<p class="first" id="P2">Since cochlear implant function involves direct depolarization
of spiral ganglion
neurons (SGNs) by applied current, SGN physiological health must be an important factor
in cochlear implant (CI) outcomes. This expected relationship has, however, been difficult
to confirm in implant recipients. Suggestively, animal studies have demonstrated both
acute and progressive SGN ultrastructural changes (notably axon demyelination), even
in the absence of soma death, and corresponding altered physiology following sensorineural
deafening. Whether such demyelination occurs in humans and how such changes might
impact CI function remains unknown. To approach this problem, we incorporated SGN
demyelination into a biophysical model of extracellular stimulation of SGN fibers.
Our approach enabled exploration of the entire parameter space corresponding to simulated
myelin diameter and extent of fiber affected. All simulated fibers were stimulated
distally with anodic monophasic, cathodic monophasic, anode-phase-first (AF) biphasic,
and cathode-phase-first (CF) biphasic pulses from an extracellular disc electrode
and monitored for spikes centrally. Not surprisingly, axon sensitivity generally decreased
with demyelination, resulting in elevated thresholds, however, this effect was strongly
non-uniform. Fibers with severe demyelination affecting only the most peripheral nodes
responded nearly identically to normally myelinated fibers. Additionally, partial
demyelination (<50%) yielded only minimal increases in threshold even when the
entire
fiber was impacted. The temporal effects of demyelination were more unexpected. Both
latency and jitter of responses demonstrated resilience to modest changes but exhibited
strongly non-monotonic and stimulus-dependent relationships to more profound demyelination.
Normal, and modestly demyelinated fibers, were more sensitive to cathodic than anodic
monophasic pulses and to CF than AF biphasic pulses, however, when demyelination was
more severe these relative sensitivities were reversed. Comparison of threshold crossing
between nodal segments demonstrated stimulus-dependent shifts in action potential
initiation with different fiber demyelination states. For some demyelination scenarios,
both phases of biphasic pulses could initiate action potentials at threshold resulting
in bimodal latency and initiation site distributions and dramatically increased jitter.
In short, simulated demyelination leads to complex changes in fiber sensitivity and
spike timing, mediated by alterations in action potential initiation site and slowed
action potential conduction due to non-uniformities in the electrical properties of
axons. Such demyelination-induced changes, if present in implantees, would have profound
implications for the detection of fine temporal cues but not disrupt cues on the time
scale of speech envelopes. These simulation results highlight the importance of exploring
the SGN ultrastructural changes caused by a given etiology of hearing loss to more
accurately predict cochlear implantation outcomes.
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