DESCRIPTION: State the application's broad, long-term objectives and specific aims, making reference to the health relatedness of the project. Describe concisely the research design and methods for achieving these goals. Avoid summariesof past accomplishments and the use of the first person. This abstract is meant to serve as a succinct and accurate description of the proposed work when separated from the application. If the application is funded, this description, as is, will become public information. Therefore, do not include proprietary/confidential information. DO NOT EXCEED THE SPACE PROVIDED. This is a revised submission of a proposal to use psychophysics and brain imaging to investigate the brain activity associated with the processing of environmental visual information presented to the auditory system in blind and sighted individuals. Peter Meijer developed the first camera-based auditory display to preserve a significant amount of environmental visual information in sound, while taking into account the major constraints imposed by both the human auditory system and the frequency-time uncertainty relation (The vOICe, U.S. Patent 5,097,326). The vOICe results in a vision substitution tool for the blind providing a means of presenting live image-to-sound converted scenery and permits the study of cross-modal plasticity. Three groups of subjects will be studied: sighted controls, blind, and sighted-blindfolded subjects,. We will compare results across and within groups before and after training in the use of the image-to-sound conversion system. Training will be conducted daily for four weeks and will combine formal instruction using controlled exercises and more naturalistic, immersive use of the vOICe by the subject while navigating the environment in the laboratory. Three main tasks of decoding and processing visual information by the auditory system will be studied to address: (1) Topographic organization, (2) Mechanisms of object identification, and (3) Object constancy. Behavioral measures, functional magnetic resonance imaging (fMRI), and transcranial magnetic stimulation (TMS) will be used. We expect to find significant differences between the groups of subjects in the behavioral measures and brain activity associated with the processing of image-to-sound converted information. This study will provide critical insights into the mechanisms underlying cross-modal plasticity and processing of environmental spatial visual information presented via the auditory system in blind, as well as about metamodal object and space representation. Image-to-sound conversion may eventually become a suitable prosthesis for the blind. PERFORMANCE SITE(S) (organization, city, state) Beth Israel Deaconess Medical Center KEY PERSONNEL. See instructions. Use continuation pages as neededto provide the required information in the format shown below. Start with Principal Investigator. List all other key personnel in alphabetical order, last namefirst. Name Organization Role on Project Alvaro Pascual-Leone, MD, PhD Beth Israel Deaconess Med Ctr PI Gottfried Schlaug, MD, PhD Beth Israel Deaconess Med Ctr Co-investigator Peter Meijer, PhD Philips Research Consultant Amir Amedi, PhD Beth Israel Deaconess Med Ctr Co-investigator, Post-doc Disclosure Permission Statement. Applicable to SBIR/STTR Only. Seeinstructions. O Yes I I No PHS 398 (Rev. 05/01) Page 2 Number pages consecutively at the bottom throughout Form Page 2 the application. Do not use suffixes such as 2a, 2b. Principal Investigator/Program Director (Last, First, Middle): PASCUAL-LEONE, Alvaro The name of the principal investigator/program director must be provided at the top of each printed page and each continuation page. RESEARCH GRANT