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Title:
FREQUENCY DISCRIMINATION METHOD IN THE COCHLEA
Document Type and Number:
WIPO Patent Application WO/2019/009850
Kind Code:
A2
Abstract:
The invention explains the distinction of the sounds having different frequencies in the inner ear with a new mechanism. This mechanism has the potential to radically change the hearing theories and the hearing technologies depending on them.

Inventors:
UZUN, Cem (Trakya Üniversitesi Rektörlüğü, Edirne, TR)
BULUT, Erdoğan (Trakya Üniversitesi Rektörlüğü Sağlık Bilimleri Fakültesi, Edirne, TR)
ÖZTÜRK, Levent (Trakya Üniversitesi Rektörlüğü Tıp Fakültesi Fizyoloji, Edirne, TR)
Application Number:
TR2018/050025
Publication Date:
January 10, 2019
Filing Date:
January 25, 2018
Export Citation:
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Assignee:
TRAKYA ÜNİVERSİTESİ REKTÖRLÜĞÜ (Balkan Yerleşkesi, Edirne, 22030, TR)
International Classes:
G10B1/00
Attorney, Agent or Firm:
YALÇINER, Uğur G. (YALÇINER PATENT & CONSULTING LTD.) (Remzi Oğuz Arık Mah. Tunus Cad. No:85/3-4, Çankaya/Ankara, 06680, TR)
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Claims:
CLAIMS

A method which enables the distinction of sounds having different frequencies in the inner ear, characterized in that it comprises the steps of:

active movement of the outer hair cells to provide for the frequency distinction and modulation of this movement through olivocochlear fibres and performing the frequency discrimination of the cochlea by means of the olivocochlear system through outer hair cells

in forming a response to the sound stimulus or coding of the sound in the inner ear, formation of the high frequency sounds in the basal, middle and apex regions of the cochlea, medium or low frequency sounds forming a response likewise in the basal, middle, apex regions of the cochlea.

A method according to claim 1, characterized in that the outer hair cell electromotile responses of the tonotopic map resonate specifically to the frequency by being modulated by means of the medial branch of the olivocochlear system and perform the frequency discrimination.

Description:
FREQUENCY DISCRIMINATION METHOD IN THE COCHLEA

Technical Field

Since the theories that explain how the human ear distinguishes sounds at different frequencies are insufficient, efficiency of the hearing measurement devices and hearing aid prosthetics (for example, cochlear implants, hearing devices, etc) not being at the desired level is a fundamental problem. The invention explains the distinction of the sounds having different frequencies in the internal ear with a novel mechanism. This mechanism has the potential to change the hearing theories and accordingly, the basic operation principal of the hearing technologies.

Known State of the Art (Prior Art)

Realization of hearing occurs through vibration of the ossicular system in the middle ear and following the transfer of this to the membrane in the oval window with the movement of the stapes ossicle base, the liquid called perilymph in the cochlea receiving the pressure waves (i.e. sound) and the specialized mechanoelectrical receptor structure called Corti organ set on the basilar membrane in the cochlea converting the vibration it received to electrical signal and transmit it to the upper centres. Sound is a mechanical wave which can spread in the material atmosphere. The intensity of the sound is known as decibel and its vibration count per unit of time is known as frequency. In the inner ear, our hearing organ cochlea codes the sounds as intensity and frequency. This coding occurs with the specialized cellular structures in the cochlea. For the coding of the sounds through cellular structures, various hearing theories have been put forward. The theory accepted nowadays and many researchers agree upon is the wave theory (travelling wave theory-Nobel Medicine and Physiology Prize -1961) put forward by Von BEKESY. With this theory it is proposed that the tectorial membrane and hair cells are stimulated with the movement of the basilar membrane. The studies made about how the frequency discrimination in the cochlea occurs can be analysed in three periods. The first period lasted beginning from the second half of the 1700s to the end of 1940s. In the beginning of this period, it was believed that the cochlea in humans was filled with air. When it was claimed by Cotugno that the cochlea was filled with liquid for the first time in 1760, many scientists who lived in that era did not believe in it. In 1777, Meckel revealed that Cotugno was right, by showing that the cochlea was filled with liquid. The most detailed and impressive studies on explaining the structure of the cochlea came from Alfonse Corti in 1851. The inner ear drawings Corti made in that period based on his observations both caused the hearing organ to be named after him and contains details that would astonish people even today. However, in those years it was not known which part of the Corti organ was useful for what. One of the first theories on how the sound analysis occurs in the inner ear was proposed by Ohm in 1843 and at this point, it was put forth that the sound analysis should be made by a type of Fourier or spectral analysis. Twenty years after this, researcher named Helmholtz said in 1863 that various sections spread across the cochlea resonate with the sound such as a diapason depending on the frequency. Views of Helmholtz left its mark on this period which we can call the first period of sound analysis in the inner ear. The second period starts with the end of 1940s and lasts until the beginning of 1970s. In this period, the most important contributions came from George von Bekesy, which ensured him the Nobel Prize in the year 1963. Bekesy completed the vibration with stroboscope and microscopic studies on temporal bone samples and various cochlear models he obtained from cadavers in the 1960s. The studies he made have shown that the views put forth by Helmholtz do not fall in with the observations at two points. First, the vibration did not seem to be the simple resonance of independent mechanical resonators. Different areas across the cochlea appeared to be mechanically conjugated with other areas. Second, he observed wide vibration patterns which do not agree with the high degree discrimination between frequencies. These observations made him think that other additional 'fine tuning' mechanism should be present within the cochlea. Bekesy developed the theory called the travelling wave theory because of his work. The third period in sound analysis has started at the beginning of 1970s and continues. In this period, demonstration of a local electromechanical amplification process in which outer hair cells function as both the sensor and the feedback element caused the travelling wave theory developed by von Bekesy to gain great popularity. This local amplification process is performed under the control of the central nervous system. The information is transmitted to the central nervous system (1,2) by means of mechanoelectro-chemical procedure with afferent synapses of inner hair cells. Because of the cochlear anatomy, different morphological characters of the cells and tissues and the technical difficulties in the assessment, detailed information on cochlea morphology falls behind other sensorineural system. Cochlea can be defined as the sensitive membranous tissue network surrounded by the hardest bone tissue of the body and suspended within the liquids. Assessment of the internal ear tissues require methods specialized for its research. Alfonse Corti prepared the first surface preparations of this organ and defined it with radial sections. His drawings provided the correct details of most of the important structures of the membranous labyrinth even if have revealed the post mortem artefacts. Corti's work inspired other researchers who conducted further research. When the drawings of Reissner, Deiter, Boettcher, Cladius, Hensen and especially Retzius are checked against the cochlea micrograph produced by using the contemporary technology, it comes to light that the observations of Alfonse Corti are true to a large extent (3, 4). The accumulation of knowledge related to the structure of the cochlea shows parallelism with the better understanding of its functions and various hearing theories have been put forth including the resonance and telephone theories throughout the same period (1). A group of following researchers made s understand the cochlea structure and functions better. Among them, von Bekesy's travelling wave theory; Engstrom et al. defining the hair cell damage graphically by using a map called cochleagram, Davis's mechanoelectrical hearing theory, Helmholtz's place theory and Smith's endolymph ionic composition descriptions can be mentioned (3).

Hearing Theories

Even though the hydro mechanical events in the cochlea underlie the relationship between the place and frequency of the cochlea and the vibration manner of the Corti organ which produces effective sensory stimulus for hearing, the main element of the sensory transduction is receptor cells. The reason behind this is that the receptor cells are mechanoreceptors which convert mechanical energy to electrical energy (3, 4). The start of the hydro mechanical movement in the cochlea is the sound energy transmitted to the scala vestibuli through the base of the stapes and oval window stimulating the perilymph. After this stage, cochlea's two important mission starts. First of these is the transmission, which is the acoustic energy being transported p to the hair cells in the Corti organ. The second is conversion, which is the conversion of the mechanical transmission wave arriving at the hair cells in the Corti organ to chemical or electrical tension and transmission of the information to the auditory nerve. This conversion takes place in a way that the characteristics of the sound such as the fret, timbre, phase separation, intensity will not disappear and these characteristics of the sound energy are encoded by electrical stress which will be formed, and sent to the information central nervous system. The transmission mechanism of the inner ear is in the way that the vibrations which arrive up to the oval window are moved from one perilymph window to the other. However, the vibration in this liquid does not occur in the way that the molecules of the sound energy are compressed and relaxed the as in the air but with the movement of liquid columns. In this position, it is not truly a sound wave anymore. The analysis of the sound which arrive at the cochlea is explained by various theories (1,5,6).

Frequency or Telephone Theory

According to Rutterford's (1886) frequency or telephone theory; the perception of the frequencies occurs depending on the arrival frequency of the impulses in the auditory nerve. For example, it is stated that (7) a sound of 500Hz stimulates the auditory nerve 500 times subsequently. Whereas the fibres in the auditory nerve can be stimulated 1000 times per second the most. If it is thought that other nerve fibres operate synchronically on different times, the frequency theory will be valid for only the sounds under 5000Hz. For this reason, this theory has lost its validity in the light of the knowledge today.

Place Theory

According to Helmholtz's place theory (1855); basilar membrane and the Corti organ on it is a resonator just like the wires of a piano. Which means that the areas fit for the frequencies of the incoming sound waves are stimulated by vibration and perceive the sound. It is proposed for the first time with this theory that the basal area of the basilar membrane is the resonator of high frequencies and the apex is the resonator of low frequencies (8).

Volley (Spread) Theory

In Wever's (1954) Volley (spread) theory; a relation is made out between the place and frequency theory. Perception of the sounds up to 5000Hz is explained by the emergence of fast nerve impulses in the form of spreading fire. For the frequencies which exceed 5000Hz, it is explained by the place theory (9).

Travelling Wave Theory According to Von Bekesy, auditory vibrations applied to any one of the scales cause displacements in the basilar membrane, this is called the travelling wave theory, and this wave starts from the basal end of the basilar membrane and proceeds to the apex.

The spreading is both longitudinal and transversal. Again, the most important feature of this transmission wave is the amplitude raising progressively and reaching the maximum and the vibrations fading away and changing phase. After the biggest vibration area, vortex motions start in the liquid. Another important feature is that the place where these waves vibrate the largest on the basilar membrane is specific areas for each frequency. For every audible frequency, there is an unchanging 'largest vibration point' on the basilar membrane for each frequency. The area which vibrates at the biggest amplitude is at the basal area on high frequencies, i.e. close to the oval window and as the frequency of auditory energy drops, the part of the basilar membrane which vibrates the most gets closer to the apex of the cochlea and this forms a tonotopic map in the cochlea. Basilar membrane has a more stiff and narrow structure at the basal area and a more flexible and expanding structure towards the apex (Figure 1). Because of this structural feature, it has a separate maximum vibration area for each frequency (Figure 2). The frequency discrimination defined in the cochlea by Bekesy provides for the basal area of the cochlea coding high frequency sounds depending on the basilar membrane movement, middle part coding medium frequency sounds and the apex low frequency sounds and forms a tonotopic map in the cochlea. Because of his research, in addition to these findings, Bekesy proposed that the amplitude at the most vibrant part is in direct proportion with the stimulant sound intensity (10,11). Bekesy observed the travelling wave with the help of stereoscopic lighting at the 140 dB SPL sound level above the pain threshold in the cochlea on cadaver. This is a linear observation. With the movement of the basilar membrane, it is proposed that the tectorial membrane and hair cells are stimulated. However, there are many theories on the activation and spreading of the auditory energy in the cochlea. The abovementioned travelling wave theory is the most reasonable theory today and upon which many researchers agree.

Second Filter Theory It is prevalently thought that the tonotopic map of the mammalian cochlea is determined by passive mechanical features of the basilar membrane (12). For this reason, the travelling wave (first filter) does not explain the cochlear mechanics to the full and it is said that it is explained integrally with a theory (1970-1980) called the second filter -second filter theory. The second filter theory (13) is a theory proposed to explain the differences between frequency discrimination and sensitivity with the recordings measured across the basilar membrane and received from the auditory nerve.

This theory lost its importance with Brownell (14) showing the outer hair cells (DTH) electromotile responses in the cochlea, discovery of Prestin (15), motor protein which forms the electromotile responses and studies made (17) related to the olivocochlear system controlling (16) the motile responses of the efferent path together with the fast and slow phases present in the electromotile responses.

Brief Description and Purposes of the Invention

Frequency discrimination of the cochlea, the organ of hearing in the inner ear is described according to travelling theory of von Bekesy. With the studies made, it was shown that this theory does not explain the frequency discrimination to the full, however, no hypothesis or theory instead of it have been proposed which would explain the frequency discrimination of the cochlea.

Since Bekesy's observations are on cadaver and they stimulate the cochlea above the pain threshold, they both do not provide for the assessment of the cochlea on live cell structure and cause the cochlea to be stimulated linearly. In the light of the data today, it has been shown that the cochlea forms nonlinear responses and as the intensity of the stimulus decreases, the sensitivity of the cochlea to sounds increases. Bekesy says that in his observations, the frequency decomposition or discrimination in the cochlea occurs by means of the basilar membrane which presents different mechanical properties in the cochlea. On the contrary, all the cellular structures in the cochlea show different mechanical properties specific to the frequency. Before the invention, frequency discrimination of the cochlea was explained with the travelling wave theory of von Bekesy. In the light of the studies made, it was shown that this theorem does not explain the frequency discrimination of the cochlea to the full and the cochlea is now a bionic mechano-amplifier which receives the sound from cochlea, analyses and transmits it. Since the travelling wave theory is performed on the cadaver, the cellular structures not showing biological properties and the cochlea forming linear responses against the stimulus caused incorrect assessments in the sound analysis and occurrence of technical problems on the frequency discriminations in the auditory system. The productivity of the cochlear implant devices of the hearing aid prosthetics and hearing measurement devices produced based on this solution is about 70% at most and the productivity cannot exceed that.

In the present explanations, it is stated that 'basilar membrane's movement with the sound waves provides for the frequency discrimination' from the anatomic structures in the inner ear. According to the invention, not the basilar membrane movement but 'the active movement of the outer hair cells and modulation of this movement by means of olivocochlear fibres' plays the major role in providing for the frequency discrimination. This difference changes the target point anatomically in the hearing theories and the production of hearing technologies depending on it. In the present state, the basic operation principle of the technologies such as hearing aid prosthetics (cochlear implant) and hearing measurement devices (otoacoustic emission devices, etc.) is based on the travelling wave theory. According to this theorem, it is shown that in forming a response to the sound stimulus or coding of the sound in the inner ear, the high frequency sounds form in the basal of the cochlea and the responses originate from the basal and the medium or low frequency sounds form in the middle and apex area of the cochlea respectively. According to the data obtained because of the studies made in the invention, the basic operation principle of the present technologies such as the hearing measurement devices (otoacoustic emission devices, etc.) and hearing aid prosthetics (cochlear implant) will change. According to the invention, in forming a response to the sound stimulus or coding of the sound in the inner ear, the high frequency sounds form in the basal, middle and apex area of the cochlea and likewise, the medium and low frequency sounds form a response in the basal, middle and apex area (Figure 3). The invention will chance the software algorithm and hardware depending on the basic operation principle of the present devices. Description of the Illustrative Figures

Figure 1: Schematized version of the present invention - travelling wave theory

Figure2: Known state of the art-cochlear tonotopy

Figure3: Pure tone frequency stimulus forming a response in all the segments in the cochlea.

1. Beginning part of the cochlea (basal)

2. Middle part of the cochlea (middle)

3. End part of the cochlea (apex)

4. Inner hair cell line

5. Outer hair cell line

6. Basilar membrane

7. Neural connections-nerve fibrils belonging to the olivo-cochlear system

Detailed Description of the Invention

All the cellular structures in the cochlea show different mechanical properties specific to the frequency and among these cellular structures, the cell which stands out the most and shows anatomical difference is the outer hair cells. The cell size is short at the high frequency area and long in the low frequency area. The outer hair cells are isolated from each other across the cochlea, which means they do not contact each other. If frequency discrimination in the cochlea occurred across the basilar membrane only, there would not be any need for the outer hair cells to show different anatomic properties specific to the frequency. The outer hair cells can change the cell length by a motor protein (Prestin) in the cell membrane. Changes in the length of the cell can occur both through its self-stimulation property and a system (Olivocochlear System) which builds neural connection with it. These unique properties of the outer hair cells provided for us to asses it as a cell which is at the centre of the frequency discrimination and build or study on it. The invention is for the frequency discrimination of the cochlea being able to occur through the outer hair cells by means of the olivocochlear system. That is because the outer hair cells can form the cell size length changes and the frequency of the sound, which is the frequency response and the olivocochlear system can modulate these responses. In the prior art, cochlear tonotopy was explained with the travelling wave theory depending on the frequency discrimination which is formed through the basilar membrane movement. This theory forms the basic operation principle of the hearing measurement technologies and hearing aid prosthetics.

In the invention, tonotopic map outer cell electromotile responses in the cochlea are modulated by means of the medial branch of the olivocochlear system and resonate specifically to the frequency and realize the frequency discrimination. Changing of the tonotopic map will increase the productivity of the devices by changing their basic operation principle of the hearing aid prosthetics which will provide for the hearing measurement technologies and aural rehabilitation.

The subject hypothetical approach has not been applied in the literature before and assessed the cochlea by forming sound trauma or acoustic damage specific to the frequency with the pure sound acoustic trauma, both with electrophysiological tests and in the ultrastructural- cellular aspect. When acoustic trauma specific to the frequency was created in the subject measurements, it was observed that more damage was present especially at the frequency band the trauma was created while all other frequency bands were less effected by the damage.

The devices on which electrophysiological measurements were made recorded in line with Bekesy's theorem and made assessments according to it. For this reason, it was normal that damage was observed on the frequency band on which acoustic trauma was created, however, it was observed that the other frequency bands were also affected nonetheless.

This made the inventors thinks of considering the acoustic trauma in a cellular basis. When ultra structural examination was made on the cochlea under the Scanning electron microscope depending on the other frequency bands being affected, trauma regions completely different than the regionalism principle on the frequency discriminator of the cochlea, which spread to the entire cochlea which is not compatible with the electrophysiological records at the frequency band on which acoustic trauma was performed, were observed and assessed. If Bekesy's theorem was correct, there should have been damage on the outer hair cells on the region that acoustic trauma specific to the frequency was performed (at the maximum stimulus intensity 120 dB SPL-for 20 minutes) but damage on different areas spread to the entire cochlea was observed. In the light of the data obtained based on the results of this work, it was observed that the outer hair cells play an important role in the frequency discrimination and create the frequency responses of the cochlea. It was considered that the frequency responses formed were being modulated by the olivocochlear system. Since Bekesy performed his theorem on cadaver, he could not observe the cell responses and has shown that the frequency responses are formed through the movement of the basilar membrane. It is also thought that the basilar membrane movement occurring depending on the frequency Bekesy mentioned in his theorem is created by the frequency responses of outer hair cells. That is because there are sustentacular cells (they do not present morphological change specific to the frequency) on the basilar membrane and outer hair cells on top of it. Basilar membrane could only have provided support to the outer hair cells for them to enter the resonance frequency better.

Corti organ is an afferent structure on the spatial plan. As there is a receptor function in the processing of the sound and the sound waves that reach to the ear, there is also an effecter function. It is the primer structure in which the frequency specific coding is made. The specificity of the reflex members provides for the frequency discrimination. The Corti organ where the energy conversion takes place has various specialized parts for the perception of hydro mechanical changes happening in its atmosphere. Among them, inner hair cells, outer hair cells and their afferent and efferent innervations have special importance. The inner hair cells are accepted as the afferent converter or the primer receptor while the outer hair cells are regarded as the efferent converter, effecter or a secondary receptor which provides for the frequency specificity. Excitation or inhibition of the two different cells of the organ increases the communication quality in the outer world. The frequency discrimination in the cochlea may occur as a reflex activation rather than movement of the basilar membrane and this reflex activation can be performed by the inner hair cells in all cochlear segments and their reflex connections. The neural activation of the medial branch of the olivocochlear system may play a key role for the frequency discrimination with DTH and form vibration patterns for frequency discrimination on the basilar membrane.

Hypothetical approach here is that the tonotopy in the cochlea does not present regional arrangement depending on the basilar membrane movements (basal codes high frequency, middle medium frequency and the apex low frequency), frequency responses can be formed in all the segments of the cochlea (basal part codes high-medium-low frequencies) such as high frequency stimulus forming responses at the basal-middle-apex of the cochlea (Figure 2), responses can be formed in all the segments of the cochlea at the medium or low frequency stimuli.

The invention is the vibration patterns in which the basilar membrane movement forms primarily in cochlear tonotopy not creating the frequency discrimination to the full and playing a secondary role, outer hair cell electromotile responses of the tonotopic map resonating specific to the frequency by being modulated by means of the medial branch of the olivocochlear system and performing the frequency discrimination.

The advantage and the specificity of the invention is that together with explaining the frequency discrimination which could not be explained and remained as a theory until today, it will change the basic operation principle (von BEKESY-tra veiling wave theory) of the hearing aid prosthetics which operate on 60-70% productivity and all the devices assessing the hearing and make them more productive.