title: Cytochrome-c-oxidase redox changes during visual stimulation measured by near-infrared spectroscopy cannot be explained by a mere cross talk artefact.
abstract: The detection of redox changes in cytochrome-c-oxidase ([Cyt-ox]) in response to cerebral activation by non-invasive NIRS is hampered by methodological spectroscopic issues related to the modification of the Beer-Lambert law. Also, the question whether a change in the enzyme's redox-state is elicited by functional stimulation is unresolved. In a previous study, we found physiological evidence in favour of an activation-induced increase in oxidation of the enzyme [J. Cereb. Blood Flow Metab. 19 (1999) 592], while in a second study on spectroscopic cross talk, we found that the [Cyt-ox] changes to potentially be an artefact of the spectroscopic approach [J. Biomed. Opt. 7 (2002) 51]. Here, we use two different stimuli which differentially activate areas either rich or poor in [Cyt-ox] content (blob/interblob in visual cortex V1 and pale/thin stripes in V2) to further clarify this apparent discrepancy. In a first experiment, two stimuli were presented in an alternating fashion for 20 s and all stimulation periods were separated by resting periods of 40 s. We observed similar changes in [Cyt-ox] for both stimuli. To become more sensitive to the potentially very small optical changes related to changes in [Cyt-ox], we tried to minimise global haemodynamic and metabolic effects in a second experiment by omitting the resting periods. Our hypothesis was that [Cyt-ox] changes could be fully explained by cross talk as it is predicted from our last study [J. Biomed. Opt. 7 (2002) 51]. However, in more than half of the experiments, we were not able to model the changes in Cyt-ox calculated from measured attenuation spectra as a cross talk artefact. We interpret this finding as an argument in favour of the existence of [Cyt-ox] changes in response to functional stimulation. This finding, however, does not lessen the liability of the [Cyt-ox] changes to cross talk and calls for great caution when [Cyt-ox] changes are derived from NIRS measurements based on the modified Beer-Lambert approach. Further (invasive) validation studies are required.
authors.affiliation: Department of Neurology, Charité, Humboldt University, Berlin 10117, Germany. kuludag@ucsd.edu
authors.forename: Kâmil
authors.initials: K
authors.lastname: Uludağ
authors.forename: Jens
authors.initials: J
authors.lastname: Steinbrink
authors.forename: Matthias
authors.initials: M
authors.lastname: Kohl-Bareis
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Wenzel
authors.forename: Arno
authors.initials: A
authors.lastname: Villringer
authors.forename: Hellmuth
authors.initials: H
authors.lastname: Obrig
mesh_terms: D000328:Adult; D016477:Artifacts; D001921:Brain / Q000201:enzymology*; D003576:Electron Transport Complex IV / Q000378:metabolism*; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008297:Male; D008959:Models, Neurological; D010084:Oxidation-Reduction; D010108:Oxyhemoglobins / Q000378:metabolism; D010775:Photic Stimulation; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D014793:Visual Cortex / Q000201:enzymology
chemical_list: D006454:Hemoglobins; D010108:Oxyhemoglobins; C100003:deoxyhemoglobin; D003576:Electron Transport Complex IV