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

NCT07271524 | Not Yet Recruiting

• 2 other identifiers: 2020-00127-wp73t2020-00127
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

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.

Conditions

Traumatic Brain Injury

Keywords

non-invasive brain stimulation; deep brain stimulation; subcortical; memory; neuro-imaging; transcranial temporal interference stimulation; spatial navigation; electroencephalography; traumatic brain injury

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

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

Secondary Outcomes (2)

• Brain oscillatory activity

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

• Brain structure and connectivity

  Baseline (before the intervention)

Other Outcomes (3)

• Age (years)

  Baseline (before the intervention)

• Montreal Cognitive Assessment questionnaire score

  Baseline (before the intervention)

• Frontal Assessment Battery questionnaire score

  Baseline (before the intervention)

Study Arms (2)

Active stimulation

EXPERIMENTAL

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.

Other: Transcranial electric stimulation

Control stimulation

PLACEBO COMPARATOR

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

Other: Transcranial electric stimulation

Interventions

Transcranial electric stimulation 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.

Active stimulation; Control stimulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• Clinical diagnosis of TBI
• No history of other severe neurological or psychiatric disorders

You may not qualify if:

• 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

Sponsors & Collaborators

• Friedhelm Hummel: lead
• Fondation Bertarelli: collaborator
• The Novartis Foundation: collaborator
• Clinique Romande de Readaptation: collaborator
• SNF Swiss National Foundation: collaborator
• Wyss Center for Bio and Neuroengineering: collaborator
• Fondation Akiva: collaborator
• Canton du Valais: collaborator
• University of Guadalajara: collaborator

Study Sites (2)

EPFL, Campus Biotech

Geneva, Canton of Geneva, 1202, Switzerland

Location

EPFL Valais, Clinique Romande de readaptation

Sion, Valais, 1950, Switzerland

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic; Spatial Navigation

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Spatial Behavior; Behavior

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Defitech Chair of Clinical Neuroengineering Brain Mind Institute

Study Record Dates

• First Submitted: November 14, 2025
• First Posted: December 9, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 9, 2025

Record last verified: 2025-11

Locations

CH (2)