Plasticity of Deep Brain Structures in Mild Cognitive Impairment and Healthy Aging

NCT06822283 | Completed DMC

• 1 other identifier: 2020-00127
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 2

Brief Summary

Acute and chronic cognitive impairment (TBI and MCI) is one of the most common problems in the growing and aging society of the 21st century. At an individual level, not all brain structures are affected with the same rate. There are subcortical structures less involved (e.g., the cerebellum), and other more involved (e.g., the hippocampus) in the cognitive decline with age or following a traumatism. To pave the way for personalized precision medicine in the field of cognitive preservation and recovery, there is a need for testing the impact of individually tailored innovative non-invasive neuro-technologies. In this project, we aim at testing the benefit of non-invasively stimulating subcortical structures to boost resilience in supporting motor and non-motor memory.

Conditions

Traumatic Brain Injury

Keywords

non-invasive brain stimulation; deep brain stimulation; subcortical; memory; neuro-imaging; transcranial temporal interference stimulation; motor learning

Outcome Measures

Primary Outcomes (1)

• Motor learning performance

  The primary outcome of the study is the amount of motor learning in a sequential finger-tapping task evaluated during and following training

  From baseline to 24 hours after training

Secondary Outcomes (1)

• Brain connectivity

  Baseline measure (before the intervention)

Other Outcomes (1)

• Demographic factors form

  Baseline measure (before the intervention)

Study Arms (2)

Placebo stimulation

PLACEBO COMPARATOR

Sham stimulation : ramp-up \[5 s\] immediately followed by ramp-down \[5 s\] of high-frequency currents (see Vassiliadis et al., 2023, Nat Hum Behav for more details)

Other: transcranial electric stimulation

Active stimulation

EXPERIMENTAL

Patterned stimulation (intermittent theta-burst) generating temporal interference in the striatum; see Wessel et al., 2023, Nat Neurosci. for details

Other: transcranial electric stimulation

Interventions

transcranial electric stimulation OTHER

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, we applied tTIS via surface electrodes applying a low-intensity (2mA baseline to peak), sub-threshold protocol following the safety guidelines for low-intensity transcranial electric stimulation in humans.

Active stimulation; Placebo stimulation

Eligibility Criteria

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

You may qualify if:

• TBI patients:
• 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 (1):
• 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
• Clinique Romande de Readaptation: collaborator
• HUG University hospital: collaborator
• SNF Swiss National Foundation: collaborator
• The Novartis Foundation: collaborator
• Fondation Bertarelli: collaborator
• Wyss Center for Bio and Neuroengineering: collaborator

Study Sites (2)

EPFL Valais, Clinique Romande de readaptation

Sion, Valais, 1951, Switzerland

Location

EPFL, Campus Biotech

Geneva, 1202, Switzerland

Location

Related Publications (3)

• Wessel MJ, Beanato E, Popa T, Windel F, Vassiliadis P, Menoud P, Beliaeva V, Violante IR, Abderrahmane H, Dzialecka P, Park CH, Maceira-Elvira P, Morishita T, Cassara AM, Steiner M, Grossman N, Neufeld E, Hummel FC. Noninvasive theta-burst stimulation of the human striatum enhances striatal activity and motor skill learning. Nat Neurosci. 2023 Nov;26(11):2005-2016. doi: 10.1038/s41593-023-01457-7. Epub 2023 Oct 19.

  PMID: 37857774 BACKGROUND

• Vassiliadis P, Beanato E, Popa T, Windel F, Morishita T, Neufeld E, Duque J, Derosiere G, Wessel MJ, Hummel FC. Non-invasive stimulation of the human striatum disrupts reinforcement learning of motor skills. Nat Hum Behav. 2024 Aug;8(8):1581-1598. doi: 10.1038/s41562-024-01901-z. Epub 2024 May 29.

  PMID: 38811696 BACKGROUND

• Vassiliadis P, Stiennon E, Windel F, Wessel MJ, Beanato E, Hummel FC. Safety, tolerability and blinding efficiency of non-invasive deep transcranial temporal interference stimulation: first experience from more than 250 sessions. J Neural Eng. 2024 Mar 11;21(2). doi: 10.1088/1741-2552/ad2d32.

  PMID: 38408385 RESULT

MeSH Terms

Conditions

Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

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

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: Prof. Dr. med.

Study Record Dates

• First Submitted: January 13, 2025
• First Posted: February 12, 2025
• Study Start: September 15, 2021
• Primary Completion: February 2, 2024
• Study Completion: February 2, 2024
• Last Updated: February 12, 2025

Record last verified: 2025-01

Locations

CH (2)