**3. Current research progress**

Two main research directions remain to be investigated. First, transdermal communication plays an important role in propagating the sound information captured by the microphone of the external component toward the one implanted. Conventional CIs are based on magnetic coupling, a near-field technique that uses low radio frequencies (RFs) in the range of 5–50 MHz for communication [18, 19]. The required power of conventional CIs lies around some decades milliwatts. Although this technology has been successfully applied in the majority of CIs, it suffers from low data rates, which constrain the performance of artificial hearing aids in their attempt to simulate high-quality normal hearing [20–22]. In addition, the aforementioned spectral window is used by numerous applications, which generate a great amount of interference that diminishes the quality of communication [23–25]. On the other hand, the optical activation of the auditory nerve via optogenetics has been experimentally verified, but the propagation of the spiral ganglion neuron potential through the auditory pathway toward the brain and its successful perception have yet to be demonstrated [26]. Moreover, the superiority of optical over electrical cell stimulation must be validated in order to justify the research effort toward the all-optical cochlear implant (AOCI) [17]. Recently, multiple experiments have progressed these goals by implanting novel tiny optical fibers in animals models of human sensorineural hearing loss [27–29].

#### **3.1 Communications**

To overcome the aforementioned CI restrictions, researchers have investigated the viability of transdermal wireless networks that operate in nonstandard frequencies. Owing to increased bandwidth, surprisingly high tolerance to external interference, and partial skin transparency at near-infrared wavelengths, optical wireless communications have been applied to transdermal channels instead of the traditional RFbased techniques [30, 31]. In the past decade, numerous contributions have experimentally verified the practicality of transdermal optical links [32–36]. Abita established a transdermal optical link from the inside toward the outside component of a medial system achieving high-data-rate communications [32], while Ackermann et al. investigated the design principles and tradeoffs that are entangled to opticalbased CIs [33, 37]. Moreover, Liu introduced a high-data-rate transdermal optical link for implantable biomedical systems with high energy efficiency under the assumption of deterministic misalignment [24]. Similarly, the interactions between data rate, transmission power, receiver characteristics, and tissue thickness as well as their impact on the system's performance were evaluated for transdermal optical links applied in neural signal extraction scenarios [38]. In addition, the same authors validated the proposed system by conducting *in vivo* experiments that achieved 2 <sup>10</sup><sup>7</sup> bit error rate (BER) and 100-Mbps data rate under stochastic misalignment, but with relatively high power consumption in the order of 2 mW [36]. On the contrary, a novel retroflective architecture was presented for transdermal optical links [34], while Liu proposed a bidirectional transdermal optical link [35].

Building upon the aforementioned contributions, the development of opticalbased CIs needs to leverage breakthrough technologies while taking into consideration the particularities of the transdermal and in-body optical channels, the space and energy design limitations, as well as the directionality of the optical links. Moreover, a novel information-theoretic framework is required for the design of energy-efficient physical and medium access schemes, as well as the development of simultaneous light information and power transfer policies and resource allocation strategies. Motivated by the above, recent research effort has been devoted toward delivering safety and high quality of experience in CIs and identifying the critical technology gaps and the appropriate enablers.

#### **3.2 Neural stimulation**

After communicating the information from the external environment toward the implanted component of the CI, the techniques of neural stimulation must be applied in order to excite the cochlear spiral ganglion neurons, which, in turn, will generate the desire action potential that will propagate along the acoustic nerve toward the brain. Over the years, various methods of neural stimulation have been developed. These can be categorized based on the nature of the applied stimulus as acoustic, thermal, magnetic, chemical, optical, and electrical, with the last ones being the most recognized [39]. Specifically, electrical neural stimulation is the most common technique and has been used in a wide gamut of biomedical applications [40–42]. Electrical neural stimulation applies an electrical stimulus (voltage, current [40], or charge [42]) on the target nerves that manipulates their membrane potential so that it exceeds a certain threshold and, therefore, generates or inhibits action potentials. Specifically, deep brain and cardiac muscle stimulation techniques that use voltage control mechanisms have been investigated with regard to power consumption [41, 43], while current-controlled electrical neural stimulation in CIs is characterized by power waste in the tissue that leads to limited longevity and tissue damage [40]. Voltage-controlled electrical neural stimulation is proven to be more power efficient and less complex, but with very limited stimulus tuning options that result in faster degradation of the electrode contacts. The opposite is valid for current-controlled electrical neural stimulation that can apply fine-tuned charge to the electrodes but exhibits lower power efficiency. Finally, charge control mechanisms for electrical neural stimulation have been applied on the peripheral neural system [42] and offer a middle ground between stimulus control and power consumption. Despite the control mechanism, the determining factors of electrical neural stimulation techniques include human safety, energy efficiency, stimulation waveform, and spatial resolution. The latter significantly affects the stimulation accuracy and is correlated with the distance from the targeted neurons as well as the size of the electrode, which is limited by maximum permissible charge per tissue surface and the electrode's manufacturing process. In addition, the unique characteristics of different types of neurons greatly affect their response to stimulations with variable waveform properties, such as amplitude, width, and frequency. To this end, a great amount of research effort has been devoted toward optimizing the waveform for the stimulus [44–47]. Finally, throughout the optimization procedure of electrical neural stimulation techniques, safety for humans must be ensured.

The solution to the several limitations of electrical neural stimulation was introduced almost two decades ago in the form of optical neural stimulation that uses light for the actuation and control of neurons. Specifically, light-gated ion channels found

in proteins, termed opsins, have been proven to mediate light-driven action potentials in mammalian neurons by manipulating the polarization of their membrane and, therefore, suppressing or exciting them. Optical neural stimulation is highly dependent on the type of the utilized opsin, which incentivized research toward experimentally verifying its performance in terms of precision, accuracy, frequency, and scalability [48–51]. Optical neural stimulation was successfully applied in the motor control system of rodents [48], while the causal relationship of frequency-based optical neural stimulation and behavior state transitions was verified [49]. The increased specificity of exciting neurons was illustrated through efficiently mapping the spatial distribution of synaptic inputs [50]. Moreover, a high-precision optical neural stimulation technique for inhibiting neurons with temporal fidelity was developed [51]. The performance of this technique was evaluated based on novel key performance indicators such as light sensitivity. The aforementioned works illustrate that the development of opsins offering stable performance over multiple stimulations is accompanied by long desensitization periods and short channel-off durations. To this end, research was intensified toward developing opsins with different kinetic features and wavelength sensitivity for monitoring and controlling biological processes in subcellular and cellular levels [52, 53]. A major breakthrough was achieved with the application of channelrhodopsin 2 (ChR2) in mammalian neurons that enabled accurate stimulation with light pulses [54]. Since its development, ChR2 has been heavily investigated, and multiple variants have been introduced with applications in cardiology [55–58] and neuroscience [59, 60]. The performance of these variants greatly outperforms electrical neural stimulation in terms of stimulation pulse intensity and frequency (up to 200 Hz), as well as the ability to trigger large current action potentials with higher fidelity [61, 62].
