Probing Cortical Excitability and Cognitive Function With TMS

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.