RT Journal Article SR Electronic T1 An electrically-evoked compound action potential marker for local spiral ganglion neuron degeneration: The Failure Index JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP e0954242024 DO 10.1523/JNEUROSCI.0954-24.2024 A1 Konerding, Wiebke A1 Arenberg, Julie A1 Sznabel, Dorota A1 Kral, Andrej A1 Baumhoff, Peter YR 2024 UL http://www.jneurosci.org/content/early/2024/12/09/JNEUROSCI.0954-24.2024.abstract AB 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.