Non-invasive Deep Brain Stimulation to Improve Spatial Navigation Abilities in Individuals Following Traumatic Brain Injury

N/ANot Yet RecruitingNCT07271524

Friedhelm Hummel25 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Enrollment

Conditions

Interventions

Transcranial electric stimulationOTHER

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Speed in the spatial navigation task

Participant speed (in seconds) of departure to, and reach of, object location in the virtual reality spatial navigation task.

Time frame: During intervention (approximate duration of intervention = 40 minutes, administered in a single session)

Accuracy in the spatial navigation task

Accuracy (error, in virtual meters, between correct and recalled object location) in the virtual reality spatial navigation task.

Time frame: During intervention (approximate duration of intervention = 40 minutes, administered in a single session)

Secondary Outcomes

Brain oscillatory activity

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.

Time frame: Peri-interventional (up to 1 hour; approximate duration of intervention = 40 minutes, administered in a single session)

Brain structure and connectivity

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.

Time frame: Baseline (before the intervention)