The Mystery of the Cochlear Frequency Tuning Curve

In the later 1940s, Hungarian physiologist Georg von Bekesy was perturbed by a commonly held belief regarding the perception of hearing. A long standing analogy that compared the basilar membrane (on which rests the organ of Corti, which allows us to transduce sound through hair cells) of the cochlea to a wave travelling down a skipping rope just didn’t seem right to him. He decided that it was time for him to go into the cochlea- surgically- and figure the whole mess out.



Von Bekesy transected the basilar membrane, separating the base from the apex, and found that it did not alter frequency perception in the slightest! So von Bekesy hypothesized that the waves would be in the fluid. The cochlea is, after all, filled with a fluid called endolymph (which is very similar to intracellular fluid).



But then what of the place code? For von Bekesy was certain (though it had not been proven) that for each frequency in an auditory stimulus, there was a unique place on the basilar membrane. He decided to do what any inquisitive mind must: he examined it underneath a microscope. And although he could only use low frequency stimuli (because high frequencies are so high that our eyes cannot perceive them), he found that certain places on the basilar membrane vibrate better at some frequencies than at others.



From this he drew a frequency tuning curve:



If you were to choose a different place on the basilar membrane and measure a different frequency, the curve will be the very same shape, but with the most sensitive point in a different place.

Then physiologist Bill Rhode had a very clever idea: to use the nuclear physics Mossbauer technique to measure frequency along the entire basilar membrane. The technique is done as follows: first, a tiny piece of palladium foil (which is very similar to aluminum foil) is soaked in radioactive cobalt. Next, the cochlea is gently opened and the foil is floated (from the bottom, to avoid the organ of Corti) onto the basilar membrane. The radioactive cobalt then emits gamma rays at such an incredibly high frequency that they are actually out of our acoustic range, but are still measurable. Finally, something else in the cochlea but be in the cochlea to will measure the gamma rays. If the basilar membrane (and the palladium foil) move up, the wavelengths of the gamma rays get squeezed in; or down, and pulled away (see: Doppler effect). This squeezing and stretching allows very accurate measurement of basilar membrane movement, with several benefits, the most important being that this can be done in a live animal. Using this technique, Rhode was able to determine the specific frequencies of the place code along the basilar membrane.



But in a seemingly unfortunate turn of events, the animal which was being used for this test died. Rhode would not let this stop him. He decided to perform the very same test, but this time on the deceased animal. The results produced a very strange frequency tuning curve indeed:



It looked just like the curve produced by von Bekesy in the removed cochlea seen under the microscope! Rhode decided to plot the results from the animal’s live cochlea on the same type of curve, which brings us to one of the greatest mysteries in psychoacoustic history, for the frequency tuning curve looked like this:



The curve produced from the cochlea of the dead animal (which from hereon in will be referred to as the passive curve) is but exactly what one would have expected the curve to look like (especially after the discoveries of von Bekesy). However the curve from the live animal (the active curve) is simply impossible! The basilar membrane does not have the physical capability to produce such a curve; it is far more selective (look at how low it dips) and sensitive (look at how skinny it is) than it should be...

But along came 5 experiments that explained the whole thing, done separately by Bob Harrison, Alan Cody, Weiderhold, Mario Ruggero and Charlie Liberman. Their work ultimately uncovered the truth behind the mystery of the basilar membrane and why it is that the active and passive frequency tuning curves are so vastly different. So here is how it works:

First, the stapes pushes on the oval window (following a succession of impedance mismatch solutions), in the middle ear.



This sets the fluid in the cochlea (the endolymph) into motion. The motion of the endolymph causes the hair cells to move. The outer hair cells are anchored to both the basilar membrane and the tectorial membrane, and move in a contractile way as a result of metabolic energy from a protein called prestin. The amplitude of this contracted response is equal to the membrane potential: the outer hair cells create the mechanical signal in auditory transduction.



The combination of fluid movement and outer hair cell contraction causes movement of the basilar membrane, which then also moves the inner hair cells: they are the passive transducers.

And so, we now know that Rhode’s results on the passive frequency tuning curve were as a result of a lack of metabolic activity (as in von Bekesy’s)in the outer hair cells; metabolic activity does not occur in death.

The basilar membrane is not physically capable of producing the active frequency tuning curve- not without the help of the outer hair cells, that is.

Alcohol, GABA and stress

I recently read an interesting study entitled Stimulant alcohol effects prime within session drinking behaviour, by Corbin, Fromme and Gearhardt (2009). It was looking at whether experiences arising from (or at the same time as) the consumption of alcohol contribute to consumption under or pre-emptively to stress. It made me think that perhaps drinking in response to stress is perhaps a way of regaining some sort of biological homeostatic equilibrium. Corbin, Fromme and Gearhardt's results show that those who experienced stimulant-type effects in response to alcohol consumption are more likely to consume alcohol when a stressor is present, while those who experience sedative-type effects are less likely to do so. Stressors cause anxiety, which would ultimately be suppressed by the activity of the neurotransmitter GABA (gamma-Aminobutyric acid); GABA suppresses fear and inhibits anxiety (Panksepp).



GABA is associated with the consumption of alcohol, as alcohol is thought to reinforce the movement of chloride ions, which enter the cells and render them “less sensitive to the effects of other neurotransmitters” (Barlow, Durand and Stewart 2009). This action qualifies GABA as inhibitory, and this effect may be what suppresses anxiety, when the anxiety is coupled with the consumption of alcohol.



In Corbin, Fromme and Gearhardt’s study, the stimulant effects of alcohol would cause the person to associate positive feeling with drinking. The subscales used within this study which define the difference between stimulation and sedation do not take into account the sedation of fear, but rather use sedation as qualifying something more akin to a lack of energy. This sedation is not connected to the inhibition of anxiety. Instead, the positive feelings associated with the stimulant effects would seem to be a byproduct of some level of comfort rather than being associated with symptoms of stress; the closest by definition would be excited, but in relation to the other words on the list it comes to mind as being more subjective than physical. So for those that feel stimulation with regards to alcohol consumption, that feeling is merely creating an association between drinking and positive sensation. This primes the subject in the sense that they are then likely to drink in response to discomfort or negative feeling.

What is actually happening for these people is the facilitation of GABA activity in areas of the brain associated with emotion, such as the amygdala and the amydalofugal pathway (Panksepp).



The discovery that GABA activity is coupled with the benzodiazepine receptor in what is sometimes referred to as the FEAR pathway, stretching from the amygdala to the nucleus reticularis pontis caudalis (Panksepp) certainly supports the theory that alcohol helps to suppress anxiety. This is the case because alcohol reinforces GABA activity, which inhibits the cells with benzodiazpine recetors along this so-called FEAR pathway.

Interesting stuff, thinking about why we drink and the experiences that may make us more susceptible to consumption. Alcohol consumption has become such a regular recreational activity that we don’t really consider all the factors which play into it (or I suppose maybe we just don’t want to). If we’re going to treat drinking as just another aspect of everyday life, then perhaps we should take a more objective stance on our personal biology as well...?

Barlow, D. H., Durand, V. M.., Stewart, S. H. (2009). Abnormal Psychology: An Integrative Approach. Ontario, Canada: Nelson Educaton.

Corbin, W. R., Gearhardt, A., Fromme, K. (2009). Stimulant alcohol effects prime within session drinking behaviour. Psychopharmacology, 197: 327–337.

Panksepp, J. (1998). Affective Neuroscience: The Foundations of Human and Animal Emotions. New York, New York: Oxford University Press.

The Pseudoscope

Depth perception is really neat. We have it because we have eyes that point forward, and because of the distance between them (called the interpupillary distance). This distance creates binocular disparity, which is the difference between the location of an image seen by each eye. Close one of your eyes and look at an edge, then do the same with the other eye, and you'll see what I mean. Because of these two images projected on each retina, we have a sensation of depth (although depth is not only because of this and of course is also reliant on visual cues in the environment).



This is all well and good and relatively obvious, but imagine depth perception was reversed. Such is the occurrence when using a device called the pseudoscope, which makes objects appear inside out. Apparently inside out is the opposite of depth, which sort of twists me up when I try to think about the semantics of that philosophically. The word pseudoscope is Greek and means "false view"; this term was coined by English scientist and inventor Sir Charles Wheatstone, who also invented the more useful brother of the pseudoscope, the stereoscope (as well as a bunch of other incredible devices, including the kaleidophone, which makes sound vibrations visible). But while the stereoscope is certainly useful, the pseudoscope is odd and surreal, and I have an admittedly useless tendency to prefer things that are the latter.



The pseudoscope works by reversing the images from a normal stereoscope, which makes all the parts that are convex concave and vice versa. Basically what it does is, by using optical prisms or mirrors, trade the view of the right eye for that of the left eye and vice versa.

Here is a neat-o video on making your own pseudoscope:

A Brief History of Localization of Function vs. Mass Action

It seems fairly clear that the faculties of the brain can be attributed to both localization of function and the circuitry of the full brain itself.

German physiologist Franz Joseph Gall and the area of phrenology (which he referred to as 'cranioscopy') attempted to localize mental functioning by attributing personality traits and characteristics to the shape of the skull. Phrenology held that the shape of the cranial bone was indicative of certain areas of the brain being larger or smaller than others, and thus the corresponding traits being more or less prominent.



Localization was further validated by the case studies of French physician and anatomist Paul Broca, who found that ablation of certain areas of the brain are the cause of changes in mental processing and behaviour, for example, lesioning of the anterior lobes results in aphasia. This helped to localize the region of the brain associated with speech production, now known as Broca's area, in the inferior frontal gyrus (Wernicke's area, in the superior temporal gyrus, is also pointed out in the diagram below, as it is the region associated with language comprehension).



Experimental stimulation of the cerebral cortex helped increase the validity of localization of function, especially when done on a live brain. Stimulation of a particular area can then be described based on reactions and observable resulting behaviours. Neurologists Wilder Penfield and Theodore Rasmussen stimulated areas of the cerebral cortex and recorded the various resulting actions and emotions.



The ablations done by French physiologist Jean Pierre Flourens and the subsequent ablation work of Shepherd Franz and Karl Lashley show that damaged areas of the brain can be taken over by intact areas that were previously not involved in the associated function. Lashley coined the term “mass action” to describe function in the brain.

We now know that the brain functions based on both mass action and localization. The interconnectedness of neural circuitry and the extensive length of the feedback loops of these circuits introduce the undeniable fact that the various areas of the brain are connected. These connections can be shown in such complex processes as learning, language and the interpretation of sensation, all of which involve complex connections between several structures. It is also true, however, that certain structures play specific roles in functioning, such as the difference in location between the formulation and the interpretation of language. The localization of function is a part of the unity of function. These ideas are not in opposition with each other, but rather they are very much connected and almost impossible to separate.

The Big Brain

I am a follower and extreme supporter of The Brain. My interest in The Brain is verging on obessession.