In TRD 2, we propose a program of bioengineering development to improve human functional and anatomical MRI at high magnetic field strength (7 Tesla). The overall goal of the project is to improve the spatio-temporal resolution of fMRI down to its biological limits and to allow study of the folded cortex in its natural radial and tangential coordinate system. We seek the tools to allow the study of the next level of cortical organization: columns and layers, over large regions of folded cortex. This requires high isotropic spatial resolution and improved image encoding, shimming and physiological noise control. In addition to pursuing technology for these fundamental improvements, we will bring high-resolution 7T fMRI to two new areas: 1) the brainstem and subthalamic nuclei where B0, B1+ uniformity and tissue pulsatility and physiological variance are at their worst, and 2) the study of depression and OCD patients with Deep Brain Stimulators in place. The first goal is driven by our collaborators who study pain, depression and cognitive effects where these small (~2- 3mm diameter) nuclei such as the Raphe Nuclei and Periaqueductal gray matter play an important role. The second goal (bringing fMRI and functional connectivity to bear on DBS treatment) is driven by the recent success of our collaborators in using DBS for treating psychiatric illnesses. We share their enthusiasm for this potential method as an important breakthrough in mental health treatment. But, uncertainties remain about which circuits are affected, which exact fiber bundles need to be targeted and the most efficacious stimulation protocol. It is suspected that these uncertainties are behind the variance in the outcomes seen in this nascent treatment. Functional MRI could play an important role in elucidating the mechanisms of action and thus provide feed-back to improve targeting and stimulation protocol design. These studies would require MR examinations both before and after treatment. The use of MRI with a DBS in place for research studies would likely require and Investigational Device Exhemption (IDE) from the FDA due to the danger of RF heating near the implant tip and the limited conditions indicated for clinical studies. Thus, we have formulated a number of studies we will perform together with our collaborators at the FDA Center for Devices and Radiological Health, that will lay the ground-work for ourselves and others to safely study this important patient group as well as provide better clinical imaging for these patients should they need it in the future.