ABSTRACT: The strategic plan of the NIH's BRAIN Initiative (BRAIN 2025: A scientific Vision) calls for transformative technological developments with MRI to achieve “submillimeter spatial resolution descriptions of neuronal activity, functional and structural connectivity, and network analysis in the human brain through advances in instrumentation, data acquisition and analysis techniques”. The primary aim of this grant application is specifically to undertake such technological developments. We plan to usher in the next generation MR instrumentation, and data acquisition and image reconstruction methods in order to reach and span currently unavailable spatial scales in human brain studies, going from neuronal ensembles composed of few thousand neurons to whole brain function and structural connectivity. The focus of the proposed work will be resting state- and task- or stimulus-based functional imaging (fMRI), and diffusion imaging (dMRI) methods for tractography and white-matter microstructure determination. We present a strategy, based on ample preliminary data, to develop and implement unique and novel gradients, B0 shims, RF coils, image acquisition and reconstruction methods, and previously unavailable 10.5 Tesla ultrahigh magnetic field. As a result of the cumulative gains from the proposed technologies, we anticipate an order of magnitude or more reduction in voxel volumes, thus reaching and even exceeding the resolution targets set forth in the BRAIN Initiative strategic plan. Using this new capability, we also plan to generate a publicly available database that will enable the most complete and accurate description of the functional and structural connections among gray matter locations in the human brain to date, and facilitate advanced computational modeling of how information is encoded by neural populations in the human brain. The proposed developments will be carried out by a consortium composed of investigators from the University of Minnesota Center for Magnetic Resonance Research (CMRR), Stanford University Lucas Center for Imaging, Penn State Center for NMR Research, NYU Center for Biomedical Imaging and Oxford University; together they bring to this project unique experience and track record of accomplishments in high resolution functional and diffusion imaging, ultrahigh magnetic field technology and applications, RF pulse and pulse sequence development, multichannel transmit technology, gradient design and construction, manufacturing and use of novel dielectric materials, RF coil design and construction, and image reconstruction and post- processing.