Temporal dynamics and magnitude of the blood flow response at the optic disk in normal subjects during functional retinal flicker-stimulation Charles E. Riva a,b, * , Eric Logean a , Benedetto Falsini c a Institut de Recherche en Ophtalmologie, 64 Avenue Grand Champsec, 1950 Sion, Switzerland b Medical Faculty, University of Lausanne, Lausanne, Switzerland c Institute of Ophthalmology, Catholic University of S. Cuore, Rome, Italy Received 30 June 2003; received in revised form 28 August 2003; accepted 28 August 2003 Abstract Near-infrared laser Doppler flowmetry was applied in 15 normal volunteers to record the time course and magnitude of changes in the velocity (Vel), volume (Vol) and flow (F) of blood and tissue reflectance (R) at the optic disk in response to 40 and 50 s of increased retinal neural activity. This activity was evoked by diffuse luminance flicker of the retinal posterior pole. After 20 s of flicker, the group averages of Vel, Vol, and F were significantly higher than at baseline (pre-flicker) by 12, 24 and 38%. Time constants of the increases in Vel, Vol, and F were 3.4, 12.7 and 9.1 s, respectively. The group average change in R of 1% was not significant. However, in one subject, 15 recordings from the same site of the optic disk showed a significant increase in R of 8%, with a time course similar to that of Vol. Our findings show that, in the human optic nerve, a white matter tissue, the temporal dynamics and magnitude of the response of blood flow to an increase in retinal neural activity are similar to those reported for brain gray matter. Furthermore, although the R-response could be due, in part, to changes in blood volume, other factors, such as activity-evoked tissue scattering changes, may also affect this response. q 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: Functional activity; Laser Doppler flowmetry; Neurovascular coupling; Flicker stimulation; Optic nerve blood flow The optic nerve is composed only of axons and glia and therefore has been a valuable preparation for studying the cellular mechanisms of activity-dependent changes in the extracellular space, as these are uncomplicated by the presence of synapses [10]. Now, the capability of laser Doppler flowmetry (LDF) to non-invasively monitor blood flow in this neural tissue of white matter [11,12] allows additional activity-induced physiological processes to be examined. In this paper, we report on the temporal dynamics of blood flow and near-infrared reflectance of the human optic nerve papilla during increased neural activity. The study was conducted in 15 normal observers (seven females and eight males, aged 28–62 years) with normal eye examination and excellent target fixation. Informed consent was obtained after the aim of the study and the procedures were fully explained. The research followed the tenets of the Declaration of Helsinki. LDF recordings were performed using a Topcon TRC (Topcon Inc., Tokyo, Japan) fundus camera based laser Doppler system [12,14]. Briefly, a probing laser beam at 810 nm (power at the cornea 90 mW, diameter at the fundus of , 150 mm) was directed at temporal sites of the neuro- retinal rim of the optic disk. The scattered light was collected by an optical fiber and guided to a photodetector. The aperture of this fiber (diameter at the fundus , 180 mm) was centered on the site illuminated by the laser beam. For observation, the eye fundus was illuminated with light at 826 nm. The fundus and the aperture of the optical fiber were both imaged on a CCD. The fundus camera was positioned in front of the eye so that an edge of the pupil of the tested eye could also be observed on the video monitor of the CCD camera. This allowed the observer to monitor the position of this pupil relative to the fundus camera and maintain it steady. A pinpoint of red light placed in the retinal plane of the ophthalmoscopic lens served as fixation target. The operator searched for a site of measurement deprived of large vessels by moving this target and guided by color photographs of the disk and the pitch of the Doppler sound. The output signal of the detector was analyzed using a software implemented on a NeXT 0304-3940/03/$ - see front matter q 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2003.08.069 Neuroscience Letters 356 (2004) 75–78 www.elsevier.com/locate/neulet * Corresponding author. Tel.: þ 41-27-205-7900; fax: þ41-27-205-7901.