Individualized Closed Loop TMS for Working Memory Enhancement

Prior to any study visits, all subjects will be pre-screened through a REDCap online self-report screening REDCap. The study involves 11 study visits. The first study visit will consist of a consenting and extended screening visit. All participants will have the opportunity to ask questions before signing the electronic consent form. We will complete a semi-structured clinical interview and will demonstrate TMS to ensure the participant is comfortable with all study procedures. This visit will be completed both remote and in-person. The second study visit will involve a 1-hour MRI scan. During the scan, the participant will complete multiple computerized tasks. The MRI scan will include both structural and functional scans, and those scans will be used to localize the stimulation target for the subsequent sessions. The third study visit will be a 2-hour TMS/fMRI session, and the participant will engage in behavioral tasks while interleaved rTMS rounds are delivered at different excitatory frequencies (frequency range: 2Hz-20Hz). This scan will be used to determine the optimal stimulation frequency for the individual participant. The fourth, fifth, and sixth study visits will involve neuromodulation with either the optimized frequency or the frequency least successful in moving a participants brain state, as determined from the third study visit. Each subject will receive \~3000 pulses in each session, including the pulses from the motor threshold determination. We will determine the stimulation amplitude by using the Stokes equation, which accounts for differences in cortical distance from the site relative to motor cortex (where the motor threshold is found). The seventh study visit will involve a 1-hour TMS/fMRI session while the participant is engaging in a behavioral task. This visit is designed to examine brain and behavioral changes after the first round of neuromodulation. The seventh and the eighth visit will be scheduled at least one week apart. The eighth, ninth, and tenth study visits will mirror the fourth, fifth, and sixth study visits and will involve neuromodulation with either the optimized or least-optimized individual frequency. The order of optimized and least-optimized frequencies will be counterbalanced across participants between Visit 4-6 and Visit 8-10 (i.e., half of the participants will receive stimulations of the two frequencies in one order, and the other half will receive stimulations of the two frequencies in the reverse order). The eleventh visit will mirror the seventh visit and will examine brain and behavioral changes after the second round of neuromodulation.