Symptom Based Treatment Affects Brain Plasticity - Cognitive Training in Patients With Affective Symptoms (APIC-II)

• ClinicalTrials.gov Identifier: NCT03183947
• Recruitment Status: Completed
• First Posted: June 12, 2017
• Last Update Posted: December 10, 2019
• Sponsor: RWTH Aachen University
• Information provided by (Responsible Party): RWTH Aachen University

Study Description

Brief Summary:

The aim of the study is the examination of brain plasticity on on affective symptoms after neuromodulation with fMRI (functional magnetic resonance imaging) neurofeedback. During the fMRI neurofeedback training, patients with depression as well as patients with schizophrenia are trained to consciously regulate the activity of areas which are associated with the cognitive reappraisal of emotional stimuli.The aim is to improve the patients' subjective emotional processing and perception in everyday life as well as to investigate the impact of neurofeedback on resting-state networks in the brain. Healthy participants will be investigated as control group.

Condition or disease	Intervention/treatment	Phase
Depression; Schizophrenia	Procedure: fMRI; Behavioral: Neurofeedback; Other: PANAS; Other: BDI-II; Other: ERQ	Not Applicable

Detailed Description:

The ability to regulate emotions is a central element of mental health that is significantly affected in various psychiatric disorders. Its importance for development and maintenance of depressive symptomatology has been widely shown; e.g. patients with depression have a significantly reduced ability to regulate emotions in response to negative stimuli. However, emotion regulation abilities may pose as an important resilience factor that can counteract the development of depressive symptoms. The loss of the ability to regulate emotions is not only observed in depression, but is also a core factor in negative symptoms of schizophrenia.

Cognitive reappraisal training is an established method to improve emotion regulation. The cognitive reappraisal of a stimulus or situation works by reinterpreting the emotional stimulus or situation and can change the course of the emotional response. Over the last years this form of cognitive reappraisal training has become a standard approach in the treatment of affective disorders.

The prefrontal cortex (PFC) plays an important role in emotion regulation. In line with this it has been shown that patients with reduced emotion regulation ability display impaired functioning of the PFC. Aim of the study is to train patients to consciously upregulate activity in the PFC and thereby to increase emotion regulation ability. On the behavioral level this is expected to correlate with a reduced experience of negative mood. In order to regulate the PFC, participants are instructed to use cognitive reappraisal strategies. Cognitive reappraisal is an effective and well-investigated strategy to improve emotion regulation and is a standard cognitive-behavioral psychotherapeutic intervention. During cognitive reappraisal the meaning of a picture is reinterpreted in order to reduce the emotional reaction. Recent fMRI studies have shown that cognitive reappraisal is associated with an increase in prefrontal activity and a decrease of amygdala activation.

The new technique of real-time fMRI enables subjects to influence their brain activity in certain areas based on neurofeedback. Ongoing brain activity as measured by fMRI is reported to the participants in real time via brain computer interface (BCI). In order to influence brain activity, mental strategies are usually recommended to the participants that have been shown to increase activity in the respective area. Due to the identification of contingency between feedback and mental strategies participants are able to control their own brain activity consciously. It has been shown that psychiatric symptomatology can be improved using this non-invasive technique. In the current study it will be investigated whether neurofeedback of the PFC has a positive influence on affective symptoms in patients with depression and schizophrenia, respectively. In detail it is researched whether the upregulation of activity in the PFC can lead to an increase in subjective well-being. Two groups of patients (depression (N=40) and schizophrenia (N=40)) as well as a group of healthy participants will receive neurofeedback-training of the PFC. Aim of the study is an improvement of depressive (or negative) symptoms as well as the investigation of the impact of neurofeedback on resting-state networks in the brain.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 81 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Symptom Based Treatment Affects Brain Plasticity - Cognitive Training in Patients With Affective Symptoms
• Actual Study Start Date: August 29, 2017
• Actual Primary Completion Date: December 6, 2019
• Actual Study Completion Date: December 6, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: fMRI Neurofeedback regulation of left PFC; Study related procedures included: PANAS, BDI-II, ERQ (questionnaires or evaluations)	Procedure: fMRI; collection of functional brain data for 1 hour per day; Other Name: functional magnetic resonance imaging; Behavioral: Neurofeedback; Task of the participants is to increase the activity in the selected brain region (left or right prefrontal cortex). After regulation they will get a feedback about the regulation success. (Patients: days 3 & 4; controls: Days 2 & 3); Other: PANAS; to assess the mood before and after the fMRI and after 4 weeks during a telephone interview; Other Name: Positive And Negative Affect Scales; Other: BDI-II; to assess depressive symptomatology before neurofeedback and 4 weeks after the intervention during telephone interview; Other Name: Beck's depression inventory; Other: ERQ; To assess emotion regulation strategies before and after neurofeedback training (patients: day 3&4; controls: day 2&3) and after 4 weeks during a telephone interview; Other Name: Emotion regulation questionnaire
Experimental: fMRI Neurofeedback of right PFC; Study related procedures included: PANAS, BDI-II, ERQ (questionnaires or evaluations)	Procedure: fMRI; collection of functional brain data for 1 hour per day; Other Name: functional magnetic resonance imaging; Behavioral: Neurofeedback; Task of the participants is to increase the activity in the selected brain region (left or right prefrontal cortex). After regulation they will get a feedback about the regulation success. (Patients: days 3 & 4; controls: Days 2 & 3); Other: PANAS; to assess the mood before and after the fMRI and after 4 weeks during a telephone interview; Other Name: Positive And Negative Affect Scales; Other: BDI-II; to assess depressive symptomatology before neurofeedback and 4 weeks after the intervention during telephone interview; Other Name: Beck's depression inventory; Other: ERQ; To assess emotion regulation strategies before and after neurofeedback training (patients: day 3&4; controls: day 2&3) and after 4 weeks during a telephone interview; Other Name: Emotion regulation questionnaire

Outcome Measures

Primary Outcome Measures :

1. change in self-control over neuronal activity in PFC [ Time Frame: 1 week ]
   fMRI-BCI as a measure before and after the regulation of the brain activity

Secondary Outcome Measures :

1. Changes from baseline in brain plasticity [ Time Frame: 2 weeks ]
   fMRI as a measure for brain plasticity before and after neurofeedback
2. Change in pathology (depression) [ Time Frame: 4 weeks after interventions ]
   BDI-II as a measure of the intensity and quality of depressive symptoms before training and 4 weeks following the intervention
3. specificity of left or right PFC neurofeedback [ Time Frame: 2 weeks ]
4. change in resting state brain activation [ Time Frame: 2 weeks ]
   Resting state fMRI as a measure before and after neurofeedback
5. Change in pathology (mood) [ Time Frame: 4 weeks after interventions ]
   Positive And Negative Affect Scales (PANAS) as a measure of mood before and after the fMRI and after 4 weeks during a telephone interview

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Depression according to ICD-10 (F32.x, F33.x, F31.3 or F34.x); Schizophrenia according to ICD-10 (F2x); or healthy subjects
• Fluent German language skills

Exclusion Criteria:

• any contraindication to MRI examination or claustrophobia
• pregnant or lactating women
• acute suicidal tendency
• persons incapable of giving consent

Contacts and Locations

Locations

Germany

University Hospital RWTH Aachen, Department of Psychiatry, Psychotherapy and Psychosomatics

Aachen, Germany, 52074

Sponsors and Collaborators

RWTH Aachen University

Investigators

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

More Information

Publications:

Buhle JT, Silvers JA, Wager TD, Lopez R, Onyemekwu C, Kober H, Weber J, Ochsner KN. Cognitive reappraisal of emotion: a meta-analysis of human neuroimaging studies. Cereb Cortex. 2014 Nov;24(11):2981-90. doi: 10.1093/cercor/bht154. Epub 2013 Jun 13.

Hayes JP, Vanelzakker MB, Shin LM. Emotion and cognition interactions in PTSD: a review of neurocognitive and neuroimaging studies. Front Integr Neurosci. 2012 Oct 9;6:89. doi: 10.3389/fnint.2012.00089. eCollection 2012.

Kohn N, Eickhoff SB, Scheller M, Laird AR, Fox PT, Habel U. Neural network of cognitive emotion regulation--an ALE meta-analysis and MACM analysis. Neuroimage. 2014 Feb 15;87:345-55. doi: 10.1016/j.neuroimage.2013.11.001. Epub 2013 Nov 9. Erratum in: Neuroimage. 2015 May 1;111():631.

Linden DE, Habes I, Johnston SJ, Linden S, Tatineni R, Subramanian L, Sorger B, Healy D, Goebel R. Real-time self-regulation of emotion networks in patients with depression. PLoS One. 2012;7(6):e38115. doi: 10.1371/journal.pone.0038115. Epub 2012 Jun 4.

Ochsner KN, Bunge SA, Gross JJ, Gabrieli JD. Rethinking feelings: an FMRI study of the cognitive regulation of emotion. J Cogn Neurosci. 2002 Nov 15;14(8):1215-29.

Weiskopf N, Scharnowski F, Veit R, Goebel R, Birbaumer N, Mathiak K. Self-regulation of local brain activity using real-time functional magnetic resonance imaging (fMRI). J Physiol Paris. 2004 Jul-Nov;98(4-6):357-73. Epub 2005 Nov 10. Review.

Joormann J, Gotlib IH. Emotion regulation in depression: relation to cognitive inhibition. Cogn Emot. 2010 Feb 1;24(2):281-98. doi: 10.1080/02699930903407948.

Troy AS, Wilhelm FH, Shallcross AJ, Mauss IB. Seeing the silver lining: cognitive reappraisal ability moderates the relationship between stress and depressive symptoms. Emotion. 2010 Dec;10(6):783-95. doi: 10.1037/a0020262.

• Responsible Party: RWTH Aachen University
• ClinicalTrials.gov Identifier: NCT03183947
• Other Study ID Numbers: 17-094
• First Posted: June 12, 2017
• Last Update Posted: December 10, 2019
• Last Verified: December 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by RWTH Aachen University:

fMRI; neurofeedback; emotion regulation; schizophrenia; cognitive reappraisal; depression

Additional relevant MeSH terms:

Depression; Schizophrenia; Affective Symptoms; Behavioral Symptoms; Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders