Dynamical mechanisms of neural firing irregularity and modulation sensitivity with applications to cochlear implants

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2006.Includes bibliographical references.The degree of irregularity apparent in the discharge patterns of electrically stimulated auditory-nerve fibers depends upon the stimulation rate. Whereas fibers fire regularly at low stimulation rates, the same fibers fire irregularly at high rates. The irregularity observed at high stimulation rates has been attributed to noise caused by the random open and closing of voltage-gated ion channels. This explanation however is incomplete: an additional mechanism must be operating to account for the different effects of noise at the two stimulation rates. We have identified such an additional rate-dependent mechanism. Specifically, we show in the Fitzhugh-Nagumo (FN) model that the stability to perturbations such as noise depends upon the stimulation rate. At sufficiently high rates a dynamical instability arises that accounts for the main statistical features of the irregular discharge pattern, even in the absence of ongoing physiological noise. In addition, we show that this instability accounts for both the statistical independence exhibited by different fibers in the stimulated population and their sensitivity to amplitude modulations applied to an ongoing stimulus.(cont.) In cochlear implants, amplitude modulations are used to encode acoustic information such as speech. Psychophysically, sensitivity to small modulations correlates strongly with speech perception, suggesting a critical role for dynamical stability/instability in speech perception. We show that rate-dependent stability/instability occurs in the classical Hodgkin-Huxley model, as well as in biophysical models of the mammalian node of Ranvier.by David E. O'Gorman.Ph.D