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

Investigation of the Plasticity of Deep Brain Structures in Mild Cognitive Impairment and Healthy Aging (PlasMA)

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.

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury
• Intervention / Treatment: Other: transcranial electric stimulation

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Geneva, Switzerland, 1202
    • EPFL, Campus Biotech
  • Valais
    • Sion, Valais, Switzerland, 1951
      • EPFL Valais, Clinique Romande de readaptation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

TBI patients:

• 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 (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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo stimulation; 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; 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.
Experimental: Active stimulation; Patterned stimulation (intermittent theta-burst) generating temporal interference in the striatum; see Wessel et al., 2023, Nat Neurosci. for details	Other: transcranial electric 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, 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain connectivity	Diffusion-weighted and resting-state MRI is performed at baseline and allows to evaluate inter-individual anatomical factors associated to the primary outcome	Baseline measure (before the intervention)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Demographic factors form	These factors including age, sex, handedness, education level and profession, time of diagnosis, physical activity, independency and quality of life, medication, cognitive status will are used to evaluate responsiveness to the intervention	Baseline measure (before the intervention)

Collaborators and Investigators

• Sponsor: Friedhelm Hummel
• Collaborators: The Novartis Foundation; Wyss Center for Bio and Neuroengineering; Clinique Romande de Readaptation; SNF Swiss National Foundation; Fondation Bertarelli; HUG University hospital

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2021
• Primary Completion (Actual): February 2, 2024
• Study Completion (Actual): February 2, 2024

Study Registration Dates

• First Submitted: January 13, 2025
• First Submitted That Met QC Criteria: February 11, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 11, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: memory; deep brain stimulation; motor learning; non-invasive brain stimulation; subcortical; neuro-imaging; transcranial temporal interference stimulation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Wounds and Injuries; Neurocognitive Disorders; Cognition Disorders; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries, Traumatic; Cognitive Dysfunction; Brain Injuries
• Other Study ID Numbers: 2020-00127 (Other Identifier: Commission cantonale d'Éthique de la Recherche sur l'être humain Vaud (CER-VD))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No