Mechanics of Hearing 2024 Discussion 1

Discussion 1: External and middle ear (S1), Hair bundle I (S2) and Otoacoustic emissions (S3) Moderators: Ernst Dalhoff1, Dáibhid Ó Maoiléidigh2and Susan Voss3 1Department of Otolaryngology, Head, and Neck Surgery, Eberhard Karls University of Tübingen, Elfriede-Aulhorn-Strasse 5, Tübingen 72076, Germany. 2Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, CA. 3Picker Engineering Program, Smith College, Northampton, 01063, MA, USA EXTERNAL AND MIDDLE EAR SESSION [Ernst Dalhoff]: We start with the session one. Maybe you’ll remember this was the middle ear session. I would say three lectures on why the middle ear is so variable. So you have some confounds. I mean for us it’s very interesting, but for the clinicians it’s maybe disturbing. The same if we think about loudness measurements. All these things are variable. And also, if I think on my latency curves, maybe you saw that these level dependences in some subjects over three months are almost perfectly reliable. In others, they vary more. And probably because of the middle ear. But somebody has a question to talk one, two, three, or four. [Hari Bharadwaj]: When we measure middle ear muscle reflexes in our lab, we found that there is actually a good deal of variability both at the threshold and at high levels. It seems to be slightly different from what Jon talked about this morning. So, I’m wondering if you had any thoughts on whether it’s like the particular metrics of use absorbed power. And I think you’re showing absorbance, the ratio itself. I don’t know if that has anything to do with that. If anyone has thoughts on that. [Sunil Puria]: There’s lots of data with LDV, Dr. Good used to have this lots of data. There’s 20 dB range in normally hearing, supposedly normal middle ears. There’s a lot of range. You should look at this. Nothing psychoacoustical, just middle ear transfer function. There’s a lot of variability. Normally. [Jonathan Siegel]: One of the things you mentioned was the difference in threshold and I was expecting to see a difference in threshold but there really doesn’t seem to be one. It has to do with how the peripheral inputs must be converging onto whatever leads to the motor neuron responses and there must be a great deal of convergence. I’m not the first one to say that by any means. But it is surprising. It’s something that makes a lot of sense if you’re worried about anti-masking because maskers below 60 dB don’t do a lot of masking. And so maybe that determines the difference between when the acoustic reflex is effective and not. But then the strength of the reflex varies tremendously. And that is a fascinating thing, but I don’t know why that is. That’s just what we’ve seen. Could be. But I think certainly somebody who has a very strong reflex ought to have some ability that reflects that. That could lead us to clues about what the reflex is there for. [Jont Allen]: I hope this is relevant, what I have to say. Many years ago, when I was at Columbia doing measurements on cats, I did more than a hundred animals. And the first thing I would do once I got the surgery under control is I’d measure the cochlear microphonic, and the eardrum voltages, CM, and I’d measure this as a function of frequency. And one time I looked at like recalling maybe 30 different animals and plotted all the data. And at one kilohertz, there was less than one dB of variation across a large number of animals. These are all pristine animals, carefully collected from a farm at that time. So we knew that we were getting good animals. And the reason I was doing it is to verify that the animal I was going to spend the night with measuring neural tuning curves had a normal middle ear because if there’s something infected, it would be the middle ear that have lice, or not lice, but bugs on the eardrum and stuff like that. And I was shocked to see that there was less than one dB of variation in the cochlear microphonic. I particularly concentrated on 1 kilohertz. There’s no variation at all in the animals. If there was one that had a problem, it was really obvious. I don’t know is that a relevant comment to anything? [Ernst Dalhoff]: Maybe the animals are sedated? [Jont Allen]: It’s opposite of what Sunil said. But I was pretty carefully controlling the situation. I was specifically trying to find out how the cochlear microphonic would vary because I’m gonna spend the night measuring neural tuning curves and I don’t want to do it on a damaged ear. [Christopher Bergevin]: I do not have anything to add to Jont comment but one thing that shocked me about this morning with the first session it seemed like there were two different types of variabilities. There was variability across individuals with regards to various things and the dynamic variability with regard to things like the rumble and whatnot. It got me thinking, I am wondering if there is any connection point, some common thread between the EMREO, the rumble, and then maybe some of the, for example, some of the things Susan was talking about with the ear canal shape. So I guess maybe I’ll just kind of, that was just a general comment, but maybe I’ll culminate it in a question, particularly to Susan. Do you have a sense for how much like fractional change percent wise that the ear canal geometry might change in an individual? Like if something like if you clench your teeth or something, it’s not just maybe middle ear muscles pointing out tympanic memory but is there any significant fractional change in the ear canal? [Susan Voss]: Wow, I haven’t thought about that before, but sitting here I would say one question I often get with these CT scans is what part of the canal is bony and what part is cartilaginous? And there is a picture in the proceedings of that because so many people have asked and we’re starting to look at that. So roughly the 15 mm, it varies but say 12 to 16 millimeters from the eardrum is bony and I would guess that probably doesn’t change when you clench, but maybe the cartilage part could, and that part is roughly another 15 mm out. When you put a probe in your canal, depending on the type of probe. it probably goes in 6 to 12 millimeters so there’s probably not a ton of cartilage there that would change when you clench. I don’t know is that helpful? [Christopher Bergevin]: Yeah, how it affects the tissue? You say bony, but is it really like a rigid tube? [Susan Voss]: It’s bone and it’s covered with skin but the skin, you can see the bone. Sunil do you have a dimension of the skin? But it’s just a thin layer of skin. Yeah, it’s pretty much bone right there. [Gabriel Alberts]: I have a separate question back to Jonathan Siegel’s presentation. Regarding the hysteresis, you mentioned that there’s a higher, I guess, change in absorptions descending. But I was wondering, I don’t remember the time scale of that adaptation, but it seemed like you always started with increasing the level and then decreasing. Did you ever start by decreasing the level and then increasing to see if there was any adaptation effect or if the absorbance change was always greater for the decreasing case? [Jonathan Siegel]: Yes, I actually did try that once. And you have to go up and then see a declining run, the enhancement. It doesn’t happen on the descending run if you start there. You have to go up and then back down again before you start to see the hysteresis. [Gabriel Alberts]: Thank you. [Dáibhid Ó Maoiléidigh]: So, I feel I have to ask, since I didn’t know about rumbles until this morning and the eyeevoked motions of the eardrum, do you think it’s possible to either speaker to rumble and then create a saccade-like motion where it may go the other way around? There was a question of to which comes first, and you’d want to know if there’s some kind of feedback. So even a bias in a saccade, for example, might help. [Sunil Puria]: Related to that, are those similar phenomena? Because the frequency ranges are similar, like 30 Hz. [Sriram Boothalingam]: That’s a great question. The answer is I don’t know, but Shaw and I were talking and we were thinking about the same thing. Are they related and can we test it in some way, either asking people to rumble and looking at their saccade, or if Stephanie is doing saccades and seeing if this is different between people who can rumble or not. It’s an open question. Yeah. [Ernst Dalhoff]: My question would be if it can go both way around, so you could also have a critical feedback loop going to, so to say, spontaneous tensor tympani actions. The question is whether you agree or what is your opinion? You said it could also go the other way around, try to move the tympanic membrane and your eyes move then and that would basically mean that you close the loop. So if this loop becomes somehow instable, it could be the reason for having spontaneous, undeliberate... [Stephanie Lovich]: I’ll just follow up. Do you know if the people are rumbling by moving their eyes? Or are they like doing something else? [Sriram Boothalingam]: Again, I don’t know. I can’t rumble. So I feel really disadvantaged having done the study and not being able to rumble. But sometimes people describe that they have to close their eyes for them to really concentrate and think about it. I don’t know what that means. If there’s a saccade, then I don’t know. [Christopher Bergevin]: I can rumble without changing my gaze. [Sunil Puria]: I could do it all the time and continuously almost. And I noticed my, it looks like my eyes are slightly moving, but it’s not like they’re going like this, but I feel like they’re moving. It could be. [Jont Allen]: So saccades are essential to your vision because if you do an experiment, and this has been done, where they use a laser or use something to measure where your eye is and they remove the saccade by moving the image along with the saccade, what happens is you go blind. You can’t see, if there’s an image constantly being projected onto the retina, it disappears. And so the whole point of the saccades is to change the field of view by a little bit on a regular basis. So it’s fundamental to vision, but it’s not fundamental to hearing. We don’t need hearing saccades. There’s no such thing as far as I know. HAIR BUNDLE I SESSION [Dáibhid Ó Maoiléidigh]: So in the interest of giving equal time to the next session, let’s move on to the next session. Are there any questions about hair bundles, what you heard about this morning? [Pim van Dijk]: I actually had a question to Dolores. So, you described how a system becoming chaotic would actually enhance its sensitivity. I mean to enhance your ability to detect a signal you actually need to improve signal to noise ratio. And doesn’t that same process also increase the noise? I think it’s sort of a general problem I have with the Hopf bifurcation also, if you have it close to critical oscillation you get a bigger response but doesn’t it also increase the noise? [Dolores Bozovic]: This is regarding question about signal-to-noise ratio. The plot, the heat map that I showed, which varied chaoticity, if you will, as well as the size of the oscillation, that was done at one specific noise level. So there you fix the noise level, you fix the input, and you’re measuring the response in some sense. There you really are sort of fixing the noise and extracting the response, which means in a way you’re measuring the signal to noise ratio. We did that at various levels of noise, and until you really take it into a very high level, the signal to noise improves. [Pim van Dijk]: So when you say fixing the noise, do you mean, I mean, the noise is a force term in your equation, right? So do you mean fixing the force, and doesn’t that then give a bigger response [Dolores Bozovic]: In this particular case, we were looking, so the noise that we’re superposing when I say fix it, it’s stochastic noise, but it’s fixed root mean square. The signal that we’re doing is then a superposed sine wave, and you average over many cycles. Right. [Ernst Dalhoff]: I have a question to you, Dolores. If I understood correctly, you said that the weak chaotic behavior produces the most sensitive system. You also said that the efferent action would lead to it. And on the other hand, maybe I misunderstood that, the efferent action is usually, at least in the mammalian system, the adapted state where you have a little bit less sensitivity [Dolores Bozovic]: I did not think that efferents induce it. I said they modulated, they changed it because we have not yet proven that efferent activation affects directly chaoticity, right, the Lyapunov exponent. We have strong hypotheses because data indicate, and there’s another study in the works where we’ll try to model it, that it will actually affect the control parameter. It will reduce the control parameter, which likely then reduces chaoticity. So currently, this is hypothesis. The results are that efferent activity reduces sensitivity, changes the size of the oscillations, changes the very self-tuning or how quickly it recovers. It changes everything. So that’s the empirical data. The interpretation, again, to be proven, but interpretation is that it affects µ, the control parameter that sets whether it oscillates or not and how far in the oscillatory regime. So by reducing that, it should be reducing chaoticity and thereby rendering the system less sensitive. [Dáibhid Ó Maoiléidigh]: Can I ask a quick question, Dolores, just while I have you up? [Dolores Bozovic]: Of course. [Dáibhid Ó Maoiléidigh]: I did a quick calculation, so you can tell me if I’m wrong. Your Lyapunov exponent was very small, so weak chaos. So, I estimated that you go through about 30 cycles of the stimulus before the trajectories diverge. And then you were talking about effects that occur when the divergence hasn’t really happened yet. So even though there’s chaos, it hasn’t really manifested yet. And yet you’re getting an increased sensitivity and increased temporal acuity. I’m trying to reconcile these two things. [Dolores Bozovic]: It shouldn’t be that small. It could be that we’re talking about it. So this was again dimensionless, which not one of the exponents are you talking about? [Dáibhid Ó Maoiléidigh]: So I’m talking about if I take the ratio of that exponent to the frequency in the Hopf normal form, if the frequency, and your Lyapunov exponent was 0.1 or so, and so 2πfis the ω, so you get about 1 over 30. [Dolores Bozovic]: I think our omega was 2π, our omega was set to 1. [Dáibhid Ó Maoiléidigh]: Right, exactly, so you can compare λto ω. And then you can get how many cycles. So I’m just trying to reconcile, the chaos hasn’t really happened yet, if you know what I mean, but you’re already getting the sensitization and the increase in speed. I wonder if it’s more related to the non-isochronicity in the dynamics and the chaos is an additional phenomenon that also comes out from the same non-isochronicity. [Dolores Bozovic]: I would have to look at the exact numbers, but I think that our λwas higher than that in the optimal regime where I showed was actually β. The plot I showed was β, the non-isochronicity, so you’re correct there. But at that particular level of noise, I would have to look what the exact λwas, but I think you’re correct. I don’t think it is 10 cycles, and again, Justin could correct me on that, but I think it was definitely smaller. [Dáibhid Ó Maoiléidigh]: Okay. [Jont Allen]: Egbert de Boer, back in 1968, developed something which he called reverse correlation. How many people do you remember this? Now, I knew Egbert pretty well and I tried to understand what was going on. Let me explain what he did. He took random noise, thermal noise, and he played it into the cochlea and he was measuring auditory nerve spikes. And every time it’d get a spike, he’d take the noise for the previous 10 or 50 milliseconds and average it together. So it was spike-correlated average noise measured from a neuron where he knew the tuning curve. And what he got is amazing. He got the impulse response of that tuning curve. And then he took signals and repeated it with that impulse response that he measured through this reverse correlation process. And he showed that it was the proper transfer function of that cochlea. I think this was amazing. And there was also some theoretical stuff that he worked on where you can take it. [Dáibhid Ó Maoiléidigh]: Jont, can you clarify which talk this is related to? [Jont Allen]: It’s related to the one we’re talking about, what is chaos. [Dáibhid Ó Maoiléidigh]: Oh, chaos. Okay, great, thank you. [Jont Allen]: So, there is an impulse response you can directly measure from neural signals there’s a theory that he quotes about this and I think it’s related. So you have chaos going on and what it’s doing it’s biasing the system up so that you’ve got a signal that’s loud enough that it’s triggering the auditory nerve and the brain is capable of figuring out what’s going on because it has the spikes and it can get the, I don’t know, I don’t understand it well enough. It’s been too long. But you should read this paper by de Boer from 68, because it’s an amazing result. And it’s kind of made us. [Dolores Bozovic]: I’ll be sure to read the paper. I’ll just clarify that we did not measure neural responses yet. That would be a very fascinating thing to look at. [Alessandro Altoè]: I have a question for you, actually. Do you know on any detector that’s man-built based on this principle like a chaotic detector that is actually usable? [Dolores Bozovic]: So the short answer is that I don’t know of one, but it almost certainly is in the sense that a lot of transistors have been, or rather I should say chaos has been studied in transistors, in lasers, et cetera. Now whether they were built to study that, I don’t know. I think they were built for something else and then chaos can arise. Typically, I think, there could be new things since, these were systems where they wanted something very specific, and they wanted something stable, so I don’t think chaos was desired result there. But I don’t know if anyone has utilized that to actually built a detector. [Alessandro Altoè]: I have a quick follow-up question. You are talking about detection, but to me you were talking about a receiver in a way that you didn’t have criterion to decide. So am I correct in assuming that you were assuming what engineer call heterodyne detection? So it’s like in the cycle, not in the amplitude? [Dolores Bozovic]: I don’t know what the electrical engineering terminology would be, I just don’t want to be imprecise. So what we were looking there is actually the sensitivity as has been used in our field, which is simply response to sine wave, right? You divide it, right? Sensitivity is response divided by forcing. In terms of deciding what is detection and what is not, in the paper that this was based on, we looked at a lot of other metrics. You can look at something called transfer entropy, which basically tells you how much information the signal, the receiver, if you will, the hair bundle is extracting from the signal. It’s related to mutual information, but one directional. So you can look at that as well as a number of other metrics. So it’s precisely because in hair cells, we don’t quite know what constitutes quote detection, because at some level there’s going to be some thresholding when it goes to neurons. So in a way, we know what’s the input, but we don’t really know what’s the output, which is why we then went ahead and studied several options. The obvious one to follow is the sensitivity, but then another is to say, let’s make no assumptions and just see what information it’s extracting. [Christopher Bergevin]: Just a comment and a question. With regard to Jont and the revcor, I think Dolores is right. She’s not measuring spikes, so it’s not applicable to what she’s doing. But if she were, I think you could go one step further, and that’s where the Wiener kernel analysis comes in. And I think Pim is actually quite knowledgeable in that. So just a general comment. But a little bit more specific. In your case, βequals zero was the isochronous case. And you said that was non-chaotic. But if you start coupling elements together, because the ear is not a single hair cell, it seems like you can get chaotic behavior. Like I know for a Vilfan and Duke model where all the oscillators are purely isochronous, there is a fairly substantial sensitivity to initial conditions. So the systems response in that regard, it seems chaotic. So do you have any comments, general comments on reconciling what a single iso versus non-isochronous thing is with regard to the bigger system as a whole? [Dolores Bozovic]: Yeah, absolutely. You need degrees of freedom, you need some complexity to the system, right? And so with one oscillator, we’ve shown that, and really even I should clarify for this particular Hopf oscillator, for this model, you need it to be non-isochronous, because if it’s one isochronous plus noise won’t do it. You could probably add complexity in a different way by some sort of feedback, for example, third equation. So it’s not the only way to get chaos, it is one way to get chaos. In a coupled system, you absolutely right, once you have that many degrees of freedom, there are different ways, you would then have to do kind of analysis on that coupled system as a whole to show in which regimes it becomes chaotic or not. For Vilpin and Duke model, I don’t know if they tested for chaos. I’m not aware that they did. As far as I remember, they showed kind of clustering of frequencies and I’m looking at Justin who’s looked at it more closely kind of for confirmation. But I’m not aware that they did any analysis of chaos. That being said, I think it would be very useful and cool to do. The one thing that we did do is we looked at how chaotic individual elements affect synchronization. I don’t think we’ve explored it, it would be nice to actually look at non-chaotic individual elements coupled where can the system then exhibit chaos. That would be very cool. OK. [Dáibhid Ó Maoiléidigh]: Thank you. I’m going to hand over to Susan for the next discussion. OTOACOUSTIC EMISSIONS SESSION [Susan Voss]: Session three is the session. Does anybody have any comments to get us started on these five talks? [Jont Allen]: I was very struck down by if you cut off the oxygen level to an animal that the non-linearity goes away. Am I right about that? Almost instantly. And then you wait a while, and it can recover. I did that experiment many, many years ago in Joe Santos’ lab, where I purposely, I had the animal, and it was a guinea pig, we were measuring I think cochlear microphonic and neural responses, and I cut off the oxygen and something like 10 seconds later, the CM went away. And then turned it back on a minute or two later and it slowly recovered. My reaction after today’s talk is that it could, I think that the oxygen level is a way of controlling the cochlear amplifier directly. I’d like to hear a discussion as to whether you think this is the most absurd thing you’ve ever heard in your life, or could that possibly be our best metric for studying the cochlear amplifier? The oxygen level, things go off, turn off inside the cochlea because it’s highly dependent on the oxygen level in the cochlea, the stria vascularis, and then you turn it back on. So this would be very cool if you had direct control of the cochlear amplifier. [Torsten Marquardt]: I didn’t say that the non-linearity goes away. So the DPOAE component so on, even went up the modulation change, the modulation pattern, indicating a shift on input-output function. [Jont Allen]: DPOAE didn’t go away? [Torsten Marquardt]: No, it was a SFOAE which dropped off which surprised us too. So the compound action potential dropped and synchronously is a SFOAE dropped altogether. [Jont Allen]: So SFOAE disappeared after let’s say 10 seconds? [Torsten Marquardt]: Yeah, there was a delay of 10 seconds. [Jont Allen]: So is SFOAE related to cochlear amplifier? [Torsten Marquardt]: Yeah, that’s why I said it might be. [Jont Allen]: Ok so I need to change my terminology. [Torsten Marquardt]: So that might be a good indicator because it’s correlated with what’s nerve was doing. The CM also remained up so change the modulation again [Jont Allen]: That’s the middle ear thing, cochlear microphonic. Okay, I am confused, never mind. [Torsten Marquardt]: So the cochlear microphonic stays up, componential potential goes down. So that is definitely indicator that the drop in oxygenation reduced the cochlear gain. And it was a big effect. [Torsten Marquardt]: Yeah, 50 dB or something like that. I mean on level I mean we have been very high stimulation levels for the CAP, so it was not threshold or something. CAP threshold would have been raised even higher, I guess. [Jont Allen]: It was reversible. [Torsten Marquardt]: Yeah, it came back. [Robert Fettiplace]: In answer to Jont’s discussion, I mean, I always understood that the hypoxia causes the complete loss of the endolymphatic potential very quickly. It goes from +80 down to 40. So you lose all receptor potentials. [Jont Allen]: We all know that. [Robert Fettiplace]: I mean, that’s what happens. And then you go put it back and it takes a while to come back. But I mean, it does drop immediately. [Rob Raphael]: if I could follow up quickly on that. You don’t want to do this too often biologically because as a cardiac people know there’s something called ischemia reperfusion injury. So you might be able to do it under control. [Karolina Charaziak]: I have a comment and a question. So the comment on the hypoxia and EP, I actually just recently was doing it by accident, I mean I had EP electrode in and trachea filled with liquid, and EP just drops immediately, and recovers. So you can just clamp the trachea and EP just drops immediately and recovers. So that’s why I think it’s related to drop of the cochlear amplification in that case. And I have one question to Torsten about your experiment. I don’t know if I read your plots correctly, but I was particularly curious about the changes in cochlear microphonic. Was this, first of all, were you measuring the distortion components of the CM or just the CM at the probe frequency? Which one was it? [Torsten Marquardt]: So I measured both. So the distortion products in the CM and to a single tone I measured the modulation sidelines which changed according also to operating point change. [Karolina Charaziak]: If I remember the plot correctly was the change in the CM very transient? Was the change in the CM very transient and then it recovered quicker than the graph when the animal was hypoxic? I’m not sure I was seeing that correctly. Or was the CM down throughout ? [Torsten Marquardt]: So the CM only changed slightly according what you would think the shift in operating point was doing. So the SFOAE, the acoustic emissions, dropped down. And it came then up again. So I also agree that deoxygenation is probably a drop in EP and that might be one in the future to record EP simultaneously as well. [Aleksander Zosuls]: Just curious, I mean, humans go hypoxia when you do routine things like dive or intense exercise. And has anyone ever noticed a psychophysical change in their hearing? Or is that might be a hard IRB to get, but could do we see this in humans? And when you did the experiments with the animals, did you know what the oxygen saturation was? [Torsten Marquardt]: So the upper graph was oxygenation level from the oximeter, and it dropped quite a bit. But we never had really, I don’t know, contact or something. I think the reading itself was wrong because the animal was fine. It was sometimes going to 80. The animal would be probably dead for too long. You saw more of the change. But that is also a question I wonder, that if you hold your breath for 30 seconds, I never see my hearing fading away. So, it’s surprising that an animal has such a strong effect on the compound action potential. [Aleksander Zosuls]: I mean, your vision definitely fades away if you do that. Why wouldn’t your hearing, but maybe it’s not as obvious. [Jont Allen]: I don’t think you want to do this experiment on yourself. Okay. So first you can measure your SpO2, your blood oxygen level with an SpO2 meter. They’re $20 at Walgreens. And if it goes below 95, I’m going to the hospital. Okay. Normally it’s about 96, 98. I can even, by breathing, I can get it go up a 100%. But if it goes down below 90, I need to be in the hospital. Okay. So you don’t want to do this experiment on yourself. You could kill yourself. [Aleksander Zosuls]: I survived. [Robert Fettiplace]: Could I ask about this acoustic fovea in the mole rat. I mean the acoustic fovea in the bats is related to that that’s where their emissions are, why do they need it? [Pim van Dijk]: Apparently, their communication sounds are close to 1 kHz. So the communication sounds that they use in their tunnels. Also apparently the tunnels are good for sound transmission near 1 kHz. Although I don’t quite understand the physics of that. But that’s what’s being said. I don’t know why 500 Hz would travel to the tunnels or 2000 or something like that. But that’s what I don’t know. Can you add something to that, Geoff? [Jont Allen]: It has to do with absorption coefficient of dirt. [Geoff Manley]: I think our view of auditory fovea has been too much orientated towards bats, and certain types of bats that only produce a constant frequency sound, and many of those have been shown to have an auditory fovea, and extreme sharpness of tuning in those areas. But if you compare that, for example, to the barn owl, which Christina showed has a prominent auditory fovea over half of the organ that covers just one octave, there is no special tuning in that area. And I think what we have in the mole rats is something similar. It is an auditory fovea that expands a certain region, but as Christina likes to say, it’s just real estate. It is an area in which a massive input to the brain of parallel fibers doing very similar things but not exactly the same and the brain uses it in the barn owl, for example, for the impossible task of catching 50 mice per night in darkness. So it enables incredibly precise auditory processing, but it’s got nothing to do with tuning. What the mole rats exactly do with all this information, we don’t know, but presumably communication in these tunnels is fairly special and they have quite complex communication, but we really don’t know enough about this process to say exactly why they need or why they benefit from a fovea. [Sunil Puria]: To add to that, do they hear by bone conduction? Maybe they’re communicating through grime vibrations. No? Yeah, that’s right, not acoustics, okay. [Pim van Dijk]: I think that there’s apparently some behavioral evidence that they actually push their head against the walls of the tunnels to use bone conduction. And also the big middle ear bones with mass in the middle ear may help for bone conduction where you shake the animal but due to inertia you got a relative motion of the ossicles. [Jont Allen]: They don’t have a pinna o when they put their head against the wall, there’s no pinna getting in the way. [Jonathan Siegel]: I want to follow up on that CM thing. Following death CM does not go away instantaneously, the electrogenic part of the EP goes away but you still have the endolymph/perilymph driving force that will continue driving the transduction long after the animal dies. And the story I learned from Russ Pfeiffer a long, long time ago was when Warren Littlefield, who preceded me, was in the lab recording from single neurons, he called Russ in the middle of the night and said, Russ, I’ve got this great unit, and I’ve done all sorts of experiments on it, and I don’t want to know what to do next. And Russ came into the lab, and he took one look at the cat. The cat was dead. And he said, Warren, you’re triggering on the CM. And so you get these large responses that decay very slowly over time. So I think that’s, I just wanted to add that little clarification. I think Pfeiffer’s name ought to be mentioned every now and then. [Robert Fettiplace]: Could I answer that question? And I’m not sure you’re quite correct. If you have no EP, then the Nernst potential for the potassium in the endolymph and the potassium in the perilymph gives you a potential across there of 40. [Jonathan Siegel]: You have about half the driving force. [Robert Fettiplace]: 40, it goes off to 40, okay? So with the electrogenic potential, which takes it up to +80, you go from +80 to 40, you’ll get no transducer current at 40. [Jonathan Siegel]: No, that’s not true. [Robert Fettiplace]: Of course it is. The resting potential would be 40. The driving force would be 40. You’d get almost no transducer current. [Jonathan Siegel]: Well, then there must be some other explanation for these potentials that persist long after death. But I think if you do the calculations, there still is the driving force. [Jont Allen]: Let’s vote on it. [Susan Voss]: I think we have about three minutes left in this discussion and we’ll open it up to comments on any of the morning talks if anybody had something else that they didn’t get a chance. Maybe there was something over here earlier. [Stefanie Gutschmidt]: I may potentially open a can of worms. Is this community clear on what the Hopf is generated by in the cochlea. Is it the fluid? Is it the feedback loop from the brain? Is it the delay from the input to the output? Is that problem solved? Is like somebody can explain like where the origin of the Hopf comes from? [Dáibhid Ó Maoiléidigh]: I will say that the origin is in studies of hair bundles, in particular hair bundles in the bullfrog sacculus. And then, but there’s no direct evidence that this activity is happening in mammalian cochlear cells. It has been modeled in hair bundles in the cochlea, and with reasonably plausible physiological parameters, but then again it hasn’t been measured. It’s possible to generate a Hopf without inducing hair bundle activity using somatic motility and feedback. And if you look in a lot of cochlear models, there are Hopf bifurcations because they’re very easy to come by, but there’s no general consensus in the community about whether this is a useful concept or its utility, and there’s different focuses on different aspects of what is generating nonlinearity and so on. So, I think it’s still really under discussion in our field about the utility of this concept and how it relates to hearing. [Jont Allen]: For 30 years I’ve been hearing people occasionally talk about Hopf bifurcations, and I’m going, what does this mean? And today, for the first time, I felt from Dalhoff’s, I take my notes here, Dalhoff’s, he talked about the scissor’s effect, and we heard about Hopf bifurcations, and I said, you know, maybe this has something to do with the cochlear amplifier. I mean, I’m not even sure what I’m talking about here. I’m trying to read my notes. But the scissors effect, what, somebody explain what the scissors effect is? [Dáibhid Ó Maoiléidigh]: I’ll just revise my previous answer. If we have convinced Jont Allen of the utility of the Hopf, I think there is a consensus in the community. [Jont Allen]: I wrote down here that I was convinced of something, but I can’t figure out what. [Sunil Puria]: Cochlear amplifier! [Ernst Dalhoff]: it’s not the scissors effect, it’s a scissor paradigm and it means that you seek the level combination which gives you the largest response. And to make that mathematically working, you have to ask the question, which combination of levels at a given amount of energy you get the largest distortion product. And this, in the end, is the ridge on the level map, the gradient. [Dáibhid Ó Maoiléidigh]: OK. I think, do we have any more pressing questions? If not, I think we’re finished with the session. So, thank you all.