1. Introduction

Globally, hearing dysfunction represents a highly widespread form of sensory disability. As estimated by the World Health Organization (WHO), over 430 million individuals globally are affected by moderate to profound hearing impairments [1]. The most frequently diagnosed hearing loss type is sensorineural, typically stemming from irreversible dysfunction or loss of cochlear hair cells, resulting in the inability to effectively transmit sound signals to the central auditory system, seriously affecting the individual’s language communication, learning ability, and social participation ability. Studies have shown that hearing impairment is closely related to the risk of cognitive decline, loneliness, depression, and neuropsychiatric diseases such as Alzheimer’s disease [2,3], and the socioeconomic burden it causes is increasing.

A cochlear implant (CI) is the primary clinical treatment for severe sensorineural hearing loss. The device implants an electrode array into the cochlea to directly stimulate the spiral ganglion neurons (SGNs) to replace the function of damaged hair cells [4]. However, traditional electrical stimulation has inherent limitations in the diffusion of current in the cochlear fluid, resulting in poor spatial selectivity and low frequency resolution, especially in multi-talker environments and complex music perception [5].

With the development of neural engineering and molecular biology, optogenetics has provided a new solution for high-precision neural regulation. This technology uses viral vectors to introduce photosensitive ion channel proteins into specific neurons, which are activated under light of a particular wavelength, thereby achieving high spatial and high temporal resolution control of neuronal populations [6]. Suppose optogenetics is applied to the cochlea and combined with a micro-light source array for multi-channel regulation. In that case, an “optical cochlear implant” (oCI) system can be constructed, theoretically achieving better hearing restoration accuracy than traditional cochlear implants.

At the same time, the brain-computer interface, as a bidirectional pathway connecting the nervous system and external devices, provides a platform support for the intelligent and personalized hearing replacement system [7]. In auditory reconstruction, BCI can not only decode external sound information, but also dynamically adjust stimulation parameters and assist in building a closed-loop control system. Combining it with optogenetics will achieve more accurate neural coding, flexible speech processing, and complex environmental adaptation.

Based on the above background, this article reviews the current research progress of optogenetics and brain-computer interfaces in auditory restoration, including their underlying technical mechanisms, representative experimental findings, and system-level implementation strategies. It also summarizes the key challenges that remain to be addressed and discusses future directions for clinical translation and interdisciplinary integration. This work aims to provide a structured reference for subsequent research and development in high-fidelity auditory neuroprosthetics.

2. Key mechanisms and system components of the cochlea optica

Given the limitations of traditional cochlear implants in frequency selectivity and hearing fidelity, several research teams have successively carried out explorations of auditory neural regulation based on optogenetic strategies. These studies, from the construction of molecular tools and neural response detection in animal models to the construction of the prototype of system engineering, provide multi-level empirical support for the conceptual verification of the “optical cochlear implant” system.

2.1. Biophysical level: verification of high-frequency activation properties of red-shifted opsins

At the biophysical level, pivotal work by Mager et al. addressed a critical limitation in optogenetic auditory stimulation: the temporal fidelity of neuronal activation at high frequencies. The team engineered and optimized f-ChrimsonR, a red-shifted channelrhodopsin variant—a light-sensitive ion channel responsive to red light (~590–630 nm) with rapid kinetic properties. Compared to earlier opsins, this variant demonstrated markedly accelerated channel gating and improved membrane trafficking, properties essential for precise temporal encoding.

To validate its function, the researchers delivered the f-ChrimsonR gene via adeno-associated viruses under a neuron-specific promoter to spiral ganglion neurons of C57BL/6J mice, a standard auditory model. Following confirmation of successful opsin expression via fluorescence imaging and immunohistochemistry, a custom optical fiber was implanted into the cochlea to deliver high-frequency red light pulses with sub-millisecond durations.

In vivo extracellular recordings evaluated SGN firing responses under varied stimulation parameters. Neurons exhibited reliable entrainment to stimulus trains up to 100–200 Hz, a range approximating the temporal features of natural auditory signals such as speech onset cues and pitch contours [6]. Notably, the vector strength and phase-locking index of SGN responses matched those elicited by acoustic clicks, signifying high temporal precision.

These results validated that f-ChrimsonR’s enhanced biophysical properties enable phase-locked spiking in auditory neurons—a cornerstone for speech and music perception. Moreover, red light minimized cochlear fluid scattering and phototoxicity, enhancing spatial confinement and biocompatibility. This work thus provided a robust biophysical and experimental basis for applying red-shifted opsins in next-generation optical cochlear implants, paving the way for subsequent endeavors to simulate the temporal envelope and spectral fine structure of real-world soundscapes.

2.2. Behavioral verification: auditory-like perceptual behavior induced by optogenetic stimulation

For behavioral verification of auditory function recovery, Keppeler et al. developed a fully integrated optogenetic auditory stimulation system, utilizing Mongolian gerbils as the animal model. This species was selected due to its auditory range and cochlear anatomy being more comparable to humans than those of mice [8]. The study aimed to determine whether optogenetic activation of spiral ganglion neurons could induce not only electrophysiological responses but also functionally meaningful perceptual experiences.

To this end, the researchers delivered f-Chrimson-EYFP—a red-light-sensitive opsin tagged with enhanced yellow fluorescent protein—into SGNs via adeno-associated virus serotype 2/6 regulated through the human synapsin promoter sequence. This ensured neuron-specific expression, primarily localized to post-synaptic auditory neurons. Following a 3–4 week incubation period to allow sufficient opsin expression, a custom-designed flexible micro-LED array was surgically implanted along the cochlear scala tympani. This array could deliver temporally precise, directional red light pulses (wavelength ≈ 630 nm) with sub-millisecond precision and adjustable intensity.

For behavioral assessment, a conditioned avoidance paradigm was employed: gerbils were trained to associate auditory cues with a mild foot shock. After conditioning, testing sessions replaced acoustic cues with patterned optogenetic stimulation. Trials were conducted in a sound-attenuated chamber, where animals initiated a trial by remaining in a designated “start zone”; upon receiving the optogenetic stimulus, they had a limited time window to move to a safe zone to avoid punishment.

Notably, animals with successful opsin expression and functional implants exhibited stimulus-dependent avoidance behavior without any acoustic signal, whereas control groups showed no such response. Their escape latency, response rate, and trial-by-trial consistency were comparable to their behavior under genuine auditory conditions. Furthermore, control experiments confirmed that LED illumination alone—without opsin expression—did not induce significant behavioral responses, verifying that the observed perception stemmed from optogenetically evoked auditory sensations rather than visual artifacts or nonspecific effects.

This study provided compelling evidence that optogenetic stimulation of SGNs can elicit subjective auditory-like experiences sufficient to drive learned behavior in mammals. It bridged the gap between cellular-level electrophysiological validation and system-level perceptual outcomes, marking a critical step toward establishing optical cochlear implants as viable alternatives to electrical stimulation-based systems.

2.3. Engineering implementation: development of a multi-channel optical cochlear implant prototype

Beyond molecular and functional validation, recent progress has increasingly focused on the engineering implementation of optical cochlear implants. A notable milestone in this domain was achieved by Tsunematsu et al., who developed and tested a prototype optical cochlear system featuring a multi-channel micro-light-emitting diode array, implanted into the cochlea of anesthetized rats [9]. Fabricated on a flexible polyimide substrate, the μLED array was designed to conform to the cochlea’s spiral anatomy, thereby minimizing insertion trauma. It incorporated multiple μLEDs with precise spatial spacing, enabling selective stimulation of distinct tonotopic regions along the cochlear spiral.

Each μLED in the array was independently addressable, allowing localized delivery of frequency-specific light pulses to adjacent spiral ganglion neurons. Light emission was regulated by a programmable driver system that modulated pulse width, repetition rate, and irradiance parameters optimized to activate opsin-expressing neurons without exceeding thermal safety thresholds. The system was also engineered for low-power consumption, anticipating future wireless or fully implantable applications.

To assess neural activation, in vivo electrophysiological recordings were performed in the inferior colliculus (IC), a midbrain structure that receives organized frequency-specific input from the cochlea. Using multichannel silicon electrode arrays, the team recorded IC neural responses to μLED stimulation at various cochlear locations. Results revealed tonotopically organized activation patterns in the IC, consistent with the spatial distribution of light delivery in the cochlea. Specifically, μLEDs positioned near the cochlear base (high-frequency region) elicited responses in medial IC sites. In contrast, apical μLEDs (low-frequency region) triggered activity in lateral IC regions—aligning with known auditory pathway topography.

This spatial fidelity of neural activation confirms the optical system’s capacity to resolve frequency components of complex sounds. The findings validate the engineering feasibility of optical cochlear implants for encoding multiple frequency channels via spatially discrete optical stimulation, with potential for significantly higher spectral resolution than traditional electrical cochlear implants. Furthermore, this study highlights the critical role of photonic-electronic integration, thermal management, and biocompatible device fabrication in developing clinically viable optical neuroprosthetics.

In summary, existing research has built a multi-level and multi-dimensional theoretical and experimental foundation for optogenetics in auditory brain-computer interfaces, from the biological optimization of photosensitive channel proteins to the verification of animal behavior levels and the realization of multi-channel system architectures. Compared with traditional electrical cochlear stimulation, this strategy has shown significant advantages in spatial stimulation accuracy, spectral encoding sophistication, and system integration potential. These studies provide solid scientific support for promoting optical cochlear systems to clinical applications in the future, and even for further development into closed-loop intelligent auditory brain-computer interfaces.

3. Technical challenges and coping strategies

The application of optogenetics and brain-computer interfaces in auditory reconstruction remains at the preclinical research stage, and its translation into viable clinical solutions is hindered by several critical technological and biological challenges. First, the anatomical structure of the cochlear-auditory nerve pathway is extremely compact and topographically organized. It comprises delicate cellular architecture, including hair cells, spiral ganglion neurons, supporting glial cells, and myelinated axonal bundles confined within a millimeter-scale volume. Any form of optical or electrical stimulation must therefore maintain strict spatial precision to avoid unintended activation of off-target regions. Likewise, temporal control is essential to preserve the rapid phase-locking capability of auditory neurons, which underpins speech perception and rhythm encoding. However, high-intensity stimulation—whether via light or current—may induce thermal damage, phototoxicity, or excitotoxic effects, especially under chronic use. As such, there is a fundamental trade-off between spatial/temporal resolution and biological tolerance, which current systems have yet to fully resolve [6].

Another key challenge lies in the hierarchical and distributed nature of auditory information processing, which spans the cochlea, cochlear nucleus, superior olivary complex, inferior colliculus, thalamus, and auditory cortex. Effective auditory perception emerges from this multi-level network's synchronous activation and dynamic modulation. Simply stimulating a single node, such as the SGNs, cannot fully reproduce the richness and context-awareness of natural hearing. Furthermore, the lack of closed-loop control in most existing systems—the inability to adjust stimulation parameters in response to real-time neural feedback—prevents adaptive encoding in changing acoustic environments. This limits the user’s ability to discriminate speech in noise or adjust to unfamiliar sounds [8].

From an engineering standpoint, the implantable device platform itself presents long-term hurdles. Biocompatibility remains a primary concern: light sources, electrode materials, and packaging layers must be non-toxic, minimally immunogenic, and stable under biological conditions. Chronic implantation is often associated with foreign body response, glial scarring, and biofouling, which degrade device performance over time. In addition, mechanical mismatch between rigid device components and soft cochlear tissue can exacerbate damage during movement. These issues collectively impact system longevity, patient safety, and functional reliability [10].

To address these obstacles, future research and development should pursue multifaceted strategies bridging molecular neuroscience, biomedical engineering, and computational modeling:

A foundational step is to build multi-level computational models that simulate the spatiotemporal propagation of stimuli across neural circuits. These models can optimize low-interference stimulation paradigms, such as spatially interleaved optical pulses or temporally modulated patterns that reduce neuron fatigue and avoid crosstalk. Incorporating channelrhodopsin variants with tailored kinetics—e.g., fast-on, fast-off opsins for precise spike control—can also enhance stimulation specificity.

Integrating neural activity monitoring techniques is equally critical for achieving adaptive modulation. For example, combining optogenetic stimulation with optical coherence tomography (OCT), electrophysiological recordings, or calcium imaging can provide real-time feedback on neural excitability and auditory perception. These data streams can feed into closed-loop control systems powered by machine learning algorithms, enabling dynamic adjustment of stimulation parameters in response to user intent, environmental noise, or fatigue [8].

Regarding system-level integration, attention must focus on material science and microsystem engineering. Developing ultra-thin, stretchable substrates, biodegradable encapsulation materials, and low-power μLED drivers will be critical for improving device comfort and stability. Wireless power transfer and bidirectional data telemetry systems will allow for fully untethered operation, reducing infection risks and enhancing user mobility. Advanced thermal management strategies, such as passive heat sinks or pulsed power modulation, must be incorporated to prevent temperature rise in confined cochlear fluid environments [11].

Ultimately, the goal is to create a next-generation intelligent auditory BCI system that can deliver spatially confined, spectrally rich, and adaptively tuned stimulation with minimal invasiveness and maximal longevity. Such a system would bridge the gap between basic research and clinical application and serve as a foundational model for other sensory neuroprosthetic platforms.

4. Conclusion

This study systematically reviews and analyzes the integrated application of optogenetics and brain-computer interface in auditory reconstruction. This article summarizes the feasibility of photosensitive channel proteins in achieving high temporal and spatial precision stimulation in the auditory pathway, evaluates the results of multiple animal experiments to verify their behavioral perception function, and analyzes the engineering implementation path in terms of micro-light source arrays, stimulation system integration, and spectrum restoration capabilities. Studies have shown that compared with traditional electrical stimulation cochleas, optical cochlear systems have significant advantages in frequency resolution, stimulation controllability, and neural response consistency, laying a technical foundation for achieving higher-fidelity auditory replacement.

The integrated application of optogenetics and brain-computer interfaces in auditory reconstruction has expanded the technical boundaries of artificial hearing devices and further promoted the expansion of brain-computer interfaces from motor control to sensory reconstruction. As a regulatory method that spans molecular biology and neural engineering, the successful application of optogenetics in the auditory system provides a new methodological reference for future multi-sensory reconstruction, personalized neural prosthesis design, and neurological disease intervention. In addition, the high-frequency resolution requirements of the auditory system itself also provide an essential model for the study of fine regulation of other sensory pathways.

The research on optogenetic auditory brain-computer interface still faces the key bottleneck of transformation from animal models to human clinical practice. Further optimization is still needed regarding biosafety, light stimulation tolerance, implant stability, and system integration. At the same time, how to introduce a closed-loop control mechanism to achieve real-time coupling of sensory input, neural feedback, and stimulation strategy will be the core direction for realizing intelligent auditory neural prosthesis [12]. Future research should also focus on integrating interdisciplinary technologies, such as combining speech recognition algorithms, deep learning neural regulation models, and flexible material science to achieve a truly high-fidelity, adjustable, and long-term applicable sensory replacement system [13,14]. Combining optogenetics and brain-computer interface through these efforts will lead to a new paradigm change in auditory neuroscience and artificial sensory systems.