Mild Cognitive Impairment (MCI)NIBS-iCOGNCT07090681
Novel Individualized Brain Stimulation, Network-based Approaches to Improve Cognition in Healthy Seniors and MCI Patients
A study testing tTIS and tTIS + TMS in people with Mild Cognitive Impairment (MCI) and Healthy Aging, run by Ecole Polytechnique Fédérale de Lausanne at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Mild Cognitive Impairment (MCI), Healthy Aging
- What is being tested?
- tTIS and tTIS + TMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 61 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 Oct 2023to 24 Oct 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Novel Individualized Brain Stimulation, Network-based Approaches to Improve Cognition in Healthy Seniors and Patients With MCI
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.
Read the 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
- Being tested
- Active Control Placebo, tTIS, tTIS + TMS
- Keywords
- NIBS, tTIS, MCI, aMCI, LB-MCI, TMS, iTBS, striatum, cerebellum
- Medical subject headings
- Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active Control PlaceboDevice
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.
tTISDevice
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 + TMSDevice
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
| Study group | Role | What they receive |
|---|---|---|
| Mild Cognitive Impairment | Experimental | Patients with mild cognitive impairment Receives: Device: Active Control Placebo; Device: tTIS; Device: tTIS + TMS |
| Healthy Elderly | Active comparator | Cognitively Unimpaired individuals older than 60 years Receives: Device: Active Control Placebo; Device: tTIS; Device: tTIS + TMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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 in intra- and inter-regional fMRI connectivity (measured by BOLD signal variations in specific brain regions expressed as z-scores) within and between cognitive brain networks will be compared between the active inerventions (tTIS and tTIS+TMS) and the active control stimulations.
Measured: The changes will be computed from the difference between connectivity at baseline and 1 hour post-stimulation.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2025
- Study start1 Oct 2023
- Primary completion24 Oct 2024
- Study completion24 Oct 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mild Cognitive Impairment (MCI)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ecole Polytechnique Fédérale de Lausanne
- Sponsor type
- University, hospital or other
- Collaborators
- Ecole Polytechnique Fédérale de Lausanne (EPFL), Campus Biotech, Masaryk University
- Responsible party
- Principal investigator, Friedhelm Hummel, Ecole Polytechnique Fédérale de Lausanne
- Investigators
- Friedhelm Cristoph Hummel, Professor, Principal investigator, Defitech Chair of Clinical Neuroengineering, Neuro-X Institute (INX), École Polytechnique Fédérale de Lausanne (EPFL)Irena Rektorova, Professor, Principal investigator, Neuroscience Program, Central European Institute of Technology, Masaryk University, Brno, Czech Republic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07090681
- Sponsor's protocol ID
- 2020-00127-wp10
- Other IDs
- 320030L_197899
- Acronym
- NIBS-iCOG
- Status last verified
- Aug 2025
- First submitted
- 21 Jul 2025
- Last updated
- 7 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Nencha U, Pupikova M, di Natale M, Maceira-Elvira P, Gajdos M, Beanato E, Skarvelaki S, Jones R, Ericson I, Lamos M, Nuti A, Windel F, Ondracek D, Simo A, Vojtkova E, Spunarova K, Alvarez V, Simionescu O, Frisoni GB, Raffin E, Rektorova I, Hummel FC. Multifocal Noninvasive Deep Brain Stimulation to Enhance Cognition in Mild Cognitive Impairment: A Crossover Trial. JAMA Netw Open. 2026 Jul 1;9(7):e2621756. doi: 10.1001/jamanetworkopen.2026.21756.
PubMed 42406397
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Individualized Brain Stimulation, Network-based Approaches to Improve Cognition in Healthy Seniors and Patients With MCI
- ClinicalTrials.gov ID
- NCT07090681
- Acronym / sponsor ID
- NIBS-iCOG / 2020-00127-wp10
- Conditions
- Mild Cognitive Impairment (MCI), Healthy Aging
- Keywords
- NIBS, tTIS, MCI, aMCI, LB-MCI, TMS, iTBS, striatum
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Ecole Polytechnique Fédérale de LausanneUniversity, hospital or other
- Collaborators
- Ecole Polytechnique Fédérale de Lausanne (EPFL), Campus Biotech, Masaryk University
- Study start
- 1 Oct 2023 (actual)
- Primary completion
- 24 Oct 2024 (actual)
- Study completion
- 24 Oct 2024 (actual)
- First posted
- 29 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mild Cognitive Impairment | Experimental | Device: Active Control Placebo, Device: tTIS, Device: tTIS + TMSPatients with mild cognitive impairment |
| Healthy Elderly | Active comparator | Device: Active Control Placebo, Device: tTIS, Device: tTIS + TMSCognitively Unimpaired individuals older than 60 years |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (5 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active Control PlaceboIn 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. | Device | Healthy Elderly, Mild Cognitive Impairment |
| tTISIn 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 | Device | Healthy Elderly, Mild Cognitive Impairment |
| tTIS + TMSIn 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 | Device | Healthy Elderly, Mild Cognitive Impairment |
Primary outcome
Working memory performance
Time frame: through study completion, an average of 1 year
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.
1 secondary outcome
The neural underpinnings of NIBS-induced changes quantified by s/fMRI and network-based analytical approaches.
Time frame: The changes will be computed from the difference between connectivity at baseline and 1 hour post-stimulation.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2025.
- Derived from this study: PubMed 42406397Nencha U, Pupikova M, di Natale M, Maceira-Elvira P, Gajdos M, Beanato E, Skarvelaki S, Jones R, Ericson I, Lamos M, Nuti A, Windel F, Ondracek D, Simo A, Vojtkova E, Spunarova K, Alvarez V, Simionescu O, Frisoni GB, Raffin E, Rektorova I, Hummel FC. Multifocal Noninvasive Deep Brain Stimulation to Enhance Cognition in Mild Cognitive Impairment: A Crossover Trial. JAMA Netw Open. 2026 Jul 1;9(7):e2621756. doi: 10.1001/jamanetworkopen.2026.21756.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Friedhelm Cristoph Hummel, Professor principal investigator
Defitech Chair of Clinical Neuroengineering, Neuro-X Institute (INX), École Polytechnique Fédérale de Lausanne (EPFL)
Irena Rektorova, Professor principal investigator
Neuroscience Program, Central European Institute of Technology, Masaryk University, Brno, Czech Republic
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing tTIS and tTIS + TMS in people with Mild Cognitive Impairment (MCI) and Healthy Aging, run by Ecole Polytechnique Fédérale de Lausanne at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Czechia, Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Working memory performance (time frame: through study completion, an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07090681, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2025.