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

NCT ID: NCT07271524

Last Updated: 2025-12-09

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-31
• Study Completion Date: 2027-12-31

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.

Conditions

Traumatic Brain Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Active stimulation

Patterned stimulation (intermittent theta-burst) generating temporal interference in the hippocampal-entorhinal complex; see Beanato et al. 2024, Sci Adv (DOI: 10.1126/sciadv.ado4103) for details.

Group Type: EXPERIMENTAL

Transcranial electric stimulation

Intervention Type: OTHER

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.

Control stimulation

High-frequency (2kHz) electrical stimulation with no frequency shift, generating no temporal interference.

Group Type: PLACEBO_COMPARATOR

Transcranial electric stimulation

Intervention Type: OTHER

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.

Interventions

Transcranial electric stimulation

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.

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondation Bertarelli

UNKNOWN

Sponsor Role: collaborator

The Novartis Foundation

OTHER

Sponsor Role: collaborator

Clinique Romande de Readaptation

NETWORK

Sponsor Role: collaborator

HUG University hospital

UNKNOWN

Sponsor Role: collaborator

SNF Swiss National Foundation

UNKNOWN

Sponsor Role: collaborator

Wyss Center for Bio and Neuroengineering

OTHER

Sponsor Role: collaborator

Fondation Akiva

UNKNOWN

Sponsor Role: collaborator

Canton du Valais

UNKNOWN

Sponsor Role: collaborator

Friedhelm Hummel

OTHER

Sponsor Role: lead

Responsible Party

Friedhelm Hummel

Professor, Defitech Chair of Clinical Neuroengineering Brain Mind Institute

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

EPFL, Campus Biotech

Geneva, Canton of Geneva, Switzerland

EPFL Valais, Clinique Romande de readaptation

Sion, Valais, Switzerland

Countries

Switzerland

Facility Contacts

Friedhelm Hummel

Role: primary

friedhelm.hummel@epfl.ch

+41 27 603 23 59

Friedhelm Hummel

Role: primary

friedhelm.hummel@epfl.ch

+41 27 603 23 59

Other Identifiers

2020-00127

Identifier Type: OTHER

Identifier Source: secondary_id

2020-00127-wp73t

Identifier Type: -

Identifier Source: org_study_id