This project explores advancements in a method for imaging the function of the human brain, based on the measurements of changes in how near-infrared light diffuses through the brain (Diffuse Optical Tomography, DOT). This method is particularly useful to investigate the time course of rapid brain phenomena, such as neural activity, and the functional hemodynamic responses that follow neuronal activity in response to stimuli delivered during cognitive tasks. DOT can be applied to populations (such as small children or people who are claustrophobic or bearing metallic devices), who cannot be easily studied using other brain imaging technologies. It can also be concurrently used with standard methods such as functional magnetic resonance imaging (fMRI) and event-related brain potentials (ERPs) providing an important bridge for the understanding of the physiology underlying these methods. Importantly, DOT signals can potentially be useful in a large number of research and clinical applications, including the study of normal and abnormal brain activity in psychopathology, cognitive aging and dementia, development, and as a result of vascular brain problems, as well as for the study and diagnosis of cerebrovascular diseases from newborns to the elderly. A current limitation of this technique is that, in its current form, it only measures changes from a baseline level. In order to relate the functional data to particular brain structure, users have to rely on head-surface features or independently-collected structural MR-recordings. Here we explore the application of a methodology, called multi- distance approach, to generate absolute measurements of diffusion parameters over the entire cortical surface. These measurements can be used to reveal anatomical structures rich in hemoglobin (such as the venous sinuses), which can serve as useful anatomical landmarks for coregistration. Importantly, this structural information can be collected while recording the functional DOT data. The proposal will explore how reliable this information is, and how it can be used to precisely co-register the functional measures to anatomical brain structures. The proposed research will also explore how the transparency of the brain to near-infrared light changes with age. Preliminary data suggest strong age-related variations, with older adults showing significantly more brain transparency than younger adults. This difference may reflect changes in brain vascularization and/or cortical atrophy. The proposed research will explore the relevance of these factors, which may render this approach a useful tool for studying the health status of the cortex in a non-invasive manner. The absolute measurements of the light diffusion parameters also allows for a more quantitative study of functional DOT effects due to the activation of specific brain areas during cognitive tasks, and how they vary in different populations, as a function of age (and in principle, development and pathology). The proposed research will compare different methods for obtaining these functional images in term of their reliability, validity and signal-to-noise ratio.