Using fMRI-guided TMS to Increase Central Executive Function in Older Adults (MCI_Sub)

Summary

This is an administrative supplement to an existing project "Using fMRI-guided TMS to increase central executive function in older adults: NCT02767323" This award allows extending our existing fMRI-TMS paradigm to patients with a prodromal form of Alzheimer's Disease (AD) known as amnestic Mild Cognitive Impairment (MCI), and investigate the role of brain health factors in mediating the TMS-related memory performance benefits associated with communication between a network of frontoparietal brain regions in these populations.

The focus on focal neurostimulation at only a single site represents a fundamental gap in the approach of memory-based neurostimulation therapies. Neurostimulation affects multiple sites within a cortical network, but these global effects have not been used as targets for stimulation because of limited knowledge about what influence these localized sites have on global changes in brain state. To address this problem, multimodal neuroimaging tools and network modeling approaches developed though the parent U01 project will be used, to demonstrate how focal neurostimulation improves the efficacy of TMS for enhancing memory function. These goals will be addressed in the Administrative Supplement under our two specific aims. First, network-guided TMS will be applied to optimize memory success based in the frontoparietal network (FPN) in a new group of MCI patients. A new form of TMS targeting that involves modeling of the global network to understand how the controllability of a stimulation site evokes changes in widespread brain networks will be tested. Second, structural and functional factors affecting the efficacy of individualized network-guided TMS will be identified to ameliorate deficits in MCI. By creating a multimodal model of neural deficits related to MCI, network-guided TMS will be adjusted to demonstrate how the MCI brain might compensate for these neural deficits. The parent U01 project has made foundational advances towards these goals, as we have demonstrated the ability of to selectively enhance and reduce working memory performance in healthy older adults. In the current Administrative Supplement this paradigm will be extended to a group of MCI participants in order to test the hypothesis that excitatory rTMS to the working memory network can provide positive outcomes for patients with pre-clinical AD. The proposed work will provide an important tool for studying the stability and controllability of network connectivity of memory states in the aging brain, as well as new information on the effectiveness of brain stimulation technologies as a therapeutic approach for cognitive decline.

Conditions

• Mild Cognitive Impairment

Interventions

DEVICE

rTMS

excitatory 5Hz rTMS will be used

DEVICE

Sham rTMS

an electrical sham coil reproducing the same clicking sound and tactile sensation than the active rTMS will be used

Sponsors & Collaborators

• National Institute on Aging (NIA)

  collaborator NIH

• Duke University

  lead OTHER

Principal Investigators

• Lawrence G Appelbaum · Duke University

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Model

FACTORIAL

Eligibility

Min Age

55 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2019-11-25

Primary Completion

2020-02-27

Completion

2020-02-27

FDA Device

Yes

Countries

• United States

Study Locations