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Completed

NCT Number: NCT05515952

Interleaved TMS-fMRI for Hippocampal Stimulation: Modeling Dose-Response Relationship in Amnestic Mild Cognitive Impairment

Emerging evidence indicates that dysfunction of hippocampal synaptic plasticity, which precedes neuronal degeneration during the progression of Alzheimer's disease (AD), underlies the hallmark cognitive impairment. Although there are currently no effective disease modifying treatments for AD, recent preclinical studies in animal models of AD have suggested that repetitive transcranial magnetic stimulation (rTMS) promotes hippocampal synaptic plasticity and, ultimately, improves learning and memory abilities. Interleaved TBS-MRI is a paradigm, which allows the investigators to study human brain functionality with real-time MRI, to better understand modulations of brain activity in response to the non-invasive brain stimulation, TBS. The interleaved TBSfMRI paradigm can more accurately estimated the immediate brain activity compared to the offline TBS-MRI studies in which TBS is applied outside the MRI. With this interleaved TBS-MRI approach, the investigators will be able to measure immediate changes in targeted brain activity, such as hippocampus activation, following each TBS session. This approach has created the unprecedented potential enabling the investigators to model the dose-dependent effects of TBS more accurately on brain function.

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Key information

Conditions

Mild Cognitive Impairment Cognition Disorders Cognitive Dysfunction Mental Disorders Neurocognitive Disorders

Age range

50 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Bioscience Research Laboratory

Tucson, Arizona, 85719, United States

About this study

The overarching goal of this proposed project is to maximize TBS effects to non-invasive spaced TBS in MCI. For the comparison, the investigators will include cognitively normal adults. There will be a screening session plus three consecutive days including baseline outcome measures on Day 1, TMS interventions and outcome measures on Day 2, and follow-up measurements on Day 3. In this project, on Day 2, participants will receive three TBS blocks inside the MRI scanner with each TBS block separated by 30-90 minutes to enhance the possibility of maximizing the TBS effect. This will be repeated in two blocks, each with a different TMS protocol. The protocols will be in randomized order.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 50-80 years
  • MCI clinical criteria: (a) self- or informant-reported cognitive complaint; (b) preserved independence in functional abilities; and (c) absence of dementia.
  • Objective cognitive impairment supported by the following measures of general cognitive function: (a) Mini-Mental State Exam (MMSE) 24-27 (inclusive); (b) Montreal Cognitive Assessment (MoCA) 18-26 (inclusive); or (c) Clinical Dementia Rating Scale score of 0.5.
  • Right handed
  • English speaking
  • Able to attend daily intervention (Monday-Friday) for 4 days
  • Not enrolled in another interventional study within 6 months prior to beginning this study

Exclusion criteria

  • Contraindications to transcranial magnetic stimulation (TMS) or magnetic resonance imaging (MRI)
  • Other neurological disorders (e.g. stroke, head injuries, or multiple sclerosis)
  • Untreated depression
  • Current cancer treatment or other medical problems that might independently affect cognitive function
  • Clinical Dementia Rating Scale score more than 1.0

Treatment and study plan

Transcranial Magnetic Stimulation

Device

TMS is a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect on the hippocampus and determine which stimulation protocol is more beneficial to each participant.

Transcranial Magnetic Stimulation (sham)

Device

TMS is a non-invasive brain stimulation technique. The primary aim of the study will be to verify the deliverability of the TMS effect on the hippocampus and determine which stimulation protocol is more beneficial to each participant. For sham, the side of the coil that does not deliver pulses will be used.

Primary outcomes

  1. Correction Rate in Memory Association Recall

    Time frame: Immediately after intervention day (block 1 day 2) and (block 2 day 2) vs. Baseline

    Memory tasks will be implemented and measure the correct rate to assess memory function. The scale is the Face Name Associated Memory Score, and the min/max values are 0-1. A higher score indicates a better outcome.

Sponsors and collaborators

Lead sponsor

University of Arizona

Other

Collaborators

  • National Institute on Aging (NIA)

Registry information

Acronym: TMS-fMRI

Important dates

Study start
2022
Primary completion
2024
Study completion
2024
First posted
Aug 25, 2022
Registry last updated
Jul 29, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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