The spatiotemporal dynamics of neurovascular coupling during epilepsy are not well understood, and there are little data from studies of the human brain. We investigated changes in total hemoglobin (Hbt) and hemoglobin oxygenation in patients undergoing epilepsy surgery with intraoperative intrinsic optical spectroscopy (IOS) during triggered afterdischarges (ADs). We found an early (approximately 0.5 secs) focal dip in hemoglobin oxygenation, arising precisely in the stimulated gyrus that lasted for 11.5+/-10.0 secs, approximately the length of the AD (10.4+/-4.4 secs). A later oxygen overshoot and increase in blood volume occurred in the adjacent surrounding gyri. After a significant delay (approximately 20 to 30 secs), the overshoot and blood volume signal became extremely focal to the area of the onset of the AD. A smaller very late undershoot, the last phase of the 'triphasic' response, was also identified, although localization was inconsistent. In this study, we show that a 'late focal overshoot' and late Hbt signal may be extremely useful, in addition to the early dip, for the localization of seizure onset. It is likely that a separate mechanism underlies the persistent focal increase in cerebral blood volume after a long-duration cortical stimulation, compared with the nonspecific mechanism that causes the initial increase in cerebral blood flow.