Project Summery/AbstractTheta burst stimulation (TBS) is a non-invasive brain stimulation technique that has emerged asa promising therapy for mild cognitive impairment (MCI) and Alzheimers disease (AD). Howeverlittle effort has been undertaken to optimize the application of TBS for these populations. Previousanimal in vitro studies have found that TBS could induce long-term potentiation (LTP) in adult rathippocampal slices in a dose-dependent manner. The maximum LTP effect was observed afterTBS sessions were repeated three times with a 60-minute break between each session. Thedose-response curve was flattened when TBS applications did not have adequate interludes. Thispoints to an array of parameters that must be properly tuned to achieve the desired TBS effects.The purpose of the study is to investigate the effects of spaced TBS at a superficial brain regionconnected to the hippocampus in individuals with amnestic MCI (aMCI). TBS will be applied insidean MRI scanner interleaved with fMRI to visualize the immediate response to the hippocampalstimulation. Aim 1 of the study will determine the effects of spaced TBS on memory performanceand hippocampal function in individuals with aMCI. Aim 2 will establish dose-responserelationship of the spaced TBS effect. Thirty-eight individuals with aMCI will be randomly assignedto one of the two TBS groups: active TBS or sham TBS. We hypothesize that 1) the spaced TBSprotocol will enhance memory function strengthen hippocampal functional connectivity andincrease hippocampal activation compared to the sham TBS and 2) a positive dose-responserelationship of the TBS effect will be observed. By leveraging cutting edge MRI-compatible TBSfindings of our innovative study may suggest mechanisms of spaced hippocampal TBS in aMCI.Ultimately understanding how brain responds to the spaced TBS will enable development of anoptimized TBS therapeutic protocol for individuals with MCI and AD.