Thesis Jasmine CARLIER

Psychogenic non-epileptic seizures (PNES) constitute the most common subtype of functional neurological disorder (FND). The underlying pathophysiology remains unexplained and specific therapeutic tools are not present contributing to a poor prognosis and major healthcare costs. Behavioral and neuroimaging studies suggest disrupted emotional processes in PNES. However, the current data remains limited and inconsistent due to varying research methods. Therefore, PNES have been repeatedly associated with disrupted autonomic nervous system (ANS) patterns. The ANS is of particular interest because of its involvement in emotional processes. According to models, effective emotional regulation depends on a coupling between cognitive and autonomic responses. The hypothesis of a relationship between autonomic profiles, brain activity and emotional disorders in patients with PNES needs to be elucidated. An original approach to test whether PNES are linked to dysautonomic responses, consists of assessing how artificial modulation of ANS can modulate both emotional regulation and PNES. The biofeedback (BFB) is a non-invasive and efficient approach based on a neuromodulation of autonomic control. This technique has been emphasized as a potential therapeutic tool in epileptic disorders, but it has never been assessed in adult PNES. It is a promising tool for understanding the causes of emotional disorders and for developing a functional therapy for PNES.
The purpose of this project is to develop a personalized approach and an evidence-based therapeutic management, and aims to: (1) Explore the neurobiological substrates underlying emotional disorders in PNES, (2) Search for autonomic endophenotypes in patients, (3) Determine whether BFB is a beneficial therapeutic approach for the improvement of PNES, and (4) Develop a computational model of PNES. We hypothesize some PNES patients have a dysautonomic profile with a defect into the autonomic and emotional coupling, which may be improved by BFB, and this effect will be determined by a multimodal investigation and predicted by a computational analysis.
This multidisciplinary project will be part of a co-directed thesis initiating a new international collaboration between two Psychology and Neurocognition (Pr. Hot, Chambéry) and Neurology (Pr. Nguyen, Montréal, Canada) teams. Four sequential phases will be developed using an innovative experimental protocol. The first phase will investigate the emotional specificities in PNES. Based on a G power calculation, 21 subjects in 3 comparative groups each such as PNES, healthy controls and epileptic patients will be included. All subjects will perform emotional induction (T1) and re-exposure (T2) tasks combined with multimodal analyses including behaviour (B), psychophysiology (P) (heart rate variability (HRV) and skin conductance activity), and neuroimaging (N). Phase 2 will examine the therapeutic effect of HRV-BFB on PNES. Patients with PNES will carry out consecutive randomized BFB or pseudo BFB protocols for 6 weeks. Each patients will be their own control. The effects of HRV-BFB on change in seizure frequency and quality of life will be calculated. In Phase 3, patients will perform a final emotional re-exposure (T3), and B, P, and N measures will be repeated. According to the findings from Phase 1 and 2, the impact of BFB on emotional reactivity and potential changes in neurobiological patterns will be examined. In Phase 4, a computational model derived from the previous experimental data will be developed. This model will encode the influence of ANS on the occurrence of PNES, and assess the predictive value of different endophenotypes in the response to BFB. Given the major challenge posed by PNES, it seems essential to understand the underlying pathophysiology and to target it to develop an integrative personalized therapy. Finally, the large database and the computational model developed will enable further shared international collaborations.

Supervisors :
Pascal HOT - PR USMB - pascal.hotuniv-smb.fr (pascal[dot]hot[at]univ-smb[dot]fr)
Dang Khoa Nguyen - d.nguyenumontreal.ca (d[dot]nguyen[at]umontreal[dot]ca)

Keywords : Psychogenic nonepileptic seizures,Emotional regulation,Autonomic nervous system,Multimodal imaging,Biofeedback,Computational Neurosciences