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

NCT ID: NCT07090681

Last Updated: 2025-08-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 61 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-01
• Study Completion Date: 2024-10-24

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.

Detailed Description

Executive functions and particularly working memory (WM) play a crucial role in daily life and is frequently impaired in patients with mild cognitive impairment (MCI), constituting one of the driving factors that compromise quality of life and autonomy. WM specifically relies on a vast brain network of cortical and subcortical regions. Among the different subcortical structures implicated in executive functions, both striatum and cerebellum have been linked to WM performance with complementary roles. Striatum is variably affected in the course of different neurodegenerative diseases, while in contrast, the cerebellum has been associated with cognitive resilience and brain reserve, making it a promising target for interventions for cognitive enhancement.

Hence, leveraging the reciprocal striato-cerebellar connections, in this multi-center, randomized, placebo-controlled proof-of-concept trial, the investigators implemented a sequential multifocal plasticity-inducing stimulation of the striatum and the cerebellum to enhance WM in MCI patients.

The investigators will apply an excitatory intermittent theta burst (iTBS) cerebellar TMS to target the left inferior cerebellar hemisphere and transcranial temporal interference stimulation (tTIS) with the same pattern to focally neuromodulate the striatum in MCI patients. In our hypothesis, this combined sequential protocol will synergistically enhance WM performance.

The investigators will analyse not only the resulting behavioral data as the main outcome, but via multimodal neuroimaging (structural and functional magnetic resonance imaging; s/fMRI) and computational modeling methods they will dissect the network mechanisms and patterns of intrinsic connectivity changes underlying the behavioral changes.

Conditions

Mild Cognitive Impairment (MCI); Healthy Aging

Study Design

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

Study Groups

Mild Cognitive Impairment

Patients with mild cognitive impairment

Group Type: EXPERIMENTAL

Active Control Placebo

Intervention Type: 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.

tTIS

Intervention Type: 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

tTIS + TMS

Intervention Type: 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

Cognitively Unimpaired individuals older than 60 years

Group Type: ACTIVE_COMPARATOR

Active Control Placebo

Intervention Type: 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.

tTIS

Intervention Type: 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

tTIS + TMS

Intervention Type: 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

Interventions

Active Control Placebo

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.

Intervention Type: DEVICE

tTIS

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

Intervention Type: DEVICE

tTIS + TMS

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

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Ecole Polytechnique Fédérale de Lausanne (EPFL), Campus Biotech

UNKNOWN

Sponsor Role: collaborator

Masaryk University

OTHER

Sponsor Role: collaborator

Ecole Polytechnique Fédérale de Lausanne

OTHER

Sponsor Role: lead

Responsible Party

Friedhelm Hummel

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Friedhelm Cristoph Hummel, Professor

Role: PRINCIPAL_INVESTIGATOR

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

Irena Rektorova, Professor

Role: PRINCIPAL_INVESTIGATOR

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

Locations

CEITEC

Brno, , Czechia

Campus Biotech

Geneva, , Switzerland

Countries

Czechia; Switzerland

Other Identifiers

320030L_197899

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

2020-00127-wp10

Identifier Type: -

Identifier Source: org_study_id