Intracochlear Electrical Stimulation Research Articles

Impact of auditory deprivation on rats and plasticity expressionof growth associated protein-43 in auditory cortex

Objective:To explore the molecular mechanism of neural plasticity in the reconstitution following impairment of auditory system,we studied the changing levels of GAP-43 expression in the auditory cortex(AC) in the developing rats and in ototoxicity deafened rats before and after electrical intracochlear stimulation.Method:Auditory brain stem response(ABR) measurements were performed to rats of OAD,NC1,CAD and NC2 group to evaluate hearing function.We studied the changing levels of GAP-43-positive neurons expression in the auditory cortex of the OAD,NC1,EIS1 and EIS2 group and RT-PCR was performed to do semiquantitative analysis.Result:The early electrical intracochlear stimulation elevated GAP-43 level(EIS1,120.00±5.59/HP) in ipsilateral AC instead of in the contralateral AC compared with the non-stimulation group (OAD4W,93.25±4.30/HP),and the two groups had statistical difference(EIS1/OAD4W,129.17%±3.33%,P<0.05).After the late electrical intracochlear stimulation,similar to the early group,the staining level of GAP-43(EIS2,102.50±4.02/HP) in the AC was also higher than the unaffected group(OAD8W,81.67±3.76/HP),and the two groups also had statistical difference(EIS2/OAD8W,123.74%±2.70%,P<0.05).Similarly,the expression of GAP-43 mRNA had the synchronous change with the GAP-43 in the AC.Conclusion:GAP-43 has close correlation with the growth and plasticity of the AC,which can be a significant marker for auditory plasticity.

Tinnitus Suppression by Intracochlear Electrical Stimulation in Single Sided Deafness - A Prospective Clinical Trial: Follow-Up.

IntroductionEarlier studies show that a Cochlear Implant (CI), capable of providing intracochlear electrical stimulation independent of environmental sounds, appears to suppress tinnitus at least for minutes. The current main objective is to compare the long-term suppressive effects of looped (i.e. repeated) electrical stimulation (without environmental sound perception) with the standard stimulation pattern of a CI (with environmental sound perception). This could open new possibilities for the development of a “Tinnitus Implant” (TI), an intracochlear pulse generator for the suppression of tinnitus.Materials and MethodsTen patients with single sided deafness suffering from unilateral tinnitus in the deaf ear are fitted with a CI (MED-EL Corporation, Innsbruck, Austria). Stimulation patterns are optimized for each individual patient, after which they are compared using a randomized crossover design, with a follow-up of six months, followed by a 3 month period using the modality of patient’s choice.ResultsResults show that tinnitus can be suppressed with intracochlear electrical stimulation independent of environmental sounds, even long term. No significant difference in tinnitus suppression was found between the standard clinical CI and the TI.ConclusionIt can be concluded that coding of environmental sounds is no requirement for tinnitus suppression with intracochlear electrical stimulation. It is therefore plausible that tinnitus suppression by CI is not solely caused by an attention shift from the tinnitus to environmental sounds. Both the standard clinical CI and the experimental TI are potential treatment options for tinnitus. These findings offer perspectives for a successful clinical application of the TI, possibly even in patients with significant residual hearing.Trial RegistrationTrialRegister.nl NTR3374

Bilateral Changes of Spontaneous Activity Within the Central Auditory Pathway Upon Chronic Unilateral Intracochlear Electrical Stimulation.

In recent years, cochlear implants have been applied successfully for the treatment of unilateral hearing loss with quite surprising benefit. One reason for this successful treatment, including the relief from tinnitus, could be the normalization of spontaneous activity in the central auditory pathway because of the electrical stimulation. The present study, therefore, investigated at a cellular level, the effect of a unilateral chronic intracochlear stimulation on key structures of the central auditory pathway. Normal-hearing guinea pigs were mechanically single-sided deafened through a standard HiFocus1j electrode array (on a HiRes 90k cochlear implant) being inserted into the first turn of the cochlea. Four to five electrode contacts could be used for the stimulation. Six weeks after surgery, the speech processor (Auria) was fitted, based on tNRI values and mounted on the animal's back. The two experimental groups were stimulated 16 hours per day for 90 days, using a HiRes strategy based on different stimulation rates (low rate (275 pps/ch), high rate (5000 pps/ch)). The results were compared with those of unilateral deafened controls (implanted but not stimulated), as well as between the treatment groups. All animals experienced a standardized free field auditory environment. The low-rate group showed a significantly lower average spontaneous activity bilaterally in the dorsal cochlear nucleus and the medial geniculate body than the controls. However, there was no difference in the inferior colliculus and the primary auditory cortex. Spontaneous activity of the high-rate group was also reduced bilaterally in the dorsal cochlear nucleus and in the primary auditory cortex. No differences could be observed between the high-rate group and the controls in the contra-lateral inferior colliculus and medial geniculate body. The high-rate group showed bilaterally a higher activity in the CN and the MGB compared with the low-rate group, whereas in the IC and in the AC a trend for an opposite effect could be determined. Unilateral intracochlear electrical stimulation seems to facilitate the homeostasis of the network activity, since it decreases the spontaneous activity that is usually elevated upon deafferentiation. The electrical stimulation per se seems to be responsible for the bilateral changes described above, rather than the particular nature of the electrical stimulation (e.g., rate). The normalization effects of electrical stimulation found in the present study are of particular importance in cochlear implant recipients with single-sided deafness.

Counter-regulation of the AP-1 monomers pATF2 and Fos: Molecular readjustment of brainstem neurons in hearing and deaf adult rats after electrical intracochlear stimulation

Expression of the immediate-early gene fos (also known as c-fos) and phosphorylation of the product of the early response gene atf2 (pATF2) in the adult auditory brainstem can be modulated by electrical intracochlear stimulation. The Fos and pATF2 proteins are competitive monomers of the heterodimeric activator protein-1 (AP-1) transcription factor that triggers the expression of genes related to neural plasticity. Our previous findings showed that the stimulation-induced spatio-temporal pattern of Fos expression in the adult auditory system depends on hearing experience. In this study, we aimed to identify a possible correlation of pATF2 and Fos expression. Adult normal hearing and neonatally deafened rats were unilaterally stimulated with a cochlear implant (CI) for 45min, 73min, or 2h. The numbers of Fos- and pATF2-positive neurons in the anteroventral cochlear nucleus (AVCN), the lateral superior olive (LSO), and the central inferior colliculus (CIC) were evaluated. Following stimulation, an increased Fos expression was demonstrated in all these regions in hearing and deaf rats. However, in neonatally deafened rats, significantly more Fos-positive neurons emerged that did not obey a tonotopic order. Independent of hearing experience, Fos expression correlated with a locally matching decrease of pATF2 expression in AVCN and LSO, but not in CIC. We suggest that these changes in gene expression result in a shift of AP-1 dimer composition from ATF2:Jun to Fos:Jun. This change in AP-1 constellation is expected to invoke different transcriptional cascades leading to distinct modes of tissue reorganization and plasticity responses in the mature central auditory system under stimulation.

Tinnitus Suppression by Intracochlear Electrical Stimulation in Single-Sided Deafness: A Prospective Clinical Trial - Part I

Cochlear implantation is a viable treatment option for tinnitus, but the underlying mechanism is yet unclear. Is the tinnitus suppression due to the reversal of the assumed maladaptive neuroplasticity or is it the shift in attention from the tinnitus to environmental sounds and therefore a reduced awareness that reduces tinnitus perception? In this prospective trial, 10 patients with single-sided deafness were fitted with a cochlear implant to investigate the effect of looped intracochlear electrical stimulation (i.e. stimulation that does not encode environmental sounds) on tinnitus, in an effort to find optimal stimulation parameters. Variables under investigation were: amplitude (perceived stimulus loudness), anatomical location inside the cochlea (electrode/electrodes), amplitude modulation, polarity (cathodic/anodic first biphasic stimulation) and stimulation rate. The results suggest that tinnitus can be reduced with looped electrical stimulation, in some cases even with inaudible stimuli. The optimal stimuli for tinnitus suppression appear to be subject specific. However, medium-to-loud stimuli suppress tinnitus significantly better than soft stimuli, which partly can be explained by the masking effect. Although the long-term effects on tinnitus would still have to be investigated and will be described in part II, intracochlear electrical stimulation seems a potential treatment option for tinnitus in this population.

The pattern of Fos expression in the rat auditory brainstem changes with the temporal structure of binaural electrical intracochlear stimulation

The immediate-early-gene c-fos with its protein product Fos has been used as a powerful tool to investigate neuronal activity and plasticity following sensory stimulation. Fos combines with Jun, another IEG product, to form the dimeric transcription factor activator protein 1 (AP-1) which has been implied in a variety of cellular functions like neuronal plasticity, apoptosis, and regeneration. The intracellular emergence of Fos indicates a functional state of nerve cells directed towards molecular and morphological changes. The central auditory system is construed to detect stimulus intensity, spectral composition, and binaural balance through neurons organized in a complex network of ascending, descending and commissural pathways. Here we compare monaural and binaural electrical intracochlear stimulation (EIS) in normal hearing and early postnatally deafened rats. Binaural stimulation was done either synchronously or asynchronously. The auditory brainstem of hearing and deaf rats responds differently, with a dramatically increasing Fos expression in the deaf group so as if the network had no pre-orientation for how to organize sensory activity. Binaural EIS does not result in a trivial sum of 2 independent monaural EIS, as asynchronous stimulation invokes stronger Fos activation compared to synchronous stimulation almost everywhere in the auditory brainstem. The differential response to synchronicity of the stimulation puts emphasis on the importance of the temporal structure of EIS with respect to its potential for changing brain structure and brain function in stimulus-specific ways.

Optimizing intracochlear electrical stimulation to suppress tinnitus.

Research on tinnitus suppression by intracochlear electrical stimulation has gained interest over the past few decades and it has become easier to apply since the introduction of cochlear implants (CI). This study attempted to gain more insight into optimal stimulation characteristics for tinnitus suppression. Eleven subjects with unilateral CI and tinnitus were recruited from our CI clinic. Electrical stimulation, independent of acoustic sounds, was generated using their CI. The current prospective (single blinded) experimental study systematically assessed two stimulation parameters, namely current level and the anatomical stimulation site inside the cochlea and their short-term effect on tinnitus. Approximately one-third of the tested conditions were successful in which case tinnitus loudness was reduced by at least 30%. At least one successful condition was achieved for nine subjects (82%). Complete suppression was achieved in 6 out of 107 tested conditions (6%). The effect of subthreshold electrical stimulation on tinnitus suppression did not differ significantly from above threshold electrical stimulation. However, a positive relation between mean percentage tinnitus suppression and current level was observed. Pitch-matched electrical stimulation did not appear to suppress tinnitus better than other tested conditions. The majority of the subjects were able to experience tinnitus reduction through intracochlear electrical stimulation independent of acoustic sounds. Tinnitus can be reduced with audible or even inaudible, subthreshold stimuli. Clear trends in optimal stimulation characteristics were not found. Optimal stimulus characteristics for tinnitus reduction therefore appear to be highly subject-specific.

Highly Flexible Silicone Coated Neural Array for Intracochlear Electrical Stimulation.

We present an effective method for tailoring the flexibility of a commercial thin-film polymer electrode array for intracochlear electrical stimulation. Using a pneumatically driven dispensing system, an average 232 ± 64 μm (mean ± SD) thickness layer of silicone adhesive coating was applied to stiffen the underside of polyimide multisite arrays. Additional silicone was applied to the tip to protect neural tissue during insertion and along the array to improve surgical handling. Each array supported 20 platinum sites (180 μm dia., 250 μm pitch), spanning nearly 28 mm in length and 400 μm in width. We report an average intracochlear stimulating current threshold of 170 ± 93 μA to evoke an auditory brainstem response in 7 acutely deafened felines. A total of 10 arrays were each inserted through a round window approach into the cochlea's basal turn of eight felines with one delamination occurring upon insertion (preliminary results of the in vivo data presented at the 48th Annual Meeting American Neurotology Society, Orlando, FL, April 2013, and reported in Van Beek-King 2014). Using microcomputed tomography imaging (50 μm resolution), distances ranging from 100 to 565 μm from the cochlea's central modiolus were measured. Our method combines the utility of readily available commercial devices with a straightforward postprocessing step on the order of 24 hours.

Behavioral responses of deafened guinea pigs to intracochlear electrical stimulation: a new rapid psychophysical procedure

In auditory research the guinea pig is often preferred above rats and mice because of the easily accessible cochlea and because the frequency range of its hearing is more comparable to that of humans. Studies of the guinea-pig auditory system primarily apply histological and electrophysiological measures. Behavioral animal paradigms, in particular in combination with these histological and electrophysiological methods, are necessary in the development of new therapeutic interventions. However, the guinea pig is not considered an attractive animal for behavioral experiments. Therefore, the purpose of this study was to develop a behavioral task suitable for guinea pigs, that can be utilized in cochlear-implant related research. Guinea pigs were trained in a modified shuttle-box in which a stream of air was used as unconditioned stimulus (UCS). A stream of air was preferred over conventionally used methods as electric foot-shocks since it produces less stress, which is a confounding factor in behavioral experiments. Hearing guinea pigs were trained to respond to acoustic stimuli. They responded correctly within only five sessions of ten minutes. The animals maintained their performance four weeks after the right cochlea was implanted with an electrode array. After systemic deafening, the animals responded in the first session immediately to intracochlear electrical stimulation. These responses were not affected by daily chronic electrical stimulation (CES). In conclusion, the present study demonstrates that guinea pigs can be trained relatively fast to respond to acoustic stimuli, and that the training has a lasting effect, which generalizes to intracochlear electrical stimulation after deafening. Furthermore, it demonstrates that bilaterally deafened guinea pigs with substantial (∼50%) loss of spiral ganglion cells (SGCs), detect intracochlear electrical stimulation.

Effects of chronic cochlear electrical stimulation after an extended period of profound deafness on primary auditory cortex organization in cats

Extended periods of deafness have profound effects on central auditory system function and organization. Neonatal deafening results in loss of the normal cochleotopic organization of the primary auditory cortex (AI), but environmentally-derived intracochlear electrical stimulation, via a cochlear implant, initiated shortly after deafening, can prevent this loss. We investigated whether such stimulation initiated after an extended period of deafness can restore cochleotopy. In two groups of neonatally-deafened cats, a multi-channel intracochlear electrode array was implanted at 8 weeks of age. One group received only minimal stimulation, associated with brief recordings at 4-6-week intervals, over the following 6 months to check the efficacy of the implant. In the other group, this 6-month period was followed by 6 months of near-continuous intracochlear electrical stimulation from a modified clinical cochlear implant system. We recorded multi-unit clusters in the auditory cortex and used two different methods to define the region of interest in the putative AI. There was no evidence of cochleotopy in any of the minimally stimulated animals, confirming our earlier finding. In three of six chronically stimulated cats there was clear evidence of AI cochleotopy, and in a fourth cat in which the majority of penetrations were in the anterior auditory field there was clear evidence of cochleotopy in that field. The finding that chronic intracochlear electrical stimulation after an extended period of deafness is able to restore cochleotopy in some (but not all) cases has implications for the performance of patients implanted after an extended period of deafness.

Cochlear implantation for chronic electrical stimulation in the mouse

The mouse is becoming an increasingly attractive model for auditory research due to the number of genetic deafness models available. These genetic models offer the researcher an array of congenital causes of hearing impairment, and are therefore of high clinical relevance. To date, the use of mice in cochlear implant research has not been possible due to the lack of an intracochlear electrode array and stimulator small enough for murine use, coupled with the difficulty of the surgery in this species. Here, we present a fully-implantable intracochlear electrode stimulator assembly designed for chronic implantation in the mouse. We describe the surgical approach for implantation, as well as presenting the first functional data obtained from intracochlear electrical stimulation in the mouse.

Systemically Antagonizing L-Type Calcium Channels Modifies Intensity and Pattern of Fos Expression Evoked by Electrical Intracochlear Stimulation in the Adult Rat Auditory Brainstem

Specific sensory activity such as sustained acoustical or Electrical Intracochlear Stimulation (EIS) elicits electrical responses and molecular changes in neuronal subpopulations of the auditory brainstem. One of the first molecular changes observed is the expression of the immediate early gene Fos. Its protein functions as a monomer of the transcription factor Activator Protein-1 (AP-1) which triggers cascades of protein synthesis that play a crucial role in neuroplastic remodeling. We investigated the pattern of Fos expression in Anteroventral (AVCN) and Dorsal Cochlear Nucleus (DCN) and Central Inferior Colliculus (CIC) following 2 h of unilateral EIS at 1.6, 50, and 400 Hz in anesthetized untreated and nimodipine-treated rats. Our data indicate that with increasing stimulation frequency the population of cells expressing Fos changed in composition and size in AVCN, DCN, and CIC. In all investigated auditory regions, systemic nimodipine treatment, an antagonist of L-type calcium channels, resulted in a significant increase in the number of neurons expressing Fos upon EIS compared to non-treated rats at the same stimulation parameters. Apparently, antagonizing L-type calcium channels enhances the responsiveness of neurons, and thus their readiness to respond with functional changes to sensory activity, in the auditory brainstem with little influence on the tonotopic precision of the response.

Monopolar intracochlear pulse trains selectively activate the inferior colliculus.

Previous cochlear implant studies using isolated electrical stimulus pulses in animal models have reported that intracochlear monopolar stimulus configurations elicit broad extents of neuronal activation within the central auditory system-much broader than the activation patterns produced by bipolar electrode pairs or acoustic tones. However, psychophysical and speech reception studies that use sustained pulse trains do not show clear performance differences for monopolar versus bipolar configurations. To test whether monopolar intracochlear stimulation can produce selective activation of the inferior colliculus, we measured activation widths along the tonotopic axis of the inferior colliculus for acoustic tones and 1,000-pulse/s electrical pulse trains in guinea pigs and cats. Electrical pulse trains were presented using an array of 6-12 stimulating electrodes distributed longitudinally on a space-filling silicone carrier positioned in the scala tympani of the cochlea. We found that for monopolar, bipolar, and acoustic stimuli, activation widths were significantly narrower for sustained responses than for the transient response to the stimulus onset. Furthermore, monopolar and bipolar stimuli elicited similar activation widths when compared at stimulus levels that produced similar peak spike rates. Surprisingly, we found that in guinea pigs, monopolar and bipolar stimuli produced narrower sustained activation than 60 dB sound pressure level acoustic tones when compared at stimulus levels that produced similar peak spike rates. Therefore, we conclude that intracochlear electrical stimulation using monopolar pulse trains can produce activation patterns that are at least as selective as bipolar or acoustic stimulation.

A fully implantable rodent neural stimulator

The ability to electrically stimulate neural and other excitable tissues in behaving experimental animals is invaluable for both the development of neural prostheses and basic neurological research. We developed a fully implantable neural stimulator that is able to deliver two channels of intra-cochlear electrical stimulation in the rat. It is powered via a novel omni-directional inductive link and includes an on-board microcontroller with integrated radio link, programmable current sources and switching circuitry to generate charge-balanced biphasic stimulation. We tested the implant in vivo and were able to elicit both neural and behavioural responses. The implants continued to function for up to five months in vivo. While targeted to cochlear stimulation, with appropriate electrode arrays the stimulator is well suited to stimulating other neurons within the peripheral or central nervous systems. Moreover, it includes significant on-board data acquisition and processing capabilities, which could potentially make it a useful platform for telemetry applications, where there is a need to chronically monitor physiological variables in unrestrained animals.

The impact of hearing experience on signal integration in the auditory brainstem: A c-Fos study of the rat

In this study we investigated the pattern of c-Fos expression in anteroventral (AVCN) and dorsal cochlear nucleus (DCN) and central inferior colliculus (CIC) following electrical intracochlear stimulation (EIS) of anesthetized adult rats that were neonatally deafened. The animals never experienced acoustic sensations as their hair cells were destroyed by daily kanamycin injections between postnatal days 10 to 20, resulting in a rise of hearing threshold by about 90dB. Unilateral EIS was applied through a cochlear implant inserted into the medial turn of the left cochlea and lasted for 45 or 73min, 2, 3:15, or 5h. Following EIS at 50Hz, a high number of c-Fos positive nuclei were observed showing only marginal tonotopic order in ipsilateral AVCN, in DCN bilaterally, and in contralateral CIC. Quantifying the number of c-Fos positive nuclei in ipsilateral AVCN, we found a steady increase with stimulation time. By contrast, the population of neurons expressing c-Fos in DCN and CIC revealed a transient maximum at 73min. A direct comparison with our previous study (Rosskothen-Kuhl, N., Illing, R.-B., 2010. Nonlinear development of the populations of neurons expressing c-Fos under sustained electrical intracochlear stimulation in the rat auditory brainstem. Brain Res. 1347, 33–41) reveals that absence of hearing experience has far-reaching consequences for the interneuronal communication within networks of the auditory brainstem. When hearing fails, EIS entails expression of c-Fos in populations of neurons that are much larger than normally, essentially disregard tonotopic order, and lack much of spatio-temporal variations seen in hearing-experienced rats.

Vibration responses of the organ of Corti and the tectorial membrane to electrical stimulation

Coupling of somatic electromechanical force from the outer hair cells (OHCs) into the organ of Corti is investigated by measuring transverse vibration patterns of the organ of Cori and tectorial membrane (TM) in response to intracochlear electrical stimulation. Measurement places at the organ of Corti extend from the inner sulcus cells to Hensen's cells and at the lower (and upper) surface of the TM from the inner sulcus to the OHC region. These locations are in the neighborhood of where electromechanical force is coupled into (1) the mechanoelectrical transducers of the stereocilia and (2) fluids of the organ of Corti. Experiments are conducted in the first, second, and third cochlear turns of an in vitro preparation of the adult guinea pig cochlea. Vibration measurements are made at functionally relevant stimulus frequencies (0.48-68 kHz) and response amplitudes (<15 nm). The experiments provide phase relations between the different structures, which, dependent on frequency range and longitudinal cochlear position, include in-phase transverse motions of the TM, counterphasic transverse motions between the inner hair cell and OHCs, as well as traveling-wave motion of Hensen's cells in the radial direction. Mechanics of sound processing in the cochlea are discussed based on these phase relationships.

Auditory maturity and hearing performance in inner ear malformations: a histological and electrical stimulation approach

The objective of this study was to assess the auditory performance of the neural structures in response to controlled electrical stimulation period. A prospective cohort study focused on the intracochlear electrical stimulation parameters and hearing performance of patients suffering different cochlear malformations who were treated by cochlear implants constituted the study design. The study sample constituted 16 patients, suffering profound prelingual hearing impairment, diagnosed on the basis of radiological criteria as having an inner ear malformation, and who underwent cochlear implantation and were followed for 24 months. Patients with common cavities, characterized by fewer nerve structures involved, less epithelial penetration, and deficient cochlear tonotopy distribution showed have higher thresholds and electrical charges than patients with cochlear hypoplasia, who in turn have higher thresholds than patients with minor malformations (p < 0.05). Furthermore, word perception was severely compromised in patients with a common cavity malformation and was also poor in patients with cochlear hypoplasia, who were unable to discriminate more than 50% of the words and relied on visual cues as a necessary aid to communication. Better results were reached by minor malformed inner ears. To conclude, the number of nerve structures involved, epithelial penetration and deficient cochlear tonotopy are responsible of inner ear functionality.

Spiral ganglion neuron survival and function in the deafened cochlea following chronic neurotrophic treatment

Cochlear implants electrically stimulate residual spiral ganglion neurons (SGNs) to provide auditory cues for the severe-profoundly deaf. However, SGNs gradually degenerate following cochlear hair cell loss, leaving fewer neurons available for stimulation. Providing an exogenous supply of neurotrophins (NTs) has been shown to prevent SGN degeneration, and when combined with chronic intracochlear electrical stimulation (ES) following a short period of deafness (5 days), may also promote the formation of new neurons. The present study assessed the histopathological response of guinea pig cochleae treated with NTs (brain-derived neurotrophic factor and neurotrophin-3) with and without ES over a four week period, initiated two weeks after deafening. Results were compared to both NT alone and artificial perilymph (AP) treated animals. AP/ES treated animals exhibited no evidence of SGN rescue compared with untreated deafened controls. In contrast, NT administration showed a significant SGN rescue effect in the lower and middle cochlear turns (two-way ANOVA, p < 0.05) compared with AP-treated control animals. ES in combination with NT did not enhance SGN survival compared with NT alone. SGN function was assessed by measuring electrically-evoked auditory brainstem response (EABR) thresholds. EABR thresholds following NT treatment were significantly lower than animals treated with AP (two-way ANOVA, p = 0.033). Finally, the potential for induced neurogenesis following the combined treatment was investigated using a marker of DNA synthesis. However, no evidence of neurogenesis was observed in the SGN population. The results indicate that chronic NT delivery to the cochlea may be beneficial to cochlear implant patients by increasing the number of viable SGNs and decreasing activation thresholds compared to chronic ES alone.

Behavioral training enhances cortical temporal processing in neonatally deafened juvenile cats

Deaf humans implanted with a cochlear prosthesis depend largely on temporal cues for speech recognition because spectral information processing is severely impaired. Training with a cochlear prosthesis is typically required before speech perception shows improvement, suggesting that relevant experience modifies temporal processing in the central auditory system. We tested this hypothesis in neonatally deafened cats by comparing temporal processing in the primary auditory cortex (AI) of cats that received only chronic passive intracochlear electric stimulation (ICES) with cats that were also trained with ICES to detect temporally challenging trains of electric pulses. After months of chronic passive stimulation and several weeks of detection training in behaviorally trained cats, multineuronal AI responses evoked by temporally modulated ICES were recorded in anesthetized animals. The stimulus repetition rates that produced the maximum number of phase-locked spikes (best repetition rate) and 50% cutoff rate were significantly higher in behaviorally trained cats than the corresponding rates in cats that received only chronic passive ICES. Behavioral training restored neuronal temporal following ability to levels comparable with those recorded in naïve prior normal-hearing adult deafened animals. Importantly, best repetitition rates and cutoff rates were highest for neuronal clusters activated by the electrode configuration used in behavioral training. These results suggest that neuroplasticity in the AI is induced by behavioral training and perceptual learning in animals deprived of ordinary auditory experience during development and indicate that behavioral training can ameliorate or restore temporal processing in the AI of profoundly deaf animals.

Stimulationsabhängige Genexpression im zentralen auditorischen System

Acoustic or electrical stimulation activate specific populations of neurons in specific regions of the central auditory system to prepare for a molecular, structural, and functional remodeling within hours. Among the indicators for the initiation of neuronal remodeling is the expression of immediate early genes (IEGs). The IEG c-fos is one of the first genes to be expressed following sensory-evoked neuronal activity. In order to investigate activity-dependent neuroplasticity in the central auditory system we applied acute unilateral electrical intracochlear stimulation (EIS) in a rat model. By using different stimulation parameters we found that laterality, intensity, and frequency effect different kinds of neurons in different regions. We investigated the ventral and dorsal cochlear nucleus (VCN and DCN), the lateral superior olive (LSO), the central inferior colliculus (CIC), and the medial geniculate body (MGB). In each region a unique dynamic pattern of c-Fos expression was found.