Frequency-dependent fine structure in the frequency-following response: The byproduct of multiple generators

Publication date: Available online 28 January 2017
Source:Hearing Research
Author(s): Parker Tichko, Erika Skoe
The frequency-following response (FFR) is an auditory-evoked response recorded at the scalp that captures the spectrotemporal properties of tonal stimuli. Previous investigations report that the amplitude of the FFR fluctuates as a function of stimulus frequency, a phenomenon thought to reflect multiple neural generators phase-locking to the stimulus with different response latencies. When phase-locked responses are offset by different latencies, constructive and destructive phase interferences emerge in the volume-conducted signals, culminating in an attenuation or amplification of the scalp-recorded response in a frequency-specific manner. Borrowing from the literature on the audiogram and otoacoustic emissions (OAEs), we refer to this frequency-specific waxing and waning of the FFR amplitude as fine structure. While prior work on the human FFR was limited by small sets of stimulus frequencies, here, we provide the first systematic investigation of FFR fine structure using a broad stimulus set (90+ frequencies) that spanned the limits of human pitch perception. Consistent with predictions, the magnitude of the FFR response varied systematically as a function of stimulus frequency between 16.35-880 Hz. In our dataset, FFR high points (local maxima) emerged at ∼44, 87, 208, and 415 Hz with FFR valleys (local minima) emerging ∼62, 110, 311, and 448 Hz. To investigate whether these amplitude fluctuations are the result of multiple neural generators with distinct latencies, we created a theoretical model of the FFR that included six putative generators. Based on the extant literature on the sources of the FFR, our model adopted latencies characteristic of the cochlear microphonic (0 ms), cochlear nucleus (∼1.25 ms), superior olive (∼3.7 ms), and inferior colliculus (∼5 ms). In addition, we included two longer latency putative generators (∼13 ms, and ∼25 ms) reflective of the characteristic latencies of primary and non-primary auditory cortical structures. Our model revealed that the FFR fine structure observed between 16.35-880 Hz can be explained by the phase-interaction patterns created by six generators with relative latencies spaced between 0-25 ms. In addition, our model provides confirmatory evidence that both subcortical and cortical structures are activated by low-frequency (< 100 Hz) tones, with the cortex being less sensitive to frequencies > 100 Hz. Collectively, these findings highlight (1) that the FFR is a composite response; (2) that the FFR at any given frequency can reflect activity from multiple generators; (3) that the fine-structure pattern between 16.35-880 Hz is the collective outcome of short- and long-latency generators; (4) that FFR fine structure is epiphenomenal in that it reflects how volume-conducted electrical potentials originating from different sources with different latencies interact at scalp locations, not how these different sources actually interact in the brain; and (5) that as a byproduct of these phase-interaction patterns low-amplitude responses will emerge at some frequencies, even when the underlying generators are fully functioning. We believe these findings call for a re-examination of how FFR amplitude is interpreted in both clinical and experimental contexts.



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Frequency-dependent fine structure in the frequency-following response: The byproduct of multiple generators

Publication date: Available online 28 January 2017
Source:Hearing Research
Author(s): Parker Tichko, Erika Skoe
The frequency-following response (FFR) is an auditory-evoked response recorded at the scalp that captures the spectrotemporal properties of tonal stimuli. Previous investigations report that the amplitude of the FFR fluctuates as a function of stimulus frequency, a phenomenon thought to reflect multiple neural generators phase-locking to the stimulus with different response latencies. When phase-locked responses are offset by different latencies, constructive and destructive phase interferences emerge in the volume-conducted signals, culminating in an attenuation or amplification of the scalp-recorded response in a frequency-specific manner. Borrowing from the literature on the audiogram and otoacoustic emissions (OAEs), we refer to this frequency-specific waxing and waning of the FFR amplitude as fine structure. While prior work on the human FFR was limited by small sets of stimulus frequencies, here, we provide the first systematic investigation of FFR fine structure using a broad stimulus set (90+ frequencies) that spanned the limits of human pitch perception. Consistent with predictions, the magnitude of the FFR response varied systematically as a function of stimulus frequency between 16.35-880 Hz. In our dataset, FFR high points (local maxima) emerged at ∼44, 87, 208, and 415 Hz with FFR valleys (local minima) emerging ∼62, 110, 311, and 448 Hz. To investigate whether these amplitude fluctuations are the result of multiple neural generators with distinct latencies, we created a theoretical model of the FFR that included six putative generators. Based on the extant literature on the sources of the FFR, our model adopted latencies characteristic of the cochlear microphonic (0 ms), cochlear nucleus (∼1.25 ms), superior olive (∼3.7 ms), and inferior colliculus (∼5 ms). In addition, we included two longer latency putative generators (∼13 ms, and ∼25 ms) reflective of the characteristic latencies of primary and non-primary auditory cortical structures. Our model revealed that the FFR fine structure observed between 16.35-880 Hz can be explained by the phase-interaction patterns created by six generators with relative latencies spaced between 0-25 ms. In addition, our model provides confirmatory evidence that both subcortical and cortical structures are activated by low-frequency (< 100 Hz) tones, with the cortex being less sensitive to frequencies > 100 Hz. Collectively, these findings highlight (1) that the FFR is a composite response; (2) that the FFR at any given frequency can reflect activity from multiple generators; (3) that the fine-structure pattern between 16.35-880 Hz is the collective outcome of short- and long-latency generators; (4) that FFR fine structure is epiphenomenal in that it reflects how volume-conducted electrical potentials originating from different sources with different latencies interact at scalp locations, not how these different sources actually interact in the brain; and (5) that as a byproduct of these phase-interaction patterns low-amplitude responses will emerge at some frequencies, even when the underlying generators are fully functioning. We believe these findings call for a re-examination of how FFR amplitude is interpreted in both clinical and experimental contexts.



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Frequency-dependent fine structure in the frequency-following response: The byproduct of multiple generators

Publication date: Available online 28 January 2017
Source:Hearing Research
Author(s): Parker Tichko, Erika Skoe
The frequency-following response (FFR) is an auditory-evoked response recorded at the scalp that captures the spectrotemporal properties of tonal stimuli. Previous investigations report that the amplitude of the FFR fluctuates as a function of stimulus frequency, a phenomenon thought to reflect multiple neural generators phase-locking to the stimulus with different response latencies. When phase-locked responses are offset by different latencies, constructive and destructive phase interferences emerge in the volume-conducted signals, culminating in an attenuation or amplification of the scalp-recorded response in a frequency-specific manner. Borrowing from the literature on the audiogram and otoacoustic emissions (OAEs), we refer to this frequency-specific waxing and waning of the FFR amplitude as fine structure. While prior work on the human FFR was limited by small sets of stimulus frequencies, here, we provide the first systematic investigation of FFR fine structure using a broad stimulus set (90+ frequencies) that spanned the limits of human pitch perception. Consistent with predictions, the magnitude of the FFR response varied systematically as a function of stimulus frequency between 16.35-880 Hz. In our dataset, FFR high points (local maxima) emerged at ∼44, 87, 208, and 415 Hz with FFR valleys (local minima) emerging ∼62, 110, 311, and 448 Hz. To investigate whether these amplitude fluctuations are the result of multiple neural generators with distinct latencies, we created a theoretical model of the FFR that included six putative generators. Based on the extant literature on the sources of the FFR, our model adopted latencies characteristic of the cochlear microphonic (0 ms), cochlear nucleus (∼1.25 ms), superior olive (∼3.7 ms), and inferior colliculus (∼5 ms). In addition, we included two longer latency putative generators (∼13 ms, and ∼25 ms) reflective of the characteristic latencies of primary and non-primary auditory cortical structures. Our model revealed that the FFR fine structure observed between 16.35-880 Hz can be explained by the phase-interaction patterns created by six generators with relative latencies spaced between 0-25 ms. In addition, our model provides confirmatory evidence that both subcortical and cortical structures are activated by low-frequency (< 100 Hz) tones, with the cortex being less sensitive to frequencies > 100 Hz. Collectively, these findings highlight (1) that the FFR is a composite response; (2) that the FFR at any given frequency can reflect activity from multiple generators; (3) that the fine-structure pattern between 16.35-880 Hz is the collective outcome of short- and long-latency generators; (4) that FFR fine structure is epiphenomenal in that it reflects how volume-conducted electrical potentials originating from different sources with different latencies interact at scalp locations, not how these different sources actually interact in the brain; and (5) that as a byproduct of these phase-interaction patterns low-amplitude responses will emerge at some frequencies, even when the underlying generators are fully functioning. We believe these findings call for a re-examination of how FFR amplitude is interpreted in both clinical and experimental contexts.



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Frequency-dependent fine structure in the frequency-following response: The byproduct of multiple generators

Publication date: Available online 28 January 2017
Source:Hearing Research
Author(s): Parker Tichko, Erika Skoe
The frequency-following response (FFR) is an auditory-evoked response recorded at the scalp that captures the spectrotemporal properties of tonal stimuli. Previous investigations report that the amplitude of the FFR fluctuates as a function of stimulus frequency, a phenomenon thought to reflect multiple neural generators phase-locking to the stimulus with different response latencies. When phase-locked responses are offset by different latencies, constructive and destructive phase interferences emerge in the volume-conducted signals, culminating in an attenuation or amplification of the scalp-recorded response in a frequency-specific manner. Borrowing from the literature on the audiogram and otoacoustic emissions (OAEs), we refer to this frequency-specific waxing and waning of the FFR amplitude as fine structure. While prior work on the human FFR was limited by small sets of stimulus frequencies, here, we provide the first systematic investigation of FFR fine structure using a broad stimulus set (90+ frequencies) that spanned the limits of human pitch perception. Consistent with predictions, the magnitude of the FFR response varied systematically as a function of stimulus frequency between 16.35-880 Hz. In our dataset, FFR high points (local maxima) emerged at ∼44, 87, 208, and 415 Hz with FFR valleys (local minima) emerging ∼62, 110, 311, and 448 Hz. To investigate whether these amplitude fluctuations are the result of multiple neural generators with distinct latencies, we created a theoretical model of the FFR that included six putative generators. Based on the extant literature on the sources of the FFR, our model adopted latencies characteristic of the cochlear microphonic (0 ms), cochlear nucleus (∼1.25 ms), superior olive (∼3.7 ms), and inferior colliculus (∼5 ms). In addition, we included two longer latency putative generators (∼13 ms, and ∼25 ms) reflective of the characteristic latencies of primary and non-primary auditory cortical structures. Our model revealed that the FFR fine structure observed between 16.35-880 Hz can be explained by the phase-interaction patterns created by six generators with relative latencies spaced between 0-25 ms. In addition, our model provides confirmatory evidence that both subcortical and cortical structures are activated by low-frequency (< 100 Hz) tones, with the cortex being less sensitive to frequencies > 100 Hz. Collectively, these findings highlight (1) that the FFR is a composite response; (2) that the FFR at any given frequency can reflect activity from multiple generators; (3) that the fine-structure pattern between 16.35-880 Hz is the collective outcome of short- and long-latency generators; (4) that FFR fine structure is epiphenomenal in that it reflects how volume-conducted electrical potentials originating from different sources with different latencies interact at scalp locations, not how these different sources actually interact in the brain; and (5) that as a byproduct of these phase-interaction patterns low-amplitude responses will emerge at some frequencies, even when the underlying generators are fully functioning. We believe these findings call for a re-examination of how FFR amplitude is interpreted in both clinical and experimental contexts.



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Frequency-dependent fine structure in the frequency-following response: The byproduct of multiple generators

Publication date: Available online 28 January 2017
Source:Hearing Research
Author(s): Parker Tichko, Erika Skoe
The frequency-following response (FFR) is an auditory-evoked response recorded at the scalp that captures the spectrotemporal properties of tonal stimuli. Previous investigations report that the amplitude of the FFR fluctuates as a function of stimulus frequency, a phenomenon thought to reflect multiple neural generators phase-locking to the stimulus with different response latencies. When phase-locked responses are offset by different latencies, constructive and destructive phase interferences emerge in the volume-conducted signals, culminating in an attenuation or amplification of the scalp-recorded response in a frequency-specific manner. Borrowing from the literature on the audiogram and otoacoustic emissions (OAEs), we refer to this frequency-specific waxing and waning of the FFR amplitude as fine structure. While prior work on the human FFR was limited by small sets of stimulus frequencies, here, we provide the first systematic investigation of FFR fine structure using a broad stimulus set (90+ frequencies) that spanned the limits of human pitch perception. Consistent with predictions, the magnitude of the FFR response varied systematically as a function of stimulus frequency between 16.35-880 Hz. In our dataset, FFR high points (local maxima) emerged at ∼44, 87, 208, and 415 Hz with FFR valleys (local minima) emerging ∼62, 110, 311, and 448 Hz. To investigate whether these amplitude fluctuations are the result of multiple neural generators with distinct latencies, we created a theoretical model of the FFR that included six putative generators. Based on the extant literature on the sources of the FFR, our model adopted latencies characteristic of the cochlear microphonic (0 ms), cochlear nucleus (∼1.25 ms), superior olive (∼3.7 ms), and inferior colliculus (∼5 ms). In addition, we included two longer latency putative generators (∼13 ms, and ∼25 ms) reflective of the characteristic latencies of primary and non-primary auditory cortical structures. Our model revealed that the FFR fine structure observed between 16.35-880 Hz can be explained by the phase-interaction patterns created by six generators with relative latencies spaced between 0-25 ms. In addition, our model provides confirmatory evidence that both subcortical and cortical structures are activated by low-frequency (< 100 Hz) tones, with the cortex being less sensitive to frequencies > 100 Hz. Collectively, these findings highlight (1) that the FFR is a composite response; (2) that the FFR at any given frequency can reflect activity from multiple generators; (3) that the fine-structure pattern between 16.35-880 Hz is the collective outcome of short- and long-latency generators; (4) that FFR fine structure is epiphenomenal in that it reflects how volume-conducted electrical potentials originating from different sources with different latencies interact at scalp locations, not how these different sources actually interact in the brain; and (5) that as a byproduct of these phase-interaction patterns low-amplitude responses will emerge at some frequencies, even when the underlying generators are fully functioning. We believe these findings call for a re-examination of how FFR amplitude is interpreted in both clinical and experimental contexts.



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A de novo deletion mutation in SOX10 in a Chinese family with Waardenburg syndrome type 4.

A de novo deletion mutation in SOX10 in a Chinese family with Waardenburg syndrome type 4.

Sci Rep. 2017 Jan 27;7:41513

Authors: Wang X, Zhu Y, Shen N, Peng J, Wang C, Liu H, Lu Y

Abstract
Waardenburg syndrome type 4 (WS4) or Waardenburg-Shah syndrome is a rare genetic disorder with a prevalence of <1/1,000,000 and characterized by the association of congenital sensorineural hearing loss, pigmentary abnormalities, and intestinal aganglionosis. There are three types of WS4 (WS4A-C) caused by mutations in endothelin receptor type B, endothelin 3, and SRY-box 10 (SOX10), respectively. This study investigated a genetic mutation in a Chinese family with one WS4 patient in order to improve genetic counselling. Genomic DNA was extracted, and mutation analysis of the three WS4 related genes was performed using Sanger sequencing. We detected a de novo heterozygous deletion mutation [c.1333delT (p.Ser445Glnfs*57)] in SOX10 in the patient; however, this mutation was absent in the unaffected parents and 40 ethnicity matched healthy controls. Subsequent phylogenetic analysis and three-dimensional modelling of the SOX10 protein confirmed that the c.1333delT heterozygous mutation was pathogenic, indicating that this mutation might constitute a candidate disease-causing mutation.

PMID: 28128317 [PubMed - in process]

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