The Importance of Latency in the Focality of Perfusion and Oxygenation Changes Associated with Triggered after Discharges in Human Cortex

Abstract

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 (~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 (~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.

Investigation of Linear Coupling Between Single-Event Blood Flow Responses and Interictal Discharges in a Model of Experimental Epilepsy

“…Finally, 4) the choice of anesthesia (isofluorane) might also be of importance. Indeed, shorter interictal spikes (ϳ300 ms) are usually found both in humans and in animal studies using urethane and/or ketamine/xylazine anesthesia (Hirase et al 2004;Ma et al 2009a;Miyakawa et al 2003) as compared with halogenate anesthesia (e.g., halothane anesthesia in ferrets yields LFP responses of similar duration as those we report) (Schwartz and Bonhoeffer 2001).…”

“…The presence of such multiple mechanisms, possibly regulated at different spatiotemporal scales, has indeed been recently hypothesized within the context of triggered afterdischarges in human patients (Ma et al 2009a). A similar scenario might also underlie the different correlation between hemodynamic and neuronal activity reported to exist in the center of the epileptic area as compared with its periphery (Ma et al 2009b).…”

Ischemic–hypoxic mechanisms leading to hippocampal dysfunction as a consequence of status epilepticus

“…In general, data on transient exposure to hypoxia during SE are defective, since no continuous monitoring of oxygen partial pressure has been done in the animal models. On the other hand, in vivo and in vitro evidence of transient exposure to hypoxia during epileptic activity has been accumulating [54][55][56][57]. Interestingly, even subclinical seizures were associated with transient episodes of hypoxia [58].…”

LED-Based Optical Device for Chronic In Vivo Cerebral Blood Volume Measurement

“…A surface-mount broad-spectrum phototransistor (Optek OP-500) was used. The use of a dual wavelength measurement would allow separate measurements of perfusion and oxygenation [5]. …”

“…The most established, which is electrophysiological recording from electrodes, does not have the temporal or spatial sampling necessary for the acute study of neuronal activity generation and spread due to volume conduction effects [4]. Other techniques, including functional magnetic resonance imaging, positron emission tomography, and single-photon emission computed tomography, do not have sufficient resolution to record brief paroxysmal events such as interictal spikes (the synchronous firing of neuron populations) [5]. …”