Detection of Motor Cerebral Activity After Median Nerve Stimulation During General Anesthesia (STIM-MOTANA): Protocol for a Prospective Interventional Study

Background Accidental awareness during general anesthesia (AAGA) is defined as an unexpected awareness of the patient during general anesthesia. This phenomenon occurs in 1%-2% of high-risk practice patients and can cause physical suffering and psychological after-effects, called posttraumatic stress disorder. In fact, no monitoring techniques are satisfactory enough to effectively prevent AAGA; therefore, new alternatives are needed. Because the first reflex for a patient during an AAGA is to move, but cannot do so because of the neuromuscular blockers, we believe that it is possible to design a brain-computer interface (BCI) based on the detection of movement intention to warn the anesthetist. To do this, we propose to describe and detect the changes in terms of motor cortex oscillations during general anesthesia with propofol, while a median nerve stimulation is performed. We believe that our results could enable the design of a BCI based on median nerve stimulation, which could prevent AAGA. Objective To our knowledge, no published studies have investigated the detection of electroencephalographic (EEG) patterns in relation to peripheral nerve stimulation over the sensorimotor cortex during general anesthesia. The main objective of this study is to describe the changes in terms of event-related desynchronization and event-related synchronization modulations, in the EEG signal over the motor cortex during general anesthesia with propofol while a median nerve stimulation is performed. Methods STIM-MOTANA is an interventional and prospective study conducted with patients scheduled for surgery under general anesthesia, involving EEG measurements and median nerve stimulation at two different times: (1) when the patient is awake before surgery (2) and under general anesthesia. A total of 30 patients will receive surgery under complete intravenous anesthesia with a target-controlled infusion pump of propofol. Results The changes in event-related desynchronization and event-related synchronization during median nerve stimulation according to the various propofol concentrations for 30 patients will be analyzed. In addition, we will apply 4 different offline machine learning algorithms to detect the median nerve stimulation at the cerebral level. Recruitment began in December 2022. Data collection is expected to conclude in June 2024. Conclusions STIM-MOTANA will be the first protocol to investigate median nerve stimulation cerebral motor effect during general anesthesia for the detection of intraoperative awareness. Based on strong practical and theoretical scientific reasoning from our previous studies, our innovative median nerve stimulation–based BCI would provide a way to detect intraoperative awareness during general anesthesia. Trial Registration Clinicaltrials.gov NCT05272202; https://clinicaltrials.gov/ct2/show/NCT05272202 International Registered Report Identifier (IRRID) PRR1-10.2196/43870


Criterion : The research project / Critère : le projet de recherche
The overall project is original and ambitious.The already synergistic interaction between the applicant and partners and their expertise allows for a feasible research plan whose final achievements are however of high-risk and no alternative plan is provided.Yet, even if the main goal may not be achieved, there will be still "sub"-outcomes relevant to different fields such as machine learning, BCI, and EEG pattern recognition.

Criterion : The research environment / Critère : L'environnement de recherche
The applicant has already built up the multidisciplinary network -including the respective facilities -to conduct the proposed research in an outstanding environment

Final comment / Commentaire final
Ambitious and high-risk project submitted by a promising young scientist in a perfectly adequate environment.

Weaknesses / Faiblesses
He has done few international mobilities, although he has participated in some international conferences (China, Japan, USA, Wales).

General comment / Commentaire général
He has a very strong experience in MI-BCIs, in addition to having an interdisciplinary formation (cognitive sciences, computer science, psychology, and neuroscience), which will be very useful to the research he proposes to develop.
Criterion : The research project / Critère : le projet de recherche

Strengths / Forces
This proposal aims to develop an innovative MI-BCI to accurately detect the intentions of movement of patients during an AAGA (Accidental Awareness during a General Anesthesia).Specifically, the research has as a innovative goal to detect intraoperative awareness reliably by analyzing, in real-time, brain motor activity under general anesthesia with a BCI based on Median Nerve Stimulation (MNS) and innovative machine learning methods.

Weaknesses / Faiblesses
There is no evidence that movement intention induces detectable changes in EEG patterns with increasing doses of anesthetics even when using MNS.

General comment / Commentaire général
Although several chanlenges must be faced by the candidate, the research proposal is solid and the candidate has quite skill to make it.

Strengths / Forces
This research proposal will be carried out at the Laboratory of Neurophysiology and Movement Biomechanics (LNMB, Université Libre de Bruxelles), which has an international expertise in the area of EEG, evoked potentials, movement analysis and BCI.The LNMB's equipment provides the possibility to record simultaneously EEG, ERP, EMG and 3D motion in a real environment.In addition, ANT highdensity (128-l and 64 channels) EEG systems are used in parallel with the optoelectronic VICON system (10 cameras working at 100 Hz) for motion capture and synchronized to the 16 wireless electromyographic channels (DELSYS) and the Eye-tracker system (TOBII) are available to this research.Also, the LNMB guarantees all the necessary conditions (intellectual, material, and human) to ensure the success of this research.

General comment / Commentaire général
The Laboratory of Neurophysiology and Movement Biomechanics (LNMB, Université Libre de Bruxelles) has an international expertise in the area of EEG, evoked potentials, movement analysis and BCI, and has the suitable equipment necessary to this research.In addition, this research this relies on a top-level interdisciplinary consortium, combining high expertise in the fields of the medical practice of General Anesthesia, Neurosciences and Cerebral Motor activity , MNS-based BCI and Riemannian Geometry and Machine Learning Algorithms for BCIs.

Global comment / Commentaire global
The candidate has been working on brain-computer interfaces (BCI) for 6 years, and has an interdisciplinary formation (cognitive sciences, computer science, psychology, and neuroscience).He has worked on several aspects of BCIs based on Motor Imagery (MI).Regarding clinical research, the candidate has strong experience in this field, both in general anesthesia, stroke rehabilitation, and hypnosis.During his PhD and post-doctorate, he has co-authored several studies involving more than 120 participants and published more than 25 articles (including 6 journal articles) with a total of 85 citations, which demonstrates his expertise in this research field, implying in a high degree of expected success for this research proposal aiming to detect intraoperative awareness reliably by analyzing, in real-time, brain motor activity under general anesthesia with a BCI based on Median Nerve Stimulation (MNS) and innovative machine learning methods.
In additon, the Laboratory of Neurophysiology and Movement Biomechanics (LNMB, Université Libre de Bruxelles) has an international expertise in the area of EEG, evoked potentials, movement analysis and BCI, and has the suitable equipment necessary to this research.A top-level interdisciplinary consortium will part of this research, which has high expertise in the fields of the medical practice of General Anesthesia, Neurosciences and Cerebral Motor activity , MNS-based BCI and Riemannian Geometry and Machine Learning Algorithms for BCIs.

Ethical issues / Aspects éthiques
The ethical aspects of a proposal must be described, as well as the way in which the applicant(s) plan(s) to treat them.Examples of potential ethical issues use and storage of private data, handling of substances potentially damageable to the environment, research involving animals or human beings./ Les aspects éthiques d'une proposition doivent être décrits, de même que la manière dont le(s) proposant(s) prévoi(en)t de les traiter.Exemples de problèmes éthiques potentiels : utilisation et stockage de données privées, manipulation de substances pouvant créer des dommages à l'environnement, recherche sur des animaux ou des êtres humains.

Has(have) the applicant(s) taken into consideration the ethical aspects in his/her (their)
proposal ?Indicate "irrelevant" if need be./ Le(s) proposant(s) a-t-il (ont-ils) pris en compte les aspects éthiques dans son (leur) projet ?Indiquez "non applicable" le cas échéant.

Yes / Oui
Indicate an optional comment regarding the ethical aspects of the proposal./ Indiquez un commentaire optionnel relatif aux aspects éthiques de la proposition.
No comment / Pas de commentaire Rimberts PhD defense and was quite impressed how professionally he presented his results, very structured, logically set-up and very self-confidently.He actively publishes his results and is interested and knowledgable in adjacent field important for his research, such as aspects linked to deep sedation for surgery and ethical aspects of his research.His CV demonstrates that he is also active in parascientific activities such as promotion of young researchers.

Weaknesses / Faiblesses
I admit, those are difficult to find and I had to search for one.The only weakness I came across was, that in his academic record, his PhD thesis is the only one which received a "très honorable".However, I would interpret this as a sign that if Dr. Rimbert can work for goals he is fully interested in, allows him to develop and unfold his full potential.Also, I am not fully aware of the French grading system, thus, I do not know the exact differences between "très honorable" and "assez bien".

General comment / Commentaire général
I consider Dr. Sébstian Rimbert an ambitious and competent researcher with great potential for contributing significant results to the fields of neuroscience and BCI.
Criterion : The research project / Critère : le projet de recherche

Strengths / Forces
-tackles into a clinical very relevant field, i.e.Accidental Awareness during a General Anesthesia (AGAA), which can lead to posttraumatic stress disorder.
-sound background work has been already carried out, thus, solid scientific basis for the proposed work

Weaknesses / Faiblesses
The project is very ambitious and thus, has the potential to not being able to fully accomplish all the tasks.Yet, this is inherent for a project tackling into an unknown field.

General comment / Commentaire général
A high risk project, with a sound background and logical set-up time-and research-wise.Interdisciplinary expertise on board and confirmed committment of the respective people.If successful the clinical contribution of the project would be enormous.Thus, the high risk may lead to high scientific and clinical outcome.Apart from this very clinical and applied scientific aspect, the project will also contribute to a better understand the effects of anesthesia on motor cortical excitability and will provide algorithms for classification of unlabelled data.Thus, even if the main goal may not be achieved, there will be still "sub"-outcomes relevant to different fields such as machine learning, BCI, and EEG pattern recognition.
The project is ambitious as is the resarcher!

Strengths / Forces
-All facilities necessary for the project available (EEG Lab, access to patients, possibility of experimentation with propofol) -international collaboration with researchers in the different fields already set-up and...

General comment / Commentaire général
The applicant has already built up the multidisciplinary network -including the respective facilities -to conduct the proposed research

Global comment / Commentaire global
I rate the applicant as highly qualified and capable of conducting the proposed research as it builts on solid ground: with his PhD and publications he demonstrated his knowledge and also practical expertise in the respective field.
The project is highly relevant, scientifically thought through, challenging and potentially groundbreaking.

Ethical issues / Aspects éthiques
The ethical aspects of a proposal must be described, as well as the way in which the applicant(s) plan(s) to treat them.Examples of potential ethical issues use and storage of private data, handling of substances potentially damageable to the environment, research involving animals or human beings./ Fonds de la Recherche Scientifique -FNRS APPEL/CALL "BOURSES ET MANDATS/GRANTS AND FELLOWSHIPS" 2021 Chargé de recherches [CR] -RIMBERT Sébastien -EVALUATION FINAL REPORT / RAPPORT FINAL D

Fonds
de la Recherche Scientifique -FNRS APPEL/CALL "BOURSES ET MANDATS/GRANTS AND FELLOWSHIPS" 2021 Chargé de recherches [CR] -RIMBERT Sébastien -EVALUATION FINAL REPORT / RAPPORT FINAL Dis an interdisciplinary postdoctoral researcher very experienced in the field of median nerve stimulation and motor cortical excitability as well as machine learning.He, thus, combines two aspects of expertise mandatory to execute the proposed research: profound neuroscientific knowledge and potential to apply machine learning approaches to new fields and scientific challenges.I watched Dr.

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inclusion of healthy participants and patients in need of surgery; large samples thereof -combination of solid neuroscientific knowledge, such as motor excitability and pathways with braincomputer interfacing and machine learning -... -...multidisciplinary reasearch proposal, for which the applicant covers several aspects himself: machine learning, BCI, nerve stimulation -combination of basic and applied research -logically set-up work packages -contribution to the field of BCI and EEG pattern detection of unlabelled data independent of the direct success of the project with respect to the detection of AAGA -systematic research on the effect of different doses of propofol on EEG patterns elicited by median nerve stimulation and motor imagery -development of new algorithms potentially suitable to detect motor imagery pattern in unlabeled data, which are encountered under real world conditions of patients becoming aware under anesthesia; potentially transferable to other classification problems Fonds de la Recherche Scientifique -FNRS APPEL/CALL "BOURSES ET MANDATS/GRANTS AND FELLOWSHIPS" 2021 Chargé de recherches [CR] -RIMBERT Sébastien -EVALUATION FINAL REPORT / RAPPORT FINAL D'ÉVALUATION 40005428 version : 05/10/2022 -Page 7/11 The candidate has been working on brain-computer interfaces (BCI) for 6 years.He has an interdisciplinary formation (cognitive sciences, computer science, psychology, and neuroscience).He has worked on BCIs based on Motor Imagery (MI), mainly to extend the understanding of these BCIs, and to improve their efficiency, exploring different motor imaging tasks, different feedback and user training protocols.He also has contributed to the creation of new algorithms for the analysis and classification (machine learning) of EEG signals.Regarding clinical research, the candidate has strong experience in this field, both in general anesthesia, stroke rehabilitation, and hypnosis.During his PhD and post-doctorate, he has co-authored 10 studies involving more than 120 participants, publishing more than 25 articles (including 6 journal articles) with a total of 85 citations.