Optic Nerve Blood Flow Response to Flicker Can Be Described by a Second Order Linear System Model

Purpose: Neurovascular coupling (NC) in the retinal tissue is the mechanism that controls the blood flow to support neural activity associated with the process of vision. Diffuse luminance flicker increases retinal and optic nerve blood flow in humans, indicating the ability of the retina to adapt to different metabolic demands. The control system analysis allows the description of the main dynamic features of this regulation system. Methods: Six healthy adult volunteers aged 25-62 years were included in the study. Informed consent was obtained from the subjects. Blood flow was measured from the optic nerve temporal rim by means of laser Doppler flowmetry. During these measurements a 15Hz square wave diffuse flicker stimulation was applied during 1 to 8 minutes through the illumination pathway of the laser Doppler fundus camera. The time-course of the flow underwent a 10-point lagging running-averaging process and then was fitted with the equation of a modified second-order control system G(s) consisting of the cascade of a Proportional-Derivative (PD) term, a second-order Filter (F2) and an Integrator term (INT). The characteristic parameters of G(s) to be determined were: the undamped natural frequency ({omega}) of F2, the damping factor ({xi}) of F2, the gain (K) of PD, the rate time (Tv) of PD and the integrator time constant ({tau}) of INT. The values for the parameters of G(s) related to the input flow time-courses were thus obtained. Results: Flicker-induced optic nerve blood flow changes could be well fitted by the response of G(s) to the Heaviside step function (correlation R2>0.66). Characteristic parameters of G(s) were calculated as mean values {+/-} standard errors and the following results were obtained:{omega} = 2.31{+/-}1.57 rad/sec,{xi} = 0.28{+/-}0.1, K = 180.75{+/-}11.76, Tv = 2.67{+/-}1.62 sec,{tau} = 5.95{+/-}1.93 sec. Conclusions: The response of optic nerve blood flow to diffuse luminance flicker can be described by a second order linear system. Further studies are needed to establish the physiological basis of the various terms of the control cascade.