Spiral waves are a basic feature of excitable systems. Although such waves have been observed in a variety of biological systems, they have not been observed in the mammalian cortex during neuronal activity. Here, we report stable rotating spiral waves in rat neocortical slices visualized by voltage-sensitive dye imaging. Tissue from the occipital cortex (visual) was sectioned parallel to cortical lamina to preserve horizontal connections in layers III-V (500-m-thick, ϳ4 ϫ 6 mm 2 ). In such tangential slices, excitation waves propagated in two dimensions during cholinergic oscillations. Spiral waves occurred spontaneously and alternated with plane, ring, and irregular waves. The rotation rate of the spirals was ϳ10 turns per second, and the rotation was linked to the oscillations in a one-cycle-one-rotation manner. A small (Ͻ128 m) phase singularity occurred at the center of the spirals, about which were observed oscillations of widely distributed phases. The phase singularity drifted slowly across the tissue (ϳ1 mm/10 turns). We introduced a computational model of a cortical layer that predicted and replicated many of the features of our experimental findings. We speculate that rotating spiral waves may provide a spatial framework to organize cortical oscillations.

Epileptic events elicit a large focal increase in cerebral blood flow (CBF) to perfuse metabolically active neurons in the focus. Conflicting data exists, however, on whether hemoglobin saturation increases or decreases in the focus and surrounding cortex, and whether CBF increases globally or is decreased in adjacent areas. How these hemodynamic events correlate with actual changes in tissue oxygenation is also not known. Using laser Doppler flowmetry, oxygen microsensors and intrinsic optical imaging spectroscopy, we demonstrate that the dip in hemoglobin in the focus correlates with a profound but temporary decrease in tissue oxygenation despite a large increase in CBF. Furthermore, CBF simultaneously decreases in the cortex immediately adjacent to the focus. These events are then replaced with a longer duration, less focal increase in CBF, cerebral blood volume, and hyperoxygenation, the duration of which correlates with the duration of the seizure. These findings raise the question of whether transient focal hypoxia and vascular steal might contribute to progressive deleterious effects of chronic epilepsy on the adult and developing brain. Possible mechanisms based on recent astrocytebased models of neurovascular coupling are discussed.

Epileptic events initiate a large focal increase in metabolism and cerebral blood flow (CBF) to the ictal focus. In contrast, decreases in CBF have been demonstrated surrounding the focus, the etiology of which is unknown i.e. arising either from active shunting of blood or passive steal. The relationship between these events and neuronal activity and metabolism are also unknown. We investigated neurovascular and neurometabolic coupling in the ictal surround using optical imaging of light scattering and cerebral blood volume, autofluorescence imaging (AFI) of flavoproteins, direct measurements of CMRO2 and two-photon imaging of blood vessel diameter in a rat model of ictal events elicited with focal injection of 4-aminopyridine. We discovered a novel phenomenon, in which ictal events are preceded by pre-ictal vasoconstriction of blood vessels in the surround, occurring 1–5 s before seizure onset, which may serve to actively shunt oxygenated blood to the imminently hypermetabolic focus or may be due to small local decreases in metabolism in the surround. Early ictal hypometabolism, transient decreases in cell swelling and CBV in the surround are consistent with early ictal surround inhibition as a precipitating event in seizure onset as well as shaping the evolving propagating ictal wavefront, although the exact mechanism of these cerebraovascular and metabolic changes is currently unknown. AFI was extremely sensitive to the ictal onset zone and may be a useful mapping technique with clinical applications.

SUMMARYPurpose: Optical recording of intrinsic signals provides the highest combined spatial and temporal resolution with broad spatial sampling for measuring cerebral blood volume (CBV) and hemoglobin oxygenation in cerebral cortex. Few opportunities arise to apply this laboratory method to record spontaneous seizures in unanesthetized human brain during neurosurgery. We report such a rare opportunity in a man with recurrent focal epilepsy arising from a cavernous malformation. Methods: We recorded intrinsic optical signals (IOS) from human cortex intraoperatively during spontaneous seizures arising from brain surrounding a small cavernous malformation in an awake patient using only local anesthesia with simultaneous electrocorticography. The IOS was recorded at two wavelengths, one an isosbestic point for hemoglobin to measure CBV (570 nm) and the other at a wavelength more sensitive to deoxygenated hemoglobin (Hbr) (610 nm). A modified Beer-Lambert calculation was used on two separate but similar seizures to approximate changes in Hbr, CBV as well as oxygenated hemoglobin (HbO 2 ). Results: Electrographically recorded seizures (n = 3) elicited a focal increase in both Hbr and CBV that lasted for the duration of the seizure, indicating that perfusion was inadequate to meet metabolic demand. Remarkably, these hemodynamic changes preceded the onset of the seizures by ∼20 s and occurred focally over the known location of the lesion and the seizure onsets. Discussion: These findings demonstrate that the hemoglobin becomes deoxygenated in spite of large increase in CBV during spontaneous human focal seizures and that optically recorded hemodynamic events can be used both to predict and localize human focal epilepsy. Such data may someday be useful to assist in the presurgical evaluation of patients considered for epilepsy surgery and to predict the timing and location of seizure onsets. KEY WORDS: Intraoperative optical imagingHuman-Seizures-Perfusion-Oximetry.Epilepsy is a disease of the brain characterized by recurrent spontaneous seizures. These "ictal" events arise from a population of hyperexcitable neurons that exhibit increased synchronized and desynchronized activity during the course of the seizure (Schwartzkroin, 1993). Cer-