information from externally-derived information).
Current medications are inadequate with up to 40% of SZ remaining symptomatic, thus compelling the need to
understand the neurobiology underlying self-agency deficits which we believe drives psychotic experiences in
SZ. Here, we test for the first time a novel causal cognitive and neurobiological model underlying self-agency
with the aim of developing new effective treatments in SZ. In particular, we examine whether the resulting
experience of self-agency is driven by the fundamental ability to make reliable predictions about the outcomes
of one's own self-generated actions. This self-prediction ability is critical 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 ability is also critical for speech
monitoring where we continually compare what we hear while we speak with what we expect to hear. Prior
studies have shown that the medial prefrontal cortex (mPFC) is a potential neural substrate that mediates both
lower-level self-predictions during speech monitoring, and higher-level self-agency judgments during reality
monitoring in healthy controls (HC). Here, we now test whether mPFC activity can causally modulate this self-
prediction ability to impact self-agency on two different tasks of reality and speech monitoring. We propose a
longitudinal randomized controlled trial in which HC and SZ are assigned to 5 daily sessions of either active high-
frequency 10Hz transcranial magnetic stimulation (TMS) to increase mPFC activity or to sham TMS. We use
repeated measures of magnetoencephalography imaging (MEGI) to assay neural activity underlying self-agency
on reality and speech monitoring tasks from pre-to-post TMS at time-points: (i) baseline, (ii) proximal post-TMS
(i.e., right after TMS intervention), and (iii) distal post-TMS (i.e., 1 week after TMS intervention). The specific
aims are to delineate with MEGI, proximal and distal mechanisms of how active 10Hz TMS modulates mPFC
activity in HC and SZ to induce neural network and behavioral changes in self-agency in reality and speech
monitoring tasks, compared to baseline and sham. The overall hypothesis is that high frequency TMS will
increase mPFC excitability and enhance self-predictions to improve self-agency on distinct tasks of speech and
reality monitoring. If successful, this project will establish mPFC as a new biological target for TMS therapies in
SZ, and will show that mPFC provides a unitary basis for self-agency driven by reliance on self-predictions. The
lon...

## Key facts

- **NIH application ID:** 9944376
- **Project number:** 1R01MH122897-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Karuna Subramaniam
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $808,199
- **Award type:** 1
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944376

## Citation

> US National Institutes of Health, RePORTER application 9944376, Causal Role of Medial Prefrontal Neural Activity in Self-Agency in Schizophrenia (1R01MH122897-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9944376. Licensed CC0.

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