February 5 th 2002

1. February 5th 2002 Cochlear Implants for Reviewers A presentation made to the ENT section of the FDA

2. Cochlear Implants for Reviewers 1: The Design of History

3. Early Efforts: The Tonotopic Theory • Based on the work of von Békésy, most early cochlear implant researchers as-sumed that the only viable way to stim-ulate the cochlea was to place electrodes along the basilar membrane and stimulate the dendrites which were presumed to be present: “place = frequency” • Dr. Fred Linthicum of House Ear Institute subsequently demonstrated histologically that lack of hair cells generally meant lack of dendrites, and it is now universally assumed that the spiral ganglion cells within the modiolus are the site of stimulation

4. Early Efforts : The Tonotopic Theory • Dr. House accepted the tonotopic theory, and, with the help of some volunteer patients, implanted hard-wired, 5 electrode systems to develop a usable device • He found that his patients did not report great differences between “place” (tonotopic) stimulation and general stimulation (unpublished data) • This would not, could not be the case if it were required to stimulate tonotopically • Other researchers reported similar results • This was very strange— inexplicable, in fact— but the clinical result was undeniable

5. Single Electrode Implants: Overview • As a result of these clinical results, the first single electrode cochlear implants— indeed, the first practical cochlear implants of any sort— were developed • Incoming sounds were amplitude modulated on a full-time, 16-24 kHz signal and injected into the cochlea • The field developed is apparently present globally, stimulating all spiral ganglion cells and nerves simultaneously • These are “analog presentation” cochlear implants

6. Single Electrode Implants: Overview • From the beginning, it was assumed— without clear evidence and for reasons that we will explore— that multiple electrode (“multiple channel”) cochlear implants would work better • “Until… multichannel prostheses become a reality, one must consider the question of whether or not it is reasonable to continue implanting single-channel prostheses.” • “Above all, a single channel auditory input will not provide a speech input that either sounds speech-like, or is understandable.” • Bilger RC, et al. Implanted auditory prosthesis an evaluation of subjects presently fitted with cochlear implants. Trans Am Acad Ophthalmol Otolaryngol 1977 Jul-Aug;84 (4 Pt 1)ORL-677-82. • The Bilger report on a handful of early single electrode patients inferred these criticisms in 1977, before any multiple electrode devices were even available for comparison, and no data provided support such conclusions; they appear to be based entirely in theory

7. Early Efforts : Multiple electrode devices • In such a climate (as indicated by the Bilger quotes) it is not surprising that other researchers started by building multiple electrode devices; they never tried any alternatives • With early designs, it was impossible to stimulate the cochlea at multiple sites simultaneously because of unwanted signal interactions • Because of the capacitive nature of the cochlea, stimulation had to be followed by “radio silence” to allow charges to drain away • These devices used pulsatile stimulation, shifting rapidly between frequencies (sites of stimulation)

8. Early Efforts : Multiple electrode devices • Multiple electrode implants: • Incoming sounds are separated into different frequency bands • Each frequency band is assigned to a different electrode pair • When stimulating for the higher frequencies, the frequency of the stimulating signal has not been thought to be important (i.e. 1200-1500 pps is common) • Stimulation is pulsatile and discontinuous (staccato) • These are “pulsatile presentation” cochlear implants

9. Two Basic Kinds As a result of this history, there are two basic kinds of cochlear implants multiple, long electrode single, short electrode (pulsatile presentation) (analog presentation)

10. Cochlear Implants for Reviewers 2: Design, Function, Surgical Placement

11. Single Electrode Implants: Design • Many different kinds of “analog presentation” implants can be imagined, but the specific design of the current AllHear devices is rather simple • The internal receiver consists of few parts:

12. Single Electrode Implants: Design • The external processor, as yet, is likewise very simple:

13. Single Electrode Implants: Design • The external processor amplifies sounds and combines them with a 16-24 kHz carrier (amplitude modulation) • The AC output is sent through the external coil, which develops an alternating magnetic field • This field interacts with the internal coil, inducing a corresponding AC current which is sent through the electrodes • The present design processor uses “clipping” to control overloud signals

14. Single Electrode Implants: Design

15. Single Electrode Placement Insertion of no more than 6mm preserves cochlear structures and residual hearing…

16. Multiple Electrode Placement “Deep insertion” of 20mm or more is known to destroy cochlear structures and tends also to damage residual hearing…

17. Multiple (long) vs. Single (short) The contrast between the two provides for greater safety during the surgical procedure

18. Cochlear Implants for Reviewers 3: The Perception of Percept

19. Single Electrode: the perception of percept • All presently manufactured cochlear implants approved for general use in the US, Europe and Japan use multiple electrodes • If, as Dr. House found, there is little difference between patient percept whether using one or several electrodes internally, where external processor electronics are held constant.. • Why is this the case? • Why does “everyone know” that multiple electrodes are better? • The answer is the result of a cascade…

20. Single Electrode: the perception of percept • Early 3M/House processors were not designed to provide good speech reception, they were designed only to provide access to environmental sounds • This, because at the time no one thought that these new devices– cochlear implants– would actually provide patients with good enough sound so they would understand speech • Thus incoming sounds were deliberately restricted in frequency bandwidth, reflecting safety concerns, and these low expectations • This became a self-fulfilling prophecy, as a circuit diagram of the original device shows…

21. Single Electrode: the perception of percept Fretz RJ, Fravel RP. Design and function: a physical and electrical description of the 3M House cochlear implant system. Ear Hear 1985 May-Jun;6(3):14S-19S

22. Single Electrode: the perception of percept • Restricting frequencies to below 2700 Hz— eliminating some 35% of the frequencies important to understanding English— means that consonant sounds would be more difficult to hear • Indeed, these processors had several other inherent, performance-limiting problems: • They did not use modern compression, but rather “clipping”, which tends to introduce increasing distortion at full volume • They had noisy circuitry, degrading the S/N even in quiet conditions • …And they had other, “non-electrode” problems

23. Single Electrode: the perception of percept • If we were to compare two hearing aids, one of which offers the full range of frequencies important to understanding speech, and the other of which deliberately restricted frequencies (excluding some 35% of the information in speech)… • …one of which offers compression and the other of which does not… • …one of which offers a relatively clean signal and the other of which has considerable added noise… • With which one would we expect patients to do better?

24. Single Electrode: the perception of percept • The 3M/House and 3M/Vienna devices were termed “single channel”, and this was assumed to be their pivotal “defining” characteristic, even though (for example) the Vienna device was extra-cochlear! • The limits of the processor were not considered, and no data exist which offer information about how changes to single electrode, analog presentation processors affect patient percept • Does it make sense to assert, without one scintilla of supporting evidence, that the perceptual limits experienced by patients were (solely, or even primarily) due to the use of one electrode?

25. Single Electrode: the perception of percept • To gain a proper perspective on this subject, it is crucial to realize that every theoretical objection to these devices, on analysis, centers around the assumption that good frequency information cannot be provided when using a single electrode • Sound is pitch, timing, loudness; frequency is the pivot • Thus if it can be shown that such devices can provide good frequency information… • then previous assumptions are shown to be wrong… • …and any prejudice against these devices centering around the electrode must be re-examined and perhaps discarded

26. Single Electrode: the perception of percept • The issue of quality of percept is obviously central, but putting it aside for the moment, let’s examine some other facets of the comparison…

27. Cochlear Implants for Reviewers 4: Tono topics

28. Considering the T-Theory • For the sake of this discussion, let’s assume that the tonotopic theory can be stated as: • We must stimulate the cochlea according to the expected “place” of the frequency-of-interest, in order to provide a percept of that frequency • Please note the use of the word “must”, which clearly informed Dr. Bilger’s idea about this theory: • “…single channel auditory input will not provide… speech… that is understandable…”

29. “Channels”: a slight digression • “Above all, a single channel auditory input will not provide a speech input that either sounds speech-like, or is understandable.” • Simply because we have created a name for something, does that thing exist? (“multiple channel”, “single channel”) What is a channel? • It would seem that either “a channel” is a single frequency (or narrow band noise), or it has no meaning whatsoever • For multiple electrode CIs it may make sense to refer to “channels”, but it makes no sense when referring to analog presentation CIs • We believe we can demonstrate that “single channel” as a term applied to single electrode devices has no scientific content

30. Considering the T-Theory • The tonotopic theory appears to work, based on the success of present devices, and studies showing that the place of stimulation within the cochlea is associated with different pitch percepts • But is there evidence for the possibility of successful non-tonotopic stimulation? • And if so, how would one fit these two (different?) modes of stimulation into a “unified theory” of cochlear stimulation?

31. Considering the T-Theory • In fact there is good evidence for the success of non-tonotopic stimulation • For example, in Appendix G of The Audiologist's Handbook for the Mini System 22 (Cochlear Corporation, April 1993) the following quote is found: • “The [Cochlear Corporation's Mini 22] cochlear implant can produce two types of stimulation, bipolar and common ground (CG)... Typically, the lowest thresholds are obtained in CG stimulation because of the wider current spread.” • “Common ground” means currents spread globally— non-tonotopically— within the cochlea

32. Considering the T-Theory • “Wider current spread” engulfs more nerves— but studies done comparing CG to bipolar for this device do not appear to show significant differences in percept • “…results indicate that… restriction of the size of the neural population activated by individual channels of the prosthetic is not necessarily advantageous.” • Pfingst BE, Zwolan TA, Holloway LA. Effects of stimulus configuration on psychophysical operating levels and on speech recognition with cochlear implants. Hear Res 1997 Oct;112(1-2):247-60

33. Considering the T-Theory • “Bipolar” stimulation is stimulation of closely paired electrodes; “monopolar” stimulation is stimulation of an active electrode coupled to an extra-cochlear ground • Clearly, monopolar stimulation would lead to wider current spread, and should reduce frequency discrimination because it “breaks” tonotopicity… • “An assumption that bipolar stimulation should provide better speech understanding… has not been confirmed in this study. We found… no significant difference… on any tests when subjects were compared using monopolar or bipolar stimulation modes and the same coding strategy…” • Battmer RD, Martens U, Gnadeberg D, Hautle K, Lenarz T. Comparison study of patients using either the Nucleus Minisystem-22 in bipolar mode or the Nucleus 20 + 2 in monopolar mode. Ann Otol Rhinol Laryngol Suppl 1995 Sep;166:349-51

34. Considering the T-Theory • As well, no long electrode, pulsatile presentation implant currently in production reaches more than 25 mm into the cochlea, whereas the basilar membrane is generally quoted as being 35 mm long • That is, no pulsatile presentation cochlear implant stimulates the apex of the cochlea, where low frequencies (1500 Hz & lower) are apparently resolved • Yet patients using these devices apparently hear and resolve these low frequencies…

35. Considering the T-Theory • Some proponents of the tonotopic theory will tell you that such patients “hear” unstimulated low frequencies because such frequencies are at or below the firing rate of the nerves (~500 cps), or that some other mechanism (volley theory) allows for that percept • But does it make sense to assert that the cochlea has one mechanism to hear low frequencies, and another to hear high frequencies?

36. Considering the T-Theory • Occam’s razor: Rather than assuming, simply to safeguard a tenuously-based theory, that there are two mechanisms, it would make more sense to assume that there is only one mechanism being exploited in several ways… • But if there is only one mechanism, what might it be? • Consider the work of Kiang…

37. The Studies of Kiang • Kiang recorded from an electrode in a single auditory nerve axon in intact cat cochleae • Over a period of years recordings were made from hundreds of VIII nerve axons

38. The Studies of Kiang • Kiang then presented the cat’s ear with a stimulus at a certain decibel level (loudness), where the tone (frequency) was increased continuously • While this steadily rising tone at a given decibel level was being presented to the cat’s ear, Kiang recorded the frequency at which the single nerve fiber in which he had his probe began to fire, and the frequency at which it stopped firing

39. The Studies of Kiang • Then he repeated the “rising tone” stimulus at a lower decibel level, with his probe in the same nerve fiber • Eventually, at a low enough decibel level, he found that each nerve would fire at only one very specific frequency, which he called “the characteristic frequency” • At a given decibel level then, Kiang found out the range of frequencies to which a specific nerve fiber would react, and he produced charts of those reactions…

40. The studies of Kiang Recording with stimulus at 60 dB A specific nerve fiber reacts from 180 to 900 Hz at 60 dB

41. The studies of Kiang Recording with stimulus at 40 dB The same nerve fiber reacts from 330 to 500 Hz at 40 dB

42. The studies of Kiang Recording with stimulus at 20 dB The same nerve fiber reacts only to 490 Hz at 20 dB

43. Kiang’s conclusions • If the volume of the stimulating sound is high enough, a nerve fiber will fire across a broad range of frequencies • When the volume of stimulation is reduced, the nerve fires across a narrower range of frequencies • At the lowest volumes where the nerve will stimulate, only one frequency causes that nerve— and few if any others— to fire • Again, Kiang called this its “characteristic frequency”

44. Speculation… • Obviously Kiang was working with sound stimulus, not electrical stimulus • Even still, surely his work provides a useful means of thinking about electrical stimulation, because it seems sensible to assume that some or much of the preference for frequency resides within the nerve itself, and the nerve is an electrical organ… • And if the nerve has “preference”, might it not be that intense pulsatile electric fields can overwhelm the nerve’s characteristic frequency, whereas less intense, analog fields tend to allow that preference? • If so, then place stimulus must be intense stimulus, but more benign global stimulus may be analog in nature

45. Speculation… • That is, tonotopic, pulsatile stimulation works by overwhelming the nerve’s tendency to respond only at its characteristic frequency… • It can be stimulated, if we hit it hard enough • …and analog stimulation works precisely by exploiting characteristic frequency … • It will respond to its characteristic frequency, if present

46. Cochlear Implants for Reviewers 5: “Doctor, is there a pulse?” • “Digital electronics deals with 1's and 0's, the language of logic,” explains Tilde, “whereas analog electronics deals with waves, the language of sound.” • Smithsonian Magazine, February 2000, “Redefining Robots” p 96

47. Using pulses: a slight digression • The pulsatile stimulation used by CIs is locally very intense • The purpose is to cause all nerves local to the stimulus to “fire” simultaneously; to “entrain” them; to stimulate a “volley” • Consider: What this means is that the stimulation involved must necessarily result in either a single tone, or narrow band noise • Remember: it is apparently not the frequency of stimulating signal that provides the result… It is the local intensity • The number of electrodes therefore equals the number of frequencies or “channels” (CII possible exception) • Multiple electrode devices therefore offer a “set” of discrete frequencies, not a continuous range of frequencies

48. Using pulses: a slight digression • So, are nerves “digital”? Are pulses the best way to interact with them? • In fact, recent research is beginning to uncover the much more subtle, entirely more ubiquitous and rather complex analog nature of nerves • Why should we believe that the inner ear, which has never naturally produced nor experienced anything like a sharp rise-time, square wave pulse, would offer a better response to a pulsatile vs. an analog stimulus?

49. Using pulses: a slight digression • Beyond the fact that pulses were required to get multiple sites stimulated in rapid and sequential fashion, there were historical reasons for using pulses • Early (and continuing) research done on nerve stimulation required large artifacts in order to “discover” nerve responses in the electrically noisy biological environment • Recordings were made of the response to hundreds or thousands of stimuli, the results were time normalized and averaged, and a waveform resulted • Sharp rise times— which characterize pulses— were therefore the stimulus of choice, because they invoke large artifacts which are easy to see, “on average”…

50. Using pulses: a slight digression • But this is the scientific equivalent of looking for one’s keys under the streetlight • Certainly the approach yielded results, but it also encouraged researchers to believe that the only nerve responses worthy of research were large affect responses— the ones which were easiest to see • Yet such responses are arguably completely artificial, and might only be produced by using pulses to invoke them, meaning that at best they offer us a picture of a nerve under considerable stress… • The generally unchallenged idea grew up that nerves are digital, they “fire”, they are either on or off