The purpose of this study was to collect real-time bedside images of changes in cortical oxygenation during motor activity in human subjects. Cortical regional cerebral blood volume (rCBV), blood flow (rCBF), and hemoglobin saturation (rSO2) vary over time. Localized physiologic changes occur over seconds during brain activity, affording a regional mapping signal colocalizing with electrical activity; abnormalities in such regional signals are hypothesized to be associated with cerebral injury (e.g., leukomalacia after IVH). Regional hemoglobin changes can be mapped using functional MRI(fMRI) and PET, but these are not bedside monitors and thus may miss the signs that herald impending injury. Low-level visible and near-infrared light pass through human bone and tissue in small amounts, and the time of photon transit through tissue can be used to measure tissue oxygenation and reconstruct images (Benaron, Science, 1993). We generated images of adult motor cortex during hand movement. These revealed focal, contralateral increases in oxygenation with motor activity, and good spatial agreement to activation maps determined by fMRI. Mean rSO2 without activity was 70.7 ± 8.5% (n=456). With activity, mean increase was 2.0 ± 0.5%, p<0.001. As such slow optical changes occur over seconds and colocalize with fMRI vascular signals, while fast optical changes (reported elsewhere) occur over milliseconds and colocalize with EEG electrical signals, optical methods offer a single modality for exploring the spatiotemporal relationship between electrical and vascular responses in the brain. This is under study as a tool for prospectively identifying infants later diagnosed with cerebral palsy. NIH N43-NS-6-2315 & RR-00081, ONR N-00014-94-1-1024. United Cerebral Palsy Foundation, Spectro Corp. (Spectros effort supported by NIH; DAB & WFC hold equity).