Targeted Transcranial Magnetic Stimulation to Improve Hippocampal-dependent Declarative Memory Abilities

Overview

This is a pilot study of non-invasive transcranial magnetic stimulation (TMS) to improve memory in healthy adults. It will also examine treating memory deficits in older adults with amnestic mild cognitive impairment (aMCI), a condition that frequently precedes Alzheimer's disease (AD). The study will test whether a form of non-invasive brain stimulation repetitive transcranial magnetic stimulation (rTMS) can improve memory abilities in healthy young adults, healthy older adults, and older adults with aMCI by retuning memory-related brain networks. This study is a key first step which will support the long-term goal of treating memory deficits in neurological patients. It is expected that rTMS will improve memory abilities in all participants, and that the improvements in memory will be attributable to changes in the connectivity of memory-related brain networks.

Detailed description

The investigators propose a pilot study of the potential for non-invasive transcranial magnetic stimulation (TMS) to improve memory in healthy adults (young and old) and to treat memory deficits in older adults with amnestic mild cognitive impairment (aMCI). aMCI is a condition that frequently precedes Alzheimer's disease (AD), and a key symptom of aMCI is clinically significant memory loss (i.e., rapid forgetting) greater than expected for age. The investigators will test whether a form of non-invasive brain stimulation repetitive transcranial magnetic stimulation (rTMS) can improve memory abilities in healthy young adults, healthy older adults, and older adults with aMCI by retuning memory-related brain networks. This study's specific aims are to: 1) Measure changes in declarative memory performance after treatment with targeted rTMS; 2) Measure modulation of functional brain networks after treatment with targeted rTMS. To achieve these aims, the investigators will recruit participants from a standing registry and other sources, test their memory abilities, apply rTMS to a specific brain region, and then test their memory abilities again. As a control, all participants will receive sham rTMS that does not stimulate the brain in one of the two phases of participation. By testing whether real rTMS improves memory abilities more than sham rTMS, the investigators will determine whether rTMS can reliably improve memory in the populations of interest. Also, the investigators will measure changes in brain activity before and after stimulation using magnetic resonance imaging (MRI) and magnetoencephalography (MEG). This study is a key first step which will support the investigators' long-term goal of treating memory deficits in neurological patients. The investigators expect that rTMS will improve memory abilities in all participants, and that the improvements in memory will be attributable to changes in the connectivity of memory-related brain networks. This study has clear clinical and translational relevance because it adapts a novel technique addressing a key symptom of AD to new populations. The investigators expect that the findings will improve the field's understanding of memory loss in healthy aging, aMCI, and AD.

Interventions

• Device Transcranial magnetic stimulation
  Transcranial magnetic stimulation non-invasively applies very small amounts of electrical current to brain tissue; sham stimulation uses the same approach but applies little or no actual stimulation to the brain by using less power or greater distance between the head and the stimulator.

Primary outcome measures

• Changes in memory performance measured with the number of studied face-word associations recalled [Time frame: Potential changes will be assessed after each one-week rTMS treatment period. Results will be reported at the end of the study (approximately one year).]

Secondary outcome measures (1)

• Changes in intrinsic functional connectivity between the target brain region stimulated with rTMS and other brain regions. [Time frame: Potential changes will be assessed after each one-week rTMS treatment period. Results will be reported at the end of the study (approximately one year).]

Eligibility criteria

The investigators anticipate enrolling 48 subjects total:

• 16 healthy young adults (age 19-35)
• 16 healthy older adults (demographically matched to aMCI group for age, sex, and educational attainment)
• 16 older adults diagnosed with amnestic mild cognitive impairment (aMCI)

Inclusion criteria

• Adults 19 years of age and older
• Healthy adults without history of psychiatric or neurological disease OR previous diagnosis of amnestic MCI
• Must be able to provide informed consent
• Must have the ability to comply with basic instructions and have the ability to sit comfortably still for TMS, neuroimaging, and other study procedures.
• Right-handed based on self-report (pre-screening) and evaluation with a standard test.

Exclusion criteria

• Individuals who have ferrous metal implanted in their body (other than in their teeth) or any other non-removable medical and/or metallic implant
• Individuals who have increased intracranial pressure
• Individuals who have any major medical illness (e.g., cancer, HIV+, hepatitis, heart disease)
• Individuals who have confounding/dual diagnoses (e.g., comorbid mental illness and substance use disorder)
• Individuals with current diagnoses of alcohol or substance abuse/dependence
• Individuals with epilepsy, any history of seizures, or using medication that lowers seizure threshold
• Individuals with any neurological disorder other than aMCI (e.g., stroke, traumatic brain injury)
• Pregnant females --- as determined by urine pregnancy test --- will be excluded from this study due to uncertainty of the effects of MRI and TMS on the fetus
• Not right-handed based on self-report (pre-screening) or evaluation with a standard test
• Not a native English speaker.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Single blind

Primary purpose

Basic science

Study locations

United States · 1 center

• University of Nebraska Medical Center — Omaha

Identifiers

NCT: NCT03574207 · 0096-18-FB

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗