Novel, Individualized Brain Stimulation, Network-based Approaches to Improve Cognition

NCT04986787 | Unknown

• 1 other identifier: GF21-13462L
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

Impaired working memory (WM) plays a crucial role in normal aging, in mild cognitive impairment (MCI) and cognitive decline associated with dementia, such as Alzheimer's disease (AD). The aging-related differences in WM are hypothesized to be based on various neurobiological origins, for example alterations in the dynamic interplay between the large-scale brain networks have proven an important role. Recent studies have shown that non-invasive brain stimulation (NIBS) methods can modulate neuronal activity, plasticity and large-scale brain network interactions. The investigators hypothesize that multifocal NIBS can improve WM. By successive and concurrent stimulation of multiple brain regions of the WM network by transcranial alternating current stimulation (tACS) and/or repetitive transcranial magnetic stimulation (rTMS) the investigators will study dynamic interactions between distinct cortico-cortical and subcortico-cortical brain areas. By leveraging multimodal systems neuroscience information during multifocal stimulation, the investigators expect to acquire better mechanistic understand through which NIBS acts on the brain and improves cognitive functions, such as WM.

Conditions

Mild Cognitive Impairment; Healthy Aging

Keywords

non-invasive brain stimulation; tACS; TMS; cognition; working memory; MCI; healthy ageing; EEG; neuroimaging (MRI); oscillatory activity

Outcome Measures

Primary Outcomes (1)

• Working memory performance

  We will compare the baseline-normalized reaction time and error rate of a N-back task between the real and sham stimulation condition in a cross-over design.

  through study completion, an average of 1 year

Secondary Outcomes (4)

• The reproducibility of the outcomes of this proof-of-concept brain stimulation in MCI between centers

  through study completion, an average of 1 year

• The neural underpinning 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.

• The neural underpinning of NIBS-induced changes quantified by EEG.

  Baseline and 1 hour after the delivery of real or sham intervention - cross-over design.

• Transfer of the acquired WM abilities during the intervention into a daily-life relevant scenario as assessed by The Virtual Supermarket Shopping Task.

  through study completion, an average of 1 year

Study Arms (4)

Entrainment with personalized bi-focal fronto-parietal synchronized tACS in HV - within-frequency

EXPERIMENTAL

double-blind, randomized, sham-controlled, cross-over trials assessing the effects of individualized fronto-parietal tACS on a visual working memory task in aged HV

Device: tACS

Entrainment with personalized bi-focal fronto-parietal synchronized tACS in HV - cross-frequency

EXPERIMENTAL

double-blind, randomized, sham-controlled, cross-over trials assessing the effects of individualized cross-frequency fronto-parietal tACS stimulation on a visual WM task in aged HV

Device: tACS

Cerebellar rTMS to modify the effects of cortico-cortical, fronto-parietal tACS in HV

EXPERIMENTAL

double-blind, randomized, sham-controlled, cross-over trial assessing the effects of cerebellar stimulation on individualized fronto-parietal tACS stimulation during a visual WM task in aged HV

Device: tACS; Device: TMS

Neuromodulation protocol in MCI patients (precise protocol to be chosen on results of previous arms)

EXPERIMENTAL

double-blind, randomized, sham-controlled, cross-over trials assessing the effects of individualized striatal TIS combined with cereberal TMS on a visual working memory task in MCI patients

Device: TMS; Device: TIS

Interventions

tACS DEVICE

a non-invasive brain stimulation technique that allows interaction with endogenous cortical oscillatory rhythms

Cerebellar rTMS to modify the effects of cortico-cortical, fronto-parietal tACS in HV; Entrainment with personalized bi-focal fronto-parietal synchronized tACS in HV - cross-frequency; Entrainment with personalized bi-focal fronto-parietal synchronized tACS in HV - within-frequency

TMS DEVICE

a noninvasive procedure that uses magnetic fields to stimulate nerve cells in the brain, it will be specifically cerebellar stimulation

Cerebellar rTMS to modify the effects of cortico-cortical, fronto-parietal tACS in HV; Neuromodulation protocol in MCI patients (precise protocol to be chosen on results of previous arms)

TIS DEVICE

temporal interference stimulation targeted to striatum, a non-invasive brain stimulation technique that allows interaction with endogenous cortical oscillatory rhythms deep in the brain

Neuromodulation protocol in MCI patients (precise protocol to be chosen on results of previous arms)

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• normal cognitive performance as assessed by a cognitive screening for healthy subjects
• mild cognitive impairment as assessed by detailed cognitive testing ± positive AD diagnostic biomarkers for MCI subjects

You may not qualify if:

• Psychiatric disorders including major depression, major vascular lesions, or other brain pathologies that might present with cognitive decline.

Sponsors & Collaborators

• Masaryk University: lead
• Swiss Federal Institute of Technology: collaborator

Study Sites (1)

Ceitec Masaryk University

Brno, 62500, Czechia

RECRUITING

Related Publications (8)

• Saunders NL, Summers MJ. Attention and working memory deficits in mild cognitive impairment. J Clin Exp Neuropsychol. 2010 Apr;32(4):350-7. doi: 10.1080/13803390903042379. Epub 2009 Sep 25.

  PMID: 19787522 BACKGROUND

• Johnson EL, Dewar CD, Solbakk AK, Endestad T, Meling TR, Knight RT. Bidirectional Frontoparietal Oscillatory Systems Support Working Memory. Curr Biol. 2017 Jun 19;27(12):1829-1835.e4. doi: 10.1016/j.cub.2017.05.046. Epub 2017 Jun 9.

  PMID: 28602658 BACKGROUND

• Roux F, Uhlhaas PJ. Working memory and neural oscillations: alpha-gamma versus theta-gamma codes for distinct WM information? Trends Cogn Sci. 2014 Jan;18(1):16-25. doi: 10.1016/j.tics.2013.10.010. Epub 2013 Nov 19.

  PMID: 24268290 BACKGROUND

• Kornblith S, Buschman TJ, Miller EK. Stimulus Load and Oscillatory Activity in Higher Cortex. Cereb Cortex. 2016 Sep;26(9):3772-84. doi: 10.1093/cercor/bhv182. Epub 2015 Aug 18.

  PMID: 26286916 BACKGROUND

• Eldaief MC, Halko MA, Buckner RL, Pascual-Leone A. Transcranial magnetic stimulation modulates the brain's intrinsic activity in a frequency-dependent manner. Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21229-34. doi: 10.1073/pnas.1113103109. Epub 2011 Dec 12.

  PMID: 22160708 BACKGROUND

• Anderkova L, Pizem D, Klobusiakova P, Gajdos M, Koritakova E, Rektorova I. Theta Burst Stimulation Enhances Connectivity of the Dorsal Attention Network in Young Healthy Subjects: An Exploratory Study. Neural Plast. 2018 Mar 13;2018:3106918. doi: 10.1155/2018/3106918. eCollection 2018.

  PMID: 29725346 BACKGROUND

• Novakova L, Gajdos M, Rektorova I. Theta-burst transcranial magnetic stimulation induced cognitive task-related decrease in activity of default mode network: An exploratory study. Brain Stimul. 2020 May-Jun;13(3):597-599. doi: 10.1016/j.brs.2020.01.015. Epub 2020 Jan 31. No abstract available.

  PMID: 32289683 BACKGROUND

• Plechata A, Sahula V, Fayette D, Fajnerova I. Age-Related Differences With Immersive and Non-immersive Virtual Reality in Memory Assessment. Front Psychol. 2019 Jun 11;10:1330. doi: 10.3389/fpsyg.2019.01330. eCollection 2019.

  PMID: 31244729 BACKGROUND

MeSH Terms

Conditions

Cognitive Dysfunction

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Friedhelm C. Hummel

  Ecole Polytechnique Fédérale de Lausanne

  PRINCIPAL INVESTIGATOR

• Irena Rektorova

  CEITEC Masaryk University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Monika Pupikova

CONTACT

+420 549 49 8313; monika.pupikova@ceitec.muni.cz

Traian Popa

CONTACT

traian.popa@epfl.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 19, 2021
• First Posted: August 3, 2021
• Study Start: September 1, 2021
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: May 25, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (1)