A delayed class of BOLD waveforms associated with spreading depression in the feline cerebral cortex can be detected...

An application of independent component analysis to blood oxygenation level- dependent MRI (BOLD-MRI) results was used to detect cerebrovascular changes that followed the initiation of cortical spreading depression (CSD) in feline brain. The cortical images were obtained from a horizontal plane at 28 s intervals before, and for 1.4-1.75 h after, KCl dissolved in agar (KCl/agar) had been directly applied to the left suprasylvian gyrus of 13 anesthetized cats for 10 min. It successfully resolved, for the first time, a novel class of prolonged, and delayed, biphasic BOLD waveforms. These were larger in amplitude ( approximately 20%), longer lasting and more delayed in onset (13-33 min) than the brief propagating (90 s) BOLD increase ( approximately 4%) already known to be associated with CSD on earlier occasions. Furthermore, such changes occurred in localized regions on the hemisphere ipsilateral to the site of stimulus application in 4 out of 5 control subjects rather than themselves generating propagating waves. Finally, the biphasic waveforms were consistently abolished in the 4 experimental animals studied following the i.v. administration of sumatriptan (0.3 mg kg(-1)), an antimigraine 5-HT(1B/1D) agonist, 15 min before the application of the transient stimulus. They were abolished in 2 out of 4 animals following the intraperitoneal (i.p.) administration of SB-220453 (tonabersat: 10 mg kg(-1), 90 min before stimulus application), a novel anticonvulsant that has recently been reported to inhibit CSD. ICA has thus been successful in detecting a novel localized, as opposed to propagating, signal of potential physiological significance hidden in complex BOLD- MRI data, whose sensitivity to sumatriptan may relate it to the cerebrovascular changes reported in the headache phase of migraine.