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

Real-time fMRI Neurofeedback as a Tool to Mitigate Auditory Hallucinations in Patients With Schizophrenia - R33 Phase

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.

Study Overview

• Status: Recruiting
• Conditions: Schizophrenia; Treatment-resistant Schizophrenia; Auditory Hallucination
• Intervention / Treatment: Other: stg-rt-fMRI-Neurofeeback; Other: sham-rt-fMRI-Neurofeedback

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.

• Study Type: Interventional
• Enrollment (Anticipated): 104
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Margaret Niznikiewicz, PhD; Phone Number: 617-855-2570; Email: lstone@mclean.harvard.edu
• Study Contact Backup: Name: Lena Stone; Email: lstone@mclean.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Brockton, Massachusetts, United States, 02301
      • Recruiting
      • Boston VA Healthcare System, Brockton
      • Contact: Lena Stone; Phone Number: 617-855-2570; Email: LSTONE@MCLEAN.HARVARD.EDU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: stg-rt-fMRI; will receive feedback from the STG	Other: stg-rt-fMRI-Neurofeeback; the patients will receive real-time feedback from the brain activity of the superior temporal gyrus
Sham Comparator: sham-rt-fMRI; will receive feedback from the motor cortex	Other: sham-rt-fMRI-Neurofeedback; the patients will receive real-time feedback from the brain activity of the somato-motor cortex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
percent change in the STG BOLD signal, post- relative to pre-NFB	does real-time fMRI neurofidback reduce BOLD activity in STG, post NFB	0-4 weeks post intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
reduction in scores on Psychotic Symptoms Rating Scale, post- relative to pre, NFB	does real-time fMRI neurofidback reduce auditory hallucinations, post NFB	0-4 weeks post intervention
percent change in the MPFC-PCC connectivity measure, post- relative to pre-NFB.	Does real time NFB reduce connectivity in MPFC-PCC, post NFB	0-4 weeks post intervention

Collaborators and Investigators

• Sponsor: Boston VA Research Institute, Inc.
• Collaborators: Mclean Hospital; Cambridge Health Alliance; Northeastern University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Anticipated): June 30, 2024
• Study Completion (Anticipated): June 30, 2024

Study Registration Dates

• First Submitted: March 8, 2022
• First Submitted That Met QC Criteria: March 24, 2022
• First Posted (Actual): March 29, 2022

Study Record Updates

• Last Update Posted (Actual): September 22, 2022
• Last Update Submitted That Met QC Criteria: September 20, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: MRI; Neurofeedback; Connectivity; Auditory-Hallucination; brain-activity; default-mode-network; superior temporal gyrus
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Schizophrenia Spectrum and Other Psychotic Disorders; Perceptual Disorders; Schizophrenia; Hallucinations
• Other Study ID Numbers: 4R33MH113751-03 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: The Clinical, Cognitive and Imaging data will be made publicly available

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No