Modulation of Sense of Agency With Non-invasive Brain Stimulation and Mindfulness-based Stress Reduction Therapy

NCT05086380 | Completed

• 1 other identifier: 2020-02283
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 1

Brief Summary

A conversion disorder is a dysfunction of the nervous system in which no structural damage can be demonstrated. However, it must be distinguished from other psychiatric disorders such as psychosis or depression. There are a variety of signs of the disease, such as muscle paralysis, uncontrolled tremors or cramps. In rarer cases, blindness, deafness or numbness may occur. Diagnosing this complex disorder has always been a challenge for neurologists and psychiatrists. This study investigates the effects of transcranial magnetic stimulation (TMS) on the general well-being and symptoms of conversion disorder and other neurological disorders and in comparison to healthy subjects. The TMS method allows to target specific areas of the brain by means of magnetic fields. This technique is not painful and does not have long-lasting effects. In addition, the study investigates the effects of mindfulness-based stress reduction on the general well-being and symptoms of conversion disorder and other neurological disorders and compared to healthy subjects. This technique is not painful and has no long-lasting effects. Furthermore, the study examines movement patterns and symptoms of patients compared to healthy controls while they are in a virtual reality. Finally, the study examines patients' brain activity while playing a game targeting the sense of agency in real time, which is recorded with an MRI scanner. The study includes a maximum of twelve sessions in total (ten sessions of approximately 1.5-2 hours each and two sessions each overnight). The planned study methods include TMS, (real-time and normal) magnetic resonance tomography of the brain (MRI "tube"), virtual- and augmented reality (AR/VR), questionnaires, blood, saliva, and motion sensors (e.g., fitness bracelet), and participation in the 8-week mindfulness program.

Conditions

Functional Neurological Symptom Disorder; Neurological Diseases or Conditions

Outcome Measures

Primary Outcomes (4)

• Change in objective Performance Agency Task (TMS)

  The changes in objective performance on the behavioural tasks targeting the sense of agency using the score of an agency task played in the Magnetic Resonance Imaging (MRI) scanner, on a computer or in Virtual Reality before and after brain stimulation (transcranial magnetic stimulation, TMS). The performance is measured by counting the number of targets hit minus the number of obstacles hit during the computer game \[-\].

  Visit 1 (at baseline), visit 2 (one week after baseline), visit 3 (two weeks after baseline), visit 7 to 11 (12 - 16 weeks)

• Change in subjective Performance Agency Task (TMS)

  The changes in objective and subjective performance on the behavioural tasks targeting the sense of agency using questionnaires before and after brain stimulation. Participants rate their performance on a visual analog scale (VAS) from 0 to 10 \[-\].

  Visit 1 (at baseline), visit 2 (one week after baseline), visit 3 (two weeks after baseline), visit 7 to 11 (12 - 16 weeks)

• Change in objective Performance Agency Task (MBSR)

  The objective performance on the behavioural tasks targeting the sense of agency using the score of an agency task played in the MRI scanner, on a computer or in Virtual Reality before and after a therapeutic intervention (mindfulness-based stress reduction, MBSR).The performance is measured by counting the number of targets hit minus the number of obstacles hit during the computer game \[-\].

  Visit 4 (at least 1 week after visit 3), visit 5 (8 weeks after visit 4), visit 7 to 11 (12 - 16 weeks)

• Change in subjective Performance Agency Task (MBSR)

  The subjective performance on the behavioural tasks targeting the sense of agency using questionnaires before and after a therapeutic intervention (MBSR). Participants rate their performance on a visual analog scale (VAS) from 0 to 10 \[-\].

  Visit 4 (at least 1 week after visit 3), visit 5 (8 weeks after visit 4), visit 7 to 11 (12 - 16 weeks)

Secondary Outcomes (35)

• task-based fMRI measures TMS

  Visit 1 (at baseline), visit 2 (one week after baseline), visit 3 (two weeks after baseline)

• resting-state fMRI measures TMS

  Visit 1 (at baseline), visit 2 (one week after baseline), visit 3 (two weeks after baseline)

• DTI measures TMS

  Visit 1 (at baseline), visit 2 (one week after baseline), visit 3 (two weeks after baseline)

• task-based fMRI measures MBSR

  Visit 4 (at least 1 week after visit 3), visit 5 (8 weeks after visit 4)

• resting-state fMRI measures MBSR

  Visit 4 (at least 1 week after visit 3), visit 5 (8 weeks after visit 4)

Study Arms (4)

FND Patients Experimental

EXPERIMENTAL

Group of patients with functional neurological disorders

Behavioral: Mindfulness-based stress reduction therapy; Device: Inhibitory TMS; Device: TMS sham; Device: Excitatory TMS; Device: Virtual Reality; Behavioral: Neurofeedback

Organic controls

ACTIVE COMPARATOR

Group of patients with organic neurological disorders

Device: Inhibitory TMS; Device: TMS sham; Device: Excitatory TMS

Healthy controls

ACTIVE COMPARATOR

Group of healthy controls

Device: Inhibitory TMS; Device: TMS sham; Device: Excitatory TMS; Device: Virtual Reality

FND Patients Comparator

ACTIVE COMPARATOR

Group of patients with functional neurological disorders

Device: Inhibitory TMS; Behavioral: Psychoeducation; Device: TMS sham; Device: Excitatory TMS; Behavioral: Neurofeedback

Interventions

Mindfulness-based stress reduction therapy BEHAVIORAL

MBSR Therapy is a structured 8-week program that employs mindfulness meditation to alleviate suffering associated with physical, psychosomatic and psychiatric disorders. The program is based upon a systematic procedure to develop enhanced awareness of moment-to-moment experience of perceptible mental processes.

FND Patients Experimental

Inhibitory TMS DEVICE

The device will be used to neuromodulate the right TPJ of participants' brain using cTBS stimulation protocol for transcranial magnetic stimulation

FND Patients Comparator; FND Patients Experimental; Healthy controls; Organic controls

Psychoeducation BEHAVIORAL

Participants will learn about the symptoms and how to cope with the symptoms

FND Patients Comparator

TMS sham DEVICE

The device will be used to neuromodulate the right TPJ of participants' brain using transcranial magnetic stimulation over the vertex

FND Patients Comparator; FND Patients Experimental; Healthy controls; Organic controls

Excitatory TMS DEVICE

The device will be used to neuromodulate the right TPJ of participants' brain using iTBS stimulation protocol for transcranial magnetic stimulation

FND Patients Comparator; FND Patients Experimental; Healthy controls; Organic controls

Virtual Reality DEVICE

The device will be used to manipulate the perception of symptoms of patients while they are playing a game in virtual/augmented reality.

FND Patients Experimental; Healthy controls

Neurofeedback BEHAVIORAL

Neurofeedback training will be applied in patients while laying in an MRI scanner. Patients will play a game, which targets the sense of agency, and will receive a real-time feedback about their performance and brain activity. They will learn to self-regulate their performance on the game in order to increase brain activity relevant for the sense of agency.

FND Patients Comparator; FND Patients Experimental

Eligibility Criteria

• Age: 17 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients:
• A diagnosis of a functional disorder (such as FND, GTS, PPD, anxiety or depression or others) according to DSM-5 diagnostic and ICD-11 criteria, or
• A diagnosis of an organic neurological disorder such as stroke, multiple sclerosis (MS), neuromuscular, or movement disorder
• Aged \> 16 years old
• Willing to participate in the study (by signing the ICF)
• Capable of judgement
• healthy controls:
• Aged \> 16 years old
• Willing to participate in the study (by signing the ICF)
• Capable of judgement

You may not qualify if:

• Presence of comorbid psychiatric disorders such as psychosis, current major and severe depression episode, autistic spectrum disorder
• Past surgery in the brain
• History of alcohol or drug abuse
• Botulinum toxin injection in last 3 month
• Inability to follow the procedure of the study, e.g., due to language problems
• For organic disorders only: Active severe aphasia, dementia, neglect and acute confusional state, severe pain
• For female participants: breastfeeding, pregnancy or intention to become pregnant (assessed with standard urine test prior to the enrolment in the experiment and before each visit)
• For MRI and TMS part only: Past surgery in the brain
• For MRI and TMS part only: Implanted medical devices not-compatible with MRI or TMS (e.g., cochlear implants, infusion pumps, neurostimulators, cardiac pacemakers)
• For TMS part only: History of actual or suspected epilepsy
• For TMS part only: Suspected or diagnosed labile or hypertensive blood pressure
• For Virtual Reality only: No cybersickness

Sponsors & Collaborators

• University of Fribourg: lead
• Insel Gruppe AG, University Hospital Bern: collaborator

Study Sites (1)

University of Fribourg

Fribourg, 1700, Switzerland

Location

MeSH Terms

Conditions

Conversion Disorder

Interventions

Mindfulness-Based Stress Reduction; Neurofeedback

Condition Hierarchy (Ancestors)

Somatoform Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Mindfulness; Cognitive Behavioral Therapy; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities; Biofeedback, Psychology; Mind-Body Therapies; Complementary Therapies; Therapeutics; Feedback, Psychological

Study Officials

• Selma Aybek, MD

  University of Fribourg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2021
• First Posted: October 20, 2021
• Study Start: December 10, 2021
• Primary Completion: December 16, 2024
• Study Completion: December 16, 2024
• Last Updated: March 4, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)