U.S. patent application number 13/585560 was filed with the patent office on 2013-01-03 for simultaneous delivery of electrical and acoustical stimulation in a hearing prosthesis.
Invention is credited to Ibrahim Bouchataoui, Christopher J. James, Matthijs Killian, Marc Majoral, Bastiaan van Dijk, Ernst von Wallenberg.
Application Number | 20130006328 13/585560 |
Document ID | / |
Family ID | 37574417 |
Filed Date | 2013-01-03 |
United States Patent
Application |
20130006328 |
Kind Code |
A1 |
Bouchataoui; Ibrahim ; et
al. |
January 3, 2013 |
SIMULTANEOUS DELIVERY OF ELECTRICAL AND ACOUSTICAL STIMULATION IN A
HEARING PROSTHESIS
Abstract
A cochlear prosthesis comprising an electrical signal analyser
configured to process a first frequency sub-range of a detected
sound signal for electric stimulation of the cochlea, and a delay
circuit configured to impose a delay on at least one of an
electrical signal delivery path and an acoustic signal delivery
path, to provide for delivery of the electrical stimulation to the
cochlea at a desired time relative to a time of arrival of acoustic
stimuli at the cochlea, wherein the acoustic stimuli arriving at
the cochlea and the electrical stimulation delivered to the cochlea
at the desired time substantially simultaneously stimulate the
cochlea.
Inventors: |
Bouchataoui; Ibrahim;
(Mechelen, BE) ; Majoral; Marc; (Brussels, BE)
; van Dijk; Bastiaan; (Mechelen, BE) ; von
Wallenberg; Ernst; (Muelheim, DE) ; James;
Christopher J.; (Toulouse, FR) ; Killian;
Matthijs; (Mechelen, BE) |
Family ID: |
37574417 |
Appl. No.: |
13/585560 |
Filed: |
August 14, 2012 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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11434929 |
May 17, 2006 |
8244365 |
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13585560 |
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11125334 |
May 10, 2005 |
8086319 |
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11434929 |
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Current U.S.
Class: |
607/57 |
Current CPC
Class: |
H04R 25/606 20130101;
A61N 1/36039 20170801 |
Class at
Publication: |
607/57 |
International
Class: |
A61N 1/08 20060101
A61N001/08 |
Foreign Application Data
Date |
Code |
Application Number |
May 10, 2004 |
AU |
2004902462 |
May 10, 2005 |
AU |
2005201999 |
Aug 17, 2005 |
AU |
2005203696 |
Claims
1. A bimodal hearing prosthesis comprising: an electrical signal
analyser configured to process a first frequency sub-range of a
detected sound signal for electric stimulation of the cochlea; and
a delay circuit configured to impose a delay on at least one of an
electrical signal delivery path and an acoustic signal delivery
path, to provide for delivery of the electrical stimulation to the
cochlea at a desired time relative to a time of arrival of acoustic
stimuli at the cochlea, wherein the acoustic stimuli arriving at
the cochlea and the electrical stimulation delivered to the cochlea
at the desired time substantially simultaneously stimulate the
cochlea.
2. The prosthesis according to claim 1, further comprising: an
acoustic signal analyzer configured to process a second frequency
sub-range of the detected sound signal, and acoustically deliver
the processed acoustic sound signal to the cochlea.
3. The prosthesis of claim 2, wherein the second frequency
sub-range corresponds to a residual natural hearing capability of
the cochlea.
4. The prosthesis of claim 2, wherein the acoustic signal analyzer
is further configured to process a plurality of acoustic
channels.
5. The prosthesis of claim 3, wherein the delay circuit is
configured to impose a channel-specific delay upon each acoustic
channel.
6. The prosthesis of claim 1, wherein the delay circuit is
configured to impose a delay upon the electrical signal delivery
path.
7. A hearing prosthesis comprising: an electrode array configured
to apply electrical stimuli to a recipient's cochlea; an acoustic
transponder configured to apply acoustic signals to an ear of the
recipient; and a processor configured to process a detected sound
signal and to produce signals defining electrical stimuli for
application by the electrode array to at least a portion of a
recipient's cochlea, and configured to process the detected sound
signal to produce signals defining acoustic stimuli for application
by the acoustic transponder.
8. The hearing prosthesis of claim 7, wherein: The electrical
stimuli is multi-channel electrical stimuli.
9. The hearing prosthesis of claim 7, wherein: the processor is
configured to obtain neural response measurements by using at least
one electrode of the electrode array as a sense electrode.
10. The hearing prosthesis of claim 7, wherein: the signals
defining acoustic stimuli are amplified signals.
11. The hearing prosthesis of claim 7, wherein: the signals
defining electrical stimuli correspond to a first frequency
sub-range of the detected sound signals; and the signals defining
acoustic stimuli correspond to a second frequency sub-range of the
detected sound signals that is different than the first frequency
sub-range.
12. The hearing prosthesis of claim 7, wherein: the second
frequency sub-range corresponds to a residual natural hearing
capability of the cochlea.
13. The hearing prosthesis of claim 7, wherein: the hearing
prosthesis is configured to delay delivery of at least one of the
signals defining electrical stimuli or the signals defining
acoustic stimuli.
14. The hearing prosthesis of claim 13, wherein: the delay provides
for delivery of the electrical stimulation to the cochlea at a
desired time relative to a time of arrival of the acoustic stimuli
at the cochlea.
15. The hearing prosthesis of claim 14, wherein: the acoustic
stimuli arriving at the cochlea and the electrical stimulation
delivered to the cochlea at the desired time substantially
simultaneously stimulate the cochlea.
16. A prosthesis fitting device, comprising: a device configured
to: trigger a cochlear implant; trigger an acoustical transducer;
determine at least one delay to be introduced in at least one of an
electrical signal delivery path of the cochlear implant.
17. The prosthesis fitting device of claim 16, wherein: the device
is configured to detect a neural response caused by the cochlear
implant and a neural response caused by the acoustic
transducer.
18. The prosthesis fitting device of claim 16, wherein: the device
is configured to identify a mismatch between a neural response
caused by the cochlear implant and a neural response caused by the
acoustic transducer.
19. The prosthesis fitting device of claim 18, wherein: the device
is configured to determine the at least one delay based on the
identified mismatch.
20. The prosthesis fitting device of claim 18, wherein: the device
is configured to determine a magnitude of the delay based on a
temporal mismatch between a neural response caused by the cochlear
implant and a neural response caused by the acoustic transducer.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] The present application is a divisional application of U.S.
patent application Ser. No. 11/343,929 filed May 17, 2006 (issues
as U.S. Pat. No. 8,244,265 on Aug. 14, 2012) which claims priority
from U.S. patent application Ser. No. 11/125,334, filed May 10,
2005 (issued as U.S. Pat. No. 8,086,319 on Dec. 27, 2011), which
claims priority from Australian Provisional Patent Application No.
2004902462, filed May 10, 2004. The present application further
claims priority from Australian Patent Application No. 2005203696,
filed Aug. 17, 2005, which claims priority from Australian Patent
Application No. 2005201999, filed May 10, 2005. The entire
disclosure and contents of the above-identified applications are
hereby incorporated by reference herein.
BACKGROUND
[0002] 1. Field of the Invention
[0003] The present invention relates generally to hearing
prostheses, and more particularly, to simultaneous delivery of
electrical and acoustical stimulation in a hearing prosthesis.
[0004] 2. Related Art
[0005] Hearing prostheses such as cochlear implants have been
developed to assist people who are profoundly deaf or severely
hearing impaired, by enabling them to experience a hearing
sensation representative of the natural hearing sensation. For most
such individuals the hair cells in the cochlea, which normally
transduce acoustic signals into nerve impulses to be interpreted by
the brain as sound, are absent or have been partially or completely
destroyed. Cochlear implants bypass the cochlear hair cells to
directly deliver electrical stimulation to the auditory nerve with
this electrical stimulation being representative of the sound.
[0006] Cochlear implants have traditionally included external and
internal components. A speech processor worn on the recipient's
body detects external sounds using a microphone and converts the
detected sounds into a coded signal utilizing an appropriate speech
processing strategy.
[0007] This coded signal is then sent via a transcutaneous link to
a receiver/stimulator unit implanted in the mastoid bone of the
recipient. The receiver/stimulator unit processes the coded signal
into a series of stimulation sequences which are then applied
directly to the auditory nerve via an array of electrodes
positioned within the cochlea, proximal to the modiolus of the
cochlea. One such cochlear implant is set out in U.S. Pat. No.
4,532,930, the contents of which are hereby incorporated by
reference herein.
[0008] With improvements in technology it is possible that the
external speech processor and implanted stimulator unit may be
combined to produce a totally implantable cochlear implant unit
that is capable of operating, at least for a period of time,
without the need for any external device. In such a device, a
microphone may be implanted within the body of the recipient, for
example in the ear canal or within the stimulator unit, and sound
would be detected and directly processed by a speech processor
within the stimulator unit, with the subsequent stimulation signals
delivered without the need for any transcutaneous transmission of
signals. Such a device would, however, still have the capability to
communicate with an external device when necessary, particularly
for program upgrades and/or implant interrogation, and to modify
the operating parameters of the device.
[0009] Much effort has gone into developing stimulation strategies
to provide for device customization to produce the best available
percepts for the prosthesis recipient. Nevertheless it is
acknowledged in the cochlear implant field that the percepts
produced by pulsatile electrical stimulation often sound unnatural
and somewhat harsh. Many recipients adapt to this sound and, after
some time, even find it natural. This is not always the case,
however, and some recipients may experience difficulties. For
example, for some recipients having residual hearing, the
expectation of harsh and/or unnatural sounding percepts produced by
a cochlear implant has been less attractive than simply persisting
with residual hearing, usually assisted by an acoustic hearing
aid.
SUMMARY
[0010] According to an exemplary embodiment, there is a bimodal
hearing prosthesis comprising
an electrical signal analyser configured to process a first
frequency sub-range of a detected sound signal for electric
stimulation of the cochlea; and a delay circuit configured to
impose a delay on at least one of an electrical signal delivery
path and an acoustic signal delivery path, to provide for delivery
of the electrical stimulation to the cochlea at a desired time
relative to a time of arrival of acoustic stimuli at the cochle,
wherein the acoustic stimuli arriving at the cochlea and the
electrical stimulation delivered to the cochlea at the desired time
substantially simultaneously stimulate the cochlea.
[0011] According to another exemplary embodiment, there is a
hearing prosthesis comprising:
an electrode array configured to apply electrical stimuli to a
recipient's cochlea, an acoustic transponder configured to apply
acoustic signals to an ear of the recipient, and a processor
configured to process a detected sound signal and to produce
signals defining electrical stimuli for application by the
electrode array to at least a portion of a recipient's cochlea, and
configured to process the detected sound signal to produce
BRIEF DESCRIPTION OF THE DRAWINGS
[0012] By way of example only, embodiments of the invention will be
described with reference to the accompanying drawings, in
which:
[0013] FIG. 1 is perspective view of an exemplary cochlear implant
prosthesis in which embodiments of the present invention may be
advantageously implemented;
[0014] FIG. 2 is a block diagram of one embodiment of a bimodal
hearing prosthesis for applying acoustic stimulation and electrical
stimulation to a cochlea at a controlled time relative to each
other;
[0015] FIG. 3 is a block diagram of another embodiment of a bimodal
hearing prosthesis for applying electrical stimulation to a cochlea
at a controlled time relative to normal acoustic stimulation;
[0016] FIG. 4 is a circuit block diagram of a processing path
through the acoustic signal analyzer illustrated in FIG. 2;
[0017] FIG. 5 is a flowchart of one embodiment of a method of
measuring a difference in delay between an acoustic signal delivery
path and the electrical signal delivery path.
[0018] FIG. 6A is a schematic drawing of an implementation of an
intra-operative determination of insertion depth of an electrode
array in a cochlea having residual acoustic hearing capability;
[0019] FIGS. 6B and 6C are charts of measured ECAP responses in the
implementation of FIG. 6A;
[0020] FIG. 6D is a flowchart illustrating the intra-operative
process of FIG. 6A;
[0021] FIG. 7A is a schematic drawing of post operative
determination of a patient map for a cochlea having residual
acoustic hearing capability;
[0022] FIGS. 7B and 7C are charts of measured ECAP responses in the
implementation of FIG. 7A;
[0023] FIG. 7D is a flowchart illustrating the post-operative
process of FIG. 7A;
[0024] FIG. 8 is a schematic drawing of mapping a device using both
electrical and acoustic modes of stimulation; and
[0025] FIG. 9 illustrates a system for clinical testing and/or
fitting of a cochlear implant to be used to supplement the residual
acoustic hearing capability of a cochlea.
DETAILED DESCRIPTION
[0026] Before describing the features of the present invention, it
is appropriate to briefly describe the construction of a cochlear
implant system with reference to FIG. 1.
[0027] Cochlear implants typically consist of two main components,
an external component including a sound processor 129, and an
internal component including an implanted receiver and stimulator
unit 122. The external component also includes an on-board
microphone 127. The sound processor 129 is, in this illustration,
constructed and arranged so that it can fit behind the outer ear
111. Alternative versions may be worn on the body or it may be
possible to provide a fully implantable system which incorporates
the speech processor and/or microphone into the implanted
stimulator unit. Attached to the sound processor 129 is a
transmitter coil 124 which transmits electrical signals to the
implanted receiver and stimulator unit 122 via an RF link.
[0028] The implanted component also includes a receiver coil 123
for receiving power and data from transmitter coil 124. A cable 121
extends from the implanted receiver and stimulator unit 122 to the
cochlea 112 and terminates in an electrode array 120. The electrode
array 120 comprises a plurality of electrodes 125. The signals thus
received are applied by array 120 to the basilar membrane 108
thereby stimulating the auditory nerve 109. While the cochlea is
generally spiral shaped as shown, it is convenient to describe
electrode positions and the like as being "along" the cochlea
between a basal end of the cochlea and an apical end of the cochlea
as if the cochlea were unrolled to lie straight. The operation of
such a device is described, for example, in U.S. Pat. No.
4,532,930.
[0029] Further, in certain embodiments, sound processor 129 may be
connected to an ear mold (not shown) or other similar device, such
as those commonly used with hearing aids, for delivery of acoustic
signals to the implant recipient. As will be described in greater
detail below, this permits such certain embodiments of sound
processor 129 to simultaneously deliver both electrical stimuli via
electrode array 120 and acoustic signals via a loudspeaker within
sound processor 129.
[0030] Sound processor 129 of cochlear implant 100 may perform an
audio spectral analysis of the acoustic signals to output channel
amplitude levels. Sound processor 129 may also sort the output
channel amplitude levels in order of magnitude, or flag the
spectral maxima as used in the SPEAK strategy developed by Cochlear
Ltd. Multi-channel adaptive processing may be applied, for example,
by use of the adaptive dynamic range optimization (ADRO) technique
set out in U.S. Pat. No. 6,731,767, which is hereby incorporated by
reference herein.
[0031] With the continued improvement in surgical techniques,
resulting in minimal or no damage to the internal structure of a
recipient's ear, and the increase in performance of cochlear
implants, more recipients have useful residual hearing capability.
Aspects of the present invention provide for electrical and
acoustic stimulation of the cochlea. Such bimodal stimulation takes
advantage of the recipient's residual natural hearing capability,
while supplementing that natural hearing with electrical stimuli to
convey sound information which is only partially conveyed or is not
conveyed by the natural hearing of the recipient.
[0032] The bimodal stimulation may be controlled by a speech
processor having the ability to process detected sound to produce
both electrical stimulations for application by an electrode array
and acoustic stimulations for application by a hearing aid.
Alternatively, bimodal stimulation of present invention may be
controlled by a speech processor that produces electrical
stimulation only, to be used in conjunction with acoustic
stimulation that naturally enters the ear. Alternatively, a first
speech processor for generating electrical stimulations may be used
in conjunction with a second speech processor for producing
acoustic stimulations.
[0033] Further, it is desirable to optimize the combination of
electrical and acoustical stimulation in the fitting process,
whether intra-operatively in the positioning of the electrode
array, or post-operatively in establishing an optimal recipient
map, or both. It may further be desirable to determine which
electrodes are to be active and which are to remain inactive, to
determine the frequency allocation of each active electrode so as
to optimize the combinatory hearing, and to apply channel-specific
gain to optimize the timing of delivery of stimuli by each active
electrode.
[0034] FIG. 2 is a block diagram of one embodiment of a bimodal
hearing prosthesis 200 capable of applying acoustic stimulation and
electrical stimulation to a cochlea at a controlled time relative
to each other. A microphone 202 detects sound signals and passes
corresponding electrical signals to a preprocessor 204.
Preprocessor 204 filters the electrical signals and passes a signal
component in a first frequency sub-band to an electrical signal
analyzer 208, and passes a signal component in a second frequency
sub-band to an acoustic signal analyzer 206. In this embodiment the
first frequency sub-band comprises a high frequency portion of the
audible frequency spectrum, which corresponds to a basal region of
a cochlea adjacent to which an electrode array has been positioned.
The second frequency sub-band comprises a low frequency portion of
the audible frequency spectrum, which corresponds to an apical
region of the cochlea in which residual natural hearing of the
cochlea has been retained.
[0035] Bimodal hearing prosthesis 200 of FIG. 2 further comprises a
loudspeaker 210 for acoustically stimulating the cochlea, and a
stimulator unit 212 for electrically stimulating the cochlea.
Loudspeaker 210 may, for example, be any type of loudspeaker such
as those commonly used with hearing aids. Further, any type of
mechanism may be utilized to deliver acoustic sound from
loudspeaker 210 to the implant receiver, such as, for example, an
ear mold, an ear hook, etc.
[0036] In accordance with certain embodiments of the present
invention, acoustic signal analyzer 204 and electrical signal
analyzer 208 comprise respective delay circuits 214A and 214B,
respectively, for delaying one or both of the electrical signals to
ensure substantially simultaneous stimulation of the cochlea by
loudspeaker 210 and the cochlear implant 212. Such delay circuits
214A and 214B may be any type of delay circuits now or later
developed, and may be implemented in hardware, software or any
combination thereof. For example, delay circuits may comprise one
or more commercially available digital delay integrated chips or be
implemented by software executing on a processor of signal
analyzers 206 and/or 208, respectively. Or, for example, delay
circuits for signal analyzers 206 and 208, respectively may be
implemented by a common processor used in implanting both signal
analyzers 206 and 208.
[0037] Substantial simultaneous stimulation of the cochlea is
desirable so that the implant recipient does not perceive a delay
between the two types of stimulations. Such a delay could be
bothersome to the implant recipient and interfere with the
enjoyment and/or effectiveness of the recipient's hearing. It
should be noted that FIG. 2 is a simplified diagram provided for
explanatory purposes. In actual implementations, bimodal hearing
prosthesis 200 may include various other components along both the
electrical signal delivery path 203 and acoustic signal delivery
path 205, such as, for example, equalizers, etc.
[0038] FIG. 3 is a block diagram of an alternative embodiment of a
bimodal hearing prosthesis 300 in which electrical stimulation is
applied to a cochlea at a controlled time relative to normal
acoustic stimulation. A sound signal 301 is detected by a
microphone 302, and also passes along the natural acoustic delivery
path 303 to the cochlea. Microphone 302 passes a corresponding
electrical signal along electrical signal delivery path 305 to
pre-processor 304, which in turn passes a pre-processed electrical
signal to the electrical signal analyzer 306. Analyzer 306 passes
signals to a stimulator unit 308 for electrical stimulation of the
cochlea.
[0039] Analyzer 306 comprises a delay circuit 310 for delaying the
electrical signal in order to ensure substantially simultaneous
stimulation of the cochlea by stimulator unit 308 and the sound
passing along acoustic delivery path 303.
[0040] FIG. 4 is a circuit schematic of a processing path 400
through the acoustic signal analyzer of FIG. 2 (block 204) of a
signal for acoustic stimulation of the cochlea. A sound signal is
received by microphone 200 (FIG. 2) which generates a corresponding
electrical signal that is pre-amplified, converted from analog to
digital and passed through automatic sensitivity control circuitry
in preprocessor 202 (FIG. 2). The resulting signal 402 is input to
an acoustic gain amplifier 410, and then passed through a 1:4
down-sampler 412, an input automatic gain controller (AGC) 414 and
an AGC gain 416. A filter bank 418 divides the signal into eight
frequency bands 420a . . . 420h. Each frequency band 420 is
processed by a respective AGC 422 and AGC gain 424. In accordance
with embodiments of the present invention, each channel is then
passed through an associated delay circuit 426, with each delay
circuit 426 applying a channel-specific delay. The channels are
then reconstructed by a reconstructor 428, and passed through a
volume control amplifier 430, a peak clipper 432 and a 1:4
up-sampler 434 before being passed to loudspeaker 206 (FIG. 2) for
acoustic stimulation of the cochlea. Thus, in addition to
processing path 400, an acoustic signal delivery path comprises the
propagation path of the acoustic signal from the loudspeaker,
through the outer ear and middle ear into the inner ear.
[0041] In addition to applying channel-specific delays along the
acoustic signal delivery path, the electric signal analyzer of
FIGS. 2 and 3 (blocks 208 and 306) may also be able to apply
independent channel-specific delays using delay circuits. These
channel-specific delays may be set such that selected low frequency
electrical channels are delayed for a longer time than higher
frequency electrical channels. Such an embodiment may be used to
mimic the time taken for sound to travel from a basal region of the
cochlea tonotopically corresponding to the high frequency channels
to a more apical region of the cochlea tonotopically corresponding
to the low frequency channels.
[0042] Embodiments of the present invention may further recognize
that appropriate configuration of the delay can be assessed
objectively without requiring subjective patient responses, by
detecting a neural response evoked by acoustic and/or electrical
stimulation. The sensing of the evoked neural response is
preferably performed in accordance with the method set out in U.S.
patent application Ser. No. 10/475,141 entitled "Method and
Apparatus for Measurement of Evoked Neural Response," the contents
of which are hereby incorporated by reference herein. By
eliminating the need for subjective patient responses in
determining the respective timing of delivery of acoustic and
electrical stimuli, such embodiments may be particularly
advantageous where the recipient is a young child unable to
indicate subjective responses to cochlea stimuli.
[0043] FIG. 5 is a flowchart of one embodiment of a method of
measuring a difference in delay between an acoustic signal delivery
path and the electrical signal delivery path so that the difference
in delays can be accounted for in order to ensure simultaneous
delivery of stimulation. First, at block 502, the delay along the
acoustic signal delivery path may be measured. This may be
accomplished by generating an acoustic signal, preferably of short
duration that is received by microphone 200 (or 302). The
Electrically Evoked Compound Action Potentials (ECAP) caused by
this acoustic signal may then be measured using a cochlear implant
system, such as, for example, the cochlear implant system discussed
in the above referenced U.S. patent application Ser. No.
10/475,141. The difference in time between when the acoustic signal
was generated and the time of the ECAP measurement can then be
calculated to provide the effective delay along the acoustical
signal delivery path. In one embodiment, the frequency for this
audio signal may be chosen such that it will be delivered along the
acoustic signal delivery path and not by the electrical signal
delivery path. That is, the frequency of the audio signal may
selected so that it is included in the band of frequencies that
will be provided via acoustic stimulation and not via electrical
stimulation.
[0044] Next, at block 504 the effective delay of the signal along
the electrical signal delivery path may be measured. This may be
accomplished by generating an acoustic signal that is received by
microphone 200 (or 302). The frequency for this acoustic signal is
preferably selected so that this signal will be delivered via the
electrical signal delivery path and not the acoustic signal
delivery path (i.e., the implant recipient lacks normal hearing for
this frequency). The ECAP resulting from this acoustic signal may
then be measured. The difference in time between when the acoustic
signal was generated and the time of the ECAP measurement can then
be calculated to provide the effective delay along the electrical
signal delivery path. The difference between the determined delays
along the acoustic and electrical signal delivery paths may then be
calculated at block 506. This difference may then be used at block
508 to adjust the delay circuits of the acoustic signal analyzer
204 and/or electrical signal analyzer 208 or 306 to ensure that
signals traveling along these two paths are delivered
simultaneously.
[0045] In implementing embodiments of the present invention, it is
desirable to implant the electrode array without affecting the
residual hearing, whether by adversely influencing the fluid
dynamics of the inner ear or by damaging inner ear structures. The
risk of such damage, and in particular the likelihood of
perforating of the basilar membrane which would destroy all
remaining hearing, increases with insertion depth of the electrode
array. Damage to the lateral or modiolar wall of the cochlea may
also occur during implantation. A partial insertion of the array
reduces the risk of such damage. On the other hand, use of suitable
surgical implantation techniques and suitable electrode arrays may
enable complete insertion with an acceptable risk of such damage,
in accordance with certain aspects of the present invention.
[0046] Further, it is desirable to optimize the combination of
electrical and acoustical stimulation in the fitting process,
whether intra-operatively in the positioning of the electrode
array, or post-operatively in establishing an optimal patient map,
or both. It may further be necessary to determine which electrodes
are to be active and which are to remain inactive, and to determine
the frequency allocation of each active electrode so as to optimize
the combinatory hearing.
[0047] It should be appreciated that a recipient's residual hearing
capability can be assessed objectively without requiring subjective
recipient responses by detecting a neural response evoked by
acoustic and/or electrical stimulation. For instance, an electrode
of the electrode array may be used as a sense electrode for sensing
an evoked neural response. The sensing of the evoked neural
response is preferably performed in accordance with the method set
out in International Patent Publication Number WO 02/082,982, the
contents of which are hereby incorporated by reference herein. By
eliminating the need for subjective recipient responses in
determining a residual hearing capability, embodiments of the
present invention enable intra-operative determination of residual
hearing, thus providing for the ability to intra-operatively
determine optimal insertion depth or position of the electrode
array. Further, measurement of the evoked neural response can be
used to objectively post-operatively optimize the electrode mapping
configuration for each electrode position along the cochlea, for a
recipient with residual hearing.
[0048] Such embodiments of the present invention also recognize the
difficulty in precisely mapping a particular frequency to a
position on the cochlea corresponding to that frequency. That is,
it is difficult to accurately define an appropriate insertion depth
for a partial insertion of an electrode array based on a previously
measured audiogram of the cochlea. Further, it is difficult to know
an actual depth to which an array has been inserted, even when
imaging the array and cochlea during insertion, for example by
X-ray.
[0049] Similarly, once an array is inserted, whether partially or
fully, it is difficult to accurately map frequency bands to
electrodes to correspond to a position of each electrode along the
cochlea. This problem is compounded by the fact that an acoustic
stimulation position for a particular frequency may not necessarily
correspond to an appropriate electrical stimulation position for
that frequency. Incorrect array positioning and/or incorrect
frequency allocation to electrodes will lead to shifted frequency
delivery to the cochlea, and can lead to contraposition of the
acoustically delivered frequency range against the electrically
delivered frequency range.
[0050] However, by sensing the evoked neural response, such
embodiments of the invention enable such frequency vs. position
determinations to be carried out with reference to an actual
position of the sense electrode.
[0051] Such objective measurement of the residual hearing
capability of the cochlea may further be particularly advantageous
where the recipient is a young child unable to indicate subjective
responses to auditory stimuli, and thus unable to assist in
measurement of an audiogram. A cut-off frequency at the limit of
the residual hearing is preferably also determined with reference
to objective neural measurements rather than a subjective
audiogram. One reason to prefer objective measurement of the
cut-off frequency is that the limited frequency resolution of a
partially damaged cochlea raises the possibility that a stimuli of
a first frequency will produce a subjective response in the
patient, but only because that frequency raises a neural response
in auditory nerves which are typically considered to relate to a
different (usually lower) frequency. In such circumstances, the
auditory nerve relating to the first frequency may be inoperable,
yet stimulation at that frequency causes a subjective response,
which may lead to an incorrect conclusion that the auditory nerves
relating to the first frequency are operable. To the contrary, an
objective interactive measurement of a neural response may avoid
this problem. Additionally or alternatively, use of the TEN test
developed by Moore et al (Moore, B. C. J., Glasberg, B. R., Stone,
M. A., 2004, A new version of the TEN test with calibrations in dB
HL. Ear Hear. 25, 478-487) may be used to accurately measure the
position of residual hearing in the cochlea.
[0052] To obtain a detailed impression of the residual hearing
capability of the cochlea and of how electrical and acoustic
stimulation will interact, several measurements of the neural
response are preferably obtained. To address the localized
sensitivity of the cochlea to electrical stimuli, the neural
response evoked by an electrical stimulus at a specific location
along the cochlea is preferably obtained, for a plurality of
positions along the cochlea. Further, the neural response evoked by
acoustic stimulation at specific frequencies is preferably
determined by applying a short duration acoustic stimulus of
specific frequency and using an electrode in a position
tonotopically corresponding to that frequency to measure the neural
response evoked by the acoustic stimulation, for a plurality of
frequencies in the range audible to normal hearing. Additionally,
the interaction between acoustic stimuli and electrical stimuli is
preferably assessed by recording electrically evoked compound
action potentials in the presence of acoustic masker stimuli, and
also recording acoustically evoked compound action potentials in
the presence of electrical masker stimuli. An appropriate
electrical masker stimuli may comprise a forward masking paradigm,
with a burst of electrical masker preceding the acoustical signal.
An electrical masker stimuli may comprise a pulse burst at a rate
equal to the mapping rate on a single electrode. An acoustic masker
stimuli may comprise broadband or narrowband noise at high levels,
with narrowband noise suitable for investigating tonotopic
(frequency to location) characteristics of the cochlea.
[0053] It should be noted that, as explained by Fourier theory,
there may be a conflict between generating both short duration
signals and frequency specific signals. For example, the shortest
acoustic signal, a click, has a broad spectrum and the sharpest
frequency (a tone) has infinite duration. As noted above, it is
preferable to measure ECAPs using short duration stimuli in order
make it easier to synchronize the response with the acoustic
signal. As such, the duration and frequency (or frequency band) of
the signal are preferably chosen with this in mind Options for
generating acceptable short duration frequency specific signals for
use in embodiments of the invention include, but are not limited
to, using a band pass filtered click (i.e., filtering a click with
a bandpass filter tuned to the desired frequency) or using a very
short tone pip. These techniques are well known to those of skill
in the art and are commonly used in clinical measurements such as
electro-cochleography (ECOG) measurements, measurements of compound
action potentials with a needle electrode on the cochlear bone, and
auditory brainstem response (ABR) measurement, such as ABR
measurements where external scalp electrodes are used.
[0054] The amplitude of compound action potentials produced by
acoustic stimuli and electrical stimuli are around the same order
of magnitude and thus interfere in a measurable way. To provide for
such measurements, a system could be used comprising a cochlear
implant with neural response measurement and recordal capabilities,
software to drive appropriate stimulus and measurement procedures,
and an acoustic stimulator.
[0055] Features of another embodiment of the present invention are
illustrated in FIGS. 6A to 6D. In this embodiment, an optimal
insertion depth of an electrode array is intra-operatively
determined. In recipients with residual hearing it is difficult to
determine a suitable depth of insertion of the electrode array due
to difficulties in precisely determining the location of the
electrode, or due to difficulties in precisely determining the
location of surviving neural elements that still can respond to
acoustical stimulation. In this embodiment, since residual hearing
usually exists on the more apical (lower frequency) part of the
cochlea; the electrode array is introduced only until the point
where usable hearing begins. An advantage of this technique is that
trauma is reduced to a minimum, and that the cochlear mechanics and
fluid dynamics (especially at the point where residual hearing is
present) are minimally influenced. That is, no portion of the
electrode array is positioned adjacent to the apical portion of the
cochlea having residual acoustic hearing capability, and the array
is thus less likely to interfere with or damage the residual
acoustic hearing ability of that portion of the cochlea, while
providing electrical stimulation to the basal portion of the
cochlea lacking in acoustic hearing capability. Accordingly,
surgical trauma to the apical portion of the cochlea may be avoided
or minimized by this method.
[0056] The optimal insertion depth is determined intra-operatively
during the insertion of the electrode array, by investigating the
interaction between electrically evoked and acoustically evoked
neural responses locally at the point of insertion of the tip of
the electrode array. The electrode array is advanced by increments
into the cochlea, with the interaction being determined after each
incremental advance. When an increase of the interaction strength
is determined the insertion is halted, or the electrode may be
slightly withdrawn, as the electrode tip has then reached a point
where residual hearing exists.
[0057] In one embodiment, the interaction between the electrical
and acoustical interaction is evaluated as follows. Initially, the
most apical electrode records a first compound action potential
evoked by application of an electrical stimulus of a given
amplitude. The most apical electrode is then used to record a
second compound action potential evoked by application of an
essentially identical electrical stimulus of the same amplitude, in
the presence of a background acoustic noise, preferably a narrow
band background acoustic stimulus of a frequency substantially
corresponding to the position of the tip electrode, applied to the
cochlea. Should the first recorded ECAP and the second recorded
ECAP be substantially identical, it can be assumed that the apical
electrode of the array is yet to reach the residual functional
`normal hearing` part of the cochlea. However, should the first
recorded ECAP and the second recorded ECAP substantially differ,
this gives an indication that the presence of masking acoustic
noise is evoking a component of neural response which interferes
with that evoked by the electrical stimulus. Accordingly, the
portion of the cochlea proximal to the apical electrode exhibits
residual acoustic hearing capability.
[0058] In another embodiment, the frequency where the hearing loss
starts is determined using an audiogram. This frequency may then be
used in determining the location in the cochlea where the hearing
loss starts. For example, in an embodiment, the electrode array is
stimulated at its tip at the frequency corresponding to the start
of useful hearing. The electrode array is then advanced by
increments into the cochlea with the interaction being determined
after each incremental advance as with the above-described example.
This process is then repeated until the tip of the electrode array
reaches the point where the first recorded ECAP and second recorded
ECAP substantially differ. This location is then determined to be
the location where hearing loss starts. As such, this embodiment
differs from the above embodiment in that in this embodiment the
frequency is kept constant during insertion.
[0059] This procedure is schematically indicated in FIG. 6A. At
620, the recipient's audiogram is displayed, with considerable
residual acoustic hearing capability evident in the low
frequencies. A cut-off frequency for useful hearing is indicated at
line 621, which also marks the location in the unrolled cochlea
diagrams 624 and 627 where residual hearing terminates. In the
unrolled cochlea, the area 625, 628 of the cochlea that can be
measurably masked by a broadband acoustical masking stimulation is
indicated by a hashed background. If the electrode array 622 is
inserted with the tip in the deaf part of the cochlea (cochlea
diagram 624) and an ECAP is recorded at the apical electrode with
and without a background acoustical masker, no difference in ECAP
amplitude is expected, as indicated by the ECAP graph of FIG. 6B.
However, when the electrode array tip is introduced into the
acoustically maskable region 628 (corresponding to the region
containing residual hearing), as shown in cochlea diagram 627, the
ECAP amplitude with a background acoustical masker present varies
significantly from that of the unmasked NRT, as indicated by the
ECAP graph of FIG. 6C. As illustrated, in this example, the ECAP
amplitude with a background acoustical masker present is lower than
that of the unmasked NRT. However, in other examples, the ECAP
amplitude with a background acoustical masker present may be higher
than that of the unmasked NRT.
[0060] FIG. 6D is a flowchart of one embodiment of the
intra-operative process illustrated in FIGS. 6A to 6C. At block 630
the process commences, after which the electrode array is
incrementally advanced by a small amount into the cochlea at block
531. An electrical stimulus is then applied at block 632 in the
absence of acoustic stimulation, and a first ECAP denoted
ECAP.sub.x is recorded at block 633 using the apical electrode of
the array. Subsequently, another electrical stimulus substantially
identical to the first stimulus is applied at block 634
simultaneously with an acoustical masking stimulation. The apical
electrode is again used at block 635 to measure a second ECAP,
denoted ECAP.sub.y. At block 636 a comparison is made between
ECAP.sub.x and ECAP.sub.y. Should ECAP.sub.x be substantially
identical to ECAP.sub.y, this indicates that the presence of the
acoustic masking signal has made no measurable difference to the
evoked neural response, thus indicating that there exists no
residual acoustic hearing capability at the current position of the
apical electrode. Accordingly, the process returns to block 531 at
which the electrode array is again incrementally advanced into the
cochlea and the process is repeated to determine whether residual
acoustic hearing capability exists at the new location of the
apical electrode. Should ECAP.sub.x be different to ECAP.sub.y,
this indicates that the presence of the acoustic masking signal has
made a difference to the evoked neural response, thus indicating
that residual acoustic hearing capability exists at the present
position of the apical electrode. Accordingly, at block 637 the
insertion is halted and the process ends at block 638.
[0061] In addition to merely determining a point at which residual
acoustic hearing capability commences, the process may further
include assessing a relative strength of the acoustic hearing
capability beyond the threshold, by further inserting the electrode
array during the operation for such assessment, and withdrawing the
array to its desired post operative position prior to the
conclusion of the operation.
[0062] In one embodiment the electrode array has a number of
electrodes which is significantly greater than the number of
channels to be applied by the speech processing scheme to be
implemented. Such an electrode is set out in International
Publication No. WO 03/003791, the contents of which are hereby
incorporated by reference herein. Providing an increased number of
electrodes from which to choose for use in applying each signal
channel recognizes that, depending on the surgical implantation
process, some of the electrodes may be positioned adjacent the
apical portion of the cochlea and thus may be inactivated, and/or
some of the electrodes may be positioned outside the basal end of
the cochlea. Providing an electrode array with sufficiently many
electrodes ensures that a sufficient number of the electrodes are
adjacent that portion of the cochlea which lacks adequate residual
acoustic hearing capability. Such embodiments cater for the
application of, for example, all 22 signal channels of an ACE
speech processing scheme to only that portion of the cochlea which
lacks adequate residual acoustic hearing capability, and provide
for finer frequency resolution between signal channels over that
portion of the cochlea. To enable such fine frequency resolution,
the speech processing scheme implemented is preferably applied to a
subset of the audible frequency range tonotopically corresponding
to the portion of the cochlea lacking adequate residual acoustic
hearing capability.
[0063] Alternatively, once a suitable depth of insertion has been
determined, a selection may be made of a suitable length electrode
to implant. That is, the electrode used for the above determination
of suitable insertion depth may be withdrawn, and an electrode of
suitable length may be selected and then implanted to the
appropriate insertion depth to conclude the surgical procedure.
However, care must be taken to avoid or limit damage to the cochlea
during such an operative procedure.
[0064] Once such partial insertion is complete, a patient map
should be determined to allocate suitable frequencies and
amplitudes (i.e., C and T levels) to each electrode of the
partially inserted array. In particular, in allocating frequency
bands to electrodes in the patient map, it is desirable to avoid:
(a) the tip electrode(s) applying frequencies which are heard
naturally in the more apical part of the cochlea (potentially
leading to a "duplicate perception" at that frequency); or (b) the
tip electrode frequency being too high and leaving a frequency
"gap" which is neither heard naturally nor conveyed
electrically.
[0065] FIG. 7A illustrates a further embodiment of the present
invention, in which the electrode array 742 is inserted fully
within the cochlea, and involving a post-operative decision as to
which electrodes to inactivate and which to include in the patient
map. At 740 the residual hearing capability of the recipient is
illustrated, indicating significant residual hearing at low
frequencies, up to a threshold 741. Threshold 741 also indicates a
position along the cochlea at which the residual hearing portion
743 terminates. In this embodiment, only a subset of electrodes are
active in the map. Thus the natural pathway for delivery of
acoustic sound is utilized to the extent that it still exists,
while electrical stimuli are provided to convey sound information
which is no longer perceptible by the cochlea and/or to supplement
sound information only partially perceptible by the cochlea.
Accordingly, the implant recipient will receive natural sounding
percepts from those portions of the cochlea having hearing
capability. This technique is advantageous in that when the hearing
loss progresses over time, the patient map can be adjusted
accordingly, without the need for further surgical
intervention.
[0066] However, once again, in order to determine an optimal
patient map it is desirable to assess the interaction between
electrical and acoustic stimulation along the cochlea, in order to
determine the physical point 741 in the cochlea at which electrical
stimulation begins to interfere with (useful) acoustical
stimulation.
[0067] FIG. 7D is a flowchart illustrating a process for
determining a suitable patient map for the implant configuration
set out in FIGS. 7A through 7C. At block 750 the process begins,
and at block 751 a sense electrode is set to be a first electrode
of the array. At block 752 an electrical stimulus is applied in the
absence of any acoustic stimulation, and at block 753 the first
electrode is used to sense and record a first ECAP, denoted
ECAP.sub.x, evoked by the electrical stimulus applied at block
752.
[0068] Subsequently, at block 754 a substantially identical
electrical stimulus is applied, and in addition a simultaneous
acoustic stimulus is applied having at least a frequency component
tonotopically corresponding to the position of electrode n. At
block 755 the same (first) electrode is used to sense and record a
second ECAP, denoted ECAP.sub.y, evoked by the simultaneous
electrical and acoustic stimuli applied at block 754.
Alternatively, as discussed above, the frequency of the acoustic
stimulus may be set as the frequency corresponding to the point
where hearing loss begins as, for example, determined by an
audiogram. This frequency may then be kept constant as the
electrode array is incrementally inserted into the cochlea.
[0069] A comparison is then made at block 756 of ECAP.sub.x and
ECAP.sub.y. Should ECAP.sub.x be substantially identical to
ECAP.sub.y, as shown in FIG. 7B, then this indicates that the
presence or absence of acoustic stimulation has made no measurable
difference, and thus indicates that residual hearing capability
does not exist proximal to the first electrode. In this event the
first electrode is at block 657 included in the patient map in
order that the first electrode is used to apply electrical stimuli
to the cochlea to convey sound information tonotopically
corresponding to the position of that electrode, due to the natural
hearing no longer conveying such sound information. Alternatively,
should the comparison made at block 756 reveal that ECAP.sub.x is
not substantially identical to ECAP.sub.y, as shown in FIG. 7C,
then this indicates that the presence of the acoustic masking
stimulus has made a difference to the evoked neural response, thus
indicating that residual acoustic hearing capability exists
proximal to the first electrode. In this event, electrode n (n=1)
is excluded from the patient map at block 758. This process is
repeated for all electrodes of the array by incrementing n at block
759, unless all electrodes have been assessed, in which case
n=n.sub.max and decision 760 causes the process to end at block
761.
[0070] It is to be appreciated that the interaction between
electrical and acoustic stimuli may be assessed in an alternate
manner. For instance, the interaction may alternatively or
additionally be assessed by applying a narrowband acoustic stimulus
and recording an evoked CAP using a sense electrode tonotopically
corresponding to the frequency of the narrowband stimulus. Then a
substantially identical narrowband acoustic stimulus may be applied
simultaneously with a masking electrical stimulation (for example
applied by an electrode adjacent to the sense electrode), and again
recording an evoked CAP. This process may be repeated for
acoustically applied frequencies throughout the normal hearing
range with a tonotopically corresponding sense electrode for each
frequency.
[0071] Once an assessment has been made of the interaction between
acoustic and electrical stimuli along the cochlea an "interaction
map" of the cochlea may be produced, of the type illustrated by
audiogram 744 in FIG. 7A. Such an interaction map may be used in
conjunction with conventional audiometry to determine a suitable
cut off frequency 741, to determine where in the cochlea electrical
stimulation does not influence the acoustic hearing capability, to
map the processor on the non interacting electrodes only, using a
frequency allocation table (FAT) that only stimulates those
frequencies that are not represented and conveyed by the auditory
system naturally.
[0072] The audiogram shown in FIG. 7A is representative of the most
common type of hearing loss in which a cochlea loses hearing
ability at high frequencies. However it is to be appreciated that,
for a cochlea where hearing capability is deficient in alternate
ways, such as the loss of low frequency capability, the embodiment
of FIGS. 3A to 3D can still be used to provide for electrical
supplementation of residual acoustic hearing capability, wherever
that capability may exist in the operating frequency range.
[0073] The embodiments shown in FIGS. 6A to 6D and FIGS. 7A to 7D
may each be incorporated into a bimodal hearing prosthesis of the
present invention. FIG. 8 illustrates a bimodal device in
accordance with the embodiment of FIGS. 2, and 7A to 7D. Once the
cut off frequency 871 (corresponding to "cut-off electrode") has
been determined, whether by the method set out in FIG. 6B or FIG.
7B, electrical stimuli may be applied in one mode above that
frequency, and acoustic stimuli may be applied in the other mode
below that frequency. At 870 the determined masking profile is
displayed. Portion 873 of the cochlea is where residual acoustic
hearing capability exists. Knowing the acoustic cut off frequency
of that residual hearing, and knowing which electrode is located at
the cut off boundary 871 in the cochlea, it is possible to separate
detected sound 875 into two components. Below the cut-off frequency
the sound is amplified and applied to the ear acoustically, by low
pass filter 876 and transducer 877. The portion of the detected
sound above the cut off frequency is processed by a high pass
filter 878 and a cochlear implant speech processor 879 and mapped
to those electrodes that are in the non-functional part of the
cochlea. In this way the accessible frequency range is optimized,
and the interaction between acoustic and electric hearing is
minimized. It should be noted that the speech processor 879 of FIG.
8 corresponds to the electrical signal analyzer 208 of FIG. 2, and
as discussed above, may include a delay circuit for ensuring that
both acoustic and electrical stimulations are substantially
simultaneously delivered to the cochlea (i.e., the implant
recipient does not perceive a delay (or a substantial delay)
between the two signals).
[0074] It is to be appreciated that electrical stimulation may also
be used to supplement the application of acoustic stimulation to
the portion 873 of the cochlea having partial residual hearing.
Such supplemented electrical stimulation may be mapped to have a
strength to complement the residual audiogram strength along the
cochlea in region 873. Such embodiments provide for a transition
from purely acoustic hearing at the apical end of the cochlea to
purely electrical stimulation at the basal end of the cochlea, with
a central portion of the cochlea having both acoustic and
electrical stimulation applied thereto and the central portion of
the cochlea being relied upon to convey both acoustic and
electrical stimulation. Should the residual hearing be inadequate,
electrical stimulation may be applied by all electrodes of the
array, with apical electrodes being mapped to have a strength which
complements the residual acoustic hearing strength of the portion
873 of the cochlea.
[0075] Further, high pass filter 878 may be excluded where an
appropriate patient map exists in speech processor 879 which
inactivates apical electrodes of the array.
[0076] FIG. 9 illustrates a system 900 for clinical testing and/or
fitting of a cochlear implant 902 to be used to supplement the
residual acoustic hearing capability of a cochlea. A trigger signal
901 is applied electrically via the electrode array of the cochlear
implant 902 and acoustically via headphones 903. The trigger signal
in the system 900 illustrated is generated by a personal computer
(PC) with infrared connection via L34, a digital to analogue
converter and a clinical audiometer to the headphones 903, and via
L34, PCI and a Sprint speech processor to the cochlear implant 902.
The PC-infrared-L34-DAC connection may alternatively be provided by
a triggerable signal generator with analogue output. For example,
system 900 may be used in obtaining intra-operative NRT recordings
of both electrical and acoustic stimuli to determine suitable array
insertion depths.
[0077] System 900 may further be used to determine suitable delays
to be introduced in order to ensure accurate timing of the delivery
of electrical stimulations relative to acoustic stimulations. Such
an embodiment recognizes that, due to the differing pathways for
delivery of acoustic stimuli and electric stimuli to the cochlea,
neural responses caused by electrical stimuli may be mistimed
relative to neural responses caused by acoustic stimuli. In certain
circumstances such as mistiming may reduce the intelligibility of
speech or otherwise have an undesirable effect on sound perception
by the user. Should neural responses to acoustic stimuli arise
after neural responses to electrical stimuli, for instance due to
the time of transmission from the outer ear, through the middle
ear, into the inner ear and via the basilar membrane, an
appropriate delay in applying electrical stimulation is preferably
introduced. The timing of the electrical stimulations relative to
the timing of the acoustic stimulations may be optimized by use of
neural response measurements, such as those discussed above, and
appropriate adjustments are preferably made to the delay in
delivery of electrical stimuli by for example adjusting the delays
of delay circuits included in the electrical signal delivery path
and/or the acoustic signal delivery path such as was discussed
above with regards to FIGS. 2-4.
[0078] Uses of embodiments of the present invention include
research and auditory states monitoring, in which a bimodal speech
processor could generate an acoustical stimulus and record the
resulting CAP, comparing it to previous CAP recordings. If the
recipient's hearing is further deteriorating and refitting is
needed, this could be detected automatically by such a system.
Embodiments of the present invention may further provide for high
resolution audiogram imaging in combination with classical
audiometry, and may provide for detection of double peaks in the
neural response.
[0079] It is to be appreciated that determination of tonotopic
cochlear positions in this document is not limited to a classical
determination of cochlear position relative to frequency or pitch.
In particular, it is to be appreciated that existing formulae to
relate cochlear position to pitch, such as Greenwood's formulae (J.
Acoust. Soc. Am. Vol 87, No 6, June 1990) may not always be
sufficiently accurate in relation to tonotopic cochlear positions
for electrical stimuli.
[0080] Any discussion of documents, acts, materials, devices,
articles or the like which has been included in the present
specification is solely for the purpose of providing a context for
the present invention. It is not to be taken as an admission that
any or all of these matters form part of the prior art base or were
common general knowledge in the field relevant to the present
invention as it existed before the priority date of each claim of
this application.
[0081] Throughout this specification the word "comprise", or
variations such as "comprises" or "comprising", will be understood
to imply the inclusion of a stated element, integer or step, or
group of elements, integers or steps, but not the exclusion of any
other element, integer or step, or group of elements, integers or
steps.
[0082] It will be appreciated by persons skilled in the art that
numerous variations and/or modifications may be made to the
invention as shown in the specific embodiments without departing
from the spirit or scope of the invention as broadly described. The
present embodiments are, therefore, to be considered in all
respects as illustrative and not restrictive.
[0083] All documents, patents, journal articles and other materials
cited in the present application are hereby incorporated by
reference.
* * * * *