Neuromodulation of Memory in Aging

NCT05460468 | Recruiting DMC FDA Device

• 1 other identifier: Pro00110872
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed research will use closed-loop transcranial magnetic stimulation (TMS) based on individualized brain networks to establish parameters that can reliably control brain states. This will be tested in healthy aging and mild cognitive impairment (MCI) cohorts. The investigators will study network activation and neural oscillatory mechanisms underlying the network that regulates working memory and then target this network using closed-loop TMS to the Prefrontal Cortex. Investigators will measure the impact of TMS on working memory performance and task-based neural activity. The project will use brain stimulation and network modeling techniques to enhance working memory in healthy older adults and MCI and will demonstrate the value of closed-loop, network-guided TMS for future clinical applications.

Conditions

Mild Cognitive Impairment; MCI

Keywords

TMS; Transcranial Magnetic Stimulation; Memory

Outcome Measures

Primary Outcomes (4)

• Working Memory Task

  The difference in memory accuracy between TMS conditions (random vs. ordered vs. sham stimulation) on a working memory task. Each trial of the task consists of stimulus presentation of an array of letters, a delay period in which subjects alphabetize the letters, and probe period where subjects indicate whether the number corresponds to the alphabetized position of the letter probe presented. Memory is subsequently assessed as a function of TMS condition.

  Collected during TMS-EEG (Day 4)

• Functional network connectivity

  Functional network connectivity/activity is estimated by comparing the hemodynamic time courses of two or more regions of the brain. The correlation between the time courses of each pair of regions is termed functional network connectivity. The Working Memory Network (WMN) is identified by comparing fMRI-based functional network connectivity for high vs low working memory load (e.g., remembering 4 versus 3 items).

  Collected during the initial neuroimaging session (Day 2)

• Vascular density (VAD)

  This measure of neurovascular brain health, vascular density (VAD), as estimated by an automated method of segmenting veins with a magnetic resonance imaging (MRI) sequence known as susceptibility weighted imaging. This measure can be used to estimate the dilation of cerebral veins, and therefore VAD.

  Collected during the second neuroimaging session (Day 3)

• EEG-based connectivity

  EEG data will be source reconstructed to a fine-grained grid and timecourses of the solution points are averaged per region and per subject. The imaginary part of the coherence (iCoh) of averaged EEG source signals will be assessed within the alpha and theta frequency bands to build EEG-based connectivity matrices ("connectomes") for alpha- and theta-based connectivity, for each subject.

  Collected during TMS-EEG (Day 4)

Secondary Outcomes (7)

• Montreal Cognitive Assessment (MoCA)

  Collected during the initial screening visit (Day 1)

• National Institutes of Health (NIH) Toolbox Cognitive Battery

  Collected during the initial screening visit (Day 1)

• Hopkins Verbal Learning Test (HVLT-2)

  Collected during the initial screening visit (Day 1)

• Brief Visuospatial Memory Test (BVMT-R)

  Collected during the initial screening visit (Day 1)

• Number Span Forwards/ Backwards

  Collected during the initial screening visit (Day 1)

Study Arms (3)

TMS-Randomized

EXPERIMENTAL

Three different closed-loop conditions will be tested, each triggered by the presence of a sustained period of alpha-band power. In the first condition, arrhythmic TMS trains with a stochastic (randomized) inter-pulse interval, will be used to disrupt cortical alpha oscillations and thus be expected to enhance memory performance.

Device: Transcranial Magnetic Stimulation

TMS-Ordered

EXPERIMENTAL

Three different closed-loop conditions will be tested, each triggered by the presence of a sustained period of alpha-band power. In the second condition, rhythmic (ordered) alpha-frequency TMS trains, with the expectation that this alpha stimulation will further entrain a synchronization during the task and thereby worsen memory performance.

Device: Transcranial Magnetic Stimulation

TMS-Sham

SHAM COMPARATOR

Three different closed-loop conditions will be tested, each triggered by the presence of a sustained period of alpha-band power. In a third condition, sham stimulation will be delivered at the same randomized inter-pulse interval, but with no TMS delivered to the brain.

Device: Transcranial Magnetic Stimulation

Interventions

Transcranial Magnetic Stimulation DEVICE

Transcranial magnetic stimulation (TMS) is a noninvasive procedure that uses magnetic fields to stimulate nerve cells in the brain to improve a variety of cognitive conditions, and to probe the dynamics of normal brain function.

Also known as: TMS rTMS

TMS-Ordered; TMS-Randomized; TMS-Sham

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• English Speaking
• Willing to provide consent

You may not qualify if:

• History of any Axis I DSM-V disorder, excluding major depressive disorder or generalized anxiety disorders
• Current history of substance abuse or dependence (excluding nicotine)
• Intracranial implants (e.g. aneurysms clips, shunts, stimulators, cochlear implants, or electrodes), cardiac pacemakers, or vagus Nerve stimulation device
• Increased risk of seizure for any reason, including prior diagnosis of epilepsy, seizure disorder, increased intracranial pressure, or history of significant head trauma with loss of consciousness for ≥ 5 minutes.
• Neurological disorder including, but not limited to: space occupying brain lesion; any history of seizures, history of cerebrovascular accident; fainting, cerebral aneurysm, Dementia, Hungtington chorea; Multiple Sclerosis.
• Current use of medications known to lower the seizure threshold and/or affect working memory

Sponsors & Collaborators

• Duke University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

Duke University Hospital

Durham, North Carolina, 27710, United States

RECRUITING

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

• Simon W Davis, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

• Andy Liu, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Simon W Davis, PhD

CONTACT

9196841243; simon.davis@duke.edu

Emily Finch, BA

CONTACT

9196682842; emily.finch@duke.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: This is a within-subjects design, such that both active and sham stimulation (i.e., masking) trials will occur in all subjects.
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study has three Aims and thus three models. For Aim 1, the primary outcome measure is fMRI BOLD. Researchers will estimate the dose-response relationship between TMS intensity and BOLD response in two cortical sites for response to TMS. For Aim 2 the primary outcome measure is impact of closed-loop TMS treatment on working memory task performance. For Aim 3, the primary outcome measure is the strength of mediation of brain health (e.g., vascular density) predictors of cognition.

Study Record Dates

• First Submitted: June 6, 2022
• First Posted: July 15, 2022
• Study Start: March 28, 2024
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027
• Last Updated: October 14, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)