Use of Non-Invasive Measures to Predict Cochlear Synapse Counts

Publication date: Available online 13 October 2018

Source: Hearing Research

Author(s): Naomi F. Bramhall, Garnett P. McMillan, Sharon G. Kujawa, Dawn Konrad-Martin

Abstract

Cochlear synaptopathy, the loss of synaptic connections between inner hair cells and auditory nerve fibers, has been documented in animal models of aging, noise, and ototoxic drug exposure, three common causes of acquired sensorineural hearing loss in humans. In each of these models, synaptopathy begins prior to changes in threshold sensitivity or loss of hair cells; thus, this underlying injury can be hidden behind a normal threshold audiogram. Since cochlear synaptic loss cannot be directly confirmed in living humans, non-invasive assays will be required for diagnosis. In animals with normal auditory thresholds, the amplitude of wave 1 of the auditory brainstem response (ABR) is highly correlated with synapse counts. However, synaptopathy can also co-occur with threshold elevation, complicating the use of the ABR alone as a diagnostic measure. Using an age-graded series of mice and a partial least squares regression approach to model structure-function relationships, this study shows that the combination of a small number of ABR and distortion product otoacoustic emission (DPOAE) measurements can predict synaptic ribbon counts at various cochlear frequencies to within 1-2 synapses per inner hair cell of their true value. In contrast, the model, trained using the age-graded series of mice, overpredicted synapse counts in a small sample of young noise-exposed mice, perhaps due to differences in the underlying pattern of damage between aging and noise-exposed mice. These results provide partial validation of a noninvasive approach to identify synaptic/neuronal loss in humans using ABRs and DPOAEs.

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Use of Non-Invasive Measures to Predict Cochlear Synapse Counts

Publication date: Available online 13 October 2018

Source: Hearing Research

Author(s): Naomi F. Bramhall, Garnett P. McMillan, Sharon G. Kujawa, Dawn Konrad-Martin

Abstract

Cochlear synaptopathy, the loss of synaptic connections between inner hair cells and auditory nerve fibers, has been documented in animal models of aging, noise, and ototoxic drug exposure, three common causes of acquired sensorineural hearing loss in humans. In each of these models, synaptopathy begins prior to changes in threshold sensitivity or loss of hair cells; thus, this underlying injury can be hidden behind a normal threshold audiogram. Since cochlear synaptic loss cannot be directly confirmed in living humans, non-invasive assays will be required for diagnosis. In animals with normal auditory thresholds, the amplitude of wave 1 of the auditory brainstem response (ABR) is highly correlated with synapse counts. However, synaptopathy can also co-occur with threshold elevation, complicating the use of the ABR alone as a diagnostic measure. Using an age-graded series of mice and a partial least squares regression approach to model structure-function relationships, this study shows that the combination of a small number of ABR and distortion product otoacoustic emission (DPOAE) measurements can predict synaptic ribbon counts at various cochlear frequencies to within 1-2 synapses per inner hair cell of their true value. In contrast, the model, trained using the age-graded series of mice, overpredicted synapse counts in a small sample of young noise-exposed mice, perhaps due to differences in the underlying pattern of damage between aging and noise-exposed mice. These results provide partial validation of a noninvasive approach to identify synaptic/neuronal loss in humans using ABRs and DPOAEs.

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Use of Non-Invasive Measures to Predict Cochlear Synapse Counts

Publication date: Available online 13 October 2018

Source: Hearing Research

Author(s): Naomi F. Bramhall, Garnett P. McMillan, Sharon G. Kujawa, Dawn Konrad-Martin

Abstract

Cochlear synaptopathy, the loss of synaptic connections between inner hair cells and auditory nerve fibers, has been documented in animal models of aging, noise, and ototoxic drug exposure, three common causes of acquired sensorineural hearing loss in humans. In each of these models, synaptopathy begins prior to changes in threshold sensitivity or loss of hair cells; thus, this underlying injury can be hidden behind a normal threshold audiogram. Since cochlear synaptic loss cannot be directly confirmed in living humans, non-invasive assays will be required for diagnosis. In animals with normal auditory thresholds, the amplitude of wave 1 of the auditory brainstem response (ABR) is highly correlated with synapse counts. However, synaptopathy can also co-occur with threshold elevation, complicating the use of the ABR alone as a diagnostic measure. Using an age-graded series of mice and a partial least squares regression approach to model structure-function relationships, this study shows that the combination of a small number of ABR and distortion product otoacoustic emission (DPOAE) measurements can predict synaptic ribbon counts at various cochlear frequencies to within 1-2 synapses per inner hair cell of their true value. In contrast, the model, trained using the age-graded series of mice, overpredicted synapse counts in a small sample of young noise-exposed mice, perhaps due to differences in the underlying pattern of damage between aging and noise-exposed mice. These results provide partial validation of a noninvasive approach to identify synaptic/neuronal loss in humans using ABRs and DPOAEs.

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Use of Non-Invasive Measures to Predict Cochlear Synapse Counts

Publication date: Available online 13 October 2018

Source: Hearing Research

Author(s): Naomi F. Bramhall, Garnett P. McMillan, Sharon G. Kujawa, Dawn Konrad-Martin

Abstract

Cochlear synaptopathy, the loss of synaptic connections between inner hair cells and auditory nerve fibers, has been documented in animal models of aging, noise, and ototoxic drug exposure, three common causes of acquired sensorineural hearing loss in humans. In each of these models, synaptopathy begins prior to changes in threshold sensitivity or loss of hair cells; thus, this underlying injury can be hidden behind a normal threshold audiogram. Since cochlear synaptic loss cannot be directly confirmed in living humans, non-invasive assays will be required for diagnosis. In animals with normal auditory thresholds, the amplitude of wave 1 of the auditory brainstem response (ABR) is highly correlated with synapse counts. However, synaptopathy can also co-occur with threshold elevation, complicating the use of the ABR alone as a diagnostic measure. Using an age-graded series of mice and a partial least squares regression approach to model structure-function relationships, this study shows that the combination of a small number of ABR and distortion product otoacoustic emission (DPOAE) measurements can predict synaptic ribbon counts at various cochlear frequencies to within 1-2 synapses per inner hair cell of their true value. In contrast, the model, trained using the age-graded series of mice, overpredicted synapse counts in a small sample of young noise-exposed mice, perhaps due to differences in the underlying pattern of damage between aging and noise-exposed mice. These results provide partial validation of a noninvasive approach to identify synaptic/neuronal loss in humans using ABRs and DPOAEs.

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Kinematic differences between neutral and flat feet with and without symptoms as measured by the Oxford Foot Model

Publication date: Available online 13 October 2018

Source: Gait & Posture

Author(s): C.M. Kerr, A.B. Zavatsky, T. Theologis, J. Stebbins

Abstract

Background

Flatfoot is a common presentation in children. It is usually asymptomatic, though a small number of children experience pain. Foot function during flatfoot walking is rarely considered, yet as an activity that places significant demands on the feet, this could explain the differences in terms of symptoms.

Research Question

This paper investigates walking patterns in neutral and flat feet, with and without symptoms, to determine which kinematic parameters are associated with symptomatic flat feet.

Methods

This is a retrospective study in which one hundred and six children between five and 18 years old were assessed by a physiotherapist for foot posture. Each foot was classified into one of four groups, giving 98 asymptomatic neutral, 47 asymptomatic mild flat, 29 asymptomatic flat, and 38 symptomatic flat feet with complete data for analysis. Using Plug-In-Gait and Oxford-Foot-Model markers, walking kinematics were measured, along with ground reaction forces. Median values of 14 lower limb joint angles were calculated at foot strike, midstance, and foot off. Each foot was treated as an independent sample. ANOVA and ANCOVA (with the speed-related variable relative stride length as the covariate) and post-hoc tests were used to assess whether angles differed between groups.

Results

The symptomatic flat feet showed significant differences from asymptomatic groups (most commonly the neutral feet) in terms of hip flexion, knee flexion and varus, hindfoot inversion-eversion, and forefoot abduction-adduction. Increased forefoot abduction occurred throughout stance phase in symptomatic flatfooted participants compared to all asymptomatic groups.

Significance

The results suggest that foot motion in the transverse plane is closely associated with the presence of symptoms in flat feet and that this is accompanied by changes in the kinematics of the ankle, knee, and hip.

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Kinematic differences between neutral and flat feet with and without symptoms as measured by the Oxford Foot Model

Publication date: Available online 13 October 2018

Source: Gait & Posture

Author(s): C.M. Kerr, A.B. Zavatsky, T. Theologis, J. Stebbins

Abstract

Background

Flatfoot is a common presentation in children. It is usually asymptomatic, though a small number of children experience pain. Foot function during flatfoot walking is rarely considered, yet as an activity that places significant demands on the feet, this could explain the differences in terms of symptoms.

Research Question

This paper investigates walking patterns in neutral and flat feet, with and without symptoms, to determine which kinematic parameters are associated with symptomatic flat feet.

Methods

This is a retrospective study in which one hundred and six children between five and 18 years old were assessed by a physiotherapist for foot posture. Each foot was classified into one of four groups, giving 98 asymptomatic neutral, 47 asymptomatic mild flat, 29 asymptomatic flat, and 38 symptomatic flat feet with complete data for analysis. Using Plug-In-Gait and Oxford-Foot-Model markers, walking kinematics were measured, along with ground reaction forces. Median values of 14 lower limb joint angles were calculated at foot strike, midstance, and foot off. Each foot was treated as an independent sample. ANOVA and ANCOVA (with the speed-related variable relative stride length as the covariate) and post-hoc tests were used to assess whether angles differed between groups.

Results

The symptomatic flat feet showed significant differences from asymptomatic groups (most commonly the neutral feet) in terms of hip flexion, knee flexion and varus, hindfoot inversion-eversion, and forefoot abduction-adduction. Increased forefoot abduction occurred throughout stance phase in symptomatic flatfooted participants compared to all asymptomatic groups.

Significance

The results suggest that foot motion in the transverse plane is closely associated with the presence of symptoms in flat feet and that this is accompanied by changes in the kinematics of the ankle, knee, and hip.

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