Central Auditory Plasticity Research Articles

Noise Induced Hearing Loss and Tinnitus-New Research Developments and Remaining Gaps in Disease Assessment, Treatment, and Prevention.

Long-term noise exposure often results in noise induced hearing loss (NIHL). Tinnitus, the generation of phantom sounds, can also result from noise exposure, although understanding of its underlying mechanisms are limited. Recent studies, however, are shedding light on the neural processes involved in NIHL and tinnitus, leading to potential new and innovative treatments. This review focuses on the assessment of NIHL, available treatments, and development of new pharmacologic and non-pharmacologic treatments based on recent studies of central auditory plasticity and adaptive changes in hearing. We discuss the mechanisms and maladaptive plasticity of NIHL, neuronal aspects of tinnitus triggers, and mechanisms such as tinnitus-associated neural changes at the cochlear nucleus underlying the generation of tinnitus after noise-induced deafferentation. We include observations from recent studies, including our own studies on associated risks and emerging treatments for tinnitus. Increasing knowledge of neural plasticity and adaptive changes in the central auditory system suggest that NIHL is preventable and transient abnormalities may be reversable, although ongoing research in assessment and early detection of hearing difficulties is still urgently needed. Since no treatment can yet reverse noise-related damage completely, preventative strategies and increased awareness of hearing health are essential.

Speech Perception and Gap Detection Performance of Single-Sided Deafness under Noisy Conditions

Background and ObjectivesMany studies have reported no benefit of sound localization, but improved speech understanding in noise after treating patients with single-sided deafness (SSD). Furthermore, their performances provided a large individual difference. The present study aimed to measure the ability of speech perception and gap detection in noise for the SSD patients to better understand their hearing nature.Subjects and MethodsNine SSD patients with different onset and period of hearing deprivation and 20 young adults with normal hearing and simulated conductive hearing loss as the control groups conducted speech perception in noise (SPIN) and Gap-In-Noise (GIN) tests. The SPIN test asked how many presented sentences were understood at the +5 and -5 dB signal-to-noise ratio. The GIN test was asked to find the shortest gap in white noise with different lengths in the gap.ResultsCompared to the groups with normal hearing and simulated instant hearing loss, the SSD group showed much poor performance in both SPIN and GIN tests while supporting central auditory plasticity of the SSD patients. Rather than a longer period of deafness, the large individual variance indicated that the congenital SSD patients showed better performance than the acquired SSD patients in two measurements.ConclusionsThe results suggested that comprehensive assessments should be implemented before any treatment of the SSD patient considering their onset time and etiology, although these findings need to be generalized with a large sample size.

Human central auditory plasticity: A review of functional near-infrared spectroscopy (fNIRS) to measure cochlear implant performance and tinnitus perception.

ObjectiveFunctional near‐infrared spectroscopy (fNIRS) is an emerging noninvasive technology used to study cerebral cortex activity. Being virtually silent and compatible with cochlear implants has helped establish fNIRS as an important tool when investigating auditory cortex as well as cortices involved with hearing and language processing in adults and during child development. With respect to this review article, more recently, fNIRS has also been used to investigate central auditory plasticity following hearing loss and tinnitus or phantom sound perception.MethodsHere, we review the currently available literature reporting the use of fNIRS in human studies with cochlear implants and tinnitus to measure human central auditory cortical circuits. We also provide the reader with detailed reviews of the technology and traditional recording paradigms/methods used in these auditory‐based studies.ResultsThe purpose of this review article is to summarize theoretical advancements in our understanding of the neurocognitive mechanisms underlying auditory processes and their plasticity through fNIRS research of human auditory performance with cochlear implantation and plasticity that may contribute to the central percepts of tinnitus.ConclusionfNIRS is an emerging noninvasive brain imaging technology that has wide reaching application that can be applied to human studies involving cochlear implants and tinnitus.Level of EvidenceN/A

Cortical cross-modal plasticity following deafness measured using functional near-infrared spectroscopy

Evidence from functional neuroimaging studies suggests that the auditory cortex can become more responsive to visual and somatosensory stimulation following deafness, and that this occurs predominately in the right hemisphere. Extensive cross-modal plasticity in prospective cochlear implant recipients is correlated with poor speech outcomes following implantation, highlighting the potential impact of central auditory plasticity on subsequent aural rehabilitation. Conversely, the effects of hearing restoration with a cochlear implant on cortical plasticity are less well understood, since the use of most neuroimaging techniques in CI recipients is either unsafe or problematic due to the electromagnetic artefacts generated by CI stimulation. Additionally, techniques such as functional magnetic resonance imaging (fMRI) are confounded by acoustic noise produced by the scanner that will be perceived more by hearing than by deaf individuals. Subsequently it is conceivable that auditory responses to acoustic noise produced by the MR scanner may mask auditory cortical responses to non-auditory stimulation, and render inter-group comparisons less significant. Uniquely, functional near-infrared spectroscopy (fNIRS) is a silent neuroimaging technique that is non-invasive and completely unaffected by the presence of a CI. Here, we used fNIRS to study temporal-lobe responses to auditory, visual and somatosensory stimuli in thirty profoundly-deaf participants and thirty normally-hearing controls. Compared with silence, acoustic noise stimuli elicited a significant group fNIRS response in the temporal region of normally-hearing individuals, which was not seen in profoundly-deaf participants. Visual motion elicited a larger group response within the right temporal lobe of profoundly-deaf participants, compared with normally-hearing controls. However, bilateral temporal lobe fNIRS activation to somatosensory stimulation was comparable in both groups. Using fNIRS these results confirm that auditory deprivation is associated with cross-modal plasticity of visual inputs to auditory cortex. Although we found no evidence for plasticity of somatosensory inputs, it is possible that our recordings may have included activation of somatosensory cortex that masked any group differences in auditory cortical responses due to the limited spatial resolution associated with fNIRS.

Age effects on tinnitus and hearing loss in CBA/CaJ mice following sound exposure.

Tinnitus is a maladaptive neuropathic condition that develops in humans and laboratory animals following auditory insult. In our previous study we demonstrated that sound exposure leads to development of behavioral evidence of tinnitus in a sample of exposed mice. However, this tinnitus mouse model did not account for long-term maladaptive plasticity or aging, factors that are commonly linked to the human tinnitus population. Therefore the same group of mice was monitored for tinnitus for 360 days post exposure. Tinnitus was assessed behaviorally by measuring gap-induced pre-pulse suppression of the acoustic startle (GPIAS). Cochlear histology was performed on both control (unexposed) and experimental mice to determine whether sound exposure caused any evident cochlear damage. We found that 360 days after exposure the vast majority of exposed mice exhibited similar gap detection deficits as detected at 84 days post exposure. These mice did not demonstrate significant loss of inner/outer hair cells or spiral ganglion neurons compared to the control sample. Lastly, we demonstrated that GPIAS deficits observed in exposed animals were unlikely exclusively caused by cochlear damage, but could be a result of central auditory maladaptive plasticity. We conclude that CBA/CaJ mice can be considered a good animal model to study the possible contribution of age effects on tinnitus development following auditory insult.

Central auditory plasticity indexed by mismatch negativity

Introduction Unilateral hearing loss (UHL) represents a particular model for investigating the functional auditory plasticity in humans. Normally, monaural stimulation produces a normal pattern of a contralateral dominance. With UHL, this pattern changes. Objective The aim of the study was to investigate the effects of UHL side and age at onset on auditory processing. Design Mismatch negativity (MMN) was recorded in response to speech and tone stimuli. Study sample This study included two groups: the control (50 bilateral normal hearing) and study (206 UHL patients) groups. This group was further classified according to UHL side and age at UHL onset. Results In controls, higher speech-evoked MMN amplitude was recorded in the right ear. The study group showed impaired speech-evoked MMN in either left or right UHL patients, especially in early onset UHL patients. Tone-evoked MMN was not affected in controls or UHL patients. Conclusion Cortical reorganization induced by UHL occurs mainly in patients with left-side affection. Speech processing is affected in UHL irrespective of the affected side, especially in early onset patients.

Neuromagnetic Index of Hemispheric Asymmetry Prognosticating the Outcome of Sudden Hearing Loss

The longitudinal relationship between central plastic changes and clinical presentations of peripheral hearing impairment remains unknown. Previously, we reported a unique plastic pattern of “healthy-side dominance” in acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL). This study aimed to explore whether such hemispheric asymmetry bears any prognostic relevance to ISSNHL along the disease course. Using magnetoencephalography (MEG), inter-hemispheric differences in peak dipole amplitude and latency of N100m to monaural tones were evaluated in 21 controls and 21 ISSNHL patients at two stages: initial and fixed stage (1 month later). Dynamics/Prognostication of hemispheric asymmetry were assessed by the interplay between hearing level/hearing gain and ipsilateral/contralateral ratio (I/C) of N100m latency and amplitude. Healthy-side dominance of N100m amplitude was observed in ISSNHL initially. The pattern changed with disease process. There is a strong correlation between the hearing level at the fixed stage and initial I/Camplitude on affected-ear stimulation in ISSNHL. The optimal cut-off value with the best prognostication effect for the hearing improvement at the fixed stage was an initial I/Clatency on affected-ear stimulation of 1.34 (between subgroups of complete and partial recovery) and an initial I/Clatency on healthy-ear stimulation of 0.76 (between subgroups of partial and no recovery), respectively. This study suggested that a dynamic process of central auditory plasticity can be induced by peripheral lesions. The hemispheric asymmetry at the initial stage bears an excellent prognostic potential for the treatment outcomes and hearing level at the fixed stage in ISSNHL. Our study demonstrated that such brain signature of central auditory plasticity in terms of both N100m latency and amplitude at defined time can serve as a prognostication predictor for ISSNHL. Further studies are needed to explore the long-term temporal scenario of auditory hemispheric asymmetry and to get better psychoacoustic correlates of pathological hemispheric asymmetry in ISSNHL.

Co-administration of Cisplatin and Furosemide Causes Rapid and Massive Loss of Cochlear Hair Cells in Mice

The expanding arsenal of transgenic mice has created a powerful tool for investigating the biological mechanisms involved in ototoxicity. However, cisplatin ototoxicity is difficult to investigate in mice because of their small size and vulnerability to death by nephrotoxicity. To overcome this problem, we developed a strategy for promoting cisplatin-induced ototoxicity by coadministration of furosemide a loop diuretic. A dose-response study identified 200mg/kg of furosemide as the optimal dose for disrupting the stria vascularis and opening the blood-ear barrier. Our analysis of stria pathology indicated that the optimal period for administering cisplatin was 1h after furosemide treatment. Combined treatment with 0.5mg/kg of cisplatin and 200mg/kg furosemide resulted in only moderate loss of outer hair cells in the basal 20% of the cochlea, only mild threshold shifts and minimal loss of distortion product otoacoustic emission (DPOAE). In contrast, 1mg/kg of cisplatin plus 200mg/kg of furosemide resulted in a permanent 40-50dB elevation of auditory brainstem response thresholds, almost complete elimination of DPOAE, and nearly total loss of outer hair cells. The widespread outer hair cell lesions that develop in mice treated with cisplatin plus furosemide could serve as extremely useful murine model for investigating techniques for regenerating outer hair cells, studying the mechanisms of cisplatin and furosemide ototoxicity and assessing the perceptual and electrophysiological consequences of outer hair cell loss on central auditory plasticity.

Central Auditory Mechanisms Associated with Cochlear Implantation: An Overview of Selected Studies and Comment

Recently, the evaluation of the role of the central auditory system in the utilization of cochlear implants has received much attention. In order to fully understand the results of cochlear implantation, one must have an understanding of how the brain is influenced by electrical stimulation of the auditory nerve. This review provides an overview of the structure and function of the central auditory nervous system and the changes that occur as a result of cochlear implant use. Evidence of central auditory plasticity is discussed highlighting key imaging and evoked potential studies.

Neural modulation in inferior colliculus and central auditory plasticity

The neural modulation in central auditory system plays an important role in perception and processing of sound signal and auditory cognition. The inferior colliculus (IC) is both a relay station in central auditory pathway and a sub-cortical auditory center doing the sound signal processing. IC is also modulated by the descending projections from the cortex and auditory thalamus, medial geniculate body, and these neural modulations not only can affect ongoing sound signal processing but can also induce plastic changes in IC.

Central auditory plasticity after carboplatin-induced unilateral inner ear damage in the chinchilla: Up-regulation of GAP-43 in the ventral cochlear nucleus

Inner ear damage may lead to structural changes in the central auditory system. In rat and chinchilla, cochlear ablation and noise trauma result in fiber growth and synaptogenesis in the ventral cochlear nucleus (VCN). In this study, we documented the relationship between carboplatin-induced hair cell degeneration and VCN plasticity in the chinchilla. Unilateral application of carboplatin (5 mg/ml) on the round window membrane resulted in massive hair cell loss. Outer hair cell degeneration showed a pronounced basal-to-apical gradient while inner hair cell loss was more equally distributed throughout the cochlea. Expression of the growth associated protein GAP-43, a well-established marker for synaptic plasticity, was up-regulated in the ipsilateral VCN at 15 and 31 days post-carboplatin, but not at 3 and 7 days. In contrast, the dorsal cochlear nucleus showed only little change. In VCN, the high-frequency area dorsally showed slightly yet significantly stronger GAP-43 up-regulation than the low-frequency area ventrally, possibly reflecting the high-to-low frequency gradient of hair cell degeneration. Synaptic modification or formation of new synapses may be a homeostatic process to re-adjust mismatched inputs from two ears. Alternatively, massive fiber growth may represent a deleterious process causing central hyperactivity that leads to loudness recruitment or tinnitus.

The effect of long-term unilateral deafness on the activation pattern in the auditory cortices of French-native speakers: influence of deafness side

BackgroundIn normal-hearing subjects, monaural stimulation produces a normal pattern of asynchrony and asymmetry over the auditory cortices in favour of the contralateral temporal lobe. While late onset unilateral deafness has been reported to change this pattern, the exact influence of the side of deafness on central auditory plasticity still remains unclear. The present study aimed at assessing whether left-sided and right-sided deafness had differential effects on the characteristics of neurophysiological responses over auditory areas. Eighteen unilaterally deaf and 16 normal hearing right-handed subjects participated. All unilaterally deaf subjects had post-lingual deafness. Long latency auditory evoked potentials (late-AEPs) were elicited by two types of stimuli, non-speech (1 kHz tone-burst) and speech-sounds (voiceless syllable/pa/) delivered to the intact ear at 50 dB SL. The latencies and amplitudes of the early exogenous components (N100 and P150) were measured using temporal scalp electrodes.ResultsSubjects with left-sided deafness showed major neurophysiological changes, in the form of a more symmetrical activation pattern over auditory areas in response to non-speech sound and even a significant reversal of the activation pattern in favour of the cortex ipsilateral to the stimulation in response to speech sound. This was observed not only for AEP amplitudes but also for AEP time course. In contrast, no significant changes were reported for late-AEP responses in subjects with right-sided deafness.ConclusionThe results show that cortical reorganization induced by unilateral deafness mainly occurs in subjects with left-sided deafness. This suggests that anatomical and functional plastic changes are more likely to occur in the right than in the left auditory cortex. The possible perceptual correlates of such neurophysiological changes are discussed.

Human central auditory plasticity associated with tone sequence learning.

We investigated learning-related changes in amplitude, scalp topography, and source localization of the mismatch negativity (MMN), a neurophysiological response correlated with auditory discrimination ability. Participants (n = 32) underwent two EEG recordings while they watched silent films and ignored auditory stimuli. Stimuli were a standard (probability = 85%) and two deviant (probability = 7.5% each for high [HD] and low [LD]) eight-tone sequences that differed in the frequency of one tone. Between recordings, subjects practiced discriminating the HD or LD from the standard for 6 min. The amplitude of the LD MMN increased significantly across recordings in both groups, whereas the amplitude of the HD MMN did not. The LD was easier to discriminate than was the HD. Thus, practicing either discrimination increased the MMN for the easier discrimination. Learning and changes in the LD MMN amplitude were highly correlated. Source localizations of event-related potentials (ERPs) to all stimuli revealed bilateral sources in superior temporal regions. Compared with the standard ERP, the LD ERP revealed a stronger source in the left superior temporal region in both recordings, whereas the right-sided source became stronger after learning. Consistent with prior studies of auditory plasticity in animals and humans, tone sequence learning induced rapid neurophysiological plasticity in the human central auditory system. The results also suggest that there is asymmetric hemispheric involvement in tone sequence discrimination learning and that discrimination difficulty influences the time course of learning-related neurophysiological changes.

Enhanced frequency discrimination near the hearing loss cut-off: a consequence of central auditory plasticity induced by cochlear damage?

Patients with steeply sloping hearing losses of cochlear origin may exhibit enhanced difference limens for frequency (DLFs) near the cut-off frequency (Fc) of their hearing loss. This effect has been related to observations in deafened animals of an over-representation of Fc in the primary auditory cortex. However, alternative interpretations in terms of peripheral mechanisms have not been eliminated. In the present study, we assessed the possible role of two peripheral mechanisms [loudness cues and spontaneous otoacoustic emissions (SOAEs)] in a group of patients with high-frequency hearing loss. We tested first whether the DLF enhancement effect was still observed under conditions where subjects could not rely on loudness cues to perform the frequency discrimination task. To achieve this, we adjusted the nominal level of each stimulus so that it fell on an equal loudness contour measured at very fine (1/8 octave) frequency intervals, and we roved the level of each stimulus over a large range (12 dB). Under these conditions, the DLF enhancement was still observed in all patients; this demonstrates that the effect cannot be explained simply by loudness cues. We then screened the patients for SOAEs to test whether the DLF enhancement effect could be explained by the presence of such emissions in the vicinity of the Fc. None of the patients exhibited SOAEs. Finally, we tested whether the patients had cochlear dead regions, i.e. regions lacking functional inner hair cells and/or auditory nerve fibres. Using a refined version of a non-invasive clinical test for the identification of dead regions, we assessed the presence of such regions in fine frequency steps (1/4 octave) up to very high frequencies. All of the patients had cochlear dead regions. The first two findings support the hypothesis that DLF enhancement is due to injury-induced central reorganization in the auditory system. The last one is consistent with neurophysiological data in animals, which suggest that complete deprivation from auditory input at certain cochlear sites may be a necessary condition for the occurrence of injury-induced cortical reorganization.

Central auditory plasticity

Page Ten January 2003 • Vol. 56 • No. 1 It’s January again, and time to put 2002 behind us. As usual, the past year introduced us to some new and interesting personalities. We now know that Vin Diesel is a person, not a truck, SpongeBob could be a sponge, the Rally Monkey probably is a monkey, and Anna Nicole is... Well, we’re still working on that one. In their own ways, our Page Ten personalities for 2002 were equally interesting. My thanks to Ruth Bentler, Theresa Ching, Greg Flamme, Carol Flexer, Richard Gans, Linda Hood, Bob Keith, George Lindley, Brad Stach, and Rick Talbott for their excellent contributions. While the 2002 team will be tough to beat, you’ll be glad to hear that we have another impressive array of guest authors lined up for the new year. We’re leading off 2003 with Kelly Tremblay, PhD, assistant professor at the University of Washington in Seattle and director of the Brain and Behavior Laboratory. You’re probably familiar with Dr. Tremblay’s noted work over the past several years in the area of auditoryrelated brain behavior. Her publication on central auditory plasticity was named Ear and Hearing’s outstanding article of 2001, and her name comes up frequently in The Hearing Journal’s annual Best of Audiology section recognizing exceptional articles from the previous year. She is a regular contributor to Audiology Today, and serves as editorial assistant for several other audiology journals. When she isn’t collecting data, Kelly says she enjoys the outdoors. If you think this simply means a Saturday morning bike ride to the neighborhood Starbucks, think again. One of her recent “outings” was a trek in the Himalayas of Nepal! In her Page Ten article, Dr. Tremblay reviews much of the latest research on central auditory plasticity, and she lends us important insights into the potential clinical applications of this research. Through tests such as the late cortical AEPs, we know that peripheral auditory pathologies can cause changes in brain function. How does this relate to early intervention? To cochlear implant use? To hearing aid use? To hearing aid benefit? Can we use this information to help structure (and individualize) our auditory rehabilitative strategies? Kelly addresses all these questions and more. I think you’ll find this intriguing article an excellent way to start off your audiologic new year!

Hearing after congenital deafness: central auditory plasticity and sensory deprivation.

The congenitally deaf cat suffers from a degeneration of the inner ear. The organ of Corti bears no hair cells, yet the auditory afferents are preserved. Since these animals have no auditory experience, they were used as a model for congenital deafness. Kittens were equipped with a cochlear implant at different ages and electro-stimulated over a period of 2.0-5.5 months using a monopolar single-channel compressed analogue stimulation strategy (VIENNA-type signal processor). Following a period of auditory experience, we investigated cortical field potentials in response to electrical biphasic pulses applied by means of the cochlear implant. In comparison to naive unstimulated deaf cats and normal hearing cats, the chronically stimulated animals showed larger cortical regions producing middle-latency responses at or above 300 microV amplitude at the contralateral as well as the ipsilateral auditory cortex. The cortex ipsilateral to the chronically stimulated ear did not show any signs of reduced responsiveness when stimulating the 'untrained' ear through a second cochlear implant inserted in the final experiment. With comparable duration of auditory training, the activated cortical area was substantially smaller if implantation had been performed at an older age of 5-6 months. The data emphasize that young sensory systems in cats have a higher capacity for plasticity than older ones and that there is a sensitive period for the cat's auditory system.

Central auditory plasticity: changes in the N1-P2 complex after speech-sound training.

To determine whether the N1-P2 complex reflects training-induced changes in neural activity associated with improved voice-onset-time (VOT) perception. Auditory cortical evoked potentials N1 and P2 were obtained from 10 normal-hearing young adults in response to two synthetic speech variants of the syllable /ba/. Using a repeated measures design, subjects were tested before and after training both behaviorally and neurophysiologically to determine whether there were training-related changes. In between pre- and post-testing sessions, subjects were trained to distinguish the -20 and -10 msec VOT /ba/ syllables as being different from each other. Two stimulus presentation rates were used during electrophysiologic testing (390 msec and 910 msec interstimulus interval). Before training, subjects perceived both the -20 msec and -10 msec VOT stimuli as /ba/. Through training, subjects learned to identify the -20 msec VOT stimulus as "mba" and -10 msec VOT stimulus as "ba." As subjects learned to correctly identify the difference between the -20 msec and -10 msec VOT syllabi, an increase in N1-P2 peak-to-peak amplitude was observed. The effects of training were most obvious at the slower stimulus presentation rate. As perception improved, N1-P2 amplitude increased. These changes in waveform morphology are thought to reflect increases in neural synchrony as well as strengthened neural connections associated with improved speech perception. These findings suggest that the N1-P2 complex may have clinical applications as an objective physiologic correlate of speech-sound representation associated with speech-sound training.

Deafferentation-induced changes in protein kinase C expression in the rat cochlear nucleus

Isoforms of the signal transducing molecule, protein kinase C (PKC), may play a role in neural plasticity following sensory deafferentation. To explore the role of PKC in central auditory plasticity, we studied the effect of auditory deafferentation on the expression of PKC βI, βII, γ, and δ in the rat dorsal (DCN) and ventral cochlear nucleus (VCN), using immunocytochemistry. Male rats were treated with kanamycin and furosemide to induce hair cell loss. At various intervals post-treatment, brains were perfusion-fixed and processed for immunocytochemistry. Following deafferentation, we observed a gradual increase in PKC βI immunoreactivity (ir) in the deepest layers of the DCN, possibly representing synapses of primary afferents or parallel fibers on unlabeled neurons. Correlated with this, we observed an increase in the number of neurons in the deep DCN that showed PKC δ ir. In controls, we observed PKC γ ir in small ovoid cells concentrated in the middle layer of the DCN. From days 4 through 14 after deafferentation, we found an increase in the intensity of staining of these cells, with a return toward control levels by day 28. Finally, Purkinje-like cells (PLC) in the VCN, which express only PKC δ in control rats, began to express PKC γ after deafferentation, correlated with increased expression of calbindin D28k in PLC. Thus PKC isoforms are differentially regulated in the CN following deafferentation, supporting a role for PKC in auditory plasticity.