title: The fast optical signal--robust or elusive when non-invasively measured in the human adult?
abstract: Near infrared spectroscopy (NIRS) can detect vascular changes in cerebral cortical tissue elicited by functional stimulation. For some 10 years, another optical signal has been reported to be accessible by NIRS. This signal has been reported to correlate to the electrophysiological response rendering NIRS an exquisite non-invasive approach to investigate neurovascular coupling in the human adult. Due to their typical latency of up to hundreds of milliseconds, these signals have been termed "fast" optical signals and have been postulated to stem from scatter changes in neuronal tissue, as a fingerprint of the electrophysiological response. Here, we utter a less optimistic view on the non-invasive detectability of these changes in the human, motivated by an upper limit signal size estimation, predicting a signal size by orders of magnitude smaller than those previously reported. Also, we discuss the influence of small stimulus correlated movement artifacts potentially mimicking a fast optical signal. Based on invasive studies, we perform an upper limit estimation for changes in intensity and mean time of flight, which can be expected assuming a scatter change in the cerebral cortex while measuring on the surface of the head of an adult subject. Since the resulting numbers are far below those previously reported, we constructed a simple system, which minimizes technical noise. The system allows us to detect rather small intensity changes (2 x 10(-3)%) when averaging over approximately 3000 stimuli. Despite this outstandingly low noise level of the system, we find a reliable change in response to a sub-motor-threshold steady state median nerve stimulation in just one single subject (8 subjects examined, 4 subjects twice). Exceeding the motor threshold leads to large stimulus related artifacts, on a similar time scale and with comparable amplitude as previously reported signals. To check for potential modality specific problems, we next performed a visual stimulation study, avoiding potential motor artifacts. For the steady state visually evoked response, no subject yielded a reliable result (11 subjects examined, 4 subjects twice). The paper discusses these findings by a review of the literature on fast optical signals and their being accessible in the adult human.
authors.affiliation: Division of Optical Neuroimaging, Berlin NeuroImaging Center, Schumannstrasse 20/21, 10098 Berlin, Germany. jens.steinbrink@charite.de
authors.forename: Jens
authors.initials: J
authors.lastname: Steinbrink
authors.forename: Florian C D
authors.initials: FC
authors.lastname: Kempf
authors.forename: Arno
authors.initials: A
authors.lastname: Villringer
authors.forename: Hellmuth
authors.initials: H
authors.lastname: Obrig
mesh_terms: D000328:Adult; D000465:Algorithms; D000818:Animals; D016477:Artifacts; D002415:Cats; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003952:Diagnostic Imaging; D005073:Evoked Potentials, Somatosensory / Q000502:physiology; D006339:Heart Rate / Q000502:physiology; D006624:Hippocampus / Q000033:anatomy & histology / Q000502:physiology; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D016014:Linear Models; D008475:Median Nerve / Q000502:physiology; D010775:Photic Stimulation; D010812:Physical Stimulation; D019265:Spectroscopy, Near-Infrared / Q000706:statistics & numerical data*