Hearing map estimation based on in-vivo acoustic chirp

Abstract

Presented herein are systems and methods of providing acoustic stimulation to a human subject in order to evoke an auditory response. The method includes generating a chirp signal, where generating the chirp signal includes adding a plurality of frequency signals, each frequency signal being delayed in the chirp signal based on its associated frequency-specific basilar membrane delay, the frequency-specific basilar delay being determined as a function of an in-vivo frequency-specific basilar membrane delay.

Description

[0001] Cross-references to related applications

[0002] This application claims priority to European patent application EP21153126.4, filed on January 25, 2021, entitled "Auditory Map Estimation Based on In Vivo Acoustic Chirp", the entire contents of which are incorporated herein by reference. Technical Field

[0003] The present invention relates to acoustic chirping stimulation and audiogram systems and methods, advantageously based on measured in vivo basement membrane time delay. Background Technology

[0004] It is known in the art that when testing a patient's hearing, auditory stimuli are delivered to the ear to elicit an auditory response. The magnitude of this auditory evoked response typically depends on the number of neurons activated by the stimulus. As a result, click stimuli that simultaneously output a wide frequency range can be used to obtain a greater auditory response.

[0005] However, sound transduction in the human ear is mediated by basilar membrane (BM) waves, whose delay increases with distance from the base of the cochlea. Therefore, due to the travel time through the cochlea from the basal region (high-frequency region) to the more apical region (low-frequency region), a tap stimulus does not elicit simultaneous stimulation across a range of frequencies along the cochlea. This leads to a blurred auditory evoked response.

[0006] Shore and Nutall were the first to apply the concept of chirp to auditory electrophysiology. See Shore SE, Nutall AL. High-synchrony cochlear compound action potentials evoked by risingfrequency-swepttone bursts. J Acoust Soc Am. 1985 Oct; 78(4): 1286-95. (1985), which is incorporated herein by reference in its entirety. In the process of chirp generation, the timing of each frequency component within the burst is modulated to compensate for the cochlear propagation time, thereby improving the temporal synchronicity of neurons and a greater auditory response.

[0007] Numerous studies have been conducted to measure BM delay. Specifically, autopsy studies have been performed in various mammalian species and humans. Another method for measuring BM delay is to indirectly estimate it by deriving frequency response characteristics from auditory brainstem responses, electrocochleography (ECG), or the OAE. Some of these estimates have led to the assertion that BM delay is much longer in humans than in typical laboratory animals. See Neely ST, Norton SJ, Gorga MP, Jesteadt W. Latency of auditory brain-stem responses and otoacoustic emissions using toneburst stimulus. behavioralmeasurements.Proc.Natl.Acad.Sci.USA 2002;99:3318–3323;and Harte JM,Pigasse G,Dau T.Comparison of cochlear delay estimates using otoacoustic emissions andauditorybrainstem responses.J Acoust Soc Am. 2009 Sep; 126(3): 1291-301. doi: 10.1121 / 1.3168508.), each of which is incorporated herein by reference in its entirety. Ruggero and Temchin were the first to estimate in vivo BM delay in the human cochlea, obtained by correcting postmortem BM data based on the effect of death on BM vibration in experimental animals. See Ruggero MA, Temchin AN. Similarity of traveling-wave delays in the hearing organs of humans and other tetrapods. J Assoc Res Otolaryngol. 2007 Jun; 8(2): 153-66, which is incorporated herein by reference in its entirety.

[0008] To date, no model for generating chirping stimulation has been based on in vivo BM delay measurements in humans. Conversely, the delayed model is applied based on a linear description of the mechanical properties of the cochlea (see de Boer E. Acylindricalcochlea model: the bridge between two and three dimensions. Hear Res. 1980 Aug; 3(2): 109-31), which is incorporated herein by reference in its entirety; short pure tone ABR latency (see Neely et al., 1988); stimulus frequency otoacoustic emission latency (see Shera and Guinan, 2000); derivative band ABR latency (see Don M, Ponton CW, Eggermont JJ, Kwong B. The effects of sensory hearing loss oncochlear filter times estimated from auditory brainstem response latencies. JAcoust Soc Am. 1998 Oct; 104(4): 2280-9. doi: 10.1121 / 1.423741), which is incorporated herein by reference in its entirety; and auditory evoked compound action potentials (Elberling C, J, Don M. Evaluating auditory brainstem responses to different chirp stimulus at three levels of stimulation. J Acoust Soc Am. 2010 Jul; 128(1): 215-23. doi: 10.1121 / 1.3397640, which is incorporated herein by reference in its entirety. Furthermore, Elberling et al. (2010) found in a large cohort of normally hearing subjects that responses to various chirped signals were level-dependent. This could be explained by changes in the upward propagation of the stimulus and the delay in cochlear nerve stimulation.

[0009] It is now recognized that many cochlear implant candidates retain good residual hearing. Unlike traditional hearing aids, which only amplify and modify sound signals, cochlear implants are based on direct electrical stimulation of the auditory nerve. Typically, a cochlear implant electrically stimulates neural structures in the inner ear in such a way that it obtains an auditory impression that most closely resembles normal hearing.

[0010] like Figure 1As shown, a normal ear transmits sound through the outer ear 101 to the tympanic membrane (eardrum) 102. The tympanic membrane 102 moves the bones of the middle ear 103 (malleus, incus, and stapes), which vibrate the oval window of the cochlea 104. The cochlea 104 is a long, narrow tube that spirals about two and a half turns around its axis. It includes a superior canal called the scala vestibulae and a inferior canal called the scala tympani, which are connected by the cochlear canal. The cochlea 104 forms an upright spiral cone with a center called the cochlear axis, where the spiral ganglion cells of the auditory nerve 113 are located. In response to the sound received from the middle ear 103, the fluid-filled cochlea 104 acts as a transducer to generate electrical impulses that are transmitted to the cochlear nerve 113 and ultimately to the brain.

[0011] A typical cochlear implant may include two parts: an audio processor 111 and an implantable stimulator 108. The audio processor 111 typically includes a microphone, a power supply (battery) for the entire system, and a processor for signal processing of the acoustic signals to extract stimulation parameters. The audio processor 111 may be an external, behind-the-ear (BTE-) device, a single unit integrating the processor, battery pack, and coil, or it may be implantable.

[0012] Stimulator 108 generates a stimulation pattern (based on extracted audio information) which is transmitted via electrode wire 109 to the implanted electrode array 110. Typically, the electrode array 110 includes multiple electrodes on its surface that provide selective stimulation to the cochlea 104. For example, each electrode of a cochlear implant is typically stimulated by a signal within a designated frequency band of the inner ear tissue, a so-called stimulation channel. The designated frequency band of an electrode is typically based on its placement within the cochlea, with electrodes closer to the base of the cochlea typically corresponding to higher frequency bands. Electrodes used to describe the invention and throughout this specification refer to both physical electrode contacts and virtual electrode contacts, regardless of whether they are used for stimulation or measurement. Therefore, in the following text, electrode refers to both physical electrode contact 112 and virtual electrode contact.

[0013] The stimulation channel corresponds to a physical electrode contact 112, that is, an electrode contact physically existing at a specific location on the electrode array 110 (physical stimulation channel), or corresponds to a virtual electrode (virtual stimulation channel) generated by synchronously stimulating a pair of adjacent physical electrode contacts 112 at a certain fixed current ratio. When stimulating a pair of adjacent physical electrode contacts 112, the electric fields of the pair of adjacent physical electrode contacts are superimposed, and the (previously stated) ratio determines the strength of the two electric fields relative to each other; therefore, the superimposed total electric field can be represented by a virtual electrode located between the two physical electrode contacts 112. As long as the superimposed total electric field can be represented by an electric field, which will be generated by stimulating a single virtual electrode contact, a pair of physical electrode contacts 112 is defined as adjacent. For example, a ratio of 0.5 determines that the same current is applied to the two physical electrode contacts 112, and in effect, the total electric field approximately corresponds to an electric field that will be generated by a virtual electrode located approximately in the middle between the two physical electrode contacts on the electrode array 110. A ratio of 0.3 determines that 30% of the total delivery current is applied to one of the two physical electrode contacts, while 70% is applied to the corresponding physical electrode contact. In practice, this corresponds to a virtual electrode located between the two physical electrode contacts, but (typically) closer to the contact where 70% of the current is applied.

[0014] The exact same method applies to measurements as to stimulation. Here, instead of stimulation signals, the measurement signals recorded at adjacent physical electrode contacts 112 are weighted. The weighting factor represents a virtual electrode contact, as described above, representing the electrode contact between two physical electrode contacts. This weighted measurement signal can then be correlated with a specific (acoustic) frequency, such as the frequency to be tested, for example, the Greenwood function as a mapping and / or computed tomography, or both.

[0015] The connection between the BTE audio processor and the stimulator is typically established via a radio frequency (RF) link. Note that both stimulation energy and stimulation information are transmitted via the RF link. Typically, a digital data transmission protocol with a bit rate of hundreds of kBit / s is used.

[0016] For optimal auditory performance, strategy-related mapping parameters can be repeatedly adjusted periodically to program the cochlear implant system to the specifications and needs of its user. This is especially true for electrical dynamic range (DR), which is defined by the maximum comfortable loudness (MCL) and threshold (THR) charge level of each electrode and strongly influences performance. MCL indicates the level of perceived loudness that is comfortable; while THR typically indicates the threshold of hearing. Typically, an increase in MCL, or M-level stimulation amplitude, is observed during the first year post-implantation, along with a decrease in electrode impedance (EIV). Stability of stimulation level and EIV usually occurs after approximately three months.

[0017] In clinical practice, audiologists typically adjust the mapping parameters at several times according to a fixed schedule. If a patient with audiology complains of dysfunction or poor function of the audiology system, additional consultation may be necessary.

[0018] It can be difficult to measure audiograms in patients with residual hearing who have received cochlear implants, especially children. Therefore, an objective method for estimating audiograms would be useful. Obtaining an audiogram is necessary in the programming of a processor, which includes information such as cutoff frequencies that determine which parts of the cochlea are acoustically stimulated and which are electrically stimulated, or a combination thereof; selects which electrodes to activate or deactivate; and modifies frequency distribution or AGC parameters.

[0019] In addition to requiring objective audiogram testing methods for cochlear implant users with residual hearing, minimizing testing time is also important. Therefore, precise compensation for cochlear propagation time, which leads to increased temporal synchronicity of neurons, can be a way to increase response amplitude, thereby increasing measurement sensitivity, i.e., increasing accuracy, allowing for lower stimulus levels, and further shortening testing time. Summary of the Invention

[0020] According to one embodiment of the present invention, a method is provided for providing acoustic stimulation to a human subject to elicit an auditory response. The method includes generating a chirped signal, wherein generating the chirped signal includes adding a plurality of frequency signals, each frequency signal being delayed within the chirped signal to compensate for its associated frequency-specific basilar membrane delay, the frequency-specific basilar membrane delay being determined as a function of a measured in vivo frequency-specific basilar membrane delay.

[0021] According to a relevant embodiment of the invention, the method may further include acoustically providing a chirped signal to the human subject to elicit an auditory response. The human subject may have an implanted cochlear implant, and the auditory response is measured using the inner ear cochlea.

[0022] According to a further related embodiment of the invention, the method may further include measuring the in vivo frequency-specific basilar membrane delay at least in part by either: measuring the in vivo frequency-specific basilar membrane delay in a plurality of individuals; or measuring the in vivo frequency-specific basilar membrane delay in the human subject. Measuring the frequency-specific basilar membrane delay may include measurement using electrocochleography (ECG). Measurement using ECG may include providing an acoustic tone stimulus and measuring the cochlear microphonic organ (CM) response via electrodes of an implanted cochlear implant. The location of each electrode may be determined based on computed tomography; thereby deriving a characteristic frequency associated with each electrode using a Greenwood function, and thus the electrode being measured is the electrode having the characteristic frequency that best matches the acoustic frequency of the provided tone stimulus.

[0023] According to another related embodiment of the invention, the function of the measured frequency-specific basilar membrane delay may include a polynomial function or an exponential estimate. Lower frequency signals among the plurality of frequency signals may have less delay compared to higher frequency signals. Generating the chirped signals may include setting each frequency signal in the chirped signals to the same amplitude and / or loudness perception level as the human subject.

[0024] According to another related embodiment of the invention, the human subject has an implanted cochlear implant. The method may further include at least partially using electrocochleography to measure the frequency-specific basilar membrane delay in the human subject. The chirped signal is acoustically provided to the human subject to elicit an auditory response. The response is measured using electrocochleography.

[0025] According to another embodiment of the invention, a system for providing acoustic stimulation to a human subject to elicit an auditory response is proposed. The system includes a controller configured to generate a chirped signal, wherein generating the chirped signal includes adding a plurality of frequency signals, each frequency signal being delayed within the chirped signal to compensate for its associated frequency-specific basement membrane delay, the delay being determined as a function of the measured in vivo frequency-specific basement membrane delay.

[0026] According to a relevant embodiment of the invention, the system may further include a transducer. The controller may be configured to provide the chirped signal to the transducer to induce an auditory response in the human subject. The system may further include a cochlear implant for implantation in the human subject, wherein the auditory response is measured using electrocochleography.

[0027] According to a further related embodiment of the invention, the in vivo frequency-specific basement membrane delay may be based on in vivo frequency-specific basement membrane delays measured from multiple individuals.

[0028] According to another related embodiment of the invention, the system may further include a transducer and a cochlear implant for implantation in the human subject. The controller is configured to: provide acoustic tone stimulation to the transducer to evoke an auditory response in the human subject; determine the frequency-specific basilar membrane delay in the human subject from the auditory response to the tone stimulation measured using electrocochleography; and provide the chirped signal to the transducer to evoke an auditory response from the chirped signal in the human subject. The controller may be configured to determine the location of each electrode based on computed tomography; derive a characteristic frequency associated with each electrode using a Greenwood function; and measure the cochlear microphone (CM) response on the electrodes, the cochlear microphone (CM) response having the characteristic frequency that best matches the acoustic frequency of the provided tone stimulation.

[0029] In another related embodiment of the invention, the function of the measured frequency-specific basement membrane delay may include estimation using a polynomial or exponential function. The controller may be configured to set each frequency signal in the chirped signal to the same amplitude and / or loudness perception level as the human subject.

[0030] According to another embodiment of the present invention, a method is provided for determining a frequency-specific basilar membrane delay in a human subject having an implanted cochlear implant. The method includes providing the human subject with an acoustic tone stimulus to evoke an auditory response in the human subject, the acoustic tone stimulus comprising acoustic short tones of a plurality of frequencies. The response of the cochlear microphone (CM) to the acoustic tone stimulus is measured using electrocochleography. The frequency-specific basilar membrane delay in the human subject is determined for each of the plurality of frequencies.

[0031] According to a relevant embodiment of the invention, the method may further include generating chirped signals, wherein the frequencies in the chirped signals are time-delayed to compensate for their corresponding frequency-specific basilar membrane delays. The chirped signals may be acoustically provided to a human subject to elicit an auditory response.

[0032] According to another related embodiment of the invention, the method may include deriving the location of each electrode based on computed tomography; and deriving a characteristic frequency associated with each electrode using a Greenwood function. The cochlear microphone (CM) response is measured using the electrode having the characteristic frequency that best matches the frequency of the provided tonal stimulus. The method may include using polynomial or exponential function estimation to determine the in vivo frequency-specific basilar membrane delay of the human subject for each of the plurality of frequencies.

[0033] According to another embodiment of the invention, a system is provided for determining a frequency-specific basilar membrane delay in a human subject having an implanted cochlear implant. The system includes a controller configured to: provide the human subject with an acoustic tone stimulus via a transducer to evoke an auditory response in the human subject, the acoustic tone stimulus comprising acoustic short tones of a plurality of frequencies; measure the response of the cochlear microphone (CM) to the acoustic tone stimulus using electrocochleography; and determine, for each of the plurality of frequencies, a frequency-specific basilar membrane delay in vivo in the human subject.

[0034] According to a relevant embodiment of the invention, the controller may also be configured to generate chirped signals, wherein frequencies in the chirped signals are time-delayed to compensate for their corresponding frequency-specific basilar membrane delays. The controller may further be configured to acoustically provide the chirped signals to a human subject via the transducer to induce an auditory response.

[0035] According to another embodiment of the invention, the controller may be further configured to: derive the location of each electrode based on computed tomography; derive a characteristic frequency associated with each electrode using a Greenwood function; and measure the cochlear microphonic organ (CM) response using the electrode having the characteristic frequency that best matches the acoustic frequency of the provided tonal stimulus. The controller may be further configured to determine, for each of the plurality of frequencies, a frequency-specific basilar membrane delay in the human subject, including estimation using a polynomial or exponential function.

[0036] According to another embodiment of the present invention, a method is provided for generating an audiogram of a human subject with an implanted cochlear implant based on objective measurements. The cochlear implant includes an electrode array comprising a plurality of electrodes, each electrode associated with a characteristic frequency. The method includes acoustically stimulating the subject with a chirped signal to evoke an auditory response in the human subject. The chirped signal includes a plurality of frequency signals, each frequency signal being delayed within the chirped signal to compensate for a frequency-specific basilar membrane delay associated therewith, the basilar membrane delay being determined as a function of a measured in vivo frequency-specific basilar membrane delay. Evoked auditory responses are measured on one or more of the electrodes. An auditory threshold of the human subject is determined based on the evoked auditory response. An audiogram of the human subject is determined based on the measured auditory threshold.

[0037] According to relevant embodiments of the present invention, electrocochleography of the inner ear can be used to measure the evoked auditory response. The auditory response may be a cochlear microphonon (CM) response (hair cell potential), an auditory nerve tone (ANN) response, or a combination thereof.

[0038] According to a further embodiment of the invention, the location of each electrode in the cochlea can be derived based on computed tomography. The Greenwood function can be used to derive the characteristic frequencies associated with each electrode.

[0039] According to a further related embodiment of the invention, the measurement and determination may include the method of determining whether the chirped signal elicits a response on each electrode. If there is no response on any given electrode, the chirped signal is reconstructed by increasing the frequency associated with the unresponsive electrode; the subject is acoustically stimulated with the reconstructed chirped signal; and the determination is repeated with the reconstructed chirped signal. If a response is measured at all frequencies: the chirped signal is reconstructed by decreasing the signal at each frequency of the chirped signal; the subject is acoustically stimulated with the reconstructed chirped signal to evoke an auditory response in the human subject; an auditory threshold is saved when the electrode no longer provides a response to the chirped signal; whether the chirped signal elicits a response on any electrode is determined; and the reconstruction, acoustic stimulation, saving, and determination are repeated until no response is recorded on any electrode.

[0040] In a further related embodiment of the invention, the method may further include modifying the fitting parameters of the cochlear implant based on the audiogram. The in vivo frequency-specific basilar membrane delay may be measured at least in part based on either: measuring the in vivo frequency-specific basilar membrane delay in multiple individuals; or measuring the in vivo frequency-specific basilar membrane delay in the human subject. Measurements using electrocochleography may include providing acoustic tone stimulation and measuring the cochlear microphonic organ (CM) response via electrodes of the implanted cochlear implant.

[0041] According to another embodiment of the invention, a system is provided for generating an audiogram of a human subject with an implanted cochlear implant based on objective measurements. The cochlear implant includes an electrode array comprising a plurality of electrodes, each electrode associated with a characteristic frequency. The system includes a transducer. A controller is configured to generate a chirped signal, wherein generating the chirped signal includes adding a plurality of frequency signals, each frequency signal within the chirped signal being delayed based on a frequency-specific basilar membrane delay associated therewith, the delay being determined as a function of a measured in vivo frequency-specific basilar membrane delay. The controller is further configured to: provide the chirped signal to the transducer to evoke an auditory response in the human subject; measure the evoked auditory response on one or more of the electrodes; determine an auditory threshold of the human subject based on the evoked auditory response; and generate an audiogram of the human subject based on the measured auditory threshold.

[0042] According to a relevant embodiment of the invention, electrocochleography of the inner ear is used to measure the evoked auditory response. The auditory response may be one of a cochlear microphonon (CM) response (hair cell potential), an auditory nerve tone (ANN) response, or a combination thereof. The controller may be further configured to derive the location of each electrode in the cochlea based on computed tomography; and to derive the characteristic frequencies associated with each electrode using a Greenwood function.

[0043] In a further related embodiment of the invention, during measurement and determination, the controller may be further configured as follows: Determine whether the chirped signal elicits a response on each electrode. If there is no response on any given electrode: reconstruct the chirped signal by increasing the frequency associated with any electrode that does not respond; acoustically stimulate the subject with the reconstructed chirped signal; and repeat the determination with the reconstructed chirped signal. If a response is measured at all frequencies: reconstruct the chirped signal by decreasing the signal at each frequency of the chirped signal; auditorily stimulate the subject with the reconstructed chirped signal; when the electrodes no longer provide a response, save the auditory threshold; determine whether the chirped signal elicits a response on any electrode; and repeat reconstruction, acoustic stimulation, saving, and determination until no response is recorded on any electrode.

[0044] In a further related embodiment of the invention, the controller may be configured to modify the fitting parameters of the cochlear implant based on the audiogram. The controller may be configured to measure the in vivo frequency-specific basilar membrane delay at least in part by measuring the in vivo frequency-specific basilar membrane delay in a plurality of individuals; or by measuring the in vivo frequency-specific basilar membrane delay in the human subject. When performing the measurement, the controller may be configured to use intracochlear electrocochleography, wherein the controller is configured to provide acoustic tone stimulation and measure the cochlear microphonic organ (CM) response via electrodes of the implanted cochlear implant.

[0045] According to another embodiment of the present invention, a system is provided for generating an audiogram of a human subject with an implanted cochlear implant based on objective measurements. The cochlear implant includes an electrode array comprising a plurality of electrodes, each electrode being associated with a characteristic frequency. The system includes: means for acoustically stimulating the subject with a chirped signal to elicit an auditory response in the human subject, the chirped signal comprising a plurality of frequency signals, each frequency signal within the chirped signal being delayed based on a frequency-specific basilar membrane delay associated therewith, the delay being determined as a function of the measured in vivo frequency-specific basilar membrane delay; means for measuring the evoked auditory response on one or more electrodes; means for determining an auditory threshold of the human subject based on the evoked auditory response; and means for generating an audiogram of the human subject based on the measured auditory threshold.

[0046] In a relevant embodiment of the invention, electrocochleography can be used to measure the evoked auditory response, and the response is at least one of a cochlear microphonon (CM) response (hair potential), an auditory nerve tone (ANN) response, or a combination thereof. The system may further include means for deriving the location of each electrode in the cochlea based on computed tomography; and means for deriving the characteristic frequencies associated with each electrode using a Greenwood function. The system may further include means for modifying the fitting parameters of the cochlear implant based on an audiogram. Attached Figure Description

[0047] Referring to the accompanying drawings and the following detailed description, the foregoing features of the embodiments will be more readily understood, wherein:

[0048] Figure 1 A conventional cochlear implant system according to an embodiment of the present invention is shown;

[0049] Figure 2A flowchart illustrating the process of providing acoustic stimulation to a human subject to evoke an auditory response according to an embodiment of the present invention is shown.

[0050] Figure 3 A schematic diagram of an exemplary system for measuring and determining frequency-specific BM delay using electrocochleography of the inner ear, according to an embodiment of the present invention, is shown.

[0051] Figure 4 An example of an electrocochlear electrograph recording of the inner ear according to an embodiment of the present invention is shown;

[0052] Figure 5 An example of fitting the measurement delay of a basement membrane (BM) delay specific to an in vivo frequency determined using a delay function for frequencies of 250, 500, 1000, 2000, and 4000 Hz, according to an embodiment of the present invention, is shown.

[0053] According to various embodiments of the present invention, Figure 6A A single-frequency signal with a defined delay is shown, which can be used to generate a chirped signal. Figure 6B It shows how to add Figure 6A The chirping signal generated by the frequency signal shown in the figure, and Figure 6C The generated chirped signal is shown based on a fitted frequency range of 250-4010Hz and linearly increased by 20Hz;

[0054] Figure 7 A flowchart illustrating an illustrative embodiment of the invention, showing a process for obtaining an audiogram of a human subject with an implanted cochlear implant based on objective measurements; and

[0055] Figure 8 A flowchart illustrating a process for implementing cochlear implant delay according to an embodiment of the present invention is shown. Detailed Implementation

[0056] In an illustrative embodiment, a system and method are provided in which in vivo frequency-specific basilar membrane (BM) delays at multiple frequencies are measured and determined. These in vivo frequency-specific BM delays can be advantageously used to generate chirped signals in which frequency signals are delayed within the chirped signal based on their associated frequency-specific BM delays, resulting in improved neuronal temporal synchrony and a greater auditory response. The chirped signals can be used, for example, to auditorily stimulate cochlear implant subjects, thus, using electrocochleography of the inner ear, an audiogram based on objective measurements of residual hearing can be obtained. Details are described below.

[0057] Figure 2This is a flowchart of a method for providing acoustic stimulation to a human subject to elicit an auditory response according to an embodiment of the present invention. In step 201, in vivo frequency-specific basilar membrane (BM) delays at multiple frequencies are measured and determined. A chirped signal is then generated, wherein each frequency signal is delayed within the chirped signal based on its associated frequency-specific BM delay, which is determined as a function of the measured / determined in vivo frequency-specific BM delay. The chirped stimulation is designed to compensate for time delays in the auditory periphery in an attempt to increase temporal synchronization between neurons, which are typically asynchronously activated by brief stimuli (e.g., clicks). Furthermore, the use of in vivo frequency-specific BM delays in the generation of the chirped signal results in improved neuronal temporal synchronization and a greater auditory response compared to the conventional use of in vitro measured / determined frequency-specific BM delays.

[0058] In step 201, measuring the in vivo frequency-specific BM delay may include measuring the in vivo frequency-specific BM delay in multiple individuals. Various statistical methods, as known in the art, can then be used to generate a chirped signal. For example, in step 203, the average of the determined in vivo frequency-specific BM delays can be used to generate a chirped signal. The resulting chirped signal can then typically be used across a large range of human subjects, or as an initial chirped signal for patient-specific measurements and fitting.

[0059] Optionally, in step 201, the determined in vivo frequency-specific basilar membrane delay can be based on a measurement of the in vivo frequency-specific basilar membrane delay for a specific cochlear implant user (i.e., a patient-specific measurement). Then, in step 203, the generated chirp signal can be used for further testing of the cochlear implant user. Determining the patient-specific in vivo frequency-specific basilar membrane delay can generate a more accurate chirp signal for the subject cochlear implant user, rather than using, for example, the average of these values ​​obtained from a large range of human subjects.

[0060] In step 201, measuring and determining the frequency-specific BM delay can be achieved using electrocochleography of the inner ear cochlea. Figure 3A schematic diagram of an exemplary system for measuring and determining frequency-specific BM delay using electrocochleography according to an embodiment of the present invention is shown. Auditory evoked potentials in the inner ear cochlea are recorded from electrodes of a cochlear implant 301 inserted into the scala tympani of a patient. Acoustic stimulation is provided to the ear canal using a transducer 303 that can be inserted into the ear. The transducer can be connected to a signal generator 305 that generates the acoustic signal. A controller 307 may include software for controlling the system. The controller 307 may be a PC communicating with an interface unit connected to the cochlear implant 301 via an external coil. When recording begins, the controller 307 may trigger the signal generator 305, which then auditorily stimulates the patient with a chirped signal. The responses from the individual electrodes of the cochlear implant 301 can then be recorded. Based on this response, the controller 307 can determine the frequency-specific BM delay and, for example, generate a chirped signal that can be used for further acoustic testing.

[0061] Measurements using electrocochleography (ECG) of the inner ear can include providing acoustic tone stimulation and measuring the cochlear microphonic organ (CM) response via electrodes implanted in the cochlear implant. The cochlear microphonic organ (CM) in EEG is an alternating current reflecting the waveform of the acoustic stimulus. It is governed by receptor potentials in the outer hair cells of the organ of Corti. Because the electrical displacement of the CM is proportional to that of the BM, the delay time can be measured, for example, by the time it takes for the CM to reach its first peak or, more commonly, for the CM to reach 10% of its maximum amplitude. According to embodiments of the invention, Figure 4 The inner ear cochlear ECochG recording (black line) and the delay t when the CM reaches 10% of its maximum amplitude are shown. 10％ And in 1 st Delay t at maximum peak max Example. The gray line is the BP-filtered signal. The stimulus used is a short 500Hz tone applied at 0ms. Other suitable methods or definitions for determining the delay can also be used; for example, the delay could be when CM reaches 20% of its maximum amplitude (t...). 20％ In another implementation, a cross-correlation function can be used to calculate the delay time. This calculation can determine the peak value of the cross-correlation, or determine the delay as the minimum delay of the cross-correlation function exceeding a predetermined threshold. The cross-correlation function can be normalized, and the predetermined threshold can be 0.75 or 0.9. In one implementation, the delay time is derived from the digitally sampled measurement signal r. k The cross-correlation function can be:

[0062]

[0063] Where D is the number of samples in one period of the measured signal, for example, in Figure 4In this context, a 500Hz short tone is defined as a single cycle from one zero-crossing with a positive slope to the next zero-crossing with a positive slope, and L is the length of the cross-correlation window (L>D). The cross-correlation m... d The time lag varies from 0 to 1 and is independent of the absolute level (normalization). The time lag is the number of samples d, where m is the distance between samples d and d. d Exceeding a certain threshold. In one implementation, the threshold exceeds 0.75 or 0.9. The delay is ultimately determined by dividing d by the measured signal r. k The time is calculated based on the sampling rate. In this embodiment, bandpass filtering of the measurement signal is only required by higher or lower order harmonics, and D is used to determine the period of the measurement signal whose delay should be determined, i.e., 250Hz, 500Hz, etc., and applied to the measurement signal r. k High-order or low-order harmonics can be filtered out by using band-stop filtering or appropriate band-pass filtering.

[0064] When performing electrocochleography (ECG) of the inner ear, the acoustic stimulation provided can include auditory short tones of various frequencies, with stimulation levels reaching, but not limited to, the maximum comfort level. For example, short tones of 250, 500, 1000, 2000, and 4000 Hz can be provided, and the response at the electrode associated with a specific frequency region can be measured. More specifically, the position and / or insertion angle of each electrode in the cochlear implant can be determined based on computed tomography. The Greenwood function can then be used to derive the characteristic frequencies associated with each electrode. The response to a particular short tone can then be measured at the electrode having the characteristic frequency that best matches the acoustic frequency of the provided short tone.

[0065] The delay determined at each of the provided frequencies can then be fitted using, but is not limited to, polynomial or exponential function estimation. For example, according to an embodiment of the invention, Figure 5 An example of fitting the measured delay based on the in vivo frequency-specific basement membrane (BM) delay is shown, which is determined for five different frequencies of 250, 500, 1000, 2000, and 4000 Hz using a delay function estimated by the function (y = kf^(-d)). See Don M, Eggermont JJ. Analysis of the click-evoked brainstem potentials in man unsing high-pass noise masking. J.A. C. Soc. Am. 1978 Apr; 63(4): 1084-92. doi: 10.1121 / 1.381816, which is incorporated herein by reference in its entirety.

[0066] Return to reference Figure 2Step 203 involves generating a chirped signal after determining the in vivo frequency-specific basement membrane (BM) delay across frequencies. Figure 6A A single-frequency signal with a defined delay that can be used to generate a chirped signal is shown. Each frequency signal in the chirped signal can be set to the same amplitude and / or loudness perception level as a human subject. According to embodiments of the invention, such as... Figure 6B As shown, the resulting chirp signal is then generated by adding a frequency signal, without restriction.

[0067] In an illustrative embodiment of the invention, the generated chirped signal can be used, for example, in subsequent audio tests to auditorily stimulate a human subject, thereby evoking an auditory response. Preferably, objective measurements can be performed. For example, objective measurements are based on, but not limited to, electrocochleography (ECG) (if the subject has an implanted cochlear implant) or ABR measurements. In various embodiments, the measurements can be used to generate an audiogram of the human subject.

[0068] As mentioned above, it is sometimes difficult to measure audiograms in patients with residual hearing who have received cochlear implants, especially children. Therefore, it would be useful to have an objective method for estimating audiograms. Data obtained from audiograms can be used to fit various parameters of the cochlea, such as determining which part of the cochlea is acoustically stimulated and which part is electrically stimulated, or which part of the cochlea is stimulated by a combination of electrical and acoustic stimulation, or selecting which electrodes to activate or deactivate, or changing the cutoff frequency assigned to the frequency distribution of the stimulation channel or AGC parameters.

[0069] Figure 7 This is a flowchart illustrating the process of obtaining an audiogram of a human subject with an implanted cochlear implant based on objective measurements, according to an illustrative embodiment of the present invention. This process can be performed by... Figure 3 The system shown can be used, but is not limited to this system.

[0070] In step 701, as described above, an acoustic stimulus is applied to the subject using a chirped signal that compensates for / determines the in vivo frequency-specific basilar membrane (BM) delay. This chirped signal advantageously maximizes the temporal synchronization between neurons within the cochlea, thereby increasing the response amplitude and thus improving measurement sensitivity, i.e., increasing accuracy, allowing for lower stimulus levels, and additionally shortening test time. Initially, the amplitude of each frequency can be set to a predetermined value, which can be, for example, below or close to the amplitude expected to elicit a response.

[0071] Then, in step 703, an electrocochleography of the inner ear can be used to check whether a response has been obtained at each electrode. This response can be, but is not limited to, a cochlear microphonic organ (CM) response (hair cell potential) or an auditory nerve tone (ANN) response. If no response is found at the specific frequency being tested (associated with the electrode), then in step 705, the chirp signal is recalculated as the amplitude of the frequency associated with that electrode increases. For example, the amplitude of this frequency can be increased by 5 dB or 10 dB, but is not limited to this.

[0072] In step 707, upon receiving responses at all frequencies (each frequency associated with one electrode), each individual frequency in the chirped signal is reduced (e.g., reduced by 5 dB), and in step 709, the subject is acoustically stimulated with this recalculated chirp. In step 711, the amplitude at which a measured response to a frequency is no longer detectable is saved as a threshold for that amplitude. Step 705 is repeated until no response is observed at any frequency, i.e., step 713 has obtained the threshold amplitudes for all test frequencies. Then, in step 715, an audiogram (showing the measured thresholds) can be generated. To improve the accuracy of the measured threshold amplitudes, the above process can be repeated several times.

[0073] exist Figure 7 In the above process, the frequencies associated with the electrodes can be determined from postoperative CT scans. Based on the CT scans, information about the position of each electrode in the cochlea, as well as the insertion angle and estimated excitation frequency, can be determined, for example, using the Greenwood function. Correlations can then be established between electrodes excited at frequencies closest to their characteristic frequencies.

[0074] In various embodiments of the invention, obtaining accurate knowledge about frequency-specific time delays within the human cochlea can advantageously help improve audio coding strategies in cochlear implants. It has been shown that hearing-impaired patients with varying degrees of hearing loss have different time delays caused by “artificial” processing within their hearing aids or cochlear implant audio processors. See, for example, Zirn S, Arndt S, Aschendorff A, Wesarg T. Interaural stimulation timing in single-sided deafcochlear implant users. Hear Res. 2015 Oct; 328: 148-56. doi: 10.1016 / j.heares.2015.08.010, the entire text of which is incorporated herein by reference. Interaural stimulation timing mismatch can limit the accuracy of transient binaural processing. By applying frequency-specific time delays to the cochlear implant audio processor, cochlear implant users can achieve the same or near-the same time delays compared to individuals with normal bilateral hearing. This may become even more important as the indications for cochlear implantation continue to expand.

[0075] For individuals with unilateral hearing loss who have a cochlear implant on the non-hearing side, equal time delays are particularly important. Another group of particular interest may be individuals with normal or near-normal low-frequency hearing retention after cochlear implantation (Lorens et al., 2008). Typically, these individuals have much higher expectations for their auditory performance compared to other cochlear implant candidates. These individuals usually reach the upper limit effect of speech tests in quiet conditions and expect greater improvements in speech tests in noisy environments and spatial hearing abilities.

[0076] Note that simply implementing a BM traveling wave delay in the cochlear implant's audio processor is usually insufficient; an additional 1 ms delay is required. Although the BM delay represents a delay in the traveling wave, BM vibrations in the corresponding sensory receptor cells are also stimulated, and they release neurotransmitters into the synaptic cleft. After this process, the stimulus only stimulates the auditory nerve fibers. The release of the transducer is frequency-independent and takes approximately 1 ms. See Temchin AN, Recio-Spinoso A, van Dijk P, Ruggero MA. Wiener kernels of chinchilla auditory-nerve fibers: verification using responses to tones, clicks, and noise and comparison with basilar-membrane vibrations. J Neurophysiol. 2005 Jun; 93(6): 3635-48, which is incorporated herein by reference in its entirety. This frequency independence has also been previously demonstrated in human subjects. The first positive peak P1 of the electrically evoked compound action potential occurs 0.6–0.8 ms after stimulation, and this is independent of the location of the stimulated cochlea. See, for example, Polak M, Hodges AV, King JE, Balkany TJ. Further prospective findings with compound action potentials from Nucleus 24 cochlear implants. Hear Res. 2004 Feb; 188(1–2): 104–16, which is incorporated herein by reference in its entirety. For electrical stimulation, neurotransmitter release does not occur; therefore, this delay should be included in the total time delay.

[0077] Figure 8 A flowchart illustrating the process for implementing cochlear implant delay is shown. In step 801, as described above, the in vivo frequency-specific basilar membrane (BM) delay is measured / determined for each frequency channel of the cochlear implant. In step 803, a corresponding offset equal to the measured / determined in vivo frequency-specific basilar membrane (BM) delay is applied to the corresponding filter in each channel of the cochlear implant. In step 805, an additional 1-millisecond offset is added to each offset. Therefore, a more accurate interaural time difference (ITD) can be achieved between the two ears, a crucial clue for locating sound sources.

[0078] Embodiments of the present invention can be implemented in part using any conventional computer programming language. For example, preferred embodiments can be implemented using procedural programming languages ​​(e.g., "C") or object-oriented programming languages ​​(e.g., "C++", Python). Alternative embodiments of the invention can be implemented as pre-programmed hardware elements, other related components, or a combination of hardware and software components.

[0079] The implementation can also be implemented in part as a computer program product used with a computer system, such as the controller described above. Such an implementation may include a series of computer instructions fixed on a tangible medium (e.g., a computer-readable medium (e.g., a disk, CD-ROM, ROM, or hard disk)) or transmitable to the computer system via a modem or other interface device (e.g., a communication adapter connected to a network via a medium). This medium may be a tangible medium (e.g., an optical or analog communication line) or a medium implemented using wireless technology (e.g., microwave, infrared, or other transmission technologies). This series of computer instructions embodies all or part of the functionality described earlier with respect to the system. Those skilled in the art will understand that such computer instructions can be written in various programming languages ​​for many computer architectures or operating systems. Furthermore, these instructions can be stored in any storage device, such as semiconductor, magnetic, optical, or other storage devices, and can be transmitted using any communication technology, such as optical, infrared, microwave, or other transmission technologies. Such computer program products are intended to be distributed as removable media with accompanying printed or electronic documentation (e.g., shrink wrapping software), pre-loaded with a computer system (e.g., on system ROM or hard disk), or distributed via a network (e.g., the Internet or the World Wide Web) from a server or electronic bulletin board. Of course, some embodiments of the invention can be implemented as a combination of software (e.g., computer program products) and hardware. Furthermore, other embodiments of the invention can be implemented as entirely hardware or entirely software (e.g., computer program products). Although various exemplary embodiments of the invention have been disclosed, it will be apparent to those skilled in the art that various changes and modifications will achieve some of the advantages of the invention without departing from the true scope of the invention.

Claims

1. A method for generating audiograms of human subjects with cochlear implants based on objective measurements, characterized in that, The cochlear implant includes an electrode array comprising a plurality of electrodes, each electrode being associated with a characteristic frequency, and the method includes: The subject is acoustically stimulated with a chirped signal to induce an auditory response in the human subject. The chirped signal comprises a plurality of frequency signals, each of which is delayed within the chirped signal to compensate for its associated frequency-specific basement membrane delay, which is determined as a function of a measured in vivo frequency-specific basement membrane delay. Measure the evoked auditory response on one or more of the electrodes; The auditory threshold of the human subject is determined based on the induced auditory response; The human subject's audiogram was generated based on the measured auditory threshold.

2. The method according to claim 1, characterized in that, The evoked auditory response was measured using electrocochleography of the inner ear.

3. The method according to claim 1, characterized in that, The auditory response is at least one of the following: cochlear microphonus (CM) response, auditory nerve tone (ANN) response, or a combination thereof.

4. The method according to claim 1, characterized in that, Further includes: The location of each electrode in the cochlea was derived using computed tomography. as well as The characteristic frequencies associated with each electrode are derived using the Greenwood function.

5. The method according to claim 1, characterized in that, Measurement and determination include: Determine whether the chirping signal elicits a response on each electrode; If there is no response at any given electrode, then: The chirp signal is reconstructed by increasing the frequency associated with any unresponsive electrode; The subject was acoustically stimulated with a reconstructed chirped signal; and The reconstructed chirp signal is repeatedly used to determine this; If the response is measured at all frequencies, then: The chirped signal is reconstructed by reducing each frequency signal in the chirp; The subjects were acoustically stimulated with reconstructed chirped signals in order to induce an auditory response in the human subjects; The hearing threshold is preserved when the electrodes no longer respond to the chirping signal; Determine whether the chirped signal elicits a response on any electrode; and Repeated reconstruction, acoustic stimulation, storage, and determination until no response is recorded on any electrode.

6. The method according to claim 1, characterized in that, It further includes modifying the fitting parameters of the cochlear implant based on the audiogram.

7. The method according to claim 1, characterized in that, This further includes measuring the in vivo frequency-specific basement membrane delay at least in part by any of the following methods: Measuring the in vivo frequency-specific basement membrane delay of multiple individuals; or The in vivo frequency-specific basement membrane delay of the human subject was measured.

8. The method according to claim 7, characterized in that, Measurements using electrocochleography of the inner ear include providing acoustic tone stimulation and measuring the cochlear microphone (CM) response via electrodes implanted in the cochlear implant.

9. A system for generating audiograms of human subjects with cochlear implants based on objective measurements, characterized in that, The cochlear implant includes an electrode array comprising multiple electrodes, each electrode being associated with a characteristic frequency; the system includes: speaker; The controller is configured as follows: Generating a chirped signal, wherein generating the chirped signal includes adding a plurality of frequency signals, each frequency signal being delayed within the chirped signal to compensate for its associated frequency-specific basement membrane delay, the frequency-specific basement membrane delay being determined as a function of a measured in vivo frequency-specific basement membrane delay; The chirping signal is provided to the loudspeaker to induce an auditory response in the human subject; Measure the evoked auditory response on one or more of the electrodes; The auditory threshold of the human subject is determined based on the evoked auditory response; and The human subject's audiogram was generated based on the measured auditory threshold.

10. The system according to claim 9, characterized in that, The evoked auditory response was measured using electrocochleography of the inner ear.

11. The system according to claim 10, characterized in that, The auditory response is at least one of the following: cochlear microphonus (CM) response, auditory nerve tone (ANN) response, or a combination thereof.

12. The system according to claim 9, characterized in that, The controller is further configured to: The location of each electrode in the cochlea was derived based on computed tomography imaging; and The characteristic frequencies associated with each electrode are derived using the Greenwood function.

13. The system according to claim 9, characterized in that, The controller is further configured to measure and determine: Determine whether the chirping signal elicits a response on each electrode; If there is no response at any given electrode, then: The chirped signal is reconstructed by increasing the frequency associated with any unresponsive electrode. The subject was acoustically stimulated with a reconstructed chirped signal; and The reconstructed chirp signal is repeatedly used to determine this; If the response is measured at all frequencies, then: The chirped signal is reconstructed by reducing each frequency signal in the chirp; The subjects were auditorily stimulated using a reconstructed chirp; The hearing threshold is preserved when the electrodes no longer provide a response; Determine whether the chirped signal elicits a response on any electrode; and Repeated reconstruction, acoustic stimulation, storage, and determination until no response is recorded on any electrode.

14. The system according to claim 9, characterized in that, The controller is further configured to modify the fitting parameters of the cochlear implant based on the audiogram.

15. The system according to claim 9, characterized in that, The controller is further configured to measure the in vivo frequency-specific basement membrane delay at least in part by any of the following: Measuring the specific basement membrane delay at the in vivo frequency in multiple individuals; or The in vivo frequency-specific basement membrane delay of the human subject was measured.

16. The system according to claim 15, characterized in that, During measurement, the controller is configured to use intracochlear electrocochleography, wherein the controller is configured to provide acoustic tone stimulation and measure the cochlear microphone (CM) response via electrodes of the implanted cochlear implant.

17. A system for generating audiograms of human subjects with implanted cochlear implants based on objective measurements, characterized in that, The cochlear implant includes an electrode array comprising multiple electrodes, each electrode being associated with a characteristic frequency; the system includes: An apparatus for acoustically stimulating the subject with a chirped signal to induce an auditory response in the human subject, the chirped signal comprising a plurality of frequency signals, each frequency signal being delayed within the chirped signal to compensate for its associated frequency-specific basilar membrane delay, the frequency-specific basilar membrane delay being determined as a function of a measured in vivo frequency-specific basilar membrane delay. A device for measuring evoked auditory responses on one or more electrodes; A device for determining the auditory threshold of the human subject based on the evoked auditory response; An apparatus for generating an audiogram of the human subject based on measured auditory thresholds.

18. The system according to claim 17, characterized in that, The evoked auditory response is measured using electrocochleography of the inner ear, and the response is at least one of the cochlear microphone (CM) response, auditory nerve tone (ANN) response, or a combination thereof.

19. The system according to claim 17, characterized in that, Further includes: A device for deriving the location of each electrode in the cochlea based on computed tomography; as well as The device uses the Greenwood function to derive the characteristic frequencies associated with each electrode.

20. The system according to claim 17, characterized in that, It further includes means for modifying the fitting parameters of the cochlear implant based on the audiogram.

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