# Real-time fMRI Neurofeedback as a Tool to Mitigate Auditory Hallucinations in Patients with Schizophrenia

> **NIH NIH R33** · HARVARD MEDICAL SCHOOL · 2021 · $1,019,591

## Abstract

This is a resubmission application, originally in response to RFA-MH-16-406 and consists of R61 and
R33 phases. Auditory verbal hallucinations (AH) have long been a hallmark of schizophrenia (SZ) and are one
of its major diagnostic features Andreasen and Flaum 1991; DSM-IV). They are difficult to manage with existing
treatment options. Here, we propose that neurofeedback aimed to regulate the superior temporal gyrus (STG)
activation will not only lead to activation changes in the STG, but also to changes in the default mode network
(DMN) (R61), as well as to reductions in AH (R33), and that the brain and clinical changes will be correlated
(R33). The theoretical framework for the current proposal is an AH model that assumes that AH result from
abnormalities in a network of regions including STG, and medial prefrontal cortex (MPFC) and posterior
cingulate cortex (PCC), the two latter regions are core medial hubs of DMN that are related to self-referential
processing. This model is supported by theoretical papers Northoff and Qin 2010, Alderson-Day,2016, and experimental
evidence Gur 1995, Liddle 1992, Dierks 1999 as well as our preliminary data (PD).
 In both R61 and R33 we will study SZ patients with medication resistant AH in the rt-fMRI intervention
arm and in the sham-rt-fMRI arm. In both arms, the task and the rt-fMRI session structure will be identical. The
SZ-intervention group will receive feedback from the STG while SZ-sham group will receive feedback from the
motor cortex. In addition, 2 functional fMRI tasks will examine the effect of rt-fMRI neurofeedback and of
sham-rt-fMRI on brain response.
 In the R61, we will randomly assign 48 SZ patients to either SZ-intervention (n=24) or SZ-sham-rtfMRI
(n=24). The STG targeted neurofeedback is predicted to bring changes in brain regions involved in AH (STG
and DMN) in SZ-intervention group only. The R61 GO criterion will be BOLD signal reduction in the STG, and
resting state connectivity reduction between MPFC-PCC, post rt-fMRI-feedback in SZ-intervention group.
 In the R33, SZ-intervention group (random n=52) will receive 5 sessions of rt-fMRI feedback targeting
STG, while SZ-sham group (random n=52) will receive 5 sham-rt-fMRI sessions. Based on our PD, we predict
that rt-fMRI feedback aimed at STG will reduce AH which will be, in turn, associated with reductions in the STG
activation and in the DMN connectivity (i.e., brain changes achieved in R61 and replicated in R33) in SZ-
intervention group only. Five sessions of rt-fMRI feedback will address the question of dose response at brain
and clinical levels. The impact of rt-fMRI neurofeedback and of sham-rt-fMRI on AH (primary outcome), and
on delusions, negative symptoms and working memory (WM) (exploratory outcome) will be assessed with
clinical and neuropsychological measures. In an exploratory aim, based on the existing literature Garrity 2007;
Whitfield-Gabrieli 2009; Rotarska-Jagiela 2010, we predict the improvement in delusions, negat...

## Key facts

- **NIH application ID:** 10019700
- **Project number:** 4R33MH113751-03
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** MARGARET A NIZNIKIEWICZ
- **Activity code:** R33 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,019,591
- **Award type:** 4N
- **Project period:** 2018-06-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019700

## Citation

> US National Institutes of Health, RePORTER application 10019700, Real-time fMRI Neurofeedback as a Tool to Mitigate Auditory Hallucinations in Patients with Schizophrenia (4R33MH113751-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10019700. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*