Periodic Reporting for period 1 - OPTOCODE (In vivo assessment of the optical cochlear implant performance: coding strategy optimization)
Período documentado: 2023-09-01 hasta 2025-11-30
Hearing loss affects millions of people worldwide, significantly impacting communication, quality of life, and social inclusion. Traditional cochlear implants (CIs), which electrically stimulate the auditory nerve, provide substantial benefits for individuals with severe hearing loss. However, electrical stimulation spreads across a broad area of the auditory nerve, limiting the number of perceptual channels and reducing the resolution of complex sounds such as speech in noisy environments. This constrains pitch perception and speech understanding in challenging listening conditions.
Optogenetics offers an innovative solution to these limitations. Optical cochlear implants (oCIs) can stimulate auditory neurons with light, which can be confined more precisely than electrical currents. This allows for reduced spread of excitation, higher frequency selectivity, and potentially a greater number of perceptual channels. Consequently, oCIs have the potential to improve sound resolution, pitch perception, and speech understanding, addressing key unmet needs in hearing restoration.
The OPTOCODE project aimed to advance the development of oCIs by optimizing their coding strategies. The project’s original objectives were:
O1: Develop a non-invasive method to determine the frequency mapping of implanted oCIs in animal models.
O2: Optimize the encoding strategy of the optical cochlear implant.
Specifically, the OPTOCODE project aimed to implement a cross-modal optimization framework to decipher the optical coding strategy for oCIs. This approach was designed to combine predictive models of acoustic-evoked and optical-evoked responses in the inferior colliculus (IC) to ultimately map sound waveforms to the optical emitters of the oCI and derive optimized stimulation strategies.
The expected impacts of the project are both scientific and translational. By establishing a framework for optimizing optical stimulation of the auditory nerve, OPTOCODE aims to advance the development of oCIs with higher spectral resolution, potentially improving pitch perception, speech understanding in noisy environments, and overall quality of life for CI users. Strategically, the project aligns with European priorities for innovation in neurotechnology and medical devices and addresses societal challenges related to sensory impairments.
Optogenetics offers an innovative solution to these limitations. Optical cochlear implants (oCIs) can stimulate auditory neurons with light, which can be confined more precisely than electrical currents. This allows for reduced spread of excitation, higher frequency selectivity, and potentially a greater number of perceptual channels. Consequently, oCIs have the potential to improve sound resolution, pitch perception, and speech understanding, addressing key unmet needs in hearing restoration.
The OPTOCODE project aimed to advance the development of oCIs by optimizing their coding strategies. The project’s original objectives were:
O1: Develop a non-invasive method to determine the frequency mapping of implanted oCIs in animal models.
O2: Optimize the encoding strategy of the optical cochlear implant.
Specifically, the OPTOCODE project aimed to implement a cross-modal optimization framework to decipher the optical coding strategy for oCIs. This approach was designed to combine predictive models of acoustic-evoked and optical-evoked responses in the inferior colliculus (IC) to ultimately map sound waveforms to the optical emitters of the oCI and derive optimized stimulation strategies.
The expected impacts of the project are both scientific and translational. By establishing a framework for optimizing optical stimulation of the auditory nerve, OPTOCODE aims to advance the development of oCIs with higher spectral resolution, potentially improving pitch perception, speech understanding in noisy environments, and overall quality of life for CI users. Strategically, the project aligns with European priorities for innovation in neurotechnology and medical devices and addresses societal challenges related to sensory impairments.
The OPTOCODE project focused on establishing frameworks to deliver optimal optical stimulation patterns for the optical cochlear implant (oCI).
Project objectives and focus:
Early in the project, objective O1—developing a non-invasive method to determine the frequency mapping of implanted oCIs—was not pursued further. Preliminary experiments indicated that auditory brainstem responses were too noisy to obtain reliable frequency maps within a feasible timeframe. The data collected during these attempts were analyzed and included in a peer-reviewed publication (Alekseev et al., 2025). Consequently, most project resources were fully directed toward objective O2, optimizing coding strategies using electrophysiology, optogenetics, and computational modeling.
In vivo opsin characterization:
Two opsins, CHREEF and FYTC, were tested in mice and gerbils to determine activation thresholds, kinetics, and suitability for oCI applications. FYTC demonstrated fast kinetics and effective activation with blue-light micro-LEDs, providing a validated stimulation parameter space for future oCI experiments. This characterization was crucial to defining feasible optical stimulation protocols given recording time constraints (Roos et al., 2025).
Acoustic IC recordings and predictive modeling:
A multielectrode recording pipeline was established for efficient measurement of population activity in the inferior colliculus (IC) of Mongolian gerbils. High-quality data from these recordings were used to develop a neural network model capable of predicting IC population responses to acoustic stimuli in near real-time (less than three hours). These results were presented at the Optogenetics Meeting 2025 and received a poster award.
Optical stimulation framework:
While the full cross-modal optimization combining acoustic and optical models has not yet been completed, the framework for optical stimulation has been established. The critical parameter space for optical stimulation, informed by opsin characterization and in vivo optogenetic activation, has been defined, providing a foundation for ongoing experiments.
Prior work integration:
Collaboration with a student supervised prior the OPTOCODE project led to a publication (Kondylidis et al., 2025) exploring fundamental sound preprocessing in the healthy cochlea. Although no optical implant was used in that study, the insights gained informed the predictive modeling framework for the current project.
Project limitations and mitigation:
The main limitation was the delayed delivery of hardware for optical stimulation. This delay was mitigated by securing an additional six months of funding from the institute, allowing the experimental component of O2 to be completed during 2026.
Summary:
Overall, the project successfully established key experimental and modeling frameworks for optimizing oCI coding strategies, including opsin characterization, IC recording pipelines, and acoustic response prediction models. These achievements lay the foundation for ongoing and future optical stimulation experiments aimed at realizing the full potential of optical cochlear implants.
Project objectives and focus:
Early in the project, objective O1—developing a non-invasive method to determine the frequency mapping of implanted oCIs—was not pursued further. Preliminary experiments indicated that auditory brainstem responses were too noisy to obtain reliable frequency maps within a feasible timeframe. The data collected during these attempts were analyzed and included in a peer-reviewed publication (Alekseev et al., 2025). Consequently, most project resources were fully directed toward objective O2, optimizing coding strategies using electrophysiology, optogenetics, and computational modeling.
In vivo opsin characterization:
Two opsins, CHREEF and FYTC, were tested in mice and gerbils to determine activation thresholds, kinetics, and suitability for oCI applications. FYTC demonstrated fast kinetics and effective activation with blue-light micro-LEDs, providing a validated stimulation parameter space for future oCI experiments. This characterization was crucial to defining feasible optical stimulation protocols given recording time constraints (Roos et al., 2025).
Acoustic IC recordings and predictive modeling:
A multielectrode recording pipeline was established for efficient measurement of population activity in the inferior colliculus (IC) of Mongolian gerbils. High-quality data from these recordings were used to develop a neural network model capable of predicting IC population responses to acoustic stimuli in near real-time (less than three hours). These results were presented at the Optogenetics Meeting 2025 and received a poster award.
Optical stimulation framework:
While the full cross-modal optimization combining acoustic and optical models has not yet been completed, the framework for optical stimulation has been established. The critical parameter space for optical stimulation, informed by opsin characterization and in vivo optogenetic activation, has been defined, providing a foundation for ongoing experiments.
Prior work integration:
Collaboration with a student supervised prior the OPTOCODE project led to a publication (Kondylidis et al., 2025) exploring fundamental sound preprocessing in the healthy cochlea. Although no optical implant was used in that study, the insights gained informed the predictive modeling framework for the current project.
Project limitations and mitigation:
The main limitation was the delayed delivery of hardware for optical stimulation. This delay was mitigated by securing an additional six months of funding from the institute, allowing the experimental component of O2 to be completed during 2026.
Summary:
Overall, the project successfully established key experimental and modeling frameworks for optimizing oCI coding strategies, including opsin characterization, IC recording pipelines, and acoustic response prediction models. These achievements lay the foundation for ongoing and future optical stimulation experiments aimed at realizing the full potential of optical cochlear implants.
The OPTOCODE project has advanced the field of optical cochlear implants (oCIs) by establishing experimental and computational frameworks that go beyond current approaches.
In vivo opsin testing for hearing restoration:
Two engineered opsins opsins, CHREEF and FYTC, were tested in vivo in mice and gerbils to evaluate their suitability for optogenetic hearing restoration. FYTC demonstrated fast kinetics and effective activation with blue-light creee-LEDs, providing a validated parameter space for optical stimulation protocols. These results expand the available toolkit for oCI development and provide essential data for optimizing light-based auditory stimulation.
Cross-modal optimization framework:
The project established the first pipeline for cross-modal optimization of the oCI, designed to integrate predictive models of acoustic and optical stimulation responses in the inferior colliculus. While full implementation of the optical predictive model is ongoing, the framework and parameterization of the optical stimulation space have been defined, creating a foundation for systematic mapping of sound waveforms to optical emitters. This approach represents a novel method for optimizing optical coding strategies, potentially improving frequency selectivity and perceptual resolution in future oCIs.
In vivo opsin testing for hearing restoration:
Two engineered opsins opsins, CHREEF and FYTC, were tested in vivo in mice and gerbils to evaluate their suitability for optogenetic hearing restoration. FYTC demonstrated fast kinetics and effective activation with blue-light creee-LEDs, providing a validated parameter space for optical stimulation protocols. These results expand the available toolkit for oCI development and provide essential data for optimizing light-based auditory stimulation.
Cross-modal optimization framework:
The project established the first pipeline for cross-modal optimization of the oCI, designed to integrate predictive models of acoustic and optical stimulation responses in the inferior colliculus. While full implementation of the optical predictive model is ongoing, the framework and parameterization of the optical stimulation space have been defined, creating a foundation for systematic mapping of sound waveforms to optical emitters. This approach represents a novel method for optimizing optical coding strategies, potentially improving frequency selectivity and perceptual resolution in future oCIs.