Traumatic Brain Injury
Conditions
Keywords
non-invasive brain stimulation, deep brain stimulation, subcortical, memory, neuro-imaging, transcranial temporal interference stimulation, spatial navigation, electroencephalography, traumatic brain injury
Brief summary
Impairments in spatial memory and spatial navigation are commonly reported amongst patients presenting post-traumatic brain injury (TBI). In this study, the investigators examine the effect of non-invasive deep brain stimulation of the hippocampal-entorhinal complex (HC-EC), a key region supporting navigation abilities, on spatial navigation performance in TBI patients. Using a virtual reality task where participants must first encode and later recall the location of objects in a virtual arena, the investigators contrast performance while active versus control stimulation is applied to the HC-EC. The investigators additionally record brain activity using electroencephalography (EEG) prior to, during, and after task performance to characterize the neural correlates of spatial navigation abilities in TBI patients, and how they are affected by stimulation.
Detailed description
Patients will perform a virtual reality spatial navigation task comparable to that used previously by Beanato and colleagues (2024; DOI: 10.1126/sciadv.ado4103). Patients will perform 4 blocks of task, each lasting approximately 10 minutes; during the full duration of each block, either active or control transcranial temporal interference stimulation (tTIS) will be applied in an interleaved manner, and EEG recordings will be collected. Resting-state EEG recordings will also be collected prior to and following task performance. Structural, diffusion-weighted, and resting-state MRI scans will additionally be performed during a prior baseline session.
Interventions
Transcranial temporal interference stimulation (tTIS) is an innovative non-invasive brain stimulation approach, in which two or more independent stimulation channels deliver high-frequency currents in the kHz range (oscillating at f1 and f1 + Δf). These high-frequency currents are assumed to be too high to effectively modulate neuronal activity. Still, by applying a small shift in frequency, they result in a modulated electric field with the envelope oscillating at the low-frequency Δf (target frequency) where the two currents overlap. The peak of the modulated envelope amplitude can be steered towards specific areas located deep in the brain, by tuning the positions of the electrodes and the current ratio across stimulation channels. Here, the investigators apply tTIS via surface electrodes applying a low-intensity, sub-threshold protocol following the safety guidelines for low-intensity transcranial electric stimulation in humans.
Sponsors
Fondation Bertarelli
The Novartis Foundation
Clinique Romande de Readaptation
HUG University hospital
SNF Swiss National Foundation
Wyss Center for Bio and Neuroengineering
Fondation Akiva
Canton du Valais
Friedhelm Hummel
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Clinical diagnosis of TBI * No history of other severe neurological or psychiatric disorders
Exclusion criteria
* Unable to consent * Severe neuropsychiatric (e.g., major depression, severe dementia) or unstable systemic diseases (e.g., severe progressive and unstable cancer, life threatening infectious diseases) * Severe sensory or cognitive impairment or musculoskeletal dysfunctions prohibiting to understand instructions or to perform the experimental tasks * Inability to follow or non-compliance with the procedures of the study * Contraindications for NIBS or MRI: * Electronic or ferromagnetic medical implants/device, non-MRI compatible metal implant * History of seizures * Medication that significantly interacts with NIBS being benzodiazepines, tricyclic antidepressants and antipsychotics * Regular use of narcotic drugs * Pregnancy * Request of not being informed in case of incidental findings * Concomitant participation in another trial involving probing of neuronal plasticity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Accuracy in the spatial navigation task | During intervention (approximate duration of intervention = 40 minutes, administered in a single session) | Accuracy (error, in virtual meters, between correct and recalled object location) in the virtual reality spatial navigation task. |
| Speed in the spatial navigation task | During intervention (approximate duration of intervention = 40 minutes, administered in a single session) | Participant speed (in seconds) of departure to, and reach of, object location in the virtual reality spatial navigation task. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Brain oscillatory activity | Peri-interventional (up to 1 hour; approximate duration of intervention = 40 minutes, administered in a single session) | Resting-state and task-related EEG recordings are collected, and metrics of oscillatory activity are extracted to characterize the neural activity associated to the primary outcome. |
| Brain structure and connectivity | Baseline (before the intervention) | Structural, diffusion-weighted, and resting-state MRI scans are performed during the baseline session and are used to evaluate inter-individual anatomical factors associated to the primary outcome. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Montreal Cognitive Assessment questionnaire score | Baseline (before the intervention) | Participant score on the Montreal Cognitive Assessment questionnaire will be collected to examine its influence on individual responsiveness to the intervention. |
| Frontal Assessment Battery questionnaire score | Baseline (before the intervention) | Participant score in the Frontal Assessment Battery questionnaire will be collected to examine its influence on individual responsiveness to the intervention. |
| Age (years) | Baseline (before the intervention) | Participant age will be recorded to examine its influence on individual responsiveness to the intervention. |
Countries
Switzerland
Outcome results
None listed