Comparison of single-cell spike rate and timing in response to cochlear implant and acoustic stimulation

Müller, Michaela (2024): Comparison of single-cell spike rate and timing in response to cochlear implant and acoustic stimulation. Dissertation, LMU München: Graduate School of Systemic Neurosciences (GSN)

Abstract

Spatial hearing plays a crucial role in everyday communication and navigation. Sound localization in the horizontal plane relies on interaural level difference (ILD) as well as interaural time difference (ITD) cues. The lateral superior olive (LSO) and the medial superior olive (MSO) integrate excitatory and inhibitory synaptic inputs from both ears to generate our brain’s sensitivity to these cues. ITD is the dominant binaural cue for sound localization in noisy environments. However, individuals with hearing impairment or deafness, which are common sensory deficits, face challenges in interacting with their environment. Cochlear implants (CIs), electronic devices that bypass hair cells and directly stimulate the auditory nerve, offer a solution to restore spatial hearing in these individuals. Although CI patients are able to use ILDs, achieving good ITD processing remains a challenge. Understanding the underlying causes of poor ITD detection in CI patients and the effects of electrical stimulation on the binaural integration process for ITD detection is crucial. This thesis focuses on investigating the differences between CI-based and acoustic stimulation of the auditory brainstem and their impact on fundamental principles of binaural integration. While low-frequency neurons in the MSO are primarily responsible for ITD processing in individuals with normal hearing, the envelope ITD information provided by CIs, combined with implantation techniques, is presumed to primarily stimulate higher frequency regions of the cochlea, thus activating the LSO pathway. In this study, we conducted in vivo electrophysiological recordings from monaural inputs to the LSO, specifically the anterior ventral part of the cochlear nucleus (AVCN) and medial nucleus of the trapezoid body (MNTB). We used click-train stimuli with varying inter-click intervals (ICIs) to examine potential differences in the temporal precision of action potential (AP) firing between electrical and acoustic stimulation. Mongolian gerbils (Meriones unguiculatus) served as an animal model because of their closer resemblance than other rodents to the human low- and high-frequency hearing ranges. Using this electrophysiological data, we employed a spike-count comparison model to predict ITD sensitivity in the LSO during CI-based stimulation. This model allowed us to compare our electrophysiological findings with model data and predict changes in ITD sensitivity during electric stimulation. A significant aspect of this thesis was the establishment of two essential methods that laid the foundation for the new experimental paradigm in the laboratory. We developed a technique for acute CI implantation, deafening, and electrical stimulation of the auditory brainstem to obtain in vivo electrophysiological recordings from single neurons during CI stimulation. Additionally, a histology protocol using Technovit® 9100 was implemented to verify the correct placement of the implant within the cochlea. The acute CI implantation technique yielded stable and reproducible results, ensuring the feasibility of using this experimental design for future studies. The objective of the Technovit® 9100 histology protocol was not fully realized, as the CI was not evident in the histological sections of the Mongolian gerbil cochlea. Analysis of the electrophysiological results revealed differences between electrical and acoustic stimulation in the auditory brainstem. We observed a tendency of higher spike probability for lower stimulation rates and significantly reduced jitter in electrically stimulated cells in both the AVCN and MNTB. Interestingly, the precise timing of electrical stimulation in the auditory nerve was maintained even with the involvement of more synapses in the AVCN and MNTB. This finding shows that the neural detection of ITDs must adeptly adjust to altered input statistics when exposed to CI stimulation, as opposed to the conditions observed in acoustic hearing. The model indicates that the LSO is ITD-sensitive to electrical inputs and that the hyper-precision observed in our electrophysiological recordings from the AVCN and MNTB is transferred to the LSO. Importantly, the model suggests that the reduced jitter found in the electrical physiological data leads to a lateralization effect because of hyper-accurate ITD processing in the LSO. Furthermore, when we changed the electrically modeled jitter level to the one found in acoustic recordings, we exhibited a substantial recovery in the ITD coding capacity of the LSO model. Thus, this study highlights the critical role of input jitter as a key parameter in shaping ITD sensitivity in the LSO during CI-based sound localization.

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Themengebiete: 500 Naturwissenschaften und Mathematik ; 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie
• Fakultäten: Graduate School of Systemic Neurosciences (GSN)
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 20. Juni 2024
• 1. Bericht­erstatter:in: Pecka, Michael