PROJECT SUMMARY / ABSTRACT The Organizing Concept of the parent Phase II COBRE in Stroke Recovery is that better understanding of the experience-dependent nature of neural plasticity allows us to investigate and exploit inherent neural recovery processes, develop and translate novel mechanism-based interventional strategies, and ultimately improve the function and quality of life of individuals recovering from stroke. And Overall Specific Aim 2 focuses on strengthening innovative scientific cores that support/advance stroke recovery research – such as the Brain Stimulation and Neuroimaging Cores. Transcranial magnetic stimulation-functional magnetic resonance imaging (TMS-fMRI) is a technology initially developed over 20 years ago by investigators of the COBRE in Stroke Recovery. This technique established the utility of TMS beyond its application as an intervention by using it to interrogate neural network function by “perturbing” or “probing” neurocircuits with TMS and observing causal whole-brain responses with concurrent fMRI. The existing technology used by COBRE investigators has significant limitations. In direct alignment with the Organizing Concept and Overall Specific Aim above, we propose to acquire the first-in-class, state-of-the art interleaved MagVenture TMS-fMRI Research System with MR-compatible neuronavigation to advance precision rehabilitation for stroke recovery. We will integrate the system with our existing research-dedicated Siemens 3T Prisma MRI. The new system will provide: 1. Greater flexibility in targeted cortical regions: positioning of the TMS coil in our 12-channel birdcage coil is substantially hindered. The new system uses two ultraslim 7-channel array head receiving coils enabling flexible and reliable targeting of all cortical regions. 2. Improved quality of fMRI data: the distance between the participant’s head and the birdcage coil results in far lower signal to noise ratio (SNR). The new system’s surface arrays show a five- fold SNR increase over the traditional bird cage coil. Further, artifact in acquired MR images from the TMS coil is avoided. 3. Capability for in-scanner neuronavigation: we have no capability for in-scanner tracking of the TMS coil placement on the head. This is especially problematic as small shifts in coil placement or angle and/or head movement can result in TMS being delivered off target and at variable doses. The neuronavigation available in the MagVenture system will substantially improve data quality. 4. Capability for in-scanner repetitive TMS (rTMS): our existing system does not have cooling capacity for the TMS coil. As such, we can only deliver single pulses of TMS and not rTMS. The proposed system has an air-cooled coil to allow us to directly test rTMS protocols in the scanner, including high-demand stimulation patterns, without overheating. This will allow COBRE investigators to test the near-immediate, circuit-level effects of novel rTMS dosing and pulse sequences such as ...