Probing Cortical Excitability and Cognitive Function With TMS

NCT03652012 | Completed Results DMC FDA Device

• 1 other identifier: 1707654427
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The overarching purpose of this study is to develop a technique that is capable of identifying neurophysiological biomarkers sensitive enough to detect preclinical dementia by integrating Transcranial Magnetic Stimulation (TMS) and Functional Magnetic Resonance Imaging (fMRI). More specifically, this project has two specific aims:

• 1\. To characterize cortical excitability and its relation to cognitive function using single-pulse TMS paradigm in Mild Cognitive Impairment (MCI) and healthy older adults.
• 2\. To delineate cortical plasticity and its association to cognitive function using repetitive TMS paradigm and resting-state fMRI in MCI and healthy older adults. Techniques to artificially and precisely stimulate brain tissue are increasingly recognized as valuable tools both in clinical practice and in cognitive neuroscience studies among healthy individuals. Transcranial magnetic stimulation (TMS) is a non-invasive approach to stimulate the brain. Importantly, unlike other invasive brain stimulation techniques (e.g., surgical deep brain stimulation), no surgery, anesthesia, or sedation is involved. Instead, TMS involves placing a magnetic coil on the surface of the head. This coil then generates a magnetic field that is about the same strength as the magnetic field used by MRI machines, and when this magnetic field rapidly alternates, the neurons under the coil are excited. Extensive guidelines have been published by experts in the field to ensure safe use, and the thousands of patients \& research participants who have received TMS in compliance with these guidelines demonstrate the safety of this practice. Depending on the method of use, TMS is very versatile -- it can be used to study research questions pertaining to the neural circuitry of the brain, it can be used as a diagnostic device, and it can be used therapeutically to treat various neurological conditions. In this study, the investigators intend to further study the potential for diagnostic applications of TMS. More specifically, TMS and brain imaging techniques will be used in combination in order to more sensitively diagnose dementia - perhaps even before symptoms emerge. Right now, there is no reliable method for doing so and it is difficult to distinguish between the forgetfulness of healthy aging and the early signs of disease. Our approach may provide a more sensitive diagnostic tool, which is likely to improve clinical outcomes.

Conditions

Cognitive Dysfunction

Keywords

Mild Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• Cortical Excitability: Resting Motor Threshold (RMT).

  Resting motor threshold (rMT) was determined using the Parameter Estimation by Sequential Testing (PEST) algorithm during a single-pulse transcranial magnetic stimulation (TMS) protocol. Surface electromyography (EMG) was used to record motor evoked potentials (MEPs) from the target muscle. rMT was defined as the minimum stimulation intensity over the motor cortex hotspot required to elicit an MEP of at least 50 μV in peak-to-peak amplitude in 50% of trials. Stimulation intensity on the TMS device is expressed as a percentage of the maximum stimulator output (MSO), which ranges from 1-100% on the TMS device. Accordingly, rMT values are also reported in %MSO.

  Up to 10 minutes. This is a single day trial. Testing session will last a total of 3 hours.

Secondary Outcomes (4)

• Cortical Excitability: Stimulus Response Curve. Measured With EMG, This Measures Motor Response to Various Intensities of Magnetic Pulse Stimuli

  Up to 30 minutes. This is a single day trial. Testing session will last a total of 3 hours.

• Cortical Excitability: Cortical Silent Period. Measured With EMG, This is a Direct Measure of Cortical Inhibition.

  Up to 10 minutes. This is a single day trial. Testing session will last a total of 3 hours.

• Baseline Functional Magnetic Resonance Imaging (fMRI) to Observe Functional Activation of Brain Networks Prior to Intervention.

  Up to 30 minutes. This is a single day trial. Testing session will last a total of 3 hours.

• Post Functional Magnetic Resonance Imaging (fMRI): Change in Functional Connectivity Following TMS.

  Up to 30 minutes. This is a single day trial. Testing session will last a total of 3 hours.

Study Arms (2)

Mild Cognitive Impairment

EXPERIMENTAL

The following revised Mayo Clinic criteria for MCI (Petersen, et al. 2014) will be used: (1) cognitive concern expressed by a physician, informant, participant, or nurse; (2) impairment in 1 or more cognitive domains (memory, language, visuospatial skills, or executive functions); (3) essentially normal functional activities; and (4) absence of dementia. Individuals with MCI will have Mini-Mental State Exam (MMSE, Appendix 19) scores between 18 and 23 (inclusive) and have a Clinical Dementia Rating Scale score of 0.5. This group will undergo Transcranial Magnetic Stimulation (TMS) protocol.

Device: Transcranial Magnetic Stimulation (TMS)

Healthy Controls

ACTIVE COMPARATOR

Participants who are matched for age and gender. This group will undergo Transcranial Magnetic Stimulation (TMS) protocol.

Device: Transcranial Magnetic Stimulation (TMS)

Interventions

Transcranial Magnetic Stimulation (TMS) DEVICE

TMS in a non-invasive brain stimulation technique. In this study, we will use TMS to excite brain tissue in the motor cortex and measure the subsequent motor response in the hand. This 'intervention' will be the same in both cohorts, as we are interested in how this motor response to TMS may vary across two distinct cohorts.

Healthy Controls; Mild Cognitive Impairment

Eligibility Criteria

• Age: 60 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The following revised Mayo Clinic criteria for MCI will be used: (1) cognitive concern expressed by a physician, informant, participant, or nurse; (2) impairment in 1 or more cognitive domains (memory, language, visuospatial skills, or executive functions); (3) essentially normal functional activities; and (4) absence of dementia. Individuals with MCI will have Mini-Mental State Exam (MMSE, Appendix 19) scores between 18 and 23 (inclusive) and have a Clinical Dementia Rating Scale score of 0.5.
• Health controls will be screened with MMSE

You may not qualify if:

• Contraindications to MRI
• Contraindications to TMS
• history of stroke
• clinical diagnosis of dementia
• diagnosis of neuropsychiatric disorder
• left handed

Sponsors & Collaborators

• University of Arizona: lead

Study Sites (1)

University of Arizona

Tucson, Arizona, 85721, United States

Location

Related Publications (1)

• Sundman MH, Lim K, Ton That V, Mizell JM, Ugonna C, Rodriguez R, Chen NK, Fuglevand AJ, Liu Y, Wilson RC, Fellous JM, Rapcsak S, Chou YH. Transcranial magnetic stimulation reveals diminished homoeostatic metaplasticity in cognitively impaired adults. Brain Commun. 2020 Nov 27;2(2):fcaa203. doi: 10.1093/braincomms/fcaa203. eCollection 2020.

  PMID: 33376989 BACKGROUND

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

Results Point of Contact

• Title: Dr Ying-hui Chou
• Organization: University of Arizona

yinghuichou@arizona.edu

5206217447

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Psychology, Cognition and Neural Systems Program

Study Record Dates

• First Submitted: April 27, 2018
• First Posted: August 29, 2018
• Study Start: April 3, 2018
• Primary Completion: March 4, 2020
• Study Completion: March 4, 2020
• Last Updated: June 11, 2025
• Results First Posted: June 11, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)