Probing Cortical Excitability and Cognitive Function in Mild Cognitive Impairment With Transcranial Magnetic Stimulation
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University of Arizona
- Enrollment
- 40
- Locations
- 2
- Primary Endpoint
- Cortical Excitability: Resting Motor Threshold (RMT).
Study Overview
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:
-
- To characterize cortical excitability and its relation to cognitive function using single-pulse TMS paradigm in Mild Cognitive Impairment (MCI) and healthy older adults.
-
- 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.
Detailed Description
In total, 60 participants will be recruited to participate in this trial. The investigators aim to recruit 30 patients with MCI and 30 age-matched healthy adults. The age range for inclusion will be 18-80, and the mean age of the healthy cohort will be matched with the mean age of the MCI cohort. 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.
This study protocol comprises a single testing visit, comprised of four separate components: a) Resting-state fMRI, b) Single-pulse TMS paradigm, c) theta-burst rTMS paradigm, and d) a brief motor task performed on an iPad.
These tasks will be repeated before and after the theta-burst rTMS paradigm (c). Therefore, the testing visit is:
(a) --> (d) --> (b) --> (c) --> (b) --> (a) --> (d)
This protocol will enable investigators to study the following both before and after the rTMS paradigm: 1) connectivity patterns comprising the functional networks of the brain, 2) measures of cortical excitability derived from single-pulse TMS, and 3) upper extremity motor speed & acuity.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 60 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •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.
- •Health controls will be screened with MMSE
Exclusion Criteria
- •Contraindications to MRI
- •Contraindications to TMS
- •history of stroke
- •clinical diagnosis of dementia
- •diagnosis of neuropsychiatric disorder
- •left handed
Outcomes
Primary Outcomes
Cortical Excitability: Resting Motor Threshold (RMT).
Time Frame: Up to 10 minutes. This is a single day trial. Testing session will last a total of 3 hours.
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.
Secondary Outcomes
- 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.)
Investigators
Ying-hui Chou
Assistant Professor of Psychology, Cognition and Neural Systems Program
University of Arizona