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Sense of Agency and Stress in Functional Neurological Disorders

English title Sense of Agency and Stress in Functional Neurological Disorders
Applicant Aybek Rusca Selma
Number 176985
Funding scheme SNSF Professorships
Research institution Universitätsklinik für Neurologie Inselspital Universität Bern
Institution of higher education University of Berne - BE
Main discipline Neurology, Psychiatry
Start/End 01.11.2018 - 31.10.2022
Approved amount 1'583'722.00
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All Disciplines (2)

Discipline
Neurology, Psychiatry
Neurophysiology and Brain Research

Keywords (7)

Conversion Disorder; Agency; functional MRI; Mindfulness Meditation; Transcranial magnetic stimulation; Functional Neurological disorder; Stress

Lay Summary (French)

Lead
Ce projet propose de mieux comprendre le mécanisme responsable d’une maladie neurologique fréquente mais mal connue du grand publique et négligée par la recherche scientifique : les troubles neurologiques fonctionnels.
Lay summary

Contenu et objectif du travail de recherche

Ces troubles se manifestent par des : 1. pertes de force (bras, jambe, visage), 2. Mouvements incontrôlables (tremblement, crampes, secousses) 3. Malaises avec parfois perte de connaissance. Un point commun à ces troubles et que les patients perdent le contrôle volontaire de leur corps (ou le sens d’être les agents de leurs actions: sens de l’agencement)

Le sens de l’agencement est lié au bon fonctionnement d’une région du cerveau en particulier (la jonction temporo-pariétale droite : JTP).

Ce projet va étudier s’il est possible de modifier le fonctionnement de la JTP au moyen de la neuromodulation (application d’un champ électrique sur le crâne).

De plus ce projet va étudier si le stress influence cette région et si on peut améliorer les symptômes par un programme de réduction du stress (méditation sur 8 semaines).

 

Contexte scientifique et social du projet de recherche

Ce projet relève de la recherche fondamentale puisqu’il va étudier les mécanismes cérébraux responsable de cette maladie mais aussi de la recherche clinique car il va tester l’effet d’une méthode (réduction du stress) sur les symptômes. Il fera donc avancer les connaissances dans le but d’amener un meilleur soin aux patients à l’avenir. 

Mots-clés

Trouble neurologique fonctionnel – Neurologie – Psychiatrie – Stress – IRM fonctionnelle – Neuromodulation – Biomarqueurs

Direct link to Lay Summary Last update: 03.10.2018

Responsible applicant and co-applicants

Employees

Publications

Publication
A Review and Expert Opinion on the Neuropsychiatric Assessment of Motor Functional Neurological Disorders.
DL Perez, S Aybek, S Popkirov, K Kozlowska, CD Stephen, J Anderson, R Shura, S Ducharme, A Carson, M Hallett, TR Nicholson, J Stone, WC LaFrance, behalf of the American Neuropsychiatric Association Committee for Research (On (2020), A Review and Expert Opinion on the Neuropsychiatric Assessment of Motor Functional Neurological Disorders., in The Journal of neuropsychiatry and clinical neurosciences, online.
Evidence-Based Practice for the Clinical Assessment of Psychogenic Nonepileptic Seizures: A Report From the American Neuropsychiatric Association Committee on Research.
G Baslet, SN Bajestan, S Aybek, M Modirrousta, JP D Clin Psy, A Cavanna, DL Perez, SS Lazarow, G Raynor, V Voon, S Ducharme, WC LaFrance (2020), Evidence-Based Practice for the Clinical Assessment of Psychogenic Nonepileptic Seizures: A Report From the American Neuropsychiatric Association Committee on Research., in The Journal of neuropsychiatry and clinical neurosciences, online-online.
Functional Neurological (Conversion) Disorder: A Core Neuropsychiatric Disorder.
DL Perez, S Aybek, TR Nicholson, K Kozlowska, DB Arciniegas, WC LaFrance (2020), Functional Neurological (Conversion) Disorder: A Core Neuropsychiatric Disorder., in The Journal of neuropsychiatry and clinical neurosciences, online-online.
Gender, Abuse, and Functional Movement Disorders: From His-story to the Future.
MJ Edwards, S Aybek (2020), Gender, Abuse, and Functional Movement Disorders: From His-story to the Future., in Movement disorders clinical practice, 167-168.
Neural correlates of sense of agency in motor control: A neuroimaging meta-analysis.
GA Zito, R Wiest, S Aybek (2020), Neural correlates of sense of agency in motor control: A neuroimaging meta-analysis., in PloS one, online-online.
Outcome measurement in functional neurological disorder: a systematic review and recommendations.
S Pick, DG Anderson, AA Asadi-Pooya, S Aybek, G Baslet, BR Bloem, A Bradley-Westguard, RJ Brown, AJ Carson, T Chalder, M Damianova, AS David, TR Nicholson (2020), Outcome measurement in functional neurological disorder: a systematic review and recommendations., in Journal of neurology, neurosurgery, and psychiatry, 638-649.
Outcome Measures for Functional Neurological Disorder: A Review of the Theoretical Complexities.
TR Nicholson, A Carson, MJ Edwards, LH Goldstein, M Hallett, B Mildon, G Nielsen, C Nicholson, DL Perez, S Pick, J Stone, group collaborators are as follows FND-COM (2020), Outcome Measures for Functional Neurological Disorder: A Review of the Theoretical Complexities., in The Journal of neuropsychiatry and clinical neurosciences, 33-42.
Transcranial magnetic stimulation over the right temporoparietal junction influences the sense of agency in healthy humans.
GA Zito, LB Anderegg, K Apazoglou, RM Müri, R Wiest, MG Holtforth, S Aybek (2020), Transcranial magnetic stimulation over the right temporoparietal junction influences the sense of agency in healthy humans., in Journal of psychiatry & neuroscience : JPN, 271-278.
Abnormal postural behavior in patients with functional movement disorders during exposure to stress.
GA Zito, K Apazoglou, A Paraschiv-Ionescu, K Aminian, S Aybek (2019), Abnormal postural behavior in patients with functional movement disorders during exposure to stress., in Psychoneuroendocrinology, 232-239.
Corticolimbic fast-tracking in functional neurological disorders: towards understanding of the 'dynamic lesion' of Jean-Martin Charcot.
(2019), Corticolimbic fast-tracking in functional neurological disorders: towards understanding of the 'dynamic lesion' of Jean-Martin Charcot., in Journal of neurology, neurosurgery, and psychiatry, 845.
Functional movement disorders.
S Galli, M Béreau, E Magnin, T Moulin, S Aybek (2019), Functional movement disorders., in Revue neurologique, 244-251.
Modification of both functional neurological symptoms and neuroimaging patterns with a good anatomoclinical concordance: a case report.
S Galli, S Aybek, S Chokron, T Moulin, E Magnin (2019), Modification of both functional neurological symptoms and neuroimaging patterns with a good anatomoclinical concordance: a case report., in BMC neurology, 270.
What Does Neuroscience Tell Us About the Conversion Model of Functional Neurological Disorders?
A Cretton, RJ Brown, WC LaFrance, S Aybek (2019), What Does Neuroscience Tell Us About the Conversion Model of Functional Neurological Disorders?, in The Journal of neuropsychiatry and clinical neurosciences, 24-32.
What Is the Role of a Specialist Assessment Clinic for FND? Lessons From Three National Referral Centers.
S Aybek, SC Lidstone, G Nielsen, L MacGillivray, CL Bassetti, AE Lang, MJ Edwards (2019), What Is the Role of a Specialist Assessment Clinic for FND? Lessons From Three National Referral Centers., in The Journal of neuropsychiatry and clinical neurosciences, 79-84.
Current Concepts in Diagnosis and Treatment of Functional Neurological Disorders.
AJ Espay, S Aybek, A Carson, MJ Edwards, LH Goldstein, M Hallett, K LaFaver, WC LaFrance, AE Lang, T Nicholson, G Nielsen, M Reuber, V Voon, J Stone, F Morgante (2018), Current Concepts in Diagnosis and Treatment of Functional Neurological Disorders., in JAMA neurology, 1132-1141.
Metacognition of visuomotor decisions in conversion disorder.
I Bègue, R Blakemore, J Klug, Y Cojan, S Galli, A Berney, S Aybek, P Vuilleumier (2018), Metacognition of visuomotor decisions in conversion disorder., in Neuropsychologia, 251-265.
Prevalence of functional (psychogenic) parkinsonism in two Swiss movement disorders clinics and review of the literature.
G Frasca Polara, V Fleury, J Stone, A Barbey, PR Burkhard, F Vingerhoets, S Aybek (2018), Prevalence of functional (psychogenic) parkinsonism in two Swiss movement disorders clinics and review of the literature., in Journal of the neurological sciences, 37-45.
Stressful life events and maltreatment in conversion (functional neurological) disorder: systematic review and meta-analysis of case-control studies.
L Ludwig, JA Pasman, T Nicholson, S Aybek, AS David, S Tuck, RA Kanaan, K Roelofs, A Carson, J Stone (2018), Stressful life events and maltreatment in conversion (functional neurological) disorder: systematic review and meta-analysis of case-control studies., in The lancet. Psychiatry, 307-320.

Collaboration

Group / person Country
Types of collaboration
ARTORG center, University Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
Institut de la Moelle et du Cerveau-Paris France (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Hôpitaux Universitaires Genevois (HUG)- Geneva Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Medical Image Processing Lab- EPFL Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Cognitive Neuropsychiatry (IoP) - London Great Britain and Northern Ireland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
Support Center for Advanced Neuroimaging (SCAN)-Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Clinical Neuroscience Bern Annual Meeting 2020 Poster The Effect of a Mindfulness-Based Stress Reduction Program in Functional Neurological Disorder - Study Design and Preliminary Results 23.10.2020 Berne, Switzerland Bühler Janine;
Clinical Neuroscience Bern Annual Meeting 2020 Poster Altered Cortisol Awakening Response in Functional Neurological Disorders 23.10.2020 Berne, Switzerland Weber Samantha;
Grand Rounds Neurology, Massachusetts General Hospital Individual talk From Hysteria to Functional Neurological Disorders: what has Neuroscience taught us? 18.07.2020 Boston (virtual), United States of America Aybek Rusca Selma;
Annual meeting American Epilepsy Society (AES) Talk given at a conference Psychogenic Nonepileptic Seizures: From Challenges to Practical Management 06.12.2019 Baltimore, United States of America Aybek Rusca Selma;
Department for BioMedical Research Day Poster The brain networks of agency and prior beliefs. Evidence from fMRI in healthy humans 13.11.2019 Bern, Switzerland Zito Giuseppe;
Department for BiomMedical Research Day Poster Machine Learning Analysis of Resting-State Functional Connectivity data identifies the right Nucleus Caudate as a most discriminant region in Functional Neurological Disorders 13.11.2019 Berne, Switzerland Weber Samantha;
4thOHBM Alpine Chapter Meeting Talk given at a conference Transcranial magnetic stimulation over the right temporo-parietal junction influences the sense of agency in healthy subjects 09.11.2019 Innsbruck, Austria Zito Giuseppe;
International Congress of Parkinson’s disease and Movement Disorders (MDS) Talk given at a conference Connecting Pathophysiology and Risk Factors to Clinical Care in Functional Movement Disorders 23.09.2019 Nice, France Aybek Rusca Selma;
Clinical Neuroscience Bern Annual Meeting 2019 Poster Identification of Functional Neurological Disorders by a Support Vector Machine Classifier based on the Resting-State Functional Connectivity 14.06.2019 Bern, Switzerland Weber Samantha;
Italian Academy of Movement Disorders (Accademia Limp-Dismov) Talk given at a conference Neuroimaging 14.06.2019 Verona, Italy Aybek Rusca Selma;
12th European Conference on Tourette Syndrome and Tics Disorders Talk given at a conference Functional Neurological Disorders 15.05.2019 Hannover, Germany Aybek Rusca Selma;


Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Disorder of Mind and Brain Scientific American International 2020

Awards

Title Year
SNF Mobility fellowship 2019

Associated projects

Number Title Start Funding scheme
147997 L'hypothèse du stress dans le Trouble de Conversion 01.09.2014 Ambizione

Abstract

Background and rationale: Functional neurological disorder (FND) (formerly Hysteria/Conversion disorder) is a disabling and frequent disorder. This field of medicine suffers from a lack of research and no targeted treatment option is available. A better understanding of the mechanisms is needed. Evidence for abnormal sensori-motor processing (agency) and stress dysregulation exists. The link between the two has never been studied.Overall objective: Explore the links betweens abnormal agency and stress in FND.Specific Aims: 1) study the neural correlates of agency with neuroimaging (fMRI)2) study their correlation with biological stress parameters (cortisol and amylase)3) study the effect of transcranial magnetic stimulation (rTMS) on agency by targeting a key node of the network; the right temporo-parietal junction (rTPJ)4) study the effect of mindfulness-based stress reduction (MBSR) therapy on agency, stress and clinical outcome.Methods: Two main prospective studies over the 4 years will address these 4 aims. STUDY A will include 60 FND patients and 40 healthy controls in an fMRI agency task. Subjects will be randomized in a single-blind design to receive real or sham TMS on the rTPJ before repeating the same fMRI agency task. Cortisol and amylase will be analysed in saliva samples. STUDY B will include 80 FND patients in a randomized trial to receive either 8-week MBSR or treatment as usual. The agency task, stress and clinical measures will be collected before and after the intervention. A 6 months follow-up will look at clinical outcome. Expected results: We hypothesize that 1) the agency network is abnormal in FND and that TMS can change this network, when applied over the rTPJ, 2) the agency performance and related brain activations are correlated with stress parameters (the higher the stress, the poorer the agency) 3) MBSR reduces stress and improves clinical outcome and this is mediated by improvement in agency.Impact for the field: This project will contribute to the understanding of FND by bridging two current lines of research investigating HOW the symptoms are produced (agency) and WHY (stress risk factors). It will test two mechanisms by which clinical outcome could be improved; neuromodulation and stress reduction therapy, which will open new lines of research on targeted treatments.
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