WO2024151894A1 - Rapid assessment of temporal processing, such as from the peripheral and central auditory pathway, using dynamic amplitude modulated stimuli - Google Patents

Abstract

A method of assessing the temporal processing of an individual includes generating and providing to the individual through a sound generation apparatus a dAM tone, receiving a number of electroencephalogram (EEG) signals measured from the individual in response to the dAM tone, determining an envelope following response (EFR) signal from the number of EEG signals, and estimating a temporal modulation transfer function (tMTF) based on the EFR signal using a spectrally specific analysis scheme. A system including a controller implements the described method.

Description

RAPID ASSESSMENT OF TEMPORAL PROCESSING, SUCH AS FROM THE PERIPHERAL AND CENTRAL AUDITORY PATHWAY, USING DYNAMIC AMPLITUDE MODULATED STIMULI CROSS REFERENCE TO RELATED APPLICATIONS: [0001] This application claims priority to U.S. Provisional Patent Application Serial No. 63/479,768, filed on January 13, 2023 and titled “Rapid Assessment of Temporal Processing, Such as From The Peripheral and Central Auditory Pathway, Using Dynamic Amplitude Modulated Stimuli,” the disclosure of which is incorporated herein by reference. STATEMENT OF GOVERNMENT INTEREST: [0002] This invention was made with government support under grant # W81XWH-21-1-0602 awarded by the ARMY/MRMC. The government has certain rights in the invention. FIELD OF THE INVENTION: [0003] The present invention pertains to the assessment of the temporal processing of an individual, such as temporal processing associated with hearing (e.g., from the peripheral and central auditory pathways of the brain), and, in particular, to a system and method of assessing such temporal processing of an individual using dynamically varying amplitude modulated tones, electroencephalogram (EEG) signals obtained from the individual in response to the tone(s), and a specially designed spectrally specific analysis scheme. BACKGROUND OF THE INVENTION: [0004] Perception of speech and other natural sounds critically depends on the auditory system’s ability to encode temporal cues, such as the envelope and fine structure, which convey complementary information present in sounds. Neural coding deficits of either cue can result in sustained auditory perceptual deficits. However, current clinical hearing tests, e.g., pure-tone audiograms, are not designed to capture these suprathreshold neural coding deficits, but instead focus primarily on near-threshold cochlear function and hearing sensitivity. Approximately one in ten patients seeking hearing health care have complaints of hearing in noise, despite normal audiometric thresholds. This unmet medical need, which remains “hidden” from the clinical gold standard (i.e., the audiogram), necessitates the development of the next generation of clinical tests of hearing fidelity. [0005] Current clinical practices use the auditory brainstem response (ABR), which aims to objectively assess hearing thresholds, as well as the relative strength of peripheral-versus-cortical generators (e.g., using wave V/I ratio) when ABR peaks are resolved and analyzed, but not the fidelity of temporal coding. The ABR is dominated by the onset component of the neural responses, whereas envelope cues are primarily encoded by sustained synchronized neural responses not captured by the ABR. In contrast, the frequency-following response (FFR) primarily reflects sustained neural responses and has rapidly gained prominence in research to assess the neural coding of spectrotemporally complex sounds, such as speech. However, these complex-FFRs lose specificity about neural generators because these generator-specific responses get smeared because of their temporal overlap. [0006] A good middle ground can be the envelope following response (EFR), which represents the polarity-tolerant (carrier-insensitive) component of FFRs to the envelope of amplitude-modulated (AM) tones. The ability of neurons to follow (or phase-lock to) the temporal envelope is biophysically constrained, such that while the auditory nerve can phase-lock to rates > 1500 Hz, neurons in the auditory cortex can phase-lock up to ~80 Hz. Thus, by changing the characteristics of the amplitude envelope, cortical, midbrain and brainstem generators can be emphasized. The EFR has been used as an objective neural correlate of perceptual performances in normal-hearing populations, e.g., to explain individual variability in AM perception, or the effect of language or musical training on temporal coding and perception. In addition, the subcortical versus cortical signatures of AM vary across hearing loss etiologies. For example, the EFR has been used to understand AM coding changes due to age-related, permanent, and noise-induced overt and “hidden” hearing loss. [0007] Despite its efficacy, EFRs are rarely used in the clinic. This is primarily because current practices involve collecting EFRs serially for each AM frequency, which is time consuming. Previous attempts to speed up data collection involves multiplexing multiple carrier- and AM-frequency combinations, and multiband harmonic complexes (with different AM frequency in different carrier bands). However, EFRs responses to such simultaneous stimulus presentations can be affected by cross-frequency auditory processing and other nonlinearities, which are irrelevant to AM processing. SUMMARY OF THE INVENTION: [0008] In one embodiment, a method of assessing the temporal processing of an individual is provided. Th method includes generating and providing to the individual through a sound generation apparatus a dynamically amplitude modulated (dAM) tone, receiving a number of electroencephalogram (EEG) signals measured from the individual in response to the dAM tone, determining an envelope following response (EFR) signal from the number of EEG signals, and estimating a temporal modulation transfer function (tMTF) and, optionally, other measures of temporal processing, based on the EFR signal using a spectrally specific analysis scheme. The tMTF may be used to diagnose and treat a hearing problem of the individual. [0009] In another embodiment, a temporal processing assessment system is provided that includes a sound generation apparatus, an EEG apparatus, and a controller coupled to the sound generation apparatus and the EEG apparatus. The controller is structured and configured to: (i) cause the sound generation apparatus to output a dAM tone to an individual, (ii) receive a number of electroencephalogram (EEG) signals from the EEG apparatus, wherein the number of EEG signals are measured from the individual in response to the dAM tone; (iii) determine an envelope following response (EFR) signal from the number of EEG signals, and (iv) estimate a temporal modulation transfer function (tMTF) and, optionally, other measures of temporal processing, based on the EFR signal. BRIEF DESCRIPTION OF THE DRAWINGS: [0010] A full understanding of the invention can be gained from the following description of the preferred embodiments when read in conjunction with the accompanying drawings in which: [0011] FIG. 1 schematically illustrates a prior art sinusoidally amplitude modulated (SAM) tone; [0012] FIG. 2 schematically illustrates a dAM tone according to an exemplary embodiment of the disclosed concept; [0013] FIG. 3 schematically illustrates an EEG processing and analysis method according to an exemplary embodiment of the disclosed concept; [0014] FIG. 4 is a block diagram of a temporal processing assessment system according to a non-limiting exemplary embodiment of the disclosed concept; [0015] FIG. 5 is a block diagram of a computing device of the system of FIG. 4; and [0016] FIG. 6 is a block diagram of an exemplary EEG cap that may be employed in connection with the disclosed concept. DETAILED DESCRIPTION OF THE INVENTION: [0017] As used herein, the singular form of “a”, “an”, and “the” include plural references unless the context clearly dictates otherwise. [0018] As used herein, the statement that two or more parts or components are “coupled” shall mean that the parts are joined or operate together either directly or indirectly, i.e., through one or more intermediate parts or components, so long as a link occurs. [0019] As used herein, the term “number” shall mean one or an integer greater than one (i.e., a plurality). [0020] As used herein, the term “controller” shall mean a programmable analog and/or digital device (including an associated memory part or portion) that can store, retrieve, execute and process data (e.g., software routines and/or information used by such routines), including, without limitation, a field programmable gate array (FPGA), a complex programmable logic device (CPLD), a programmable system on a chip (PSOC), an application specific integrated circuit (ASIC), a microprocessor, a microcontroller, a programmable logic controller, or any other suitable processing device or apparatus. The memory portion can be any one or more of a variety of types of internal and/or external storage media such as, without limitation, RAM, ROM, EPROM(s), EEPROM(s), FLASH, and the like that provide a storage register, i.e., a non-transitory machine readable medium, for data and program code storage such as in the fashion of an internal storage area of a computer, and can be volatile memory or nonvolatile memory. [0021] As used herein, the terms “component” and “system” are intended to refer to a computer related entity, either hardware, a combination of hardware and software, software, or software in execution. For example, a component can be, but is not limited to being, a process running on a processor, a processor, an object, an executable, a thread of execution, a program, and/or a computer. By way of illustration, both an application running on a server and the server can be a component. One or more components can reside within a process and/or thread of execution, and a component can be localized on one computer and/or distributed between two or more computers. [0022] As used herein, the term “dynamically varying AM (dAM) stimulus or tone” shall mean a tone or noise carrier of varying frequencies or bandwidths that are amplitude modulated in a manner that is progressively changing with time. [0023] Directional phrases used herein, such as, for example and without limitation, top, bottom, left, right, upper, lower, front, back, and derivatives thereof, relate to the orientation of the elements shown in the drawings and are not limiting upon the claims unless expressly recited therein. [0024] The disclosed concept will now be described, for purposes of explanation, in connection with numerous specific details in order to provide a thorough understanding of the disclosed concept. It will be evident, however, that the disclosed concept can be practiced without these specific details without departing from the spirit and scope of this innovation. [0025] As described in detail herein, the disclosed concept provides a new approach to efficiently assess neural AM coding using EFRs, which has been validated by the present inventors in four different species (humans, gerbils, rats, and mice). More specifically, the disclosed concept uses non-invasive EEG responses to a custom-designed sound to assess the temporal processing of an individual, in particular from the peripheral and central auditory pathway in the exemplary embodiment. The approach of the disclosed concept uses a dynamically varying AM (dAM) stimulus and the EEG responses thereto (comprising robust high-SNR EFRs) in combination with spectrally specific analyses to assess the temporal processing of an individual, in particular from the peripheral and central auditory pathway in the exemplary embodiment. The dAM stimulus uses dynamic AM that varies continuously across AM frequencies (e.g., 16-1500 Hz over 1 s, with an overall range of 0-5000 Hz to encompass the temporal processing range of most species), and therefore allows for a richer estimation of EFRs with continuously sampled AM frequency. Estimating EFRs using the dAM stimulus of the disclosed concept is more time efficient (approximately 5x faster) than prior art techniques that use sinusoidally amplitude modulated (SAM) stimuli. These dAM-stimuli-elicited EFRs are analyzed using spectrally specific tools, which provide optimal spectro-temporal resolution compared to traditional signal-processing metrics such as windowed fast Fourier transforms. The resultant EFR-metrics are highly similar to traditional EFR- metrics derived using discrete SAM stimuli. These results highlight the efficacy of the dAM-stimuli-derived EFRs of the disclosed concept to assess temporal coding by the auditory system, and open up the possibility of adding EFRs to the battery of standard battery tests in the audiology clinic. [0026] As noted elsewhere herein, neural phase-locking to the stimulus amplitude envelope has been typically probed using discrete sinusoidally amplitude modulated (SAM) tones, where both the modulator (fm) and the carrier (fc) are sinusoids (i.e., the frequency is stationary). This is illustrated in FIG. 1, which shows a SAM tone time domain waveform over 1 second at reference numeral 5, the SAM tone and its Hilbert envelope (zoomed in over 15 ms) at reference numeral 10, a spectrogram 15 of the SAM tone, a discrete Fourier transform (DFT) magnitude 20 of the SAM tone, a spectrogram 25 for the demeaned Hilbert envelope of the SAM tone, and a DFT magnitude 30 for the demeaned Hilbert envelope of the SAM tone. [0027] In contrast, as noted above, the disclosed concept employs a dAM stimulus, where the carrier frequency is constant, but the modulation frequency varies exponentially from ~16 Hz to ~1500 Hz. These values have been adopted based on subcortical and cortical tuning to amplitude modulation. This is illustrated in FIG. 2, which shows a dAM tone time domain waveform over 1 second at reference numeral 5, the dAM tone and its Hilbert envelope (zoomed in over 15 ms) at reference numeral 40, a spectrogram 45 of the dAM tone, a DFT magnitude 50 of the dAM tone, a spectrogram 55 for the demeaned Hilbert envelope of the dAM tone, and a DFT magnitude 60 for the demeaned Hilbert envelope of the dAM tone. In this example, a carrier of 3 kHz is employed with exponentially increasing AM from ~16 Hz to ~1200 Hz over 1 s. The dAM tone has an AM frequency of 500 Hz around 795 ms. The illustrated spectrograms are constructed in this example using a 64 ms window with 95% overlap using a Blackman window as the taper. [0028] Using such dynamic AM trajectories, the AM coding by the auditory system can be studied in a time-efficient manner. For example, using a 3.33 Hz presentation rate, 200 trials per AM frequency, and ½ octave steps, it takes approximately 15 minutes to complete testing from 16-2048 Hz using a conventional SAM tone. In contrast, to cover a comparable range from 16 to 1500 Hz using a dAM tone of the disclosed concept, it takes only approximately 3 minutes. Thus, the dAM stimulus of the disclosed concept offers 5x improvement in time efficiency over conventional SAM-tone-based approaches. [0029] A further aspect of the disclosed concept efficiently derives EFR amplitudes as a function of varying amplitude modulation rates, which function is also referred to as the temporal modulation transfer function (tMTF). The tMTF can be efficiently estimated according to the disclosed concept by combining the dAM stimulus described above (the exemplary embodiment being shown in FIG. 2) with certain spectrally specific analyses which are described below (the exemplary embodiment being shown in FIG. 3). The EFR in response to the dAM stimulus should track the dAM trajectory, the power along which can be extracted using spectrally specific analysis (e.g., Hilbert, frequency demodulation, and low- pass filtering in the exemplary embodiment). This power can be estimated both in the time and frequency domains (using corresponding low-pass filters in the time or frequency domain). The output of the time-domain implementation is a sampled waveform that captures EFR power along the dAM trajectory power as a function of time. Since the relationship between dAM-trajectory frequency and time is known (which is one-to-one in the exemplary embodiment), the output can be represented as dAM-trajectory power as a function of dAM-trajectory frequency. This function is a continuously sampled tMTF. [0030] To estimate a tMTF that is analogous to the traditional discretely sampled tMTF (for example at f1 Hz AM frequency), one could simply window this continuously sampled tMTF, where the (time) window is restricted to the vicinity of the f1 AM frequency (e.g., a 100-ms window). The variance of this windowed- output is an estimate of the tMTF at f1 Hz. However, frequency-domain filters offer power estimates that are less prone (more robust) to bias and variance issues due to the application of multi-taper spectrum. Thus, frequency-domain filters can be used in combination with windowing followed by a multi-taper spectral estimate. Specifically, for a single AM frequency (f1 Hz), the frequency- demodulated EFR response can be similarly windowed (for example using a 100- ms window around the points where the dAM trajectory crosses f1 Hz) and its multi-taper spectrum can be subject to a low-pass filter to estimate the tMTF at f1 Hz. In short, the tMTF can be efficiently estimated according to the disclosed concept by combining dAM stimuli with spectrally specific analyses. [0031] FIG. 3 schematically illustrates a method for estimating the tMTF using spectrally specific analyses according to an exemplary embodiment of the disclosed concept wherein the steps are labeled 1-6. As seen in FIG. 3, the method involves providing a single dAM stimulus as described herein to a patient at step 1. In response, EFRs of opposite polarities are obtained by way of EEG signals collected from the patient at step 2. Next, at step 3, the demeaned Hilbert envelope of the EFR is computed. The demeaned Hilbert envelope of the EFR is then frequency demodulated using the known dAM trajectory at step 4. To estimate the tMTF value at an AM frequency (e.g., F1), a time window is first chosen where the dAM trajectory is within a certain bandwidth (e.g., 0.2 octave). Note that since the relationship between AM frequency and time is one-to-one, the x-axis can have time or AM frequency as the unit. The tMTF value in this window can thus be estimated in two alternate ways: i) by low-pass filtering the frequency- demodulated signal in the time domain and taking the variance (=power) of the signal within the appropriate window as shown in steps 5a-6a, or ii) by windowing the frequency-demodulated signal and estimating the power in the low-pass window from its multi-taper spectrum as shown in steps 5b-6b. FIG. 3 shows the estimated tMTF produced by the method just described. [0032] FIG. 4 is a schematic diagram of a temporal processing assessment system 65 according to a non-limiting exemplary embodiment of the disclosed concept. As described in detail herein, temporal processing assessment system 65 is structured and configured to assess the temporal processing of an individual, and thus potential hearing loss or other hearing issues, by providing a number of dAM tones (e.g., as shown in FIG. 2) as a stimulus to the individual, collecting EEG signals from the individual in response to the tone which are indicative of the evoked EFR in the brain of the individual responsive to the tone, and estimating the tMTF from the evoked EFR using a specially designed spectrally specific frequency demodulation scheme as described herein (e.g., as shown in FIG. 3). [0033] Referring to FIG. 4, temporal processing assessment system 65 includes an EEG apparatus 70 that is structured and configured to record EEG signals from an individual. In the non-limiting exemplary embodiment of the disclosed concept, EEG apparatus 70 includes an EEG cap 75 having a plurality of electrodes 80 coupled thereto for collecting EEG signals from the individual as shown in FIG. 6. It will be appreciated, however, that this embodiment is meant to be exemplary only, and that other forms of an EEG apparatus 70 may also be used within the scope of the disclosed concept. As seen in FIG. 4, temporal processing assessment system 65 also includes a sound generating apparatus 85, such as a number of speakers or a set of headphones, for outputting a dAM tone as described herein. In addition, in temporal processing assessment system 65, EEG apparatus 70 and sound generating apparatus 85 are coupled to a computing device 90. Computing device 90 may be, for example and without limitation, a PC, a laptop computer, a tablet computer, a smartphone, or any other suitable device structured and configured to control operation of temporal processing assessment system 65 to perform the functionality described herein. In particular, computing device 90 is structured and configured to control sound generating component 85 to provide a dAM stimulus to the individual as described herein. Computing device 90 is also structured and configured to receive from the EEG apparatus 70 certain EEG signals that are generated in response to the dAm stimulus. Computing device 90 is further structured and configured to estimate tMTF using the spectrally specific analysis of the disclosed concept. [0034] FIG. 5 is a block diagram of computing device 90 according to one non- limiting exemplary embodiment. As seen in FIG. 5, the exemplary computing device 90 includes an input apparatus 95 (such as a keyboard), an output apparatus 100 (such as an LCD), and a controller 105. A user is able to provide input into controller 105 using input apparatus 95, and controller 105 provides output signals to output apparatus 100 to enable output apparatus 100 to display information to the user. The memory portion of controller 105 has stored therein a number of routines that are executable by a processor of controller 105. One or more of the routines implement (by way of computer/processor executable instructions) at least one embodiment of the method discussed in detail herein for assessing temporal processing and estimating tMTF of the individual. Controller 105 thus includes an EEG control/interface component 110 for interfacing with EEG apparatus 70 and receiving signals therefrom, sound generation component 120 for generating information for enabling sound generating apparatus 85 to output the dAM stimulus as described herein, and an EEG signal processing component 125 for processing the received EEG signals, including implementing the spectrally specific analyses of the disclosed concept. [0035] While specific embodiments of the invention have been described in detail, it will be appreciated by those skilled in the art that various modifications and alternatives to those details could be developed in light of the overall teachings of the disclosure. Accordingly, the particular arrangements disclosed are meant to be illustrative only and not limiting as to the scope of disclosed concept which is to be given the full breadth of the claims appended and any and all equivalents thereof.

Claims

What is claimed is: 1. A method of assessing temporal processing of an individual, comprising: generating and providing to the individual through a sound generation apparatus a dAM tone; receiving a number of electroencephalogram (EEG) signals measured from the individual in response to the dAM tone; determining an envelope following response (EFR) signal from the number of EEG signals; and estimating a temporal modulation transfer function (tMTF) based on the EFR signal using a spectrally specific analysis scheme.

2. The method according to claim 1, wherein the dAM tone employs dynamic AM that varies continuously across a plurality of AM frequencies.

3. The method according to claim 2, wherein the plurality of AM frequencies have an overall range between 0 and 5000 Hz.

4. The method according to claim 3, wherein the plurality of AM frequencies are over 1 s.

5. The method according to claim 1, wherein the dAM tone employs a carrier that has constant statistics.

6. The method according to claim 1, wherein a modulation frequency of the dAM tone varies over the plurality of AM frequencies.

7. The method according to claim 6, wherein a modulation frequency of the dAM tone varies exponentially over the plurality of AM frequencies.

8. The method according to claim 1, wherein the EFR signal comprises opposite polarities.

9. The method according to claim 1, wherein the estimating the tMTF comprises performing a Hilbert transformation on the EFR signal to produce a Hilbert transformed signal, and frequency demodulating the Hilbert transformed signal to create a frequency-demodulated signal.

10. The method according to claim 9, wherein the Hilbert transformed signal is frequency demodulated using a known trajectory of the dAM tone.

11. The method according to claim 9, wherein the estimating the tMTF further comprises choosing a time window where a dAM trajectory of the dAM tone is within a predetermined bandwidth, low-pass filtering the frequency-demodulated signal in the time domain, and taking a variance of the low-pass filtered frequency-demodulated signal within the time window.

12. The method according to claim 9, wherein the estimating the tMTF further comprises frequency windowing the frequency-demodulated signal and estimating power in the frequency windowed frequency-demodulated signal using a multi-taper spectral estimate.

13. A computer program product, comprising a non-transitory computer usable medium having a computer readable program code embodied therein, the computer readable program code being adapted to be executed to implement a method of assessing temporal processing as recited in claim 1.

14. A temporal processing assessment system, comprising: a sound generation apparatus; an EEG apparatus; and a controller coupled to the sound generation apparatus and the EEG apparatus, the controller being structured and configured to: (i) cause the sound generation apparatus to output a dAM tone to an individual, (ii) receive a number of electroencephalogram (EEG) signals from the EEG apparatus, wherein the number of EEG signals are measured from the individual in response to the dAM tone; (iii) determine an envelope following response (EFR) signal from the number of EEG signals, and (iv) estimate a temporal modulation transfer function (tMTF) based on the EFR signal.

15. The system according to claim 14, wherein the dAM tone employs dynamic AM that varies continuously across a plurality of AM frequencies.

16. The system according to claim 15, wherein the plurality of AM frequencies have an overall range between 0 and 5000 Hz.

17. The system according to claim 16, wherein the plurality of AM frequencies are over 1 s.

18. The system according to claim 14, wherein the dAM tone employs a carrier that that has constant statistics.

19. The method according to claim 13, wherein a modulation frequency of the dAM tone varies over the plurality of AM frequencies.

20. The method according to claim 19, wherein a modulation frequency of the dAM tone varies exponentially over the plurality of AM frequencies.

21. The system according to claim 14, wherein the EFR signal comprises opposite polarities.

22. The system according to claim 14, wherein the controller is configured to estimate the tMTF by performing a Hilbert transformation on the EFR signal to produce a Hilbert transformed signal, and frequency demodulating the Hilbert transformed signal to create a frequency-demodulated signal.

23. The system according to claim 22, wherein the Hilbert transformed signal is frequency demodulated using a known trajectory of the dAM tone.

24. The system according to claim 22, wherein the controller is further configured to estimate the tMTF by choosing a time window where a dAM trajectory of the dAM tone is within a predetermined bandwidth, low-pass filtering the frequency- demodulated signal in the time domain, and taking a variance of the low-pass filtered frequency-demodulated signal within the time window.

25. The system according to claim 22, wherein the controller is further configured to estimate the tMTF by frequency windowing the frequency-demodulated signal and estimating power in the frequency windowed frequency-demodulated signal using a multi-taper spectral estimate.