Real-time fMRI Neurofeedback in Patients With Schizophrenia and Auditory Hallucinations

NCT ID: NCT05299749

Last Updated: 2025-09-18

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-01
• Study Completion Date: 2026-06-30

Brief Summary

Neurofeedback intervention aimed to regulate the superior temporal gyrus (STG) activation and default mode network (DMN) connectivity as well as to reduce the auditory hallucinations (AH) schizophrenia patients with medication resistant AH.

Detailed Description

Here, the investigators 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), as well as to reductions in AH, and that the brain and clinical changes will be correlated. 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 several theoretical papers and experimental evidence well as preliminary data by the investigators (PD). In both R61 and R33 the investigators 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. This R33 phase will consist of an SZ-intervention group (random n=52) that 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 R61 phase data, the investigators 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, the investigators predict the improvement in delusions, negative symptoms and in WM score, only post-rt-fMRI neurofeedback targeting the STG and not post-sham-rt-fMRI.

Conditions

Schizophrenia; Auditory Hallucination; Treatment-resistant Schizophrenia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

stg-rt-fMRI

will receive feedback from the STG

Group Type: EXPERIMENTAL

stg-rt-fMRI-Neurofeeback

Intervention Type: OTHER

the patients will receive real-time feedback from the brain activity of the superior temporal gyrus

sham-rt-fMRI

will receive feedback from the motor cortex

Group Type: SHAM_COMPARATOR

sham-rt-fMRI-Neurofeedback

Intervention Type: OTHER

the patients will receive real-time feedback from the brain activity of the somato-motor cortex

Interventions

stg-rt-fMRI-Neurofeeback

the patients will receive real-time feedback from the brain activity of the superior temporal gyrus

Intervention Type: OTHER

sham-rt-fMRI-Neurofeedback

the patients will receive real-time feedback from the brain activity of the somato-motor cortex

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• patients diagnosed with SZ or schizoaffective disorder using DSM-5 criteria
• auditory hallucinations not responsive to pharmacology as determined by chart review and a clinical interview of SCID.

Exclusion Criteria

• neurologic illness
• major head trauma
• electroconvulsive therapy
• alcohol or drug dependence
• alcohol or drug abuse within the past five years
• verbal IQ below 70

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mclean Hospital

OTHER

Sponsor Role: collaborator

Northeastern University

OTHER

Sponsor Role: collaborator

Cambridge Health Alliance

OTHER

Sponsor Role: collaborator

Boston VA Research Institute, Inc.

OTHER

Sponsor Role: lead

Responsible Party

Margaret Niznikiewicz

Professor in Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

margaret niznikiewicz

Role: PRINCIPAL_INVESTIGATOR

Boston VA Research Institute, Inc.

Locations

Boston VA Healthcare System, Brockton

Brockton, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

margaret niznikiewicz, PhD

Role: CONTACT

margaret_niznikiewicz@hms.harvard.edu

6176534627

Clemens Bauer, phd

Role: CONTACT

c.bauer@northeastern.edu

617-870-1771

Facility Contacts

Mia Kriksciun, BA

Role: primary

mia.kriksciun@va.gov

774 826 1507

Other Identifiers

4R33MH113751-03

Identifier Type: NIH

Identifier Source: org_study_id

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