NIH Grant to Fund Genetic Hearing Loss Research at University of Miami

​The University of Miami Miller School of Medicine's department of otolaryngology has received a $3 million grant from the National Institutes of Health (NIH) for research on biological treatments and clinical diagnosis of hearing loss. With this new grant, Xue Zhong Liu, MD, PhD, a professor of otolaryngology, human genetics, biochemistry, and pediatrics and the vice chair and Marian & Walter Hotchkiss Chair in Otolaryngology who will spearhead the research as the principal investigator, and his team will expand their genomic and phenotypic deafness database for the clinical care of deaf individuals. They also plan to identify and characterize novel genes for hearing loss using state-of-the-art genomic tools, assess the impact of genomic testing on patients, and conduct preclinical studies of gene- and cell-based therapy approach of CRISPR/Cas9-mediated genome editing to treat hearing loss. Liu said in a press release that recent breakthroughs in genetic screening, gene or cell-based therapeutics, and gene editing for the inner ear can lead to novel therapies for multiple classes of hereditary hearing loss. "Together with our program for genetic hearing loss, these tools and strategies will create a clear path to clinical treatment and accelerate the advent of a new era of personalized medicine for hereditary hearing loss," he said. ​

Published: 8/25/2018 7:56:00 AM

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NIH Grant to Fund Genetic Hearing Loss Research at University of Miami

​The University of Miami Miller School of Medicine's department of otolaryngology has received a $3 million grant from the National Institutes of Health (NIH) for research on biological treatments and clinical diagnosis of hearing loss. With this new grant, Xue Zhong Liu, MD, PhD, a professor of otolaryngology, human genetics, biochemistry, and pediatrics and the vice chair and Marian & Walter Hotchkiss Chair in Otolaryngology who will spearhead the research as the principal investigator, and his team will expand their genomic and phenotypic deafness database for the clinical care of deaf individuals. They also plan to identify and characterize novel genes for hearing loss using state-of-the-art genomic tools, assess the impact of genomic testing on patients, and conduct preclinical studies of gene- and cell-based therapy approach of CRISPR/Cas9-mediated genome editing to treat hearing loss. Liu said in a press release that recent breakthroughs in genetic screening, gene or cell-based therapeutics, and gene editing for the inner ear can lead to novel therapies for multiple classes of hereditary hearing loss. "Together with our program for genetic hearing loss, these tools and strategies will create a clear path to clinical treatment and accelerate the advent of a new era of personalized medicine for hereditary hearing loss," he said. ​

Published: 8/25/2018 7:56:00 AM

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Quantitative Distribution of Choline Acetyltransferase Activity in Rat Trapezoid Body

Publication date: Available online 25 August 2018

Source: Hearing Research

Author(s): Lauren A. Linker, Lissette Carlson, Donald A. Godfrey, Judy A. Parli, C. David Ross

Abstract

There is evidence for a function of acetylcholine in the cochlear nucleus, primarily in a feedback, modulatory effect on auditory processing. Using a microdissection and quantitative microassay approach, choline acetyltransferase activity was mapped in the trapezoid bodies of rats, in which the activity is relatively higher than in cats or hamsters. Maps of series of sections through the trapezoid body demonstrated generally higher choline acetyltransferase activity rostrally than caudally, particularly in its portion ventral to the medial part of the spinal trigeminal tract. In the lateral part of the trapezoid body, near the cochlear nucleus, activities tended to be higher in more superficial portions than in deeper portions. Calculation of choline acetyltransferase activity in the total trapezoid body cross-section of a rat with a comprehensive trapezoid body map gave a value 3-4 times that estimated for the centrifugal labyrinthine bundle, which is mostly composed of the olivocochlear bundle, in the same rat. Comparisons with other rats suggest that the ratio may not usually be this high, but it is still consistent with our previous results suggesting that the centrifugal cholinergic innervation of the rat cochlear nucleus reaching it via a trapezoid body route is much higher than that reaching it via branches from the olivocochlear bundle. The higher choline acetyltransferase activity rostrally than caudally in the trapezoid body is consistent with evidence that the centrifugal cholinergic innervation of the cochlear nucleus derives predominantly from locations at or rostral to its anterior part, in the superior olivary complex and pontomesencephalic tegmentum.

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Musical and vocal emotion perception for cochlear implants users

Publication date: Available online 25 August 2018

Source: Hearing Research

Author(s): S. Paquette, G.D. Ahmed, M.V. Goffi-Gomez, A.C.H. Hoshino, I. Peretz, A. Lehmann

Abstract

Cochlear implants can successfully restore hearing in profoundly deaf individuals and enable speech comprehension. However, the acoustic signal provided is severely degraded and, as a result, many important acoustic cues for perceiving emotion in voices and music are unavailable. The deficit of cochlear implant users in auditory emotion processing has been clearly established. Yet, the extent to which this deficit and the specific cues that remain available to cochlear implant users are unknown due to several confounding factors.

Here we assessed the recognition of the most basic forms of auditory emotion and aimed to identify which acoustic cues are most relevant to recognize emotions through cochlear implants. To do so, we used stimuli that allowed vocal and musical auditory emotions to be comparatively assessed while controlling for confounding factors. These stimuli were used to evaluate emotion perception in cochlear implant users (Experiment 1) and to investigate emotion perception in natural versus cochlear implant hearing in the same participants with a validated cochlear implant simulation approach (Experiment 2).

Our results showed that vocal and musical fear was not accurately recognized by cochlear implant users. Interestingly, both experiments found that timbral acoustic cues (energy and roughness) correlate with participant ratings for both vocal and musical emotion bursts in the cochlear implant simulation condition. This suggests that specific attention should be given to these cues in the design of cochlear implant processors and rehabilitation protocols (especially energy, and roughness). For instance, music-based interventions focused on timbre could improve emotion perception and regulation, and thus improve social functioning, in children with cochlear implants during development.

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Recovery of auditory-nerve-fiber spike amplitude under natural excitation conditions

Publication date: Available online 25 August 2018

Source: Hearing Research

Author(s): Adam J. Peterson, Antoine Huet, Jérôme Bourien, Jean-Luc Puel, Peter Heil

Abstract

Knowledge of the refractory properties of auditory-nerve fibers (ANFs) is required for understanding the transduction of the graded membrane potential of the receptor cells into spike trains. The refractory properties inferred when ANFs are excited by electrical stimulation might differ from those present when ANFs are excited naturally by transmitter release from receptor cells. As a proxy for the latter, we investigated the recovery of spike amplitude with time since the previous spike in long extracellular recordings of the activity of individual ANFs from anesthetized Mongolian gerbils. Voltage traces were filtered minimally to avoid distortions of spike amplitude and timing. The amplitude of each spike was defined as the difference between its peak voltage and an extrapolated instantaneous reference voltage at the time of the peak. Spike amplitude was normalized to that of the previous spike to exclude effects of long-term changes in recording conditions. To ensure that the amplitude of the first spike in each pair was fully recovered, each spike pair was used only when preceded by an interspike interval of at least 5 ms. We find that the recovery of spike amplitude is well described by a short dead time followed by a double-exponential recovery function. Total recovery times were short (median: 0.85 ms; interquartile range: 0.74-1.00 ms) and independent of the ANF's characteristic frequency and spontaneous rate, but they increased weakly with increasing mean rate. We emphasize the differences between the recovery of spike amplitude, the recovery of spike probability from postsynaptic refractoriness, and the recovery of spike probability as reflected in the hazard-rate function. Our findings are inconsistent with the long refractory periods assumed in some models, but are consistent with the brief refractoriness assumed in the synapse model of Peterson and Heil (2018), which reproduces the stochastic properties of stationary spontaneous and sound-driven ANF spike trains.

Graphical abstract

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Quantitative Distribution of Choline Acetyltransferase Activity in Rat Trapezoid Body

Publication date: Available online 25 August 2018

Source: Hearing Research

Author(s): Lauren A. Linker, Lissette Carlson, Donald A. Godfrey, Judy A. Parli, C. David Ross

Abstract

There is evidence for a function of acetylcholine in the cochlear nucleus, primarily in a feedback, modulatory effect on auditory processing. Using a microdissection and quantitative microassay approach, choline acetyltransferase activity was mapped in the trapezoid bodies of rats, in which the activity is relatively higher than in cats or hamsters. Maps of series of sections through the trapezoid body demonstrated generally higher choline acetyltransferase activity rostrally than caudally, particularly in its portion ventral to the medial part of the spinal trigeminal tract. In the lateral part of the trapezoid body, near the cochlear nucleus, activities tended to be higher in more superficial portions than in deeper portions. Calculation of choline acetyltransferase activity in the total trapezoid body cross-section of a rat with a comprehensive trapezoid body map gave a value 3-4 times that estimated for the centrifugal labyrinthine bundle, which is mostly composed of the olivocochlear bundle, in the same rat. Comparisons with other rats suggest that the ratio may not usually be this high, but it is still consistent with our previous results suggesting that the centrifugal cholinergic innervation of the rat cochlear nucleus reaching it via a trapezoid body route is much higher than that reaching it via branches from the olivocochlear bundle. The higher choline acetyltransferase activity rostrally than caudally in the trapezoid body is consistent with evidence that the centrifugal cholinergic innervation of the cochlear nucleus derives predominantly from locations at or rostral to its anterior part, in the superior olivary complex and pontomesencephalic tegmentum.

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Musical and vocal emotion perception for cochlear implants users

Publication date: Available online 25 August 2018

Source: Hearing Research

Author(s): S. Paquette, G.D. Ahmed, M.V. Goffi-Gomez, A.C.H. Hoshino, I. Peretz, A. Lehmann

Abstract

Cochlear implants can successfully restore hearing in profoundly deaf individuals and enable speech comprehension. However, the acoustic signal provided is severely degraded and, as a result, many important acoustic cues for perceiving emotion in voices and music are unavailable. The deficit of cochlear implant users in auditory emotion processing has been clearly established. Yet, the extent to which this deficit and the specific cues that remain available to cochlear implant users are unknown due to several confounding factors.

Here we assessed the recognition of the most basic forms of auditory emotion and aimed to identify which acoustic cues are most relevant to recognize emotions through cochlear implants. To do so, we used stimuli that allowed vocal and musical auditory emotions to be comparatively assessed while controlling for confounding factors. These stimuli were used to evaluate emotion perception in cochlear implant users (Experiment 1) and to investigate emotion perception in natural versus cochlear implant hearing in the same participants with a validated cochlear implant simulation approach (Experiment 2).

Our results showed that vocal and musical fear was not accurately recognized by cochlear implant users. Interestingly, both experiments found that timbral acoustic cues (energy and roughness) correlate with participant ratings for both vocal and musical emotion bursts in the cochlear implant simulation condition. This suggests that specific attention should be given to these cues in the design of cochlear implant processors and rehabilitation protocols (especially energy, and roughness). For instance, music-based interventions focused on timbre could improve emotion perception and regulation, and thus improve social functioning, in children with cochlear implants during development.

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Recovery of auditory-nerve-fiber spike amplitude under natural excitation conditions

Publication date: Available online 25 August 2018

Source: Hearing Research

Author(s): Adam J. Peterson, Antoine Huet, Jérôme Bourien, Jean-Luc Puel, Peter Heil

Abstract

Knowledge of the refractory properties of auditory-nerve fibers (ANFs) is required for understanding the transduction of the graded membrane potential of the receptor cells into spike trains. The refractory properties inferred when ANFs are excited by electrical stimulation might differ from those present when ANFs are excited naturally by transmitter release from receptor cells. As a proxy for the latter, we investigated the recovery of spike amplitude with time since the previous spike in long extracellular recordings of the activity of individual ANFs from anesthetized Mongolian gerbils. Voltage traces were filtered minimally to avoid distortions of spike amplitude and timing. The amplitude of each spike was defined as the difference between its peak voltage and an extrapolated instantaneous reference voltage at the time of the peak. Spike amplitude was normalized to that of the previous spike to exclude effects of long-term changes in recording conditions. To ensure that the amplitude of the first spike in each pair was fully recovered, each spike pair was used only when preceded by an interspike interval of at least 5 ms. We find that the recovery of spike amplitude is well described by a short dead time followed by a double-exponential recovery function. Total recovery times were short (median: 0.85 ms; interquartile range: 0.74-1.00 ms) and independent of the ANF's characteristic frequency and spontaneous rate, but they increased weakly with increasing mean rate. We emphasize the differences between the recovery of spike amplitude, the recovery of spike probability from postsynaptic refractoriness, and the recovery of spike probability as reflected in the hazard-rate function. Our findings are inconsistent with the long refractory periods assumed in some models, but are consistent with the brief refractoriness assumed in the synapse model of Peterson and Heil (2018), which reproduces the stochastic properties of stationary spontaneous and sound-driven ANF spike trains.

Graphical abstract

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Objective Comparison of the Quality and Reliability of Auditory Brainstem Response Features Elicited by Click and Speech Sounds.

Objective Comparison of the Quality and Reliability of Auditory Brainstem Response Features Elicited by Click and Speech Sounds.

Ear Hear. 2018 Aug 23;:

Authors: Novis K, Bell S

Abstract
OBJECTIVES: Auditory brainstem responses (ABRs) are commonly generated using simple, transient stimuli (e.g., clicks or tone bursts). While resulting waveforms are undeniably valuable clinical tools, they are unlikely to be representative of responses to more complex, behaviorally relevant sounds such as speech. There has been interest in the use of more complex stimuli to elicit the ABR, with considerable work focusing on the use of synthetically generated consonant-vowel (CV) stimuli. Such responses may be sensitive to a range of clinical conditions and to the effects of auditory training. Several ABR features have been documented in response to CV stimuli; however, an important issue is how robust such features are. In the current research, we use time- and frequency-domain objective measures of quality to compare the reliability of Wave V of the click-evoked ABR to that of waves elicited by the CV stimulus /da/.
DESIGN: Stimuli were presented to 16 subjects at 70 dB nHL in quiet for 6000 epochs. The presence and quality of response features across subjects were examined using Fsp and a Bootstrap analysis method, which was used to assign p values to ABR features for individual recordings in both time and frequency domains.
RESULTS: All consistent peaks identified within the /da/-evoked response had significantly lower amplitude than Wave V of the ABR. The morphology of speech-evoked waveforms varied across subjects. Mean Fsp values for several waves of the speech-evoked ABR were below 3, suggesting low quality. The most robust response to the /da/ stimulus appeared to be an offset response. Only click-evoked Wave V showed 100% wave presence. Responses to the /da/ stimulus showed lower wave detectability. Frequency-domain analysis showed stronger and more consistent activity evoked by clicks than by /da/. Only the click ABR had consistent time-frequency domain features across all subjects.
CONCLUSIONS: Based on the objective analysis used within this investigation, it appears that the quality of speech-evoked ABR is generally less than that of click-evoked responses, although the quality of responses may be improved by increasing the number of epochs or the stimulation level. This may have implications for the clinical use of speech-evoked ABR.

PMID: 30142101 [PubMed - as supplied by publisher]

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Objective Comparison of the Quality and Reliability of Auditory Brainstem Response Features Elicited by Click and Speech Sounds.

Objective Comparison of the Quality and Reliability of Auditory Brainstem Response Features Elicited by Click and Speech Sounds.

Ear Hear. 2018 Aug 23;:

Authors: Novis K, Bell S

Abstract
OBJECTIVES: Auditory brainstem responses (ABRs) are commonly generated using simple, transient stimuli (e.g., clicks or tone bursts). While resulting waveforms are undeniably valuable clinical tools, they are unlikely to be representative of responses to more complex, behaviorally relevant sounds such as speech. There has been interest in the use of more complex stimuli to elicit the ABR, with considerable work focusing on the use of synthetically generated consonant-vowel (CV) stimuli. Such responses may be sensitive to a range of clinical conditions and to the effects of auditory training. Several ABR features have been documented in response to CV stimuli; however, an important issue is how robust such features are. In the current research, we use time- and frequency-domain objective measures of quality to compare the reliability of Wave V of the click-evoked ABR to that of waves elicited by the CV stimulus /da/.
DESIGN: Stimuli were presented to 16 subjects at 70 dB nHL in quiet for 6000 epochs. The presence and quality of response features across subjects were examined using Fsp and a Bootstrap analysis method, which was used to assign p values to ABR features for individual recordings in both time and frequency domains.
RESULTS: All consistent peaks identified within the /da/-evoked response had significantly lower amplitude than Wave V of the ABR. The morphology of speech-evoked waveforms varied across subjects. Mean Fsp values for several waves of the speech-evoked ABR were below 3, suggesting low quality. The most robust response to the /da/ stimulus appeared to be an offset response. Only click-evoked Wave V showed 100% wave presence. Responses to the /da/ stimulus showed lower wave detectability. Frequency-domain analysis showed stronger and more consistent activity evoked by clicks than by /da/. Only the click ABR had consistent time-frequency domain features across all subjects.
CONCLUSIONS: Based on the objective analysis used within this investigation, it appears that the quality of speech-evoked ABR is generally less than that of click-evoked responses, although the quality of responses may be improved by increasing the number of epochs or the stimulation level. This may have implications for the clinical use of speech-evoked ABR.

PMID: 30142101 [PubMed - as supplied by publisher]

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