Electrical Stimulation publications

Objective: The purpose of this paper is to present a chronic, preclinical, pilot study of a multi-electrode auditory nerve implant. To date, the most successful auditory neuroprosthesis is the cochlear implant, but these devices have known limitations. Intraneural stimulation of the auditory nerve is a promising alternative, but preclinical investigations of multi-electrode devices have been limited to acute or semi-chronic studies. Methods: Six cats were chronically implanted in the right auditory nerve with a 15-channel Utah Slant ArrayTM. The array's position in the internal auditory canal was confirmed using computed tomography. Electrode impedance and evoked responses were recorded regularly during the indwelling period to evaluate performance. Results: Two of the six implants met endpoint criteria at 6 months, with stable electrode impedances and robust evoked responses on at least 50% of their channels. Another two implants exhibited stable electrode impedances, but activation thresholds increased over three months. Two implants failed within the first two weeks due to device migration caused by connector-related issues. Conclusion: This study reports the first successful chronic deployment of an multi-electrode auditory nerve implant in a preclinical model. Two implanted cats exhibited stable chronic performance, marked by a consistent set of electrodes capable of eliciting evoked responses. The failure modes of the remaining four cats are discussed and recommendations are made to stabilize implant placement. The study lays a solid foundation for future chronic safety and efficacy investigations as part of an effort to translate this new neuroprosthetic technology into the clinic.

In adults with acquired hearing loss, cortical reorganization and cross‐modal plasticity critically influence the timing and outcomes of cochlear implantation. This study examined the effects of 2 weeks of bilateral auditory deprivation—induced by intense broadband noise—on the structure and gene expression in the primary auditory (A1) and visual (V1) cortices of adult rats. The results revealed that the total neuronal counts in both the A1 and V1 remained unchanged compared to controls. Morphological analysis showed no significant change in mature dendritic spine density in either region, but immature spine density was significantly reduced in the V1 cortex. Ultrastructural examination demonstrated notable synaptic alterations in the A1 cortex, including significant reductions in postsynaptic density (PSD) length, thickness, area, and synaptic vesicle number—changes that were not observed in the V1 cortex. Transcriptomic profiling indicated a region‐specific response, with 197 differentially expressed genes (DEGs) in the A1 cortex, compared to a broader alteration of 545 DEGs in the V1 cortex, which were significantly involved in neuronal signaling and synaptic transmission. These findings demonstrate that auditory deprivation induces distinct molecular and synaptic remodeling in the A1 and V1 cortices, identifying neuronal plasticity and synaptic regulation as central mechanisms for cross‐modal reorganization in the adult brain.

The cochlear implant is a widely available hearing restoration technology that can provide speech understanding in quiet environments. This technology struggles however, in noisy settings or situations involving multiple speakers. The primary cause of these performance limitations is a poor neural interface, in which the bony wall of the cochlea separates the electrode surface from the auditory nerve fibers, thus causing unwanted current spread and non-specific frequency activation. This study utilizes an alternative auditory prosthetic technology (auditory nerve implant, ANI) that enables direct auditory nerve stimulation, which provides a potentially superior neural interface and enables more precise targeting of auditory nerve fibers than traditional cochlear implants. As auditory nerve implants progress towards clinical translation, new implant designs and stimulation strategies will be created. Animal models to efficiently test and iterate through these new designs will be useful for the continued development of ANI technology. We present a viable surgical approach in the non-human primate (rhesus macaque) along with electrophysiological results that demonstrate robust activation of the auditory system at low current levels via intraneural stimulation. Our findings indicate that the rhesus macaque, which possesses an inner ear anatomy more similar to the human compared to other animal models used in the hearing field (e.g., rodents, felines and ferrets), has strong potential as a useful preclinical testbed involving an upright head model for future ANI prototypes and stimulation strategy development.

Introduction The posterior tail of the striatum receives dense inputs from sensory regions of cortex and thalamus, as well as midbrain dopaminergic innervation, providing a neural substrate for associative sensory learning. Previously, we have demonstrated that developmental hearing loss is associated with aberrant physiological states in striatal medium spiny neurons (MSNs). Methods Here we directly investigated auditory associative learning impairments in the striatum of adult Mongolian gerbils that underwent transient developmental hearing loss or sham hearing loss during the critical period of auditory development. We used electrophysiology to reveal significant changes to neuronal population responses in vivo and intrinsic and synaptic properties to medium spiny neurons in vitro as animals learned an appetitive “Go/No-Go” auditory discrimination task. For in vivo experiments a 64-channel electrode was implanted in the auditory region of the posterior tail of the striatum and neuronal recordings were carried out as animals learned the task. For in vitro experiments, corticostriatal slice preparations were made from animals on each day of training. Results In naïve animals from both groups there was limited to no phase locking to either auditory stimulus in vivo , and long term depression resulted from theta burst stimulation in vitro . Furthermore, intrinsic and synaptic properties in normal hearing animals were unaffected; however, the hearing loss group continued to show lowered synaptic inhibition, synaptic hyperexcitation, and suppressed intrinsic excitability in the hearing loss group. Starting around day 3–4 in both groups, the emergence of striatal medium spiny neuron phase locking to the auditory conditioning stimuli was observed in vivo . This occurred contemporaneous to an increased probability of theta burst induced LTP during MSN whole cell recording in vitro , and acquisition of the task as the correct rejection response significantly increased in the behaving animals. During the acquisition phase MSNs in the normal hearing group showed a significant decrease in synaptic inhibition and increase in synaptic excitation with no change to intrinsic excitability, while the MSNs in the hearing loss group showed a significant increase in synaptic inhibition, reduction of synaptic hyper excitability, and compensatory changes to intrinsic excitability that supported normal action potential generation. In both groups, synaptic properties were resolved to similar level of E/I balance that could be part of a conserved learning state. Discussion These changes to the intrinsic and synaptic properties likely support LTP induction in vivo and the strengthening of synapses between auditory inputs and MSNs that facilitate neuronal phase locking. These findings have significant implications for our understanding of striatal resilience to sensory impairments in early life, in addition to establishing a granular understanding of the striatal circuit changes that support reward driven stimulus–response learning.

Presbycusis or age-related hearing loss (ARHL) affects millions of people worldwide, increasing their risk of cognitive decline and poor quality of life. However, ARHL remains an irreversible condition due to our inability to induce inner-ear hair cell regeneration. Nevertheless, multisession epidural stimulation of the auditory cortex (AC) at the onset of ARHL prevents hearing threshold elevation in naturally aging Wistar rats. Accordingly, we hypothesized that anodal direct current (DC) stimulation of the AC may also compensate for age-related maladaptive, activity-dependent changes. Here, we examined immunocytochemical markers in the AC, including early genes (c-fos and Arc), AMPA receptors (GluR2/3), parvalbumin (PV), and GAD67, along with auditory-evoked potentials (CAEPs) recorded in both auditory and visual (VC) cortices. When comparing 6 and 18.13-month-old rats without AC simulation, we observed loss of c-fos and Arc-positive neurons and decreased GluR2/3 expression, confirming altered AC neuronal network plasticity and activation. In addition, we noted changes in PV and decreased GAD67 immunoreactivity suggesting disrupted inhibition and significantly increased wave amplitudes in CAEPs, altered AC latencies, and decreased VC responses. By contrast, electrically stimulated rats showed no significant variations in early gene markers, GluR2/3, PV, or GAD67 with age, and the amplitudes and latencies of CAEPs recorded in their AC and VC resembled those of young rat. These findings indicate that anodal DC stimulation at the onset of ARHL delays AC aging by minimizing the loss of inhibition and preventing increases in cortical excitability in Wistar rats.

Pairing vagus nerve stimulation (VNS) with sounds has improved auditory processing in the auditory cortex of normal-hearing rats and autism models of rats. This study tests the ability of VNS-sound pairing to restore auditory processing in the inferior colliculus (IC) of valproic acid (VPA)-exposed rats. Pairing VNS with tones significantly reversed the degraded sound processing in the IC in VPA-exposed rats. The findings provide evidence that auditory processing in autism rat models can be improved through VNS.

Spiral ganglion neurons (SGNs) transmit auditory information from cochlear hair cells to the brain. SGNs are thus not only important for normal hearing, but also for effective functioning of cochlear implants, which stimulate SGNs when hair cells are missing. SGNs slowly degenerate following aminoglycoside-induced hair cell loss, a process thought to involve an immune response. However, the specific immune response pathways involved remain unknown. We used RNAseq to gain a deeper understanding immune-related and other transcriptomic changes that occur in the rat spiral ganglion after kanamycin-induced deafening. Among the immune and inflammatory genes that were selectively upregulated in deafened spiral ganglia, the complement cascade genes were prominent. We then assessed SGN survival, as well as immune cell numbers and activation, in the spiral ganglia of rats with a CRISPR-Cas9-mediated knockout of complement component 3 (C3). Similar to previous findings in our lab and other deafened rodent models, we observed an increase in macrophage number and increased expression of CD68, a marker of phagocytic activity and cell activation, in macrophages in the deafened ganglia. Moreover, we found an increase in MHCII expression on spiral ganglion macrophages and an increase in lymphocyte number in the deafened ganglia, suggestive of an adaptive immune response. However, C3 knockout did not affect SGN survival or increase in macrophage number/activation, implying that complement activation does not play a role in SGN death after deafening. Together, these data suggest that both innate and adaptive immune responses are activated in the deafened spiral ganglion, with the adaptive response directly contributing to cochlear neurodegeneration.

Hearing loss can lead to long-lasting effects on the central nervous system, and current therapies, such as auditory training and rehabilitation, show mixed success in improving perception and speech comprehension. Vagus nerve stimulation (VNS) is an adjunctive therapy that can be paired with rehabilitation to facilitate behavioral recovery after neural injury. However, VNS for auditory recovery has not been tested after severe hearing loss or significant damage to peripheral receptors. This study investigated the utility of pairing VNS with passive or active auditory rehabilitation in a rat model of noise-induced hearing loss. Although auditory rehabilitation helped rats improve their frequency discrimination, learn novel speech discrimination tasks, and achieve speech-in-noise performance similar to normal hearing controls, VNS did not enhance recovery of speech sound perception. These results highlight the limitations of VNS as an adjunctive therapy for hearing loss rehabilitation and suggest that optimal benefits from neuromodulation may require restored peripheral signaling.

High‐density interconnect (HDI) technology for liquid metal (LM)‐based stretchable printed circuit boards is crucial for expanding their applicability. HDI technology provides high‐resolution multilayer circuits with a high density of components, as required for next generation of neuroprobes and ultrasonic and sensor arrays. This study presents a HDI technique utilizing laser engraved micro grooves in silicone with a protective lift‐off mask of polyvinyl alcohol (PVA) and subsequent microscale LM particle spray deposition. This approach achieves high‐resolution LM patterns and enables multilayer connectivity and high‐density integration of components simultaneously, that is, realizing HDI technology. It is demonstrated using a stretchable 0201 LED display with a density of six leads per mm 2 and a cochlear implant (CI) electrode array. The demonstrated manufacturing of the CI has the potential to enable fully automated printed circuit board manufacturing of such implants with increased precision and throughput. Implants in guinea pigs show that the CI is capable of activating the auditory neuron with electrical auditory brainstem response (eABR) and electrical compound action potential (eCAP) of high quality. Moreover, the U‐shaped cross section of the LM interconnects provides a higher mechanical shock resistance of the circuit than that of normal rectangular cross sections.

Sensory cortical areas are robustly modulated by higher-order cortices. Our previous study shows that the anterior cingulate cortex (ACC) can immediately and transiently enhance responses in the mouse auditory cortex (ACx). Here, we further examined whether strong activation of ACC neurons can induce long-term effects in mice of both sexes. To our surprise, only stimulation of cell bodies in the ACC, but not ACC-to-ACx terminal activation, induced long-term enhancement of auditory responses in the ACx. Anatomical examination showed that the ACC indirectly projects to the ACx via the rhinal cortex (RCx). High-frequency stimulation of ACC-projecting terminals to the RCx or RCx-projecting terminals to the ACx induced a similar effect as the cell body activation of ACC neurons, whereas silencing the RCx blocked this long-term enhancement. High-frequency stimulation of ACC projections to the RCx also induced long-term augmentation of sound-evoked flight behavior in male mice. These results show that the ACC promotes the long-term enhancement of auditory responses in the ACx through an indirect pathway via the RCx. SIGNIFICANCE STATEMENT In this study, we demonstrate that the anterior part of the anterior cingulate cortex (ACC) evokes long-term enhancement of auditory responses in the auditory cortex (ACx) when it is strongly activated. Importantly, instead of a direct projection, we show that the ACC implements this effect via an indirect pathway through the lateral rhinal cortex using a series of physiological, optogenetic, anatomic, and behavioral experiments. Along with a short-term effect, this long-term enhancement induced by an indirect ACC-to-ACx projection could increase the odds of survival when animals are faced with threats after a significant event.

Fear and anxiety are brain states that evolved to mediate defensive responses to threats. The defense reaction includes multiple interacting behavioral, autonomic and endocrine adjustments, but their integrative nature is poorly understood. In particular, although threat has been associated with various cardiac changes, there is no clear consensus regarding the relevance of these changes for the integrated defense reaction. Here we identify rapid microstates that are associated with specific behaviors and heart rate dynamics, which are affected by long-lasting macrostates and reflect context-dependent threat levels. In addition, we demonstrate that one of the most commonly used defensive behavioral responses—freezing as measured by immobility—is part of an integrated cardio-behavioral microstate mediated by Chx10 + neurons in the periaqueductal gray. Our framework for systematic integration of cardiac and behavioral readouts presents the basis for a better understanding of complex neural defensive states and their associated systemic functions.

The ability to localize a sound source in complex environments is essential for communication and navigation. Spatial hearing relies predominantly on the comparison of differences in the arrival time of sound between the two ears, the interaural time differences (ITDs). Hearing impairments are highly detrimental to sound localization. While cochlear implants (CIs) have been successful in restoring many crucial hearing capabilities, sound localization via ITD detection with bilateral CIs remains poor. The underlying reasons are not well understood. Neuronally, ITD sensitivity is generated by coincidence detection between excitatory and inhibitory inputs from the two ears performed by specialized brainstem neurons. Due to the lack of electrophysiological brainstem recordings during CI stimulation, it is unclear to what extent the apparent deficits are caused by the binaural comparator neurons or arise already on the input level. Here, we use a bottom-up approach to compare response features between electric and acoustic stimulation in an animal model of CI hearing. Conducting extracellular single neuron recordings in gerbils, we find severe hyper-precision and moderate hyper-entrainment of both the excitatory and inhibitory brainstem inputs to the binaural comparator neurons during electrical pulse-train stimulation. This finding establishes conclusively that the binaural processing stage must cope with highly altered input statistics during CI stimulation. To estimate the consequences of these effects on ITD sensitivity, we used a computational model of the auditory brainstem. After tuning the model parameters to match its response properties to our physiological data during either stimulation type, the model predicted that ITD sensitivity to electrical pulses is maintained even for the hyper-precise inputs. However, the model exhibits severely altered spatial sensitivity during electrical stimulation compared to acoustic: while resolution of ITDs near midline was increased, more lateralized adjacent source locations became inseparable. These results directly resemble recent findings in rodent and human CI listeners. Notably, decreasing the phase-locking precision of inputs during electrical stimulation recovered a wider range of separable ITDs. Together, our findings suggest that a central problem underlying the diminished ITD sensitivity in CI users might be the temporal hyper-precision of inputs to the binaural comparator stage induced by electrical stimulation.

Perceptual decision-making tasks are essential to many fields of neuroscience. Current protocols generally reward deprived animals with water. However, balancing animals' deprivation level with their well-being is challenging, and trial number is limited by satiation. Here, we present electrical stimulation of the medial forebrain bundle (MFB) as an alternative that avoids deprivation while yielding stable motivation for thousands of trials. Using licking or lever press as a report, MFB animals learnt auditory discrimination tasks at similar speed to water-deprived mice. Moreover, they more reliably reached higher accuracy in harder tasks, performing up to 4,500 trials per session without loss of motivation. MFB stimulation did not impact the underlying sensory behavior since psychometric parameters and response times are preserved. MFB mice lacked signs of metabolic or behavioral stress compared with water-deprived mice. Overall, MFB stimulation is a highly promising tool for task learning because it enhances task performance while avoiding deprivation.

In the post-natal mouse cochlea, type II spiral ganglion neurons (SGNs) innervating the electromotile outer hair cells (OHCs) of the ‘cochlear amplifier' selectively express the type III intermediate filament peripherin gene ( Prph) . Immunolabeling showed that Prph knockout (KO) mice exhibited disruption of this (outer spiral bundle) afferent innervation, while the radial fiber (type I SGN) innervation of the inner hair cells (~95% of the SGN population) was retained. Functionality of the medial olivocochlear (MOC) efferent innervation of the OHCs was confirmed in the Prph KO, based on suppression of distortion product otoacoustic emissions (DPOAEs) via direct electrical stimulation. However, “contralateral suppression” of the MOC reflex neural circuit, evident as a rapid reduction in cubic DPOAE when noise is presented to the opposite ear in wildtype mice, was substantially disrupted in the Prph KO. Auditory brainstem response (ABR) measurements demonstrated that hearing sensitivity (thresholds and growth-functions) were indistinguishable between wildtype and Prph KO mice. Despite this comparability in sound transduction and strength of the afferent signal to the central auditory pathways, high-intensity, broadband noise exposure (108 dB SPL, 1 h) produced permanent high frequency hearing loss (24–32 kHz) in Prph KO mice but not the wildtype mice, consistent with the attenuated contralateral suppression of the Prph KO. These data support the postulate that auditory neurons expressing Prph contribute to the sensory arm of the otoprotective MOC feedback circuit.

Fear and anxiety are brain states that evolved to mediate defensive responses to threat. While it is clear that the defense reaction includes multiple interacting behavioural, autonomic and endocrine adjustments, their integrative nature is poorly understood. In particular, threat has been associated with various cardiac changes, yet a clear consensus on their relevance for the integrated defense reaction is missing. We here define rapid microstates associated with specific behaviours and heart rate dynamics, both affected by long-lasting macrostates and reflecting context-dependent threat levels. In addition, we demonstrate that one of the most commonly used defensive behavioural responses, freezing measured by immobility, is part of an integrated cardio-behavioural microstate mediated by specific midbrain circuit elements. Our work puts forth a framework for systematic integration of cardiac and behavioural readouts that presents the basis for a better understanding of complex neural defensive states and their associated systemic functions.

The medial olivocochlear (MOC) efferent feedback circuit projecting to the cochlear outer hair cells (OHCs) confers protection from noise-induced hearing loss and is generally thought to be driven by inner hair cell (IHC) - type I spiral ganglion afferent (SGN) input. Knockout of the Prph gene ( Prph KO) encoding the peripherin type III intermediate filament disrupted the OHC - type II SGN innervation and virtually eliminated MOC – mediated contralateral suppression from noise delivered to the opposite ear, measured as a reduction in cubic distortion product otoacoustic emissions. Electrical stimulation of the MOC pathway elicited contralateral suppression indistinguishable between wildtype (WT) and Prph KO mice, indicating that the loss of contralateral suppression was not due to disruption of the efferent arm of the circuit; IHC – type I SGN input was also normal, based on auditory brainstem responses. High-intensity, broadband noise (108 dB SPL, 1 hour) produced permanent hearing loss in Prph KO mice, but not in WT littermates. These findings associate OHC-type II input with MOC efferent - based otoprotection at loud sound levels.

The protective effect of the efferent system against acoustic trauma (AT) has been shown by several experimental approaches, including damage to one ear, sectioning of the olivocochlear bundle (OCB) in the floor of the IV ventricle, and knock-in mice overexpressing outer hair cell (OHC) cholinergic receptors, among others. Such effects have been related to changes in the regulation of the cholinergic efferent system and in cochlear amplification, which ultimately reverse upon protective hearing suppression. In addition to well-known circuits of the brainstem, the descending corticofugal pathway also regulates efferent neurons of the olivary complex. In this study, we applied our recently developed experimental paradigm of multiple sessions of electrical stimulation (ES) to activate the efferent system in combination with noise overstimulation. ABR thresholds increased 1 and 2 days after AT (8–16 kHz bandpass noise at 107 dB for 90 min) recovering at AT + 14 days. However, after multiple sessions of epidural anodal stimulation, no changes in thresholds were observed following AT. Although an inflammatory response was also observed 1 day after AT in both groups, the counts of reactive macrophages in both experimental conditions suggest decreased inflammation in the epidural stimulation group. Quantitative immunocytochemistry for choline acetyltransferase (ChAT) showed a significant decrease in the size and optical density of the efferent terminals 1 day after AT and a rebound at 14 days, suggesting depletion of the terminals followed by a long-term compensatory response. Such a synthesis recovery was significantly higher upon cortical stimulation. No significant correlation was found between ChAT optical density and size of the buttons in sham controls (SC) and ES/AT + 1day animals; however, significant negative correlations were shown in all other experimental conditions. Therefore, our comparative analysis suggests that cochleotopic cholinergic neurotransmission is also better preserved after multisession epidural stimulation.

Age-related hearing loss (ARHL) is the most common sensory disorder among older people, and yet, the treatment options are limited to medical devices such as hearing aids and cochlear implants. The high prevalence of ARHL mandates the development of treatment strategies that can prevent or rescue age-related cochlear degeneration. In this study, we investigated a novel pharmacological strategy based on inhibition of the adenosine A2A receptor (A2AR) in middle aged C57BL/6 mice prone to early onset ARHL. C57BL/6J mice were treated with weekly istradefylline (A2AR antagonist; 1 mg/kg) injections from 6 to 12 months of age. Auditory function was assessed using auditory brainstem responses (ABR) to tone pips (4–32 kHz). ABR thresholds and suprathreshold responses (wave I amplitudes and latencies) were evaluated at 6, 9, and 12 months of age. Functional outcomes were correlated with quantitative histological assessments of sensory hair cells. Cognitive function was assessed using the Morris water maze and the novel object recognition test, and the zero maze test was used to assess anxiety-like behaviour. Weekly injections of istradefylline attenuated ABR threshold shifts by approximately 20 dB at mid to high frequencies (16–32 kHz) but did not improve ABR suprathreshold responses. Istradefylline treatment improved hair cell survival in a turn-dependent manner, whilst the cognitive function was unaffected by istradefylline treatment. This study presents the first evidence for the rescue potential of istradefylline in ARHL and highlights the role of A2AR in development of age-related cochlear degeneration.

Corticofugal modulation of auditory responses in subcortical nuclei has been extensively studied whereas corticofugal synaptic transmission must still be characterized. This study examined postsynaptic potentials of the corticocollicular system, i.e., the projections from the primary auditory cortex (AI) to the central nucleus of the inferior colliculus (ICc) of the midbrain, in anesthetized C57 mice. We used focal electrical stimulation at the microampere level to activate the AI (ESAI) and in vivo whole-cell current-clamp to record the membrane potentials of ICc neurons. Following the whole-cell patch-clamp recording of 88 ICc neurons, 42 ICc neurons showed ESAI-evoked changes in the membrane potentials. We found that the ESAI induced inhibitory postsynaptic potentials in 6 out of 42 ICc neurons but only when the stimulus current was 96 μA or higher. In the remaining 36 ICc neurons, excitatory postsynaptic potentials (EPSPs) were induced at a much lower stimulus current. The 36 ICc neurons exhibiting EPSPs were categorized into physiologically matched neurons (n = 12) when the characteristic frequencies of the stimulated AI and recorded ICc neurons were similar (≤1 kHz) and unmatched neurons (n = 24) when they were different (>1 kHz). Compared to unmatched neurons, matched neurons exhibited a significantly lower threshold of evoking noticeable EPSP, greater EPSP amplitude, and shorter EPSP latency. Our data allow us to propose that corticocollicular synaptic transmission is primarily excitatory and that synaptic efficacy is dependent on the relationship of the frequency tunings between AI and ICc neurons.

Nowadays, the majority of the progress in the development of implantable neuroprostheses has been achieved by improving the knowledge of brain functions so as to restore sensorial impairments. Intracortical microstimulation (ICMS) is a widely used technique to investigate site-specific cortical responses to electrical stimuli. Herein, we investigated the neural modulation induced in the primary auditory cortex (A1) by an acousto-electric transduction of ultrasonic signals using a bio-inspired intracortical microstimulator. The developed electronic system emulates the transduction of ultrasound signals in the cochlea, providing bio-inspired electrical stimuli. Firstly, we identified the receptive fields in the primary auditory cortex devoted to encoding ultrasonic waves at different frequencies, mapping each area with neurophysiological patterns. Subsequently, the activity elicited by bio-inspired ICMS in the previously identified areas, bypassing the sense organ, was investigated. The observed evoked response by microstimulation resulted as highly specific to the stimuli, and the spatiotemporal dynamics of neural oscillatory activity in the alpha, beta, and gamma waves were related to the stimuli preferred by the neurons at the stimulated site. The alpha waves modulated cortical excitability only during the activation of the specific tonotopic neuronal populations, inhibiting neural responses in unrelated areas. Greater neuronal activity in the posterior area of A1 was observed in the beta band, whereas a gamma rhythm was induced in the anterior A1. The results evidence that the proposed bio-inspired acousto-electric ICMS triggers high-frequency oscillations, encoding information about the stimulation sites and involving a large-scale integration in the brain.