Journal of the Association for Research in Otolaryngology · Aug 2025
John C. Middlebrooks, Matthew L. Richardson, Robert P. Carlyon, Harrison W. Lin
Abstract
Purpose Present-day cochlear implants (CIs) can deliver usable speech reception in quiet surroundings. Most CI users, however, show impaired sensitivity to temporal fine structure, which hampers their use of pitch contours and spatial cues to segregate competing talkers. In previous short-term animal studies, we used intraneural (IN) electrodes to stimulate pathways originating from various cochlear turns. Neurons in the inferior colliculus synchronized to apical stimulation at higher rates than to stimulation of the middle-to-basal pathways that are stimulated primarily by today’s CIs. Here, we use non-invasive recordings to test the safety and efficacy of up to 6 months of IN implantation and stimulation in cats. Methods Deafened cats (ten female, two male) were implanted with IN and/or conventional CI electrodes. The IN electrodes were single activated-iridium shanks that targeted apical-turn fibers. Scalp recordings were made from sedated animals at 2–3-week intervals. Auditory brainstem responses to single electrical pulses (eABR) tracked sensitivity and growth of responses. Frequency following responses to electrical pulse trains (eFFR) assessed brainstem temporal transmission at varying pulse rates. Results Thresholds for eABR were lower for IN than for CI stimulation, dynamic ranges were wider, and (by inference) spread of activation was more restricted. The eFFR evaluated at latencies comparable to those of inferior-colliculus spikes synchronized at maximum pulse rates averaging > 360 pulses/s for IN compared to ~ 240 pulses/s for CI stimulation. The eABR thresholds and eFFR cutoff rates were stable out to 6 months after implantation. Conclusions The results demonstrate the safety and efficacy of chronic IN stimulation in an animal model. In a future clinical device, an IN electrode could augment cochlear-implant performance by enhancing temporal acuity, thereby improving speech reception amid competing sounds.
Journal of the Association for Research in Otolaryngology · May 2025
Matthew L. Richardson, Robert P. Carlyon, Harrison W. Lin, John C. Middlebrooks
Abstract
Purpose Present-day cochlear-implant (CI) users can achieve high levels of speech reception in quiet surroundings. Nevertheless, sensitivity to the temporal pitch of sounds is limited, which contributes to deficits in speech reception amid multiple talkers and in appreciation of musical melodies. Short-term, invasive neurophysiological studies in animals have demonstrated limitations in neural phase locking in the tonotopic range of the auditory pathway that is activated by CIs. It remains an open question, however, whether those neural limitations can account for perceptual deficits in those animal species, let alone in human CI users. For that reason, we have evaluated non-invasive recordings of phase locking from cats chronically implanted with a CI. Methods Ten deafened cats (eight female) were implanted with an animal version of a clinical CI array. The electrically evoked frequency following response (eFFRs) was recorded from the scalps of sedated animals at ≥ 10 weeks post-implantation. Stimuli consisted of constant-amplitude electrical pulse trains at rates from ~ 40 to 640 pulses per second. Results Recordings of the eFFR demonstrated robust responses synchronized to electrical pulse trains across all stimulus rates. Analyses of eFFR amplitude and phase transfer functions confirmed that the eFFR, as with its normal-hearing counterpart, originates from multiple subcortical and cortical generators. The slopes of segments of eFFR phase transfer functions revealed stimulus-to-response latencies of generators that dominated the eFFR across restricted ranges of pulse rates. Those rate ranges must coincide with the limits of phase locking by putative generators at successive levels of the auditory neuroaxis and could inform our understanding of the limits to perceptual temporal acuity. Conclusion The eFFR demonstrated here in an animal model provides a valuable non-invasive measure of temporal processing in electric cochlear stimulation that can be related to ongoing perceptual measures in the same animals and is well-suited to evaluate novel modes of auditory prosthesis for enhancing temporal acuity.
Frontiers in Neuroscience · Jul 2020
Mina Sadeghi Najafabadi, Longtu Chen, Kelsey Dutta, … Monty A. Escabí
Abstract
Neural implants that deliver multi-site electrical stimulation to the nervous systems are no longer the last resort but routine treatment options for various neurological disorders. Multi-site electrical stimulation is also widely used to study nervous system function and neural circuit transformations. These technologies increasingly demand dynamic electrical stimulation and closed-loop feedback control for real-time assessment of neural function, which is technically challenging since stimulus-evoked artifacts overwhelm the small neural signals of interest. We report a novel and versatile artifact removal method that can be applied in a variety of settings, from single- to multi-site stimulation and recording and for current waveforms of arbitrary shape and size. The method capitalizes on linear electrical coupling between stimulating currents and recording artifacts, which allows us to estimate a multi-channel linear Wiener filter to predict and subsequently remove artifacts via subtraction. We confirm and verify the linearity assumption and demonstrate feasibility in a variety of recording modalities, including in vitro sciatic nerve stimulation, bilateral cochlear implant stimulation, and multi-channel stimulation and recording between the auditory midbrain and cortex. We demonstrate a vast enhancement in the recording quality with a typical artifact reduction of 25-40 dB. The method is efficient and can be scaled to arbitrary number of stimulus and recording sites, making it ideal for applications in large-scale arrays, closed-loop implants, and high-resolution multi-channel brain-machine interfaces.