Brain lactate concentration is usually assumed to be stable except when pathologic conditions cause a mismatch between glycolysis and respiration. Using newly developed 1H NMR spectroscopic techniques that allow measurement of lactate in vivo, we detected lactate elevations of 0.3-0.9 mM in human visual cortex during physiologic photic stimulation. The maximum rise appeared in the first few minutes; thereafter lactate concentration declined while stimulation continued. The results are consistent with a transient excess of glycolysis over respiration in the visual cortex, occurring as a normal response to stimulation in the physiologic range.Glucose and oxygen-the principal substrates ofbrain energy metabolism-are consumed by that organ at matched rates that ordinarily maintain stable lactate concentrations. Brain lactate elevations due to lack of oxygen or increased energy demand to the degree of status epilepticus are well-known phenomena, and extensive research on them has created a general impression that brain lactate elevation always reflects pathologic conditions. However, several recent reports suggest that brain activity within the physiologic range may cause brain lactate to rise. In an earlier study using nuclear magnetic resonance spectroscopy (MRS) in vivo, we found that lactate rose in posterior cerebral cortex of rabbits when electric shocks were delivered to the optic nerves (1). Ueki et al. (2) demonstrated lactate elevation in rat somatosensory cortex due to forepaw stimulation. In humans studied by positron emission tomography (PET), Fox et al. (3) showed that visual stimulation caused 30-50% increases in blood flow and glucose uptake of visual cortex, whereas oxygen extraction rose no more than 5%. Newly developed MRS techniques permit repeated noninvasive detection of lactate in a few cc of human brain (4-6). We have used such techniques to show that photic stimulation does indeed cause a clear, although transient, elevation of lactate in human visual cortex; a preliminary report has appeared (7).

Absence seizures are 5-10 s episodes of impaired consciousness accompanied by 3-4 Hz generalized spike-and-wave discharge on electroencephalography (EEG). The time course of functional magnetic resonance imaging (fMRI) changes in absence seizures in relation to EEG and behavior is not known. We acquired simultaneous EEG-fMRI in 88 typical childhood absence seizures from nine pediatric patients. We investigated behavior concurrently using a continuous performance task or simpler repetitive tapping task. EEG timefrequency analysis revealed abrupt onset and end of 3-4 Hz spike-wave discharges with a mean duration of 6.6 s. Behavioral analysis also showed rapid onset and end of deficits associated with electrographic seizure start and end. In contrast, we observed small early fMRI increases in the orbital/medial frontal and medial/lateral parietal cortex Ͼ5 s before seizure onset, followed by profound fMRI decreases continuing Ͼ20 s after seizure end. This time course differed markedly from the hemodynamic response function (HRF) model used in conventional fMRI analysis, consisting of large increases beginning after electrical event onset, followed by small fMRI decreases. Other regions, such as the lateral frontal cortex, showed more balanced fMRI increases followed by approximately equal decreases. The thalamus showed delayed increases after seizure onset followed by small decreases, most closely resembling the HRF model. These findings reveal a complex and long-lasting sequence of fMRI changes in absence seizures, which are not detectable by conventional HRF modeling in many regions. These results may be important mechanistically for seizure initiation and termination and may also contribute to changes in EEG and behavior.

Temporal lobe seizures are accompanied by complex behavioral phenomena including loss of consciousness, dystonic movements and neuroendocrine changes. These phenomena may arise from extended neural networks beyond the temporal lobe. To investigate this, we imaged cerebral blood flow (CBF) changes during human temporal lobe seizures with single photon emission computed tomography (SPECT) while performing continuous video/EEG monitoring. We found that temporal lobe seizures associated with loss of consciousness produced CBF increases in the temporal lobe, followed by increases in bilateral midline subcortical structures. These changes were accompanied by marked bilateral CBF decreases in the frontal and parietal association cortex. In contrast, temporal lobe seizures in which consciousness was spared were not accompanied by these widespread CBF changes. The CBF decreases in frontal and parietal association cortex were strongly correlated with increases in midline structures such as the mediodorsal thalamus. These results suggest that impaired consciousness in temporal lobe seizures may result from focal abnormal activity in temporal and subcortical networks linked to widespread impaired function of the association cortex.

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