Clinical Research Directory

TMS for iEEG Monitoring Recordings

The current study presents a unique opportunity to measure the direct effects of transcranial magnetic stimulation (TMS) by using intracranial electrodes to record neural activity in deep brain regions when TMS single pulses are delivered. If TMS can evoke downstream responses in neural networks of the human brain, it can be a feasible way to study circuit engagement and connectivity.

Non-Invasive Detection and Preservation of Neurocognitive Signals in the Peri-Death Period Using Brain-Computer Interface and Artificial Intelligence

Background: Recent electroencephalography (EEG) data indicate that the transition from clinical death to cellular death is marked by highly organized neurophysiological events, including significant surges in gamma-band power, cross-frequency coupling, and distinct spreading depolarization waves. This prospective, observational feasibility study utilizes rapid-deployment, high-density, noninvasive BCI hardware paired with proprietary AI analytics to detect, classify, and securely archive these terminal neurocognitive signals. Objectives: (1) Quantify transient gamma-band activity and cross-frequency connectivity post-clinical death; (2) Validate the efficacy of machine learning models for real-time signal classification in high-noise clinical environments; (3) Establish a highly secure, encrypted bio-informational archive of peri-life EEG data. Design: Prospective, open-label, multicenter, observational cohort (n\>20).

Dynamic Causal Modeling of Neuromodulation of Action Speed Via Targeted TMS-EEG

Stroke is a major cause of long-term disability, with cognitive and motor deficits-especially action slowing and executive dysfunction-being strong predictors of poor recovery outcomes. Recent advances in network neuroscience suggest that action speed is governed by interactions between specific prefrontal and premotor regions. However, the precise neural mechanisms underlying action slowing in stroke remain unclear, limiting the efficacy of current rehabilitation approaches. This study integrates high-density EEG, fNIRS and dynamic causal modeling (DCM), and rTMS to map and modulate the neural circuits involved in action speed. In the first phase, we will assess the role of seven key brain regions in action speed modulation by applying virtual lesions using single-pulse TMS in 60 healthy individuals. In the second phase, we will apply offline intermittent theta burst stimulation (iTBS) to the most relevant regions and evaluate its impact on action speed. Finally, in the clinical phase, we will administer individualized iTBS to 20 stroke patients to enhance action speed. Patients will be assessed at baseline, immediately post-treatment, and after one and three months to track improvements in action speed using DCM and behavioral tests. Changes in connectivity and action speed performance will be compared to healthy controls to refine treatment parameters. Secondary outcomes include executive function and daily life motor performance. Longitudinal follow-up will determine the persistence of improvements, informing future personalized rehabilitation strategies. By characterizing effective connectivity changes post-stroke, we aim to refine neuromodulation strategies and develop a personalized rTMS approach. Our hypothesis is that targeting specific regions identified through integration of EEG, fNIRS and DCM can enhance action speed, ultimately improving functional recovery. This personalized approach could lead to more effective rehabilitation protocols, tailored to individual brain damage patterns.

Neural Correlates of Goal-directed Action Observation and Execution in Children With Unilateral Cerebral Palsy

Cerebral palsy (CP) is the most common childhood-onset motor disorder, with Unilateral Cerebral Palsy (UCP)- motor impairment predominantly impacting one side of the body-representing the most frequent form of CP. Among available rehabilitation programs, Action Observation Treatment (AOT) has gained increasing attention for its demonstrated effectiveness in improving manual motor function. AOT involves the systematic observation of goal-directed actions followed by their execution/imitation and is thought to leverage the mirror mechanism and its role in motor learning. Specifically, it relies on the neurophysiological principle that observing others' actions activates the same neural structures involved in executing those actions, reflecting the engagement of the mirror neuron system (MNS). In children with CP, the feasibility and effectiveness of AOT have been shown functionally (Sgandurra et al., 2013, Buchignani et al., 2019). However, despite its theoretical grounding in MNS functioning, the neurophysiological correlates of this system in children with CP remain less characterized, with only limited investigations using functional neuroimaging (e.g., Sgandurra et al., 2020) or neurophysiological methods such as electroencephalography (EEG; e.g., Demas et al., 2019). This observational study aims to characterize the neurophysiological signatures of action execution and action observation in children aged 5-15 years with a diagnosis of UCP compared to a group of age-matched typically developing (TD) peers. To this end, non-invasive high-density EEG (hdEEG) will be used to quantify sensorimotor cortex modulation through mu-rhythm reactivity-specifically event-related desynchronization (ERD) and synchronization (ERS)-and its topographical distribution during an active visuo-motor task involving upper limbs. Mu-rhythm desynchronization (or suppression) over sensorimotor regions is a well-established marker of MNS engagement. A secondary objective is to examine the relationship between EEG measures and participants' attention, upper-limb kinematics, and manual motor function. To this purpose, participants will wear non-invasive wearable sensors to capture arm/hand kinematics, and attention will be monitored with a non-invasive eye-tracking system. Validated scales will be used to assess manual motor function. Participants will take part in one single visit of about 1.5 hours. During the EEG acquisition session, children will wear a 128-channel EEG net and complete an active visuo-motor paradigm including the observation and execution of unimanual and bimanual goal-directed actions (e.g., reaching-grasping). In the observation condition, children will watch videos depicting these actions on a computer screen while refraining from movement. In the subsequent execution condition, they will interact themselves with the same objects as in the observation condition. Throughout the same session, children's attention/gaze will be tracked via eye-tracking, and upper-limb kinematics will be recorded using wearable inertial measurement unit (IMU) sensors. Before or after EEG acquisition, manual motor function will be assessed using two standardized scales: the Assisting Hand Assessment (AHA) and the Melbourne Assessment-2 (MA-2). Data analysis will characterize the mu rhythm ERD topography and temporal dynamics during both action execution and action observation, within and between groups. Correlation analyses will explore associations between neurophysiological measures, gaze and attentional patterns, kinematic data, and motor assessments scores to elucidate how motor and attentional factors modulate sensorimotor cortical activation.

Observational Study on the Impact of Obstructive Sleep Apnea on Executive Function and Empathy Development in Children

This study aims to investigate the effects of obstructive sleep apnea (OSA) on executive function and empathy development in children aged 3-12 years. The study will compare the outcomes of different treatment approaches (surgical vs. pharmacological) in children with mild OSA and track the progression of cognitive and emotional functions over 12 months. The study will also explore potential EEG biomarkers for assessing neurological damage in OSA children.

Home-based Transcranial Direct Current Stimulation (tDCS) Compared to Duloxetine: Non-inferiority Clinical Trial (FIBROSTIM)

Fibromyalgia is characterized by widespread pain, fatigue, non-restorative sleep, and psychocognitive alterations, compromising quality of life and leading to absenteeism and early retirement. Up to 70% of patients discontinue treatment with antidepressants and anticonvulsants due to adverse effects or low efficacy, and more than 30% resort to opioid use. Given the treatment challenges and the scarcity of safe alternatives, there is growing interest in interventions such as transcranial direct current stimulation (tDCS), which has shown efficacy in improving symptoms and functionality, with low cost and few side effects. In this context, we designed a randomized, double-blind, double-dummy clinical trial to compare the non-inferiority of 28 home-based anodal tDCS (2 mA) applied over the primary motor cortex (M1) versus duloxetine 60 mg. Both treatments will be combined with physical exercise and pain education. Outcomes will be assessed through multidimensional measures of pain, functionality, global impression of improvement, and the function of the descending pain inhibitory system. Secondary outcomes include quality of life, depressive symptoms, psychophysical pain measures, and treatment adherence. An additional analysis will compare the results of sham tDCS and duloxetine placebo within the non-inferiority model. Predictors of treatment response will also be explored, including symptom severity and oscillatory patterns of cortical electrical activity, rest-activity rhythm, and autonomic function assessed by R-R interval. Furthermore, serum levels of S100-B protein, brain-derived neurotrophic factor (BDNF), and genetic variants related to neuroplasticity in the BDNF Val66Met, Catechol-O-Methyltransferase (COMT) (rs4680) (G\>A), OPRM1, and PER2 genes will be analyzed. Inflammatory markers (TNF-α, IL-1, IL-2, IL-6, IL-10, C-reactive protein) and serum endorphins will also be assessed. A total of 610 women with fibromyalgia (aged 18 to 75 years) will be randomized into three groups (2:2:1): duloxetine + sham tDCS (n=244); active tDCS + placebo (n=244); and sham tDCS + placebo (n=122). Participants will be assessed during treatment and at 3, 6, and 12 months after completing the intervention protocol. An interim analysis will be conducted when \~50% of participants (n ≈ 305) complete the 3-month follow-up by an independent, blinded Data Monitoring Committee (DMC). (i) The trial may be stopped if the conditional probability of demonstrating non-inferiority is \<10%, based on frequentist or Bayesian methods. (i) The trial will be stopped if serious adverse events (SAEs) in the active tDCS group increase by ≥30% compared to duloxetine (p \< 0.01, adjusted). (ii) Early stopping for efficacy will be considered if active tDCS demonstrates clear non-inferiority or superiority over duloxetine on the primary outcome. Superiority requires: (iii) a clinically relevant difference exceeding the non-inferiority margin (≥10% pain reduction); (ii) statistical significance (p \< 0.005, O'Brien-Fleming adjusted); and (iii) a ≥2-point (20%) improvement on the BPI, confirmed in the ITT analysis. This study aims to generate evidence to support the decision-making process of the National Committee for Health Technology Incorporation (CONITEC) regarding the availability of tDCS in the Brazilian Unified Health System (SUS). In addition, identifying predictors of response to tDCS and duloxetine, through the integration of genetic, neurophysiological, inflammatory, and psychosocial markers using machine learning algorithms, will allow for identifying factors that can personalize fibromyalgia treatment. This approach enhances clinical efficacy, reduces costs associated with ineffective interventions, and supports more accurate therapeutic decisions, expanding access to safe, effective, and sustainable care within the public healthcare system

Dynamic Neural Systems Underlying Social-emotional Functions in Older Adults

Assess the impact of a remote, app-delivered digital meditation intervention on emotional well-being of lonely older adults. Neuroimaging, electrophysiological (EEG), and autonomic physiology will be used to assess the neural correlates of the intervention. EEG and autonomic physiology will be collected while participants watch 30 min of an awe-inspiring movie. fMRI and autonomic physiology will be collected in the context of a social exploration/exploitation task.

Mindfulness Walking Intervention to Enhance Resilience (iWalk)

This study is a randomized controlled trial of the walking meditation intervention (iWalk) program, a multi-component intervention integrating walking meditation, education, and group sessions designed to enhance resilience in individuals with multiple sclerosis (MS). The objectives are to evaluate: 1. Recruitment capability and retention rates, 2. Acceptability and adherence to the intervention, 3. Feasibility of assessment procedures, and 4. Preliminary effects on psychological, physiological, and behavioral outcomes.

Study of the Correlation Between Cortical Excitability and Cytoarchitectonics of Prefrontal Cortex in Healthy Adult Participants, Using Transcranial Magnetic Stimulation Coupled to EEG and High-field MRI

Repeated transcranial magnetic stimulation (rTMS) is mainly used to treat mood disorders by addressing differences in brain function, particularly in the dorsolateral prefrontal cortex (DLPFC), which affects emotions and executive functions. The therapy aims to enhance the left DLPFC or suppress the right. It has been approved for severe major depression in several countries (Canada and Israel since 2002, USA since 2008) and is in the process of being validated in Europe but is not yet reimbursed in France. due to variable results from one study to another and lack of standardization issues. In a previous study, by recording electroencephalographic (EEG) rhythms before and after rTMS treatment of the DLPFC, the investigators showed on a small cohort of patients (n=17) with major or bipolar depression, that the responder patients showed higher EEG theta rhythms in the DLPFC but also and especially in parietal regions. This suggests that the DLPFC is part of the fronto-parietal central executive network (CEN), which is important for working memory and cognitive control. The CEN is not well connected in severe resistant depression, possibly leading to negative emotional bias. The rTMS cure of DLPFC can be interpreted as improving depressive symptoms through the normalization of the CEN by increasing DLPFC excitability and its downward connectivity. However experimental and clinical evidence for this mechanism, among others, is still to be demonstrated, and remission rates of rTMS from DLPFC in drug-resistant depression are still low (20-40%). To improve these response rates to rTMS in DLPFC, it is essential to continue research aimed at improving clinical practices through a better knowledge of the functional neuroanatomy and mechanisms of action of rTMS. This will require the definition of biomarkers allowing in particular to better target the DLPFC, this structure beeing indeed relatively poorly defined on the neuroanatomical level (large portion of the medial frontal gyrus). To this end, the investigators have set up a collaborative research program with Dr. Corey Keller, psychiatrist at Stanford University USA, which was jointly funded in 2022 by the Agence Nationale pour la Recherche (ANR) and the National Institute of Health (NIH) - FrontalProbe project "Probing the dorsolateral prefrontal cortex and central executive network for improving neuromodulation in depression". The ultimate aim of this project is to develop and test different strategies for targeting the DLPFC in the rTMS treatment of pharmaco-resistant depressive patients, following the fundamental neuroanatomical and pathophysiological hypothesis that patients will respond better to therapy if their CEN network is better modulated. This clinical trial will take place in Stanford, USA, in the years 2025-2026. Previously, the investigators are working on the development of methodological strategies aimed at preferentially activating, in a personalized way, the part of the DLPFC that projects onto the PPC. This is the subject of the present protocol, which aims to identify this subpart of the DLPFC to be targeted as a priority for modulating the CEN, through neuroanatomical measurements with high-field MRI and cortical excitability by TMS-EEG in healthy subjects. To this end, the investigators will use a small cohort of healthy subjects who will have one multimodal MRI acquisition session of at 7T and one TMS-EEG session. The 7T MRI data, acquired at the Centre de Résonance Magnétique en Biologie et Médecine (CRMBM), will be used to obtain anatomical markers of the DLPFC. TMS-EEG data, acquired at the Institut de Neurosciences de Systèmes (INS), will be used for cortical excitability measurements of the DLPFC and its projection sites, notably the PPC. At this stage, no data exchange is planned with our American partners. Firstly, the processing of MRI data will include segmentation of gray and white matter, reconstruction of the cortical surface and estimation of the different cortical layers, mainly by monitoring variations in the T1 parameter along the cortical mantle. Other MRI parameters will also be acquired to maximize the specificity of the segmentation of the DLPFC into sub-regions, firstly by identifying the part of the DLPFC that connects preferentially to the PPC using the reconstruction of fiber bundles from diffusion MRI and functional resting MRI. Secondly, during TMS-EEG acquisitions, participants will be stimulated in 3 sub-regions of the DLPFC. For each target, the analyses of the EEG data will focus on quantifying connectivity with the PPC as well as their spectral signature, which is possibly an indirect reflection of the neuronal composition of the stimulated regions. Correlation of 7T MRI and TMS-EEG data will help set optimal DLPFC targeting criteria for PPC activation. The aim is to create an MRI-based targeting procedure for clinical practice. In this sense, TMS-EEG will serve as validation of MRI markers.

Early WAKE-up Predictors After Out-of-Hospital Cardiac Arrest

WAKE-OHCA is a prospective observational substudy of the Danish Out-of-Hospital Cardiac Arrest (DANOHCA) trial, identifier NCT05895838. The aim is to collect early neuromonitoring data to identify key predictors of successful wake-up.

Neurofeedback Training for Autistic Children

The goal of this study is to learn if a new brain training method, called combined electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) neurofeedback, can improve thinking, emotions, and social functioning in children with autism spectrum disorder (ASD). It will also learn if this training is practical and safe to use with children in Hong Kong. The main questions this study aims to answer are: * Does combined EEG-fNIRS neurofeedback improve attention, emotion regulation, and social skills in children with ASD? * Is this type of neurofeedback training feasible and well-tolerated by children? Researchers will compare the new combined EEG-fNIRS training with single EEG or fNIRS training to see if it provides additional benefits. Participants will: .Receive sessions of EEG-fNIRS neurofeedback training. .Complete assessments of thinking skills, emotional regulation, and social functioning before and after training.

Rural Autistic Individuals - Supporting Expression

This research study investigates how hand gestures can support language comprehension and communication skills of hearing speaking, non-speaking, and/or minimally verbal individuals with Autism Spectrum Disorders (ASD), who are especially disadvantaged by the lack of accessible services in their rural communities. Individuals with other cognitive profiles, including Developmental Language Disorder (DLD), ADHD, Dyslexia, and others are welcome too. The study uses methods of eye tracking and recording of brain activity to understand how hand gestures adapted from signs from American Sign Language, such as \[cry\], can promote successful understanding of words like "cry". The overarching goal is to help families effectively utilize gestures to support communication with their children.

Neural Signatures of Processing the Temporal Features of Auditory Events: From Preterm Infancy to Adulthood

Premature neonates are able to discriminate phonemes and voice from 28wGA at a time the neuronal network establish contact between the environment and the cortical neurones. In the present monocentric study the investigators will analyse the response of the cortical network in premature aged between 25 and 36 wGA in response to auditory stimuli using High Resolution Electroencephalography and High Density Near Infrared Spectroscopy.

Multimodal Analysis of the Young Brain on Rhythm Perception: From Premature Neonates to Infants

Premature neonates are able to discriminate phonemes and voice from 28wGA at a time the neuronal network establish contact between the environment and the cortical neurones. In the present monocentric study the investigators will analyse the response of the cortical network in premature aged between 28 and 40 wGA in response to auditory stimuli using High Resolution Electroencephalography and High Density Near Infrared Spectroscopy

Comparing Brain Cortical Activity in Real and Immersive Virtual Reality Manual Dexterity Tasks

With advances in technology, virtual reality (VR) is increasingly used in various fields, including rehabilitation, motor learning, and neuroscience. Its ability to provide controlled, immersive, and interactive environments makes it a valuable tool for training and assessment. However, despite its growing adoption, limited evidence exists on how cortical activation in VR compares to real-world conditions. Moreover, brain cortical activity during motor tasks, such as manual dexterity tasks, remains underexplored. This study aims to compare brain cortical activity in real and immersive virtual reality settings during a manual dexterity task. Secondary objectives include: * Examining the relationship between brain cortical activity and kinematics in both conditions. * Comparing brain cortical activity between hand-tracking and controller-based interactions.

Nitrous Oxide in the Treatment of Acute Suicidal Ideation

The primary aim of the NITOS study is to investigate the potential rapid antisuicidal effects of N2O in the transdiagnostic treatment of suicidal ideation. On day 1, patients will receive either nitrous oxide (50% N2O balanced with oxygen) or placebo (50% oxygen balanced with air). Seven days after the first inhalation, a second inhalation will be performed. All patients will receive N2O at least once during this trial. While the first inhalation will be double-blind, only the patients but not the raters will be blinded to the second inhalation (day 8). For mechanism of action and prediction, a nested biomarker substudy will employ multimodal techniques including analysis of hair and blood samples, and EEG.

Investigation of the Possibility of Determining Cerebrovascular Disease Based on Hemodynamic Information of Localized Brain Regions

The purpose of this study is to compare hemodynamic information from localized brain regions between stroke patients and healthy adults using brain activity data (fNIRS and EEG) and to assess the accuracy of early stroke diagnosis and classification predictions.

Exploratory Study on Artifact Denoising of Cerebral Blood Flow and EEG Data in Ambulance Settings

The purpose is to assess the extent of digital noise occurring during the measurement of cerebral blood flow and EEG in healthy adults within an ambulance setting and to explore the possibility of identifying and correcting abnormal patterns.

Early Neuroprognostication After OHCA

This is a prospective observational substudy of the STEPCARE trial ClinicalTrials.gov Identifier: NCT05564754) with the aim to examine whether prognostication of neurological outcome after cardiac arrest can be performed earlier than the 72 h time-point recommended by guidelines today.

High Definition Transcranial Direct Current Stimulation (HD-tDCS) for Refractory Epilepsy

To observe the clinical effect and safety of transcranial electrical stimulation on patients with refractory epilepsy before and after treatment and analyze its therapeutic mechanism.

Electrophysiological Signatures of Distinct Working Memory Subprocesses That Predict Long-term Memory Success

Healthy young adults will view pictures of items while the investigators record electroencephalogram (EEG) brain activity. Then, the investigators will ask the participants to report which items the participants remember seeing. The investigators will examine how the measured brain activity relates to which pictures the participants remember.