Symptom Based Treatment Affects Brain Plasticity - the Role of Verbal Auditory Hallucinations (APIC-II)

The aim of the study is the examination of brain plasticity on verbal auditory hallucinations (AVH) after neuromodulation with fMRI (functional magnetic resonance imaging) neurofeedback. During the training of fMRI neurofeedback subjects are trained to regulate consciously the connectivity of areas which are associated with hallucinations.The aim is to improve perceived hallucinations' intensity in everyday life of the patients as well as investigating the impact of neurofeedback on resting-state networks in the brain. As control groups, control subjects without AVH and participants with AVH, but no psychiatric diagnosis will be included.

Study Overview

• Status: Completed
• Conditions: Hallucinations, Verbal Auditory
• Intervention / Treatment: Procedure: fMRI; Behavioral: Neurofeedback; Other: PANAS; Other: AVHRS; Other: SF36

Detailed Description

This study investigates the brain plasticity after neuromodulation with fMRI neurofeedback on verbal auditory hallucinations (AVH). The new technique of real-time fMRI enables subjects to influence their brain activity in certain areas based on neurofeedback. Current brain activity as measured by fMRI will be reported to the participants in real time via brain computer interface (BCI). Due to the identification of contingency between feedback and mental strategies subjects are able to control their own brain activity consciously. This provides the opportunity to control symptoms such as AVH. Neurofeedback has been tested on subjects with schizophrenia, leading to conscious control of circumscribed brain areas. Recent studies show that, in addition to the modulation of single areas, neurofeedback can also modulate connectivity between different areas. Thus, it is possible to regulate not only single brain regions but also whole networks.

AVH are a key symptom of schizophrenia. They limit social functions significantly and are resistant to the therapy with antipsychotics in 25 % of cases. AVH also occur in 6-15 % of the healthy population, without meeting any diagnostic criteria for schizophrenia or other psychiatric disorders. This study will perform a direct, not-invasive and selective modulation of networks underlying AVH and assess their neural, cognitive and emotional effects. The focus of this study is on the connectivity between auditory cortex and inferior frontal cortex. Various studies demonstrated that the auditory cortex exhibits an abnormal function in schizophrenia patients. It was shown that during AVH, auditory cortex (superior temporal lobe) and inferior frontal cortex synchronize spontaneously. These regions play an essential role in speech perception and processing. An increased synchronisation of these areas could lead to the development of AVH. This study will try to reduce frontotemporal connectivity to uncouple the regions. Increasing connectivity of both areas will serve as control condition and furthermore intensify the perceived control of the own brain activity and of the associated AVH. Thus, patients will learn which factors influence the appearance of their hallucinations.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Aachen, Germany, 52074
    • University Hospital RWTH Aachen, Department of Psychiatry, Psychotherapy and Psychosomatics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Schizophrenia according to ICD-10 (F2x) with verbal hallucinations or only verbal hallucinations (no psychiatric diagnosis) or healthy subjects without verbal hallucinations
• Fluent German language skills

Exclusion Criteria:

• addiction
• severe affective disorder
• any contraindication to MRI examination or claustrophobia
• pregnant or lactating women
• traumatic brain lesions
• acute physical or neurological impairments
• acute suicidal tendency
• Lack of informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: fMRI Neurofeedback up-regulation; Study related procedures included: PANAS, AVHRS, SF 36 (questionnaires or evaluations)	Procedure: fMRI; collection of functional brain data for 1 hour per day; Other Names: functional magnetic resonance imaging; Behavioral: Neurofeedback; Task of the participants is to increase or decrease the connectivity between selected brain regions in double-blind, randomized order. After the regulation they will get a feedback about the regulation success. (Patients and controls with AVH: days 3 & 4; controls without AVH: Days 2 & 3); Other: PANAS; to assess the mood before and after the fMRI and after 1 week during a telephone interview; Other Names: Positive And Negative Affect Scales; Other: AVHRS; to assess the intensity and quality of the hallucinations before and after the fMRI and after 1 week during a telephone interview; Other Names: Auditory Vocal Hallucinations Rating Scale; Other: SF36; questionnaire about life quality after 1 week during a telephone interview
Experimental: fMRI Neurofeedback down-regulation; Study related procedures included: PANAS, AVHRS, SF 36 (questionnaires or evaluations)	Procedure: fMRI; collection of functional brain data for 1 hour per day; Other Names: functional magnetic resonance imaging; Behavioral: Neurofeedback; Task of the participants is to increase or decrease the connectivity between selected brain regions in double-blind, randomized order. After the regulation they will get a feedback about the regulation success. (Patients and controls with AVH: days 3 & 4; controls without AVH: Days 2 & 3); Other: PANAS; to assess the mood before and after the fMRI and after 1 week during a telephone interview; Other Names: Positive And Negative Affect Scales; Other: AVHRS; to assess the intensity and quality of the hallucinations before and after the fMRI and after 1 week during a telephone interview; Other Names: Auditory Vocal Hallucinations Rating Scale; Other: SF36; questionnaire about life quality after 1 week during a telephone interview

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in self-control over neuronal connectivity	fMRI-BCI as a measure before and after the regulation of the brain activity	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes from baseline in brain plasticity	fMRI as a measure for brain plasticity before and after neurofeedback	2 weeks
Change in pathology (AVH)	Auditory Vocal Hallucinations Rating Scale (AVHRS) as a measure of the intensity and quality of the hallucinations before and after the fMRI and after 1 week during a telephone interview	1 week after interventions
number of patients and subjects with benefits from neurofeedback training		2 weeks
change in brain activation	fMRI as a measure before and after the following resting state	1 week after interventions
Change in pathology (mood)	Positive And Negative Affect Scales (PANAS) as a measure of mood before and after the fMRI and after 1 week during a telephone interview	1 week after interventions
Change in perceived quality of life	SF36 questionnaire as a measure of the quality of life before and after the fMRI and after 1 week during a telephone interview	1 week after interventions

Collaborators and Investigators

• Sponsor: RWTH Aachen University
• Investigators: Principal Investigator: Klaus Mathiak, Prof MD PhD, University Hospital RWTH Aachen, Department of Psychiatry, Psychotherapy and Psychosomatics

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): December 1, 2019

Study Registration Dates

• First Submitted: March 10, 2016
• First Submitted That Met QC Criteria: March 23, 2016
• First Posted (Estimate): March 30, 2016

Study Record Updates

• Last Update Posted (Actual): January 9, 2020
• Last Update Submitted That Met QC Criteria: January 7, 2020
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: neurofeedback; schizophrenia; fMRI; hallucination
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Perceptual Disorders; Hallucinations
• Other Study ID Numbers: 15-139