Novel Individualized Brain Stimulation, Network-based Approaches to Improve Cognition in Healthy Seniors and MCI Patients

NCT07090681 | Completed

• 2 other identifiers: 2020-00127-wp10320030L_197899
• Study Type: interventional
• Target: 61
• Locations: 2 countries
• Sites: 2

Brief Summary

Working memory (WM) relies on a vast network comprising cortical and subcortical structures and its impairment is frequent in normal aging, mild cognitive impairment (MCI) and dementia, often driving fucntional decline. Recent studies have shown that non-invasive brain stimulation (NIBS) methods can modulate neuronal activity, and brain network interactions. A significant body of literature has shown that both striatum and cerebellum are reciprocally connected and implicated in WM performance. However, to date, NIBS studies have mainly focused on cerebellar stimulation with transcranial magnetic stimulation (TMS), often yielding inconclusive or conflicting results. In the investigator hypothesis, sequential and concurrent stimulation of multiple brain regions of the WM subcortical network (i.e. targeting striatum and cerebellum) via transcranial temporal interference stimulation (tTIS) and/or repetitive transcranial magnetic stimulation (rTMS) could enhance WM performance in healthy elderly and/or MCI patients. Moreover, combining different stimulation techniques with multimodal neuroimaging and computational modeling, the investigators expect to acquire better mechanistic understanding through which different NIBS act on the brain and improves cognitive functions.

Conditions

Mild Cognitive Impairment (MCI); Healthy Aging

Keywords

NIBS; tTIS; MCI; aMCI; LB-MCI; TMS; iTBS; striatum; cerebellum

Outcome Measures

Primary Outcomes (1)

• Working memory performance

  The investigators will compare the baseline-normalized reaction time (in milliseconds) and error rate (number of correct and incorrect responses) of a visual working memory task between the active tTIS and tTIS and TMS and the placebo stimulation condition in a cross-over design.

  through study completion, an average of 1 year

Secondary Outcomes (1)

• The neural underpinnings of NIBS-induced changes quantified by s/fMRI and network-based analytical approaches.

  The changes will be computed from the difference between connectivity at baseline and 1 hour post-stimulation.

Study Arms (2)

Mild Cognitive Impairment

EXPERIMENTAL

Patients with mild cognitive impairment

Device: Active Control Placebo; Device: tTIS; Device: tTIS + TMS

Healthy Elderly

ACTIVE COMPARATOR

Cognitively Unimpaired individuals older than 60 years

Device: Active Control Placebo; Device: tTIS; Device: tTIS + TMS

Interventions

Active Control Placebo DEVICE

In this intervention, participants underwent magnetic stimulation at the neck level with a TMS coil. Ten minutes after, they received a high frequency temporal interference stimulation with an overlapping sinusoidal wave at 2KHz, without any interferent pattern.

Healthy Elderly; Mild Cognitive Impairment

tTIS DEVICE

In this intervention, participants underwent magnetic stimulation at the neck level with a TMS coil. Ten minutes after, they received active transcranial temporal interference stimulation with a patterned stimulation (intermittent theta-burst) generating temporal interference in the striatum; see Wessel et al., 2023, Nat Neurosci. for details

Healthy Elderly; Mild Cognitive Impairment

tTIS + TMS DEVICE

In this intervention, participants underwent cerebellar magnetic stimulation at the level of a predefined individual point in the inferior left cerebellar hemisphere with a TMS coil, receiving a total of 600 pulses organised in an intermittent theta-burst pattern. Ten minutes after, they received active transcranial temporal interference stimulation with a patterned stimulation (intermittent theta-burst) generating temporal interference in the striatum; see Wessel et al., 2023, Nat Neurosci. for details

Healthy Elderly; Mild Cognitive Impairment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For MCI:
• Age \> 18 years old;
• Clinical diagnosis of MCI due to possible or probable Lewy Bodies Dementia or amnestic MCI following core clinical and neuropsychological criteria.
• For Healthy Elderlies:
• Age \> 60 years old;
• Normal performance on baseline cognitive screening.

You may not qualify if:

• presence of dementia as assessed by a cognitive test battery and evaluation of daily activities, any major psychiatric disorder (including major depressive episode);
• history of another neurological disease affecting central nervous system (e.g., tumor, epilepsy, stroke, etc.);
• severe or repeated head injury;
• non-compensated systemic or oncological disease;
• presence of MRI-incompatible metal in the body (e.g., cardiac pacemaker).

Sponsors & Collaborators

• Ecole Polytechnique Fédérale de Lausanne: lead
• Ecole Polytechnique Fédérale de Lausanne (EPFL), Campus Biotech: collaborator
• Masaryk University: collaborator

Study Sites (2)

CEITEC

Brno, Czechia

Location

Campus Biotech

Geneva, 1202, Switzerland

Location

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Friedhelm Cristoph Hummel, Professor

  Defitech Chair of Clinical Neuroengineering, Neuro-X Institute (INX), École Polytechnique Fédérale de Lausanne (EPFL)

  PRINCIPAL INVESTIGATOR

• Irena Rektorova, Professor

  Neuroscience Program, Central European Institute of Technology, Masaryk University, Brno, Czech Republic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Quadruple
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 21, 2025
• First Posted: July 29, 2025
• Study Start: October 1, 2023
• Primary Completion: October 24, 2024
• Study Completion: October 24, 2024
• Last Updated: August 7, 2025

Record last verified: 2025-08

Locations

CH (1); CZ (1)