This project aims to develop a completely new concept and technology for orientation-selective manipulation of neuronal activity. Recent development in target selection has focused on shaping the stimulation field by using multichannel electrodes and current steering. However, while such approaches aim at optimizing the amplitude of the electrical field over a specified volume of interest, they do not utilize the direction of the electrical fields to specifically stimulate axons depending on their orientation and thus take advantage of the maximal excitability of axons when the electric field is parallel to the orientation of axonal body. For this purpose these researchers will develop a novel neuromodulation system that allows maximal stimulation of selected neuronal populations in tissue based on spatially oriented electric fields. Notably, the group's novel deep-brain stimulation (DBS) system can be configured to generate rotating as well as unidirectional electrical fields, thus ultimately stimulating neurons regardless of the axons' orientation. The system is based on amplitude modulated waveforms with different phases and operates in conjunction with a multichannel electrode for generating either unidirectional or rotating electrical fields. The first step will use simulations to optimize waveforms and electrode geometry to allow selective and flexible neuromodulation of neuronal populations by generating unidirectional and rotating electrical fields, respectively. The second step will implement this new and optimized technology for the preliminary proof-of-concept DBS studies in the rat brain. The researchers will monitor evoked activity using electrophysiological recording and functional MRI (fMRI). This research will ultimately have a large impact in significantly improving DBS as a biomedical research tool as well as a treatment modality.