Closed-loop Non-invasive Brain Stiumlation (CLOSEDLOOP)

Développement De La Stimulation Non-invasive En Boucle Fermée

Transcranial magnetic stimulation (TMS) is a widely used tool for exploring brain function in humans (Siebner et al. et al., 2022), which has led to new therapeutics for various psychiatric and neurological disorders (Lefaucheur et al., 2020). However, the open-loop use of this technique has raised questions about its operating principle, due to the high degree of heterogeneity of results and the small to medium observed effect sizes (Zrenner and Ziemann, 2023). To increase the response rate, it has been suggested to individualize stimulation, by adapting the TMS parameters (i.e. delivered dose, target dose, targeting, timing, etc.) to instantaneous estimates of brain brain state. Such an approach, known as closed-loop closed-loop stimulation, is currently one of the main challenges challenges in this field (closed-loop brain state-dependent stimulation). To this end, we are focusing on the combination of robotic TMS and electroencephalography (EEG) (Hernandez-Pavon et al. al., 2023). The closed-loop stimulations using this combination developed to date have two limitations: (i) they are not adaptive and focus focus mainly on calculating the phase of brain oscillations to trigger stimulation and (ii) are limited to central cortical (sensorimotor) areas, where the EEG signal-to-noise ratio is optimal.

This project aims to develop closed-loop TMS-EEG protocols that overcome these two limitations: (i) by incorporating adaptive decision modeling (AutoHS model, Harquel et al. 2017) to optimize several parameters in parallel (coil location, orientation, intensity) while using a wider range of EEG markers (evoked potentials, oscillatory activity strength, connectivity, etc.), and (ii) by integrating real-time EEG pre-processing to access any cortical target (including frontal, temporal and occipital lobes).

Study Overview

• Status: Not yet recruiting
• Conditions: Methodologic Study; Non-invasive Brain Stimulation

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Sylvain Harquel, Dr.; Phone Number: +33 (0) 4 76 74 81 56; Email: sylvain.harquel@univ-grenoble-alpes.fr
• Study Contact Backup: Name: Mircea Polosan, Prof.; Email: mpolosan@chu-grenoble.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Healthy volunteers from Grenoble and the surrounding area

Description

Inclusion Criteria:

• Signed informed consent
• Having undergone a medical examination prior to participation in research
• Affiliation with or beneficiary of a social security scheme

Exclusion Criteria:

• Contraindications (CI) to MRI, EEG, TMS practice
• Existence of a severe general medical condition: cardiac, respiratory, hematological, renal, hepatic, cancerous,
• Regular use of anxiolytics, sedatives, antidepressants, neuroleptics,
• Characterized psychiatric pathology,
• Suspicion of alcohol ingestion prior to the examination,
• Participation in other interventional research protocols in progress with exclusion period or in the preceding week.
• Persons covered by articles L1121-5 to L1121-8 of the CSP (French Public Health Code) (corresponds to all protected persons: pregnant women, parturients, nursing mothers, persons deprived of their liberty by judicial or administrative decision, persons under psychiatric care under articles L.

3212-1 and L. 3213-1 who are not covered by the provisions of article L. 1121-8, persons admitted to a health or social establishment for purposes other than research, minors, persons under legal protection or unable to express their consent).

- Personnel with a hierarchical link to the principal investigator

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Healthy subjects

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of EEG markers extracted in real-time	Quality of EEG markers extracted in real-time (evoked potentials, power and phase of brain oscillations and functional connectivity)	During the two TMS-EEG experimental sessions, at day 0 and up to day 30
Quality of EEG marker modulation	Quality of EEG marker modulation induced by TMS parameters selected by the AutoHS decision model	During the two TMS-EEG experimental sessions, at day 0 and up to day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intra-individual (inter-session) reproducibility of primary endpoint quality markers	Intra-individual (inter-session) reproducibility of primary endpoint quality markers	Contrast between the 2 TMS-EEG experimental sessions, at day 0 up to day 30

Collaborators and Investigators

• Sponsor: University Hospital, Grenoble
• Collaborators: GIPSA-lab, Grenoble, France; Laboratoire de Psychologie et NeuroCognition (LPNC), Université Grenoble Alpes

Publications and helpful links

General Publications

• Harquel S, Diard J, Raffin E, Passera B, Dall'Igna G, Marendaz C, David O, Chauvin A. Automatized set-up procedure for transcranial magnetic stimulation protocols. Neuroimage. 2017 Jun;153:307-318. doi: 10.1016/j.neuroimage.2017.04.001. Epub 2017 Apr 5.

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: September 12, 2024
• First Submitted That Met QC Criteria: September 12, 2024
• First Posted (Estimated): September 19, 2024

Study Record Updates

• Last Update Posted (Estimated): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 12, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 38RC24.0193; 2024-A01226-41 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No