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

Sponsor

Harvard Medical School (HMS and HSDM) (Other)

Overall Status

Recruiting

CT.gov ID

NCT05299749

Collaborator

Mclean Hospital (Other), Northeastern University (Other)

104

Enrollment

Location

Arms

Anticipated Duration (Months)

3.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia Auditory Hallucination Treatment-resistant Schizophrenia	Other: stg-rt-fMRI-Neurofeeback Other: sham-rt-fMRI-Neurofeedback	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

104 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 1, 2022

Anticipated Primary Completion Date :

Jun 30, 2024

Anticipated Study Completion Date :

Jun 30, 2024

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

percent change in the STG BOLD signal, post- relative to pre-NFB [0-4 weeks post intervention]
does real-time fMRI neurofidback reduce BOLD activity in STG, post NFB

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.