Electrical Stimulation publications

The ascending and descending projections of the central auditory system form multiple tonotopic loops. This study specifically examines the tonotopic pathway from the auditory thalamus to the auditory cortex and then to the auditory midbrain in mice. We observed the changes of receptive fields in the central nucleus of the inferior colliculus of the midbrain evoked by focal electrical stimulation of the ventral division of the medial geniculate body of the thalamus. The receptive field of an auditory neuron was characterized by five parameters: the best frequency, minimum threshold, bandwidth, size of receptive field, and average spike number. We found that focal thalamic stimulation changed the parametric values characterizing the recorded collicular receptive fields toward those characterizing the stimulated thalamic receptive fields. Cortical inactivation with muscimol prevented the development of the collicular plasticity induced by focal thalamic stimulation. Our data suggest that the intact colliculo-thalamo-cortico-collicular loops are important for the coordination of sound-guided plasticity in the central auditory system.

The BETA2/NeuroD1 null mouse has cochlear dysplasia. Its cochlear duct is shorter than normal, there is a lack of spiral ganglion neurons, and there is hair cell disorganization. We measured vertical movements of the tectorial membrane at acoustic frequencies in excised cochleae in response to mechanical stimulation of the stapes using laser doppler vibrometry. While tuning curve sharpness was similar between wild-type, heterozygotes, and null mice in the base, null mutants had broader tuning in the apex. At both the base and the apex, null mice had less phase lag accumulation with increasing stimulus frequency than wild-type or heterozygote mice. In vivo studies demonstrated that the null mouse lacked distortion product otoacoustic emissions, and the cochlear microphonic and endocochlear potential were found to be severely reduced. Electrically evoked otoacoustic emissions could be elicited, although the amplitudes were lower than those of wild-type mice. Cochlear cross-sections revealed an incomplete partition malformation, with fenestrations within the modiolus that connected the cochlear turns. Outer hair cells from null mice demonstrated the normal pattern of prestin expression within their lateral walls and normal FM 1-43 dye entry. Overall, these data demonstrate that while tonotopicity can exist with cochlear dysplasia, traveling wave propagation is abnormally fast. Additionally, the presence of electrically evoked otoacoustic emissions suggests that outer hair cell reverse transduction is present, although the acoustic response is shaped by the alterations in cochlear mechanics.

Transcallosal excitation and inhibition have been theorized based on the effect of callosotomy on intractable epilepsy and dichotic listening research, respectively. We studied bilateral interaction of cortical auditory neurons and found that this interaction consisted of focused facilitation and widespread lateral inhibition. The frequency modulated (FM)–FM area of the auditory cortex of the mustached bat is composed of delay-tuned neurons tuned to the combination of the emitted biosonar pulse and its echo with a specific echo delay [best delay (BD)] and consists of three subdivisions in terms of the combination sensitivity of neurons. We found that focal electric stimulation of one of these three subdivisions evoked BD shifts of delay-tuned neurons in all three subdivisions of the contralateral FM–FM area, presumably via the corpus callosum. The effect of electric stimulation of the delay-tuned neurons on the contralateral delay-tuned neurons was different depending on whether the BD of a recorded neuron was matched or unmatched in BD with that of the stimulated neurons. BD-matched neurons did not change their BDs and increased the responses at their BDs, whereas BD-unmatched neurons shifted their BDs away from the BD of the stimulated neurons and reduced their responses. The ipsilateral and contralateral BD shifts evoked by the electric stimulation were identical to each other. The contralateral modulation, in addition to the ipsilateral modulation, increases the contrast in the neural representation of the echo delay to which the stimulated neurons are tuned.

Deprivation from normal sensory input has been shown to alter tonotopic organization of the human auditory cortex. In this context, cochlear implant subjects provide an interesting model in that profound deafness is made partially reversible by the cochlear implant. In restoring afferent activity, cochlear implantation may also reverse some of the central changes related to deafness. The purpose of the present study was to address whether the auditory cortex of cochlear implant subjects is tonotopically organized. The subjects were thirteen adults with at least 3 months of cochlear implant experience. Auditory event-related potentials were recorded in response to electrical stimulation delivered at different intracochlear electrodes. Topographic analysis of the auditory N1 component (∼85 ms latency) showed that the locations on the scalp and the relative amplitudes of the positive/negative extrema differ according to the stimulated electrode, suggesting that distinct sets of neural sources are activated. Dipole modeling confirmed electrode-dependent orientations of these sources in temporal areas, which can be explained by nearby, but distinct sites of activation in the auditory cortex. Although the cortical organization in cochlear implant users is similar to the tonotopy found in normal-hearing subjects, some differences exist. Nevertheless, a correlation was found between the N1 peak amplitude indexing cortical tonotopy and the values given by the subjects for a pitch scaling task. Hence, the pattern of N1 variation likely reflects how frequencies are coded in the brain.

Outer hair cell (OHC) somatic motility plays a key role in mammalian cochlear frequency selectivity and hearing sensitivity, but the mechanism of cochlear amplification is not well understood and remains a matter of controversy. We have visualized and quantified the effects of electrically evoked OHC somatic motility within the gerbil organ of Corti using an excised cochlear preparation. We found that OHC motility induces oscillatory motion of the medial olivocochlear fibers where they cross the tunnel of Corti (ToC) in their course to innervate the OHCs. We show that this motion is present at physiologically relevant frequencies and remains at locations distal to the OHC excitation point. We interpret this fiber motion to be the result of oscillatory fluid flow in the ToC. We show, using a simple one-dimensional hydromechanical model of the ToC, that a fluid wave within the tunnel can travel without significant attenuation for distances larger than the wavelength of the cochlear traveling wave at its peak. This ToC fluid wave could interact with the cochlear traveling wave to amplify the motion of the basilar membrane. The ToC wave could also provide longitudinal coupling between adjacent sections of the basilar membrane, and such coupling may be critical for cochlear amplification.

The outer hair cell (OHC) of the mammalian inner ear exhibits an unusual form of somatic motility that can follow membrane-potential changes at acoustic frequencies. The cellular forces that produce this motility are believed to amplify the motion of the cochlear partition, thereby playing a key role in increasing hearing sensitivity. To better understand the role of OHC somatic motility in cochlear micromechanics, we developed an excised cochlea preparation to visualize simultaneously the electrically-evoked motion of hundreds of cells within the organ of Corti (OC). The motion was captured using stroboscopic video microscopy and quantified using cross-correlation techniques. The OC motion at approximately 2-6 octaves below the characteristic frequency of the region was complex: OHC, Deiter's cell, and Hensen's cell motion were hundreds of times larger than the tectorial membrane, reticular lamina (RL), and pillar cell motion; the inner rows of OHCs moved antiphasic to the outer row; OHCs pivoted about the RL; and Hensen's cells followed the motion of the outer row of OHCs. Our results suggest that the effective stimulus to the inner hair cell hair bundles results not from a simple OC lever action, as assumed by classical models, but by a complex internal motion coupled to the RL.

Based on in vitro studies, it is hypothesized that neurotrophic factor deprivation following deafferentation elicits an oxidative state change in the deafferented neuron and the formation of free radicals that then signal cell death pathways. This pathway to cell death was tested in vivo by assessing the efficacy of antioxidants (AOs) to prevent degeneration of deafferented CNVIII spiral ganglion cells (SGCs) in deafened guinea pigs. Following destruction of sensory cells, guinea pigs were treated immediately with Trolox (a water soluble vitamin E analogue)+ascorbic acid (vitamin C) administered either locally, directly in the inner ear, or systemically. Electrical auditory brainstem response (EABR) thresholds were recorded to assess nerve function and showed a large increase following deafness. In treated animals EABR thresholds decreased and surviving SGCs were increased significantly compared to untreated animals. These results indicate that a change in oxidative state following deafferentation plays a role in nerve cell death and antioxidant therapy may rescue SGCs from deafferentation-induced degeneration.

Contemporary auditory prostheses ("cochlear implants") employ arrays of stimulating electrodes implanted in the scala tympani of the cochlea. Such arrays have been implanted in some 100,000 profoundly or severely deaf people worldwide and arguably are the most successful of present-day neural prostheses. Nevertheless, most implant users show poor understanding of speech in noisy backgrounds, poor pitch recognition, and poor spatial hearing, even when using bilateral implants. Many of these limitations can be attributed to the remote location of stimulating electrodes relative to excitable cochlear neural elements. That is, a scala tympani electrode array lies within a bony compartment filled with electrically conductive fluid. Moreover, scala tympani arrays typically do not extend to the apical turn of the cochlea in which low frequencies are represented. In the present study, we have tested in an animal model an alternative to the conventional cochlear implant: a multielectrode array implanted directly into the auditory nerve. We monitored the specificity of stimulation of the auditory pathway by recording extracellular unit activity at 32 sites along the tonotopic axis of the inferior colliculus. The results demonstrate the activation of specific auditory nerve populations throughout essentially the entire frequency range that is represented by characteristic frequencies in the inferior colliculus. Compared to conventional scala tympani stimulation, thresholds for neural excitation are as much as 50-fold lower and interference between electrodes stimulated simultaneously is markedly reduced. The results suggest that if an intraneural stimulating array were incorporated into an auditory prosthesis system for humans, it could offer substantial improvement in hearing replacement compared to contemporary cochlear implants.

Objective: To evaluate sound localization acuity in a group of children who received bilateral (BI) cochlear implants in sequential procedures and to determine the extent to which BI auditory experience affects sound localization acuity. In addition, to investigate the extent to which a hearing aid in the nonimplanted ear can also provide benefits on this task. Design: Two groups of children participated, 13 with BI cochlear implants (cochlear implant + cochlear implant), ranging in age from 3 to 16 yrs, and six with a hearing aid in the nonimplanted ear (cochlear implant + hearing aid), ages 4 to 14 yrs. Testing was conducted in large sound-treated booths with loudspeakers positioned on a horizontal arc with a radius of 1.5 m. Stimuli were spondaic words recorded with a male voice. Stimulus levels typically averaged 60 dB SPL and were randomly roved between 56 and 64 dB SPL (+/-4 dB rove); in a few instances, levels were held fixed (60 dB SPL). Testing was conducted by using a "listening game" platform via computerized interactive software, and the ability of each child to discriminate sounds presented to the right or left was measured for loudspeakers subtending various angular separations. Minimum audible angle thresholds were measured in the BI (cochlear implant + cochlear implant or cochlear implant + hearing aid) listening mode and under monaural conditions. Results: Approximately 70% (9/13) of children in the cochlear implant + cochlear implant group discriminated left/right for source separations of <or=20 degrees , and, of those, 77% (7/9) performed better when listening bilaterally than with either cochlear implant alone. Several children were also able to perform the task when using a single cochlear implant, under some conditions. Minimum audible angle thresholds were better in the first cochlear implant than the second cochlear implant listening mode for nearly all (8/9) subjects. Repeated testing of a few individual subjects over a 2-yr period suggests that robust improvements in performance occurred with increased auditory experience. Children who wore hearing aids in the nonimplanted ear were at times also able to perform the task. Average group performance was worse than that of the children with BI cochlear implants when both ears were activated (cochlear implant + hearing aid versus cochlear implant + cochlear implant) but not significantly different when listening with a single cochlear implant. Conclusions: Children with sequential BI cochlear implants represent a unique population of individuals who have undergone variable amounts of auditory deprivation in each ear. Our findings suggest that many but not all of these children perform better on measures of localization acuity with two cochlear implants compared with one and are better at the task than children using the cochlear implant + hearing aid. These results must be interpreted with caution, because benefits on other tasks as well as the long-term benefits of BI cochlear implants are yet to be fully understood. The factors that might contribute to such benefits must be carefully evaluated in large populations of children using a variety of measures.

The present study is aimed to evaluate and compare loudness adaptation between normal hearing and cochlear-implant subjects. Loudness adaptation for 367-s pure tones was measured in five normal-hearing subjects at three frequencies (125, 1,000, and 8,000 Hz) and three levels (30, 60, and 90 dB SPL). In addition, loudness adaptation for 367-s pulse trains was measured in five Clarion cochlear-implant subjects at three stimulation rates (100, 991, and 4,296 Hz), three levels (10, 50, and 90% of the electric dynamic range), three stimulation positions (apical, middle and basal), and two stimulation modes (monopolar and bipolar). The method of successive magnitude estimation was used to quantify loudness adaptation. Similar to the previous results, we found that loudness adaptation in normal-hearing subjects increases with decreasing level and increasing frequency. However, we also found a small but significant loudness enhancement at 90 dB SPL in acoustic hearing. Despite large individual variability, we found that loudness adaptation in cochlear-implant subjects increases with decreasing levels, but is not significantly affected by the rate, place and mode of stimulation. A phenomenological model was proposed to predict loudness adaptation as a function of stimulus frequency and level in acoustic hearing. The present results were not fully compatible with either the restricted excitation hypothesis or the neural adaptation hypothesis. Loudness adaptation may have a central component that is dependent on the peripheral excitation pattern.

This study evaluated functional benefits from bilateral stimulation in 20 children ages 4-14, 10 use two CIs and 10 use one CI and one HA. Localization acuity was measured with the minimum audible angle (MAA). Speech intelligibility was measured in quiet, and in the presence of 2-talker competing speech using the CRISP forced-choice test. Results show that both groups perform similarly when speech reception thresholds are evaluated. However, there appears to be benefit (improved MAA and speech thresholds) from wearing two devices compared with a single device that is significantly greater in the group with two CI than in the bimodal group. Individual variability also suggests that some children perform similarly to normal-hearing children, while others clearly do not. Future advances in binaural fitting strategies and improved speech processing schemes that maximize binaural sensitivity will no doubt contribute to increasing the binaurally-driven advantages in persons with bilateral CIs.

Focal electric stimulation of the auditory cortex is well suited for exploration of the function of the corticofugal (descending) system and the neural mechanism of plasticity in the central auditory system, because it evokes changes in frequency-tuning, called best frequency (BF) shifts, as does auditory fear conditioning. The Doppler-shifted constant frequency (DSCF) area of the primary auditory cortex of the mustached bat is highly specialized for fine frequency analysis. Focal electric stimulation of the DSCF area evokes the BF shifts of ipsilateral cortical and collicular neurons away from the BF of stimulated neurons, whereas the stimulation evokes the BF shifts of contralateral cortical and collicular neurons either toward or away from the stimulated BF. The direction of contralateral BF shifts shows a flip-flop, depending on the spatial relationship between the stimulated and recorded neurons. This asymmetry in corticofugal modulation is mostly, if not totally, created by two subdivisions of the stimulated DSCF area that transmit signals to the contralateral DSCF area, presumably through the corpus callosum. This intriguing asymmetry in corticofugal modulation presumably functions for equalization of the reorganization of the frequency maps of the DSCF areas and subcortical auditory nuclei on both sides.

Auditory fear conditioning with tone bursts followed by electric leg stimulation activates neurons not only in the auditory and somatosensory systems but also in many other regions of the brain and elicits shifts in the best frequencies (BFs) of collicular and cortical neurons, i.e., reorganization of the frequency (co-chleotopic) maps in the inferior colliculus and auditory cortex (AC). What are the neural elements minimally necessary for evoking long-term cortical BF shifts? We found that: ( i ) both electric stimulation and acetylcholine applied to the AC evoke the long-term cortical BF shift as does the conditioning; ( ii ) both electric stimulation of the AC and acetylcholine applied to the inferior colliculus increase the short-term collicular BF shift evoked by the cortical electric stimulation but do not change it into long-term; and ( iii ) as this short-term collicular BF shift is blocked by atropine, the development of the long-term cortical BF shift becomes slow and small. Therefore, the most essential neural elements for evoking the long-term cortical BF shift are the AC, corticofugal feedback and the cholinergic nucleus. Our current data support the Gao–Suga model, which hypothesizes that the small short-term cortical BF shifts are evoked by tonal stimuli without the association of conditioned and unconditioned stimuli in the multisensory thalamic nuclei and that these BF shifts are augmented and changed into the large long-term BF shifts by cholinergic neurons.

Perceptual consequences of disrupted auditory nerve activity were systematically studied in 21 subjects who had been clinically diagnosed with auditory neuropathy (AN), a recently defined disorder characterized by normal outer hair cell function but disrupted auditory nerve function. Neurological and electrophysical evidence suggests that disrupted auditory nerve activity is due to desynchronized or reduced neural activity or both. Psychophysical measures showed that the disrupted neural activity has minimal effects on intensity-related perception, such as loudness discrimination, pitch discrimination at high frequencies, and sound localization using interaural level differences. In contrast, the disrupted neural activity significantly impairs timing related perception, such as pitch discrimination at low frequencies, temporal integration, gap detection, temporal modulation detection, backward and forward masking, signal detection in noise, binaural beats, and sound localization using interaural time differences. These perceptual consequences are the opposite of what is typically observed in cochlear-impaired subjects who have impaired intensity perception but relatively normal temporal processing after taking their impaired intensity perception into account. These differences in perceptual consequences between auditory neuropathy and cochlear damage suggest the use of different neural codes in auditory perception: a suboptimal spike count code for intensity processing, a synchronized spike code for temporal processing, and a duplex code for frequency processing. We also proposed two underlying physiological models based on desynchronized and reduced discharge in the auditory nerve to successfully account for the observed neurological and behavioral data. These methods and measures cannot differentiate between these two AN models, but future studies using electric stimulation of the auditory nerve via a cochlear implant might. These results not only show the unique contribution of neural synchrony to sensory perception but also provide guidance for translational research in terms of better diagnosis and management of human communication disorders.

The perception of voice similarity was examined in 5-year-old children with normal hearing sensitivity and in pediatric cochlear implant users, 5–12 years of age. Recorded sentences were manipulated to form a continuum of similar-sounding voices. An adaptive procedure was then used to determine how acoustically different, in terms of average fundamental and formant frequencies, 2 sentences needed to be for a child to categorize the sentences as spoken by 2 different talkers. The average spectral characteristics of 2 utterances (including their fundamental frequencies) needed to differ by at least 11%–16% (2–2.5 semitones) for normal-hearing children to perceive the voices as belonging to different talkers. Introducing differences in the linguistic content of the 2 sentences to be compared did not change performance. Although several children with cochlear implants performed similarly to normal-hearing children, most found the task very difficult. Pediatric cochlear implant users who scored above the group mean of 64% of words correct on a monosyllabic open-set word identification task categorized the voices more like children with normal hearing sensitivity.

This study examined the interactions between electrical stimuli presented through two channels of a cochlear implant. Experiments were conducted in anesthetized guinea pigs. Multiunit spike activity recorded from the auditory cortex reflected the cumulative effects of electric field interactions in the cochlea as well as any neural interactions along the ascending auditory pathway. The cochlea was stimulated electrically through a 6-electrode intracochlear array. The stimulus on each channel was a single 80- micro s/phase biphasic pulse. Channel interactions were quantified as changes in the thresholds for elevation of cortical spike rates. Experimental parameters were interchannel temporal offset (0 to +/-2000 micro s), interelectrode cochlear spacing (1.5 or 2.25 mm), electrode configuration (monopolar, bipolar, or tripolar), and relative polarity between channels (same or inverted). In most conditions, presentation of a subthreshold pulse on one channel reduced the threshold for a pulse on a second channel. Threshold shifts were greatest for simultaneous pulses, but appreciable threshold reductions could persist for temporal offsets up to 640 micro s. Channel interactions varied strongly with electrode configuration: threshold shifts increased in magnitude in the order tripolar, bipolar, monopolar. Channel interactions were greater for closer electrode spacing. The results have implications for design of speech processors for cochlear implants.

The present study aimed to examine the effect of noise on vowel-like suprathreshold discrimination in cochlear-implant listeners. The task was to detect an increment in level at the middle harmonic (400 Hz) in the background of a seven-harmonic complex from 100 to 700 Hz in 100-Hz steps. The task was performed in the absence (control) and presence of a white noise presented over a 20-35-dB range from inaudible to loud. The present result shows that discrimination of suprathreshold harmonic stimuli was significantly enhanced, particularly at the soft signal level, with suprathreshold noise. This result suggests that tuning of the noise level is required to optimize performance of different tasks in cochlear implants.

A direct commissural connection between cochlear nuclei provides a pathway by which binaural input can influence the processing of acoustic information through the ventral cochlear nucleus. Despite anatomical evidence to suggest the existence of such a pathway, its nature and behavior have not been investigated previously. This in vivo intracellular electrophysiological study provides direct evidence of monosynaptic (mean latency, 1.43 msec), inhibitory commissural input to T stellate cells. This inhibition is fast acting (duration, <10 msec), occurring with little synaptic delay (∼0.3 msec). Electrical stimulation also revealed the initiation of antidromic responses in the onset chopper population, signifying D stellate neurons as a source of commissural inputs. Activation of the commissural connection was most evident in response to broadband stimuli. These results provide the first compelling evidence of a fast, monosynaptic commissural pathway arising from contralateral D stellate neurons providing broadband inhibitory input to T stellate cells.

Capsaicin, the vanilloid that selectively activates vanilloid receptors (VRs) on sensory neurons for noxious perception, has been reported to increase cochlear blood flow (CBF). VR-related receptors have also been found in the inner ear. This study aims to address the question as to whether VRs exist in the organ of Corti and play a role in cochlear physiology. Capsaicin or the more potent VR agonist, resiniferatoxin (RTX), was infused into the scala tympani of guinea pig cochlea, and their effects on cochlear sensitivity were investigated. Capsaicin (20 μM) elevated the threshold of auditory nerve compound action potential and reduced the magnitude of cochlear microphonic and electrically evoked otoacoustic emissions. These effects were reversible and could be blocked by a competitive antagonist, capsazepine. Application of 2 μM RTX resulted in cochlear sensitivity alterations similar to that by capsaicin, which could also be blocked by capsazepine. A desensitization phenomenon was observed in the case of prolonged perfusion with either capsaicin or RTX. Brief increase of CBF by capsaicin was confirmed, and the endocochlear potential was not decreased. Basilar membrane velocity (BM) growth functions near the best frequency and BM tuning were altered by capsaicin. Immunohistochemistry study revealed the presence of vanilloid receptor type 1 of the transient receptor potential channel family in the hair cells and supporting cells of the organ of Corti and the spiral ganglion cells of the cochlea. The results indicate that the main action of capsaicin is on outer hair cells and suggest that VRs in the cochlea play a role in cochlear homeostasis.