A characterization of the effects on neuronal excitability due to prolonged microstimulation with chronically implanted microelectrodes

Abstract

Localized, long-lasting stimulation-induced depression of neuronal excitability (SIDNE) is a consequence of prolonged, high-frequency microstimulation in the central nervous system (CNS). It represents a persisting refractory state in the neurons and axons near the stimulating microelectrode, that occurs in the absence of histologically detectable tissue injury. It does not involve a change in synaptic efficacy and, in this respect, it differs from the more familiar phenomenon of long-term depression (LTD). Although SIDNE is ultimately reversible (after several days), it must be taken into account in the design of neural prostheses based on microstimulation in the central nervous system and in animal studies that require prolonged microstimulation in the CNS. In this study, we have characterized the phenomenon, using as the paradigm, iridium microelectrodes implanted chronically in the cat's posteroventral cochlear nucleus. Although the SIDNE may persist for several days after the end of the stimulation protocol, it does not become more severe from day to day when the stimulation protocol is repeated on successive days. The severity of the SIDNE is strongly dependent upon both the instantaneous frequency and the duty cycle of the electrical stimulation. The character of the SIDNE, including its localization to the immediate vicinity of the stimulating microelectrodes, suggests that the phenomenon is a direct consequence of the prolonged electrical excitation of the neurons close to the microelectrode. The problem of designing microstimulation systems that allow high-frequency stimulation of a neural substrate, while minimizing SIDNE are discussed.

Behavioral Determination of Stimulus Pair Discrimination of Auditory Acoustic and Electrical Stimuli Using a Classical Conditioning and Heart-rate Approach

“…Stimulation of neural tissue can lead to both temporary suppression of neural activity 13 and tissue changes such as cell loss 14 and direct brain tissue response to the electrode. 15 The described approach to implantation and behavioral testing provides a means to test both detection and discrimination of acoustic and electrical stimuli with brief training, and the ability to exert control of trial frequency.…”

Key considerations in designing a somatosensory neuroprosthesis

“…In touch, neuronal adaptation has been observed at all stages of the somatosensory hierarchy, from peripheral afferents Leung et al, 2005) to cortical neurons (Maravall et al, 2007) and is also reflected in tactile perception (Hollins et al, 1990;Ollerenshaw et al, 2014). Similarly, sustained electrical stimulation of neuronal tissue results in a desensitization of neurons to electrical stimulation (McCreery et al, 1997). In addition, direct stimulation of cortical neurons (Logothetis et al, 2010;Masse and Cook, 2010) activates both excitatory and inhibitory circuits and can lead to long-lasting depression.…”

A Flexible Platform for Biofeedback-Driven Control and Personalization of Electrical Nerve Stimulation Therapy

“…Linear regression was performed in STATA 12 to test for a statistically significant order effect, a characteristic feature of SIDNE [3]. A regression model slope coefficient that is significantly different from 0 suggests a relationship/change among the CNAP features of interest (i.e., Aγ + , B + , or C + ) and stimulus number (i.e., the sequential number assigned to each cathodal stimulus pulse within the 30-s train of stimuli delivered at 20 Hz).…”

“…These parameters are maintained until the next appointment [1,2]. Major limitations beyond the subjective nature of this approach include 1) the risk of adaption or desensitization to the stimulus, which may make the therapy less effective over time (e.g., stimulus induced depression of neuronal excitability, or SIDNE [3]), 2) the lack of feedback regarding the type and number of neurons that are activated when the therapy is effective, and 3) the risk of patient discomfort [1].…”

“…1) [4]. 2 ANC refines the electrical stimulus, within safe limits [3,[5][6][7], to selectively control nerve activation on a patient-topatient, nerve-to-nerve and neuron-to-neuron basis. By providing consistent nerve activation, ANC allows reproducible experiments to systematically delineate the therapeutic mechanisms of VNS or other form of ENS therapy.…”