Abstract
Spiral ganglion neuron (SGN) degeneration is a candidate factor for reduced hearing outcomes in cochlear implant (CI) users. However, there is no procedure available to identify CI contacts close to focal SGN degeneration in human patients. In an animal model, we assessed the impact of focal SGN degeneration on electrical responsiveness and derived an electrophysiological marker for the presence, location and size of such lesions.
We introduced cochlear micro-lesions in 13 guinea pigs (6 female) and recorded electrically-evoked compound action potentials (eCAP) after 8-12 days. These were compared to recordings from controls (N=8) and acutely lesioned cochleae (N=12). We stimulated via 6-contact CIs in monopolar configuration with symmetric, biphasic pulses of alternating polarity. We histologically assessed the lesion and its relative position to the CI-contacts.
The small lesions (230-850 µm) significantly elevated thresholds and reduced eCAP amplitudes. The effect was found at stimulation distances of 3.5 mm from the lesion. A novel eCAP marker, Failure Index (FI: maximal input/output ratio), was significantly elevated in the presence of degenerated SGN. It indicates the failure to efficiently transduce the stimulation current into neural activation (i.e., N1P1 amplitude). The FI showed classification accuracies of 80% and identified the contact closest to the lesion in ∼80% of cases within ±700 µm (∼electrode spacing) from the lesion-site and was correlated with the lesion-size.
Thus, the FI is a clinically-relevant, non-invasive marker that is suitable for clinical data sets without any a priori knowledge on lesions, when combined with the statistical method of median-splitting.
Significance Statement Spatially restricted degeneration of spiral ganglion neurons (i.e., focal lesions) in the inner ear significantly reduced responsiveness to electric stimulation via a cochlear implant (CI). An electrophysiological marker of these lesions, the Failure Index (FI), was specifically elevated in the presence of chronic degeneration, but not acute neural loss, and explained 60% of variance in lesion-size. With its potential for non-invasive assessment of focal lesions in human patients, the FI is considered highly relevant for clinical applications. If successfully transferred to the clinic, the identification of regions with reduced neural health via the FI may be used to adapt sound processor programming with the aim to improve speech intelligibility.
Footnotes
The project was granted by the MHH-plus foundation of the Hannover Medical School and supported by the MED-EL company (provided the cochlear implants) and the Deutsche Forschungsgemeinschaft (Hearing4All, DFG Exc. 2177). We thank Daniela Kühne for preparing the histological specimens and microscopy pictures and Karl-Jürgen Kühne for supervising the µCT scanning procedure.
The authors declare no competing financial interests.
