1.イントロダクション、視覚システム (1. Introduction, the visual system)

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PROFESSOR: This is our first introductory meeting
of the course, which is 9.04.
And we are going to cover vision and audition in this course,
and there are going to be two of us lecturing.
My name is Peter Schiller, and this is Chris Brown.
And I will be talking about the vision portion,
and Chris will be lecturing about the auditory portion.
Now, what I'm going to do is I'm going
to hand out the syllabi that we have, in this case,
for the first half of the course.
And that we are going to discuss in some detail
today for the first half of the lecture,
and Chris is going to discuss it for the second half.
So that is the basic plan for today.
And I will go through some of the basic procedures and issues
that we may want to deal with at this very introductory portion.
So first of all, let me talk about the reading assignments.
If you have the handout, they are ready for you.
If you look at the second page, that's
where we have the assigned readings for the vision
half of the course.
Now, for that half of the course,
the top eight assignments are all articles
in various journals.
We don't have a textbook for this portion of the course.
And then in addition to the assigned readings,
we have recommended readings that are listed there.
And then another important factor
that is listed there-- let me first
say that the lectures will be put on Stellar, in most cases,
after each lecture.
And in addition, the videos that we are now recording
will also become available, but they will not
be available until well after each lecture.
So I would advise each of you to come to the lectures
rather than hoping to read the assigned material only
or to eventually look at the videos.
The reason I'm telling you this is
that our analysis has shown that those students who
attend the lectures regularly get
much better grades on the exams than the students who do not.
So I strongly will urge all of you
to come to as many lectures as you possibly can.
Now, the additional requirement that you're
going to have for this course is to write two research reports,
one for vision and one for audition.
And the assigned written report that you need to put together
is in a paper at the bottom of the second page.
In this case, it's going to be a paper that
was written quite some years ago,
a very important and remarkable paper that has been published
by Oster and Barlow, as you can see.
And the task for you will be to not just report
what they had reported, because that's repetitious,
but to do a bit of research and write
about what has been discovered since the remarkable findings
that these two people had made at the time.
All right.
So that's the research report.
And then I want to specify the exams.
We are going to have a midterm exam,
and the exact date for this has already been set on October 23.
All right?
But as I say, you can find this, and I
will specify that in more detail in just a minute.
And then we are going to have a final exam
at the end of the term.
The exact date for this, as always at MIT,
will not have been set until probably sometime in November.
So now let me also specify the grade breakdown.
I think that's important for all of us.
The written report for each half of the course--
there's going to be one report, as I've already said,
for vision and one for audition--
and that will constitute 10% of the grade for each.
And the midterm exam, this constitutes 25%.
The final exam constitutes 55% of the overall grade.
And in that, 15% will be on vision and 40% on audition.
So if you add that up, you can see that vision and audition
are set up to be exactly equally weighed for the exams.
MICHELLE: Hi.
I'm Michelle.
I'll be helping the professors, especially with [INAUDIBLE].
PROFESSOR: So I'm Chris Brown, and I'm one of the instructors.
I'll be teaching the second half.
And my research is on two areas, brain stem auditory reflexes,
like the startle reflex and the middle ear muscle reflex.
And I also work on animal models of the auditory brain stem
implant, which is a neural prosthesis that's
used in deaf individuals.
PROFESSOR: All right.
And I'm Peter Schiller, and I work on the visual system.
And I'm a professor here in our department.
So that's very nice.
Thank you for the introductions.
And I hope, you guys, we all get to know each other.
I'm very impressed that there's so many seniors here.
That's actually unusual.
I don't remember having this high a percentage
of seniors in the class.
That's really very nice, very nice.
OK.
So now we are going to talk, for the first part
of today's lecture, about what aspects of visual processing
we are trying to understand and, therefore,
what we are going to try to cover
in this course in terms of topics.
OK?
So first of all, what we are going
to do for several lectures is to talk about the layout
and organization of the visual system itself.
Most of it we will discuss as it applies to higher mammals,
in particular monkeys and primates and humans.
Then we are going to talk about specific aspects
of visual processing.
We're going to try to understand how we adapt in vision,
and, very interestingly, how we are
able to perceive colors and process them accurately.
Another fascinating topic is how we
are capable of analyzing motion.
That's a complex, very interesting topic,
as is depth perception.
And the reason depth perception is particularly
interesting is because, as you know,
the retinal surface is essentially
a two-dimensional arrangement.
And yet from whatever falls on these two dimensions
in the left and right eyes, somehow the brain
needs to convert to be able to see the third dimension.
And as a result, several mechanisms
have evolved to accomplish that, and we
are going to discuss them.
Then, again, another very complex topic
is how we can recognize objects.
Perhaps the most complex of those
is our incredible ability to recognize faces.
And that is highlighted, of course,
by the fact that if you look at more simple organisms,
like, I don't know, monkeys, they all look the same to you.
But human beings, who are actually
more similar to each other than perhaps monkeys are,
we are really capable of telling them
apart and readily recognize them over long periods of time.
So it's a very interesting topic.
And yet another topic that we will discuss
is how we make eye movements.
As you probably know, or you're aware of,
that we are constantly moving your eye.
You make saccadic eye movements about three times a second,
thousands of times a day, hundreds of thousands of times,
to be able to see things clearly in the world.
So we are going to try to understand
how that incredible ability has evolved
and how it is realized by the brain.
OK.
So now to look at exactly how we are going to cover this,
let me go through this.
During the next lecture, which is September 9,
we are going to look at the basic layout of the retina
and the lateral geniculate system,
as well as how the visual system in general is wired.
Then on September 11, we're going
to look at the visual cortex, then
at the ON and OFF channels, so-called,
that you'll realize what they are once we talk about it.
And then there's another set of channels
that originates in the retina, which
are the midget and parasol channels.
We'll discuss those, try to figure out why did they evolve
and what is their role in being able to see
the world in realistic fashion.
Then we're going to talk about adaption and color, depth
perception, form perception.
And then we're going to have a lot of fun on October 2,
and we're going to look at illusions and also
visual prosthesis, because one of you,
in particular, is interested in that topic.
Then we are going to talk about the neural control of visually
guided eye movements.
That's going to consist of two sessions.
And then we're going to talk about motion perception
and another aspect of eye movements
when we pursue something with smooth eye movements.
And then we're going to have an overview.
And then, lastly, on October 23rd,
we are going to have the midterm exam.
That's going to cover questions from all of these lectures.
I should tell you right now that the midterm exam is going
to consist of multiple-choice questions.
So you're not going to, maybe, asked to write anything.
You're going to have to just pick
from each of the questions the correct answer.
All right.
So now what I would like to talk about next in a summary fashion
are what we call the tools of the trade.
What has happened over the many years
that scientists tried to understand
how the visual system and, for that matter the brain, works,
what kinds of methods have been employed.
And so I'm going to talk about each of these just very briefly
this time, and then they will come up repeatedly
during all of the lectures.
Now, the first method I'm going to talk about
is called psychophysics.
I'm sure most of you know what that is.
It's a scientific way to study behavior of humans and animals
to determine how well they can see.
Now, there are several procedures with this.
I'm going to describe one that's used
both in humans and monkeys.
And what you can do nowadays, you can use a color monitor,
and I will describe that in just a second.
After that, I will talk about anatomy.
I will talk about electrophysiology,
pharmacology, brain lesions, imaging, and optogenetics.
So now let's start with psychophysics in more detail.
So here is a color monitor, and either monkeys or humans
can be trained to first look at a fixation spot.
And that's important because we want to always
be able to present stimuli in selected
locations of the visual field or selected
locations along the retina.
This is particularly important, because when
you study the brain, different regions of the visual field
representation are located in different areas,
for example, in the visual cortex.
So what you do then is you can present a single stimulus
like this, and the task of the human or the monkey
is to either make a saccadic eye movement to it,
say that's where it is, or to press
a lever that's in front of them.
And then on each trial, it appears someplace else.
You can present it in many different locations,
and maybe one of those locations will
be relevant to what part of the brain you are studying.
And then what you do, you can systematically
vary all kinds of aspects of the stimulus.
You can vary the color.
You can vary the contrast.
You can vary the size.
You can vary the shape.
And by systematically varying this,
you can create curves to describe exactly how well you
can see any particular thing like,
for example, just how much contrast you
need to perceive something.
All right.
So that's called the detection task.
Now, a related task, which has also been used extensively,
is called the discrimination task.
In this case, you present a fixation spot again.
The person or the monkey fixates,
and then you present a whole bunch of stimuli, one of which
is different from the others.
And you have to select where that one had appeared,
the one that's different, by making an eye movement
or pressing the appropriate lever.
Now, when you do this, you systematically
can vary the difference between the so-called distractor
stimuli, which are all identical,
and the target until the person is
no longer able to tell the difference.
And that way you can, again, generate a curve.
And you can specify just what is the amount of difference
that you need to put in this, say,
how good are you at perceiving slightly different colors.
All right?
And by doing that systematically,
you can generate these functions using
these psychophysical procedures to determine
pretty well how you're able to see.
And now this particular approach is also very useful
when it comes to studying individuals, humans
in this case, who have some problems with vision.
So if they have a problem in seeing colors,
you can readily determine, well, what's
the magnitude of that problem?
And thereby it can tell you what procedures
might be used to try to ameliorate their shortcoming.
Now, another method that has been used extensively
in not only vision, but in many, many different areas
of studying the brain, including audition of course, is anatomy.
Numerous methods have evolved in the course of anatomists
working on these problems, and the first is a very simple one.
You just look at the whole brain.
And I'm showing this because this is a monkey brain,
and you will encounter the monkey brain repeatedly.
And it so happens that after people
have studied this extensively, they
were able to give names to just about
every gyrus or every brain area and also relate it
to what the function is of those areas.
And so, for example, just to name a few of these,
this is called the central sulcus.
I need to do one more thing here.
OK.
So this here is the central sulcus.
All right?
Just for you to remember, humans also
have a central sulcus, of course.
And this is the lunate sulcus.
And this region back here-- let's see, did I label this?
Oh, here's a couple more, the arcuate and the principalis.
You will encounter these repeatedly.
And this region back here is the one
which is the primary visual cortex in monkeys that
has been extensively studied and has
yielded remarkable discoveries about the way it works.
So that is called area V1, or primary visual cortex.
All right.
So now just another example, if I
can show you just a few examples of anatomy.
Here's another example showing what the eye looks like.
And the remarkable thing about the human eye,
and the eye of monkeys as well and primates,
is it has become highly specialized.
There's a region here which is called the fovea.
And in that region, you have a very, very dense distribution
of photoreceptors and other cells in the retina.
And because of that, you have very high acuity there.
Now, because of that, the eye movements
have to become effective for you to be able to see fine detail.
So even, for example, when you read,
what do you do when you read?
You make saccadic eye movements across a line.
Then you go down the next line three or four saccadic eye
movements, and so on down the page.
And you do that because you cannot make out the details
of letters in the periphery because, there,
the distribution of the photoreceptors and the cells
in the retina in general become less and less dense.
So that is a high degree of specialization
that we will discuss in much more detail next time.
Now then, all the fibers from the retinal ganglion
cells course across the inner surface of the retina
and go to the so-called optic nerve through which
over a million fibers from the retina project
into the nervous system.
And how they project exactly, what that's
like I will discuss in considerable detail
the next time.
Now, this area here is often also called
the blind spot, and that you don't
see even if you close one eye.
But if you do a careful experiment--
I'll explain that the next time-- you can actually map out
this little region where you don't see anything.
They're in different locations in the two eyes,
so the two blind spots do not overlap.
And so, consequently, when you look with both eyes,
you don't have a, quote, blind spot.
So that's an example of what the human retina looks like,
and this has been studied extensively
using a whole array of anatomical procedures.
Now, the third anatomical procedure I want to tell you
is labeling individual cells.
Now, the way this was done, or still is being done,
is that you slice the brain into very, very thin sections.
And you put them on a glass, and then you
can look at them under a microscope.
Now, here's an example of a cross-coronal section
of the monkey lateral geniculate nucleus.
That's one region in the brain to which the retinal ganglion
cells project.
And it's a beautifully layered structure,
which I'll describe in detail the next time.
And these little spots that you see here
are actual cells, which are labeled using a so-called Nissl
stain.
Now, another method used in staining cells
is the famous Golgi stain, which was discovered, invented,
perhaps, you could say, by Golgi, for which he received
the Nobel Prize in 1906.
The remarkable quality of those productions
is that this label-- it's a silver label-- stains not only
the cell bodies, as the Nissl stain you have just seen,
but also all the processes, the dendrites as well as the axons.
So you see a whole cell as a result
of that staining procedure.
Yet another way to do this, which
is more sophisticated nowadays, is
to record intracellularly from a cell and then inject a label.
This happens to be the so-called Procion Yellow labeling
substance.
You inject in the eye, and then you process the tissue again
in thin layers.
And this is an example of what that looks like.
So this also stains all the processes of the cell.
And the advantage here is that you
can study this cell electrophysiologically
and determine what it is like, and then
stain it so you can establish the relationship what
the cell does and what the cell looks like.
All right.
So now let's turn to the electrophysiological method,
which is a consequence of this, logical consequence of it.
Once again, here we have a monkey brain.
And what you do here, we put microelectrodes into the brain.
Now, this was a discovery that was
made around the turn of the century, little bit after.
Initially, microelectrodes were made
from very thin tubes of glass, which were heated
and then pulled so that the tip became smaller than a micron.
So it was very, very small.
Subsequently, other methods were developed.
They etched fine pieces a wire until the tip was very, very
small, and then they corded it.
And they then we were able to put these electrodes
into the brain and record single cells just like with glass
pipettes.
So the example here then is that you take a microelectrode,
put it into the brain, and then that is connected
to an amplifier system and a computer.
And when you do that, you can record from a single cell.
Now, as you well know, single cells
generate action potentials.
And that is shown here on an oscilloscope
in a schematic fashion.
And what some clever people did is
that they decided that an easy way to process information
about the manner single cells generated
action potentials is to put this signal onto a loudspeaker
system.
And so every time a cell fired, what you would literally hear
is beep, beep, like that.
OK?
And so if you shown a light on it several times,
it will go like brrrp, like that.
And the big advantage of this was
that many cells see only a tiny portion of the world.
And if you don't know where it is,
you have to take some projector or something
and move it around.
And if the receptive field is here,
you go, brrrp, brrrp, brrrp, brrrp, like that.
OK?
And so then you can map it out very accurately.
Instead of having to like with the oscilloscope, you hear it,
and that enables you to do all kinds of things, experiments,
and you don't have to look at the oscilloscope.
But you can perform all sorts of experiments,
and you can hear the responses of the cell.
Now, another method that is used extensively
in electrophysiology is called electrical stimulation.
It's a similar process.
You take a microelectrode, for example, you
put it in the brain, and then you pass electric current.
Typically, that electric current is passed in such a way as
to mimic action potentials.
So if you are to listen to when it's activated, again, brrrp,
you hear that.
But this time, instead of the cell firing,
you are firing the area there, and that then
can elicit a response, all right, all kinds of responses.
If you stimulate here, for example-- remember now,
this is the visual system in the monkey-- as
has been shown in humans, electrical stimulation elicits
a percept, a small spot, a star-like image.
In the auditory system when you stimulate,
you can hear something.
And if you stimulate in the areas that
are related to moving your eyes, then the simulation
causes a saccadic eye movement.
So all those methods are very, very good
in trying to understand better the organization of the brain
for, in this case for vision, and for eye movements.
Now, yet another method that is used--
several methods I should say-- is pharmacology.
And when you do pharmacological experiments,
one procedure is-- and many different procedures,
I'll just describe one here-- once again,
you can stick a glass pipette into the brain,
and then you can inject it.
You can inject it either with actually a syringe
or using several other methods, and you
can inject all kinds of agents.
For example, you can inject a neurotransmitter analog
or a neurotransmitter antagonist to determine what effects it
has in various parts of the brain and, in our case,
in the visual system or the ocular motor system.
Now, yet another method that has been used
is brain inactivation.
Several procedures are available to inactivate the brain.
Once again, here's a monkey brain.
And this region here that I already
told you a little bit about because
of naming the gyri there, OK, is called the frontal eye fields.
This region has something to do with moving your eyes.
So what you can do if you want to study and find out
just what does this area do, one procedure
is to-- again, here is V1-- is to make a lesion.
Now, sometimes you actually do that in a monkey.
But sometimes in some experiments,
humans may have an accident, some event when
you served in Vietnam or something,
and a region of the brain has been
removed by virtue of a bullet or something.
And that way you can find out what
is the consequence of having a lesion like that.
You can study, use a psychophysical procedure,
as I described to you, to determine just
what is the consequence of having lost this area.
This is a huge region of research.
A great many types of experiments have been done.
One of the famous individuals who had done this kind of work
is Hans-Lukas Teuber, who used to be
the chairman of our department starting way, way, way
back in 1962.
And his specialty was to study Second World War veterans who
had sustained various kinds of brain injuries.
And the basis of that, studying them
using psychophysical procedures, to assess what
various areas in the brain, what kind of functions they have,
what kinds of tasks do they perform.
Now, yet another method, which has some major advantages,
is to make reversible inactivations rather than
permanent ones.
And this you can do by, for example,
using a method of cooling.
There's a device, the so-called Peltier device,
that you can put on top of the brain.
And then electronically, you can cool the surface that
is in touch with the brain, and then
you can see what happens when you cool it.
And then when you warm it up again,
you can see what happens to recovery, which, in this case,
in almost all cases like this, leads
to full recovery and the same performance
as prior to starting the cooling.
Yes?
AUDIENCE: Can you only use this method for surface structures
or?
PROFESSOR: No.
They have now developed methods where you can actually
lower them into the brain.
And they're usually much finer, and very often they're
sort of a loop type device.
And you can lower that into the gyri or wherever you like,
and, again, do the reversible cooling.
Yes.
That's a fairly recently developed device,
and it works extremely well.
Now, yet another approach is to inject substances
into the brain that anesthetize, if you will,
a particular region after the injection,
but only for a limited time.
And then you can see how the behavior is affected.
Now, a variant of that that I referred
to before, of course, is that you can use agents that
are selective, that don't inactivate the whole area,
but for example, only affect excitatory neurotransmitters
or only affect inhibitory ones.
So you can do kinds of selective things.
And so you can establish the role
of various neurotransmitters in the role
they play in various brain areas.
Now, yet another method very recently developed,
which has been incredibly successful, is imaging.
As you probably all know, you all
know we do have an MRI facility here
in our department on the ground floor, and some of you
may even have been subjects in it.
What that does is when you put a subject
into this-- the variant of that is called
fMRI, functional Magnetic Resonance Imaging.
And so if you put a person in the magnet and you present
a certain set of stimuli repeatedly, OK,
or differential ones, whatever, the brain areas
that are active performing the analysis
that you ask them to do light up.
So that method-- here's a complex picture of that.
This is one that is in Freiberg, Germany.
This is done with monkeys again.
You have this device and you put the monkey in there.
You lower the device on it, and then you
can have the subject perform trained tasks.
And then you can analyze the brain
and look at the nature of activation.
And here's an example of that, whatever
this task is, doesn't matter.
You can see that a particular brain
region has been very heavily activated
as a result of whatever manipulation they did.
Now, there are lots and lots and lots of experiments
of this sort, and we will talk about several of those
as we look at various aspects of the visual system.
Now, the last method I want to just mention very, very briefly
is optogenetics.
That's a new method, and we have actually several people
in our department here who are using this method.
Now, this particular method-- let
me explain just very quickly what this is all about.
Does everybody know what an opsin is?
OK.
How about if I say rhodopsin?
OK.
Most of you will know that.
A rhodopsin is a set of molecules
that are in the rods in the photoreceptors,
and they are sensitive to light.
Now, there are all kinds of variants.
That's why I mentioned opsins rather than rhodopsins.
And what can be done is that you can selectivity
place these various substances into selected types of cells
in the brain.
And then, because these cells become light sensitive just
like the photoreceptors are, then when you shine light
onto the area where you had placed these opsins in cells,
you can drive them.
You can make them respond by turning the light on.
Now, the amazing thing about that
is that makes it a more powerful technique
than electrical stimulation, that you can set this up
in such a way that, for example, if you use a rhodopsin
substance that is sensitive to red light,
it will be excited by the red light.
But if you have a slightly different substance that
would be inhibited by blue light,
then you can see what happens if you excite those cells,
and then you inhibit those cells.
So this gives you two sides to the coin,
whereas electrical stimulation provides only one side.
So that's a wonderful technique.
And here's sort of a good example of that.
Here we have injected-- I shouldn't
say injected-- but genetically labeled
cells with channelrhodopsin, so-called.
And when that's done, when you shine in a blue light,
OK, you excite the cell.
And then instead, if you put in so-called halorhodopsin, OK,
halorhodopsin, then if you use yellow light
you inhibit the cells.
So that's a remarkable technique.
It's just at the very beginning of things,
so we won't talk too much about this technique
in studying the visual system yet.
But I bet you that in another 10 years
this is going to be a central topic.
All right.
So to summarize these techniques,
other than the psychophysics, just remind you again,
number one, we have electrical recording
using microelectrodes.
OK?
Then secondly, we have electrical stimulation.
Thirdly, we have injection of pharmacological agent.
Then we have methods to inactivate regions,
either permanently by lesions or reversibly by cooling
or by injecting various substances.
And lastly, we have optogenetics that
enables you to activate cells or inhibit cells
by shining light onto the brain.
So these are quite a remarkable set of techniques.
And individuals who want to become neuroscientists,
they're going to have to learn to master not maybe
all of these techniques, but certainly some of them
so that they can carry out new and original experiments
in determining how the brain works
and, in our case, of course, how the visual system works.
So that is, in essence then, what I wanted to cover.
And now we are going to move on and have Chris tell you
about his portion of the course, which
will be taught during the second half of this semester.
So as I said, next time we are going
to start talking about, first of all,
about the wiring of the visual system, the basic wiring.
And then we're going to talk about the retina in detail
and a little bit about the lateral geniculate nucleus.
That's the next lecture.
Please.
AUDIENCE: So for the eigtht readings, the eight assigned
readings that you have on here, how
will we know when to read what?
PROFESSOR: Well, that's a good question.
The sections that have to do with eye movements
that you can see, that you don't have to read until we
get to the eye movements, the latter part.
Initially, when we talk about the retina, for example,
you definitely want to read the [INAUDIBLE] paper
and the Schiller paper on parallel information processing
channels.
Then the ones that have to do with the Hermann grid
illusion and visual prosthesis, that you
don't have to cover until you come
to the section on illusions and visual prosthesis.
PROFESSOR: OK.
Welcome, everybody.
I'm Chris Brown.
And I just, in the remaining time,
wanted to give you a synopsis of what's
going to happen during the second half of the term.
So I'll be giving the lectures during the second half
on the topic of audition, or hearing.
And there's my email, chris_brown@meei.harvard.edu.
So as you can see by my email, I'm
associated with Harvard, in fact, Harvard Medical School.
And I'm in the so-called ENT department at Harvard Med
School, and that stands for Ear, Nose, and Throat.
So some of you who are going to be going to medical school
will certainly do an ENT rotation,
where you learn about the various aspects of ENT.
And much of it, of course, is the subject
of otology, what happens when people have disorders
of hearing, problems with their hearing.
And in addition, many ENT doctors
also operate on people who have head and neck cancers.
So surgeries of those two types go
on at my hospital, which is Massachusetts Eye and Ear
Infirmary.
And that's across the river in Boston,
and it is, of course, one of the main teaching hospitals for ENT
as well as ophthalmology.
There's a big Ophthalmology department
where the ophthalmologists deal with disorders
of sight and vision.
So I have an introductory reading,
which is a book chapter that I wrote, and also
with Joe Santos-Sacchi, which is actually
now in the fourth edition of a textbook
called Fundamental Neuroscience.
And I believe this book chapter is on the course website now.
And it summarizes pretty much what
I'll cover during the semester in a reading
that you could probably do in an hour or less,
and it has many of the figures that I'll use.
So if you're shopping around for a course
and want to know what's going to happen in the second half here,
you can look at that book chapter.
There's a nice textbook that I'll also
be assigning a number of readings
from throughout the term, and it's
called Auditory Neuroscience, Making Sense of Sound
by Schnupp, Nelken, and King.
And these fellows are, in the case of the first and the last,
at Oxford University, and they work on psychophysics, that is,
how we perceive hearing.
And they test humans, and they also
do a fair amount of animals psychophysics.
And in the case of Israel Nelken,
he's at Hebrew University in Israel.
And he does a lot of electrophysiological
recordings-- you heard about electrophysiology
from Peter's talk just now-- and recordings
especially from the auditory cortex.
But this is a very nice book for coverage especially
of the central auditory pathway in psychophysics.
And it's pretty cheap.
I think it's $30.
And I believe I was told earlier that you can get it,
as an MIT student, online free.
And what's good about the online edition
is there are lots of demonstrations,
each indicated by the little icon in the margin of the text.
And when you click on that demonstration,
if you have your earbuds in you can
hear what the sound demonstration is.
And I'll be doing quite a lot of sound demonstrations
through the course of the semester because I think
it livens up the class a little bit,
and this book is especially good for sound demos.
So I encourage you at least to get
the online edition of that textbook.
So also on the course website is the syllabus
for what the audition lectures will cover,
and I just put a couple here to give you a flavor.
In the first lecture on October 28th,
we'll talk about the physical characteristics of sound
and what happens to that sound when
it strikes your external, and then
your middle, and inner ears.
And associated with each lecture is an original research article
that, in this case, is Hofman, et al.,
and the title is "Relearning Sound Localization
with New Ears."
And so, in a nutshell, what they did in that research report
was they took little pieces of clay,
and they inserted them into their external ears or pinna,
and therefore distorted quite a lot your pinnae.
They couldn't do what van Gogh did,
which was cut off the pinna, but they certainly
distorted their pinnaes quite a lot on both sides.
And then they tested, using themselves
as subjects and other volunteers,
how good their ability to localize sound was.
And especially in terms of when the sound varied in elevation,
they found that there were huge differences,
that they couldn't localize sounds that were straight ahead
versus sounds that were coming from above themselves
with these distortions.
But what was funny and what harks back
to the title of the article is that when
they had the volunteers go out and live their normal lives
with these pinna distortions in for a few weeks,
then they came back into the lab and tested them again,
they found that they could now localize sounds in elevation
with these new ears.
They relearned how to localize sound.
So this is a nice demonstration of learning or plasticity,
at least in psychophysical responses.
And it also emphasizes the function
of your external ear, which helps you localize sounds
in space.
In the second lecture, we'll be talking about the receptor
cells for hearing, which are called hair cells because they
have these little appendages at their top
that looked to the early neuroanatomists like hairs.
And of course, sound is a mechanical energy
that moves the fluid in which these hair cells are immersed
and moves these little hairs or appendages
at the top of the cell, and that's
how the cell can respond then to sound.
And so hair cells are the very important receptor cells
for hearing, which are, of course, the analogs of the rods
and cones in the visual system.
And the research report associated
with our talk about hair cells will
be how a special protein called prestin is required
for electromotility, which is a function of outer hair
cells, one of the two types of hair cells,
which allows them to actually move and flux and change
their membrane links when they sense
these mechanical disturbances by their stereocilia.
So it's a pretty interesting paper
in what we call a knockout animal.
So the prestin is genetically knocked out
in this particular animal, and the sense of hearing
is then tested again in these knockout animals.
So we have a whole bunch of lectures.
I haven't indicated all them.
They're on the course website.
Toward the end of the semester, we'll have, as Peter indicated,
a written assignment for audition.
So I haven't actually thought it up yet,
but let me just give you an example.
Last year and this year, we'll be talking a lot
about neural prostheses for audition.
And the most famous neural prosthesis for audition,
of course, is the cochlear implant,
which I'll talk a little bit about later,
and it works quite well.
There's also a neural prosthesis that
goes into the auditory brainstem.
It's called the auditory brainstem implant,
and it's used in some other types
of individuals who are deaf.
And it doesn't work anywhere near as well as the cochlear
implant.
It's sometimes called a lip reading assist device
because people who have the brainstem implant
usually can't understand speech over the telephone.
They need to be facing you and looking at your lips
as you're speaking.
They need additional cues.
And so there'll be a lot of discussion
this term about the differences between these two
types of the implant, where they're
put in the auditory pathway, and why
one works much better than the other.
And that was the written assignment
for last year, which was a discussion of why the cochlear
implant works a lot better than the auditory brainstem implant.
So I'll have something along those lines that
uses the material from our course
that you can take to answer a question.
OK.
Let me just go through in a half a dozen slides or so
what I consider to be the high points
of the auditory part of the course.
About the first third of the auditory part of the course
will be a discussion of the auditory periphery.
And the periphery is usually divided
into these three basic divisions, the external ear,
which most of us think about as the ear, the pinna and the ear
canal, which leads to the tympanic membrane
here in yellow, or eardrum.
And at that point begins the middle ear.
The middle ear is an air-filled space.
If you've been on a recent plane flight
and your ears are a little bit stuffed up,
it can be very uncomfortable, especially when
the plane is coming down in altitude.
And your eardrum bulges because the eardrum is just
a very thin layer of skin, and it can bulge very easily.
But it's painful when the eardrum
bulges when the change in pressure
happens as you're descending in a plane.
In the air-filled space of the middle ear
are three small bones, the malleus, the incus,
and the stapes.
If you remember from high school biology, the hammer, the anvil,
and the stirrup.
The stirrup looks like what a cowboy has on his saddle
that he puts the cowboy boots through.
It's a very, very small bone.
In fact, it's the smallest bone in the body.
These bones are very small because they
have to vibrate in response to sound,
and so they can't be big and massive.
Massive things don't vibrate very well.
And so the stapes is sometimes encompassed by bony growths
around it and prevented from vibration
in a disease called otosclerosis.
And so at my hospital, the Massachusetts Eye
and Ear Infirmary, they do an operation
to cure that type of deafness called the stapedectomy.
So what's an -ectomy?
You medical types, what does that mean?
AUDIENCE: Removal.
PROFESSOR: It means removal, right.
So they take the stapes out.
And that's because if they just loosen it up,
the bone regrows and re-adheres the stapes from vibration.
So they replace the stapes, the natural stapes,
with a stapes prosthesis, either a little piston or a tube,
that they hook on with a wire to the incus,
and they put into the so-called foot plate area or oval
window of the cochlea, which is the next structure I'll
talk about.
And that very nicely restores the sense of hearing.
In fact, when I was a postdoc fellow at Mass Eye and Ear,
I could go watch the surgeries, and I watched a stapedectomy.
And the patient was anesthetized, but not
so much that she was really out.
She was more sedated.
And at the end of the operation, the surgeon
was adjusting the artificial prosthesis,
and the surgeon said, well, can you hear me?
And the patient didn't respond.
So he moved it around a little bit or adjusted the wire,
I don't know which.
He says, can you hear me now?
And there was no response from the patient.
And he did a little more manipulation and adjustment.
And he finally said, can you hear me?
And the patient said, why are you yelling at me?
I can hear you just fine.
So usually at the end of the operation,
the patient has become more light.
The anesthesiologist turns off the anesthesia.
And they adjust the stapes prosthesis so it works well.
So that type of operation is fairly common
and very successful to restore the so-called types
of conductive hearing loss.
These bones conduct the acoustic sensation into the cochlea.
Now, in the cochlea-- this is the structure here.
The "cochlea" is the word for the inner ear.
It comes from the Greek word "kokhlias," which means snail,
and it is certainly a snail shell-shaped capsule.
The cochlea looks like a coiled snail shell.
And inside it are the receptor cells
for hearing, the hair cells and the dendrites
of the auditory nerve fibers.
OK?
And the cochlea is a bony-filled capsule
filled with fluid and membranes and cells inside.
And this anatomy is a little bit complex,
so I brought in a model here of the auditory periphery.
So we have the external ear, the long ear canal
here, the eardrum.
It's kind of slanted here.
And this part here that I'll lift out here
is the cochlea or the inner ear, the snail shell-shaped area.
And leading from it is the yellow-colored, in this case,
auditory nerve, which sends messages from the cochlea
into the brain.
And these funny, loop-shaped structures that I'm grasping
are the semicircular canals, which
mediate the sense of balance or angular acceleration.
When you rotate your head, those hair cells in there
are sensitive to those rotations.
OK.
So I'll pass this model around.
You can take a closer look at it.
And in our hospital, the surgeons practice
on real, live specimens like that from postmortem material
because in otologic surgery there's
a lot of drilling to access, for example, the middle ear
or the inner ear.
And there's a lot of important structures
that you don't want to run into with your drill bit,
like the jugular bulb is that red thing there.
The facial nerve goes right through the middle ear.
And so the surgeons need to know their way around the middle ear
so that they can avoid important structures
and go to the right structure that they intend to operate on.
OK.
So you heard Dr. Schiller talk about electrophysiology
and recordings from individual neurons.
And a lot of what we know about how the inner ear works
comes from such types of experiments.
And this is an experiment at the top here
that gives the responses in the form of action potentials.
Each one of these blips is a little action potential,
or impulse, or response from one single auditory nerve
fiber recorded in the auditory nerve of a cat, which
is the very common model for auditory neuroscience,
or at least it was in years past.
So this response area is a mapping of sound frequency.
So this axis is tone frequency.
And the frequency of a sound wave form
is simply how many times it repeats back and forth
per second.
Frequencies that are common in human hearing
are, for example, 1,000 hertz.
This is a graph of kilohertz, tone frequency in kilohertz.
And the upper limit of human hearing
is approximately 20 kilohertz.
The lower limit of human hearing is down around 50 or 100 hertz.
In terms of smaller animals like the cat,
they're shifted up in frequency of perhaps an octave, maybe
a doubling of the frequencies that they're most sensitive to.
This auditory nerve fiber responded
to a variety of frequencies, except at the very lowest
sound level.
The y-axis is a graph of sound level.
This is very low level or soft sound,
this would be a medium sound, and this
would be a very high level sound.
At the lowest levels of sound, the auditory nerve fiber
only gave a response to frequencies
around 10 kilohertz, or 10,000 cycles per second.
There are some spontaneous firings from the nerve fiber,
and those can happen even if there's no sound presentation.
These neurons can be spontaneously active.
If you outline this response area,
you can see that it's very sharply tuned
to sound frequency.
It only responds around 10 kilohertz.
And this exquisitely sharp tuning of the auditory nerve
is the way, perhaps, that the auditory nerve sends messages
to the brain that there is only 10 kilohertz that the ears are
hearing and not 9 kilohertz and not 11 kilohertz.
OK?
If you increase the sound level to higher levels,
this auditory nerve fiber, like others,
responds to a wide variety of sound frequencies,
but it has a very sharp cut off at the high frequency edge.
Maybe at 11 kilohertz, it responds,
but 11.1 kilohertz there's no response.
So the tuning becomes broader, but there's still
a really nice, sharp, high-frequency cut off.
So what good is this for?
Well, the ear is very good at resolving frequency, saying
there's 10 kilohertz but not 9 kilohertz.
And that's very important for identification of sounds.
For example, how do we know, if we're talking on the telephone
or not seeing the subject who's talking to us,
that it's a female speaker or a male speaker
or an infant speaker?
Well, male speakers have lower frequencies
in their speech sounds.
And so right away, if we hear a lot of low frequencies
in the speech sounds, we assume we're
talking to a male speaker.
And that's, of course, a very important identification.
How do we know we're hearing the vowel A and not
the vowel E, ah or eh?
Because of the different frequencies in the speech
sounds for those two vowels.
So frequency coding is a very important subject
in the auditory pathway for identification
and distinguishing different types of sounds.
And one way we know what frequencies we're listening to
is if the auditory nerve fiber's tuned
to a particular frequency [INAUDIBLE]
responding and not the others.
Now, some very elegant studies have
been done to look at the mapping of frequency
along the spiral of the cochlea.
And what those show is that way down
at the base of the cochlea, the very highest frequencies
are sensed by the hair cells and the auditory nerve fibers
there.
And as you go more and more apically,
you arrive at first middle, and then lower frequencies.
So there's a very nice, orderly mapping
of frequency along the receptor epithelium,
or along the cochlea in the sense of hearing.
And so, obviously, the hearing organ
is set up to distinguish frequencies and identify
sounds.
OK.
So that's not the only code for sound frequency that we have.
We'll talk extensively about another code
that uses a time-coding sense.
And this comes from the way that auditory nerve fibers
so-called phase lock to the sound's waveform.
Here's a sound stimulus, and here's auditory firing, first
with no stimulus.
It's a fairly random pattern.
And here is with a stimulus turned on,
and you can see that the spikes line up during a certain phase
or part of the stimulus waveform.
And that's not that impressive until you
look at the time scale here.
As I said before, sounds that are important in human hearing
are as high in frequency as 1 kilohertz.
So if this is going back and forth 1,000 times per second,
then the scale bar here for one period would be 1 millisecond.
And so the auditory nerve is keeping track and firing only
on a certain or preferential phase of the stimulus waveform
with the capability of milliseconds.
OK?
And this is a much better phase-locking pattern
than you get in other senses.
For example, in the visual system,
when you flash the light on and off just even 100 flashes
per second, everything sort of blears out,
and you sort of don't have any phase locking
the way you do in the auditory nerves firing.
So this is a very nice coding for sound frequency that
is sort of a secondary way to code.
This is a very important coding for musical sounds.
Musical sounds, for example, like an octave,
1 kilohertz and 2 kilohertz, a doubling of sound frequency,
have very similar patterns in their temporal responses
to those two frequencies that probably
makes an octave a very beautiful musical interval to listen to.
And it appears in music of many different types of cultures.
So one of the demonstrations that I'll
play for you is an A for 40 hertz
and an octave above that, 880 hertz, and you'll
hear how beautiful the two sound together.
And then I'll mistune them, which is easy for me
to do because I'm an amateur violinist,
and I'll be doing this on a violin.
And it's pretty easy to have a mistuned octave,
and it sounds so awful and very dissonant
when you listen to it.
And one of the reasons for that, the reason for that,
is the difference in phase locking
for the two dissonant sounds versus the two consonant
sounds.
OK.
So we will talk about what happens
when you have problems with your hearing.
One of the main problems with hearing
that causes loss, complete loss of hearing,
is when the receptor cells are attacked
by various types of insults, diseases, drugs,
the aging process, stimulation, or listening
to very high-level sounds.
These can all kill the hair cells.
And in the mammalian cochlea, once the hair cells are lost
they never grow back.
And there's very active interest in trying
to get hair cells to regenerate by using
stem cells or various growth factors,
but so far that can't be achieved.
Luckily, in the auditory periphery,
even if you lose the hair cells, which
is the major cause of deafness, you
retain your auditory nerve fibers.
So these blue structures here are the auditory nerve fibers
coming from the hair cells.
And even if the hair cells are killed
by these various insults, the auditory nerve fibers,
or at least many of them, remain.
So you heard Dr. Schiller talk about electrical stimulation.
You can put an electrical stimulating electrode
in the inner ear and stimulate those remaining auditory nerve
fibers to fire impulses that are sent to the brain.
And if you hook that system up right,
you have a so-called cochlear implant.
The cochlear implant has a microphone that detects sound.
It has a processor that converts that sound into various pulses
of electrical stimulating current, which
can be applied to a system of electrodes
that is inserted into the cochlea.
The cochlea is a beautiful bony capsule.
You can snake this electrode in.
It doesn't move away.
You can glue it in place.
You can lead the electrode out to the processor that
activates it when the subject hears a sound that's
detected by the microphone.
And this cochlear implant is the most successful
neural prosthesis that's been developed.
It's implanted all the time at Mass Eye and Ear Infirmary.
It's paid for by insurance.
These days, insurance pays for a cochlear implant
in your left cochlea if you're deaf,
and it will also pay for another cochlear implant
in your right cochlea if you're deaf.
So the metric for how successful this is,
is whether the subject who's using the cochlear implant
can understand speech.
And so you can have various tests of speech.
A speaker can give a sentence, and the person can respond.
The speaker can give various simple words,
and the cochlear implant user can respond.
You can test these individuals in a very straightforward
manner.
And we will have a demonstration by a cochlear implant user.
I have an undergraduate demonstrator who's here at MIT.
And she'll come in and she'll describe and show you
her cochlear implant, and you can ask her questions.
And there, I guarantee you with this particular demonstration
that I have in mind, that she won't always
understand your questions.
I have had really great cochlear implant users
who are superstars, that understand every word.
But the more norm is they understand much of what you say
but not everything.
And this particular room is a little bit challenging.
There's some noise in the background.
It's not one-on-one, so the implant user
won't know exactly who's speaking at once.
And in this case, the person just has one ear implanted,
so her ability to localize sounds is compromised.
And she won't know who's asking the question until she sort
of zeroes in a little bit on it.
So you'll see the cochlear implant is not perfect,
but it's pretty good in its metric
for speech comprehension.
OK.
Now, I said this particular cochlear implant user only
has one implant in one ear.
To really be good at localizing sound,
we need to have two ears, and there
are the so-called binaural cues for sound localization.
Here's a subject listening to a sound source.
The sound source is emitting sound here,
and it gets to the subject's left ear first.
And a short time later, it gets to the subject's right ear.
And that's one of the cues for binaural localization of sound,
which is interaural time difference.
The velocity of sound in air is 342 meters per second.
And depending on how big your head is,
you can calculate the Interaural Time Difference.
And of course, that ITD is maximal
if the sound source is located off to one side,
and it's exactly zero if the sound source
is located straight ahead.
OK?
So that is a cue for localization of sounds.
We'll listen to sounds that differ in interaural time
difference.
We can play these through headphones for you.
And we'll have some demonstrations of that.
The other binaural cue for sound localization
is the interaural level difference.
Here is the same sound source, same subject.
This ear will experience a slightly higher sound level
than the other ear because sound can't perfectly
bend around the head.
The head creates a sound shadow.
And this is especially important for high frequencies of sound,
like above 3 kilohertz.
So that is a second binaural cue for sound localization.
We'll listen to those cues.
And we'll talk a lot about the brainstem processing
of those binaural cues for sound localization.
If you compare the visual and the auditory pathways--
this is a block diagram of the auditory pathway,
and there are a lot of brainstem nuclei.
We have the cochlear nucleus, the superior olivary complex,
and the inferior colliculus.
And these latter two get input from the two ears on the two
sides, and they probably do the bulk
of the neural processing for sound localization.
You don't have to do that so much in the visual system
because the visual system, in a sense,
has a mapping of external space already on the retina.
But remember, the inner ears map sound frequency.
And so the inner ears themselves don't know
or don't have a good cue for where
the sound is localized in space.
Instead, you need input from the two sides,
and you need a lot of neural processing
to help you determine where that sound source is
coming from in space.
OK.
So we'll talk about the neural processing
of those binaural cues.
We'll talk toward the end of the course
about the various auditory cortical fields.
These are the cortical fields in the side of the cat's brain.
So this is the front of the brain.
This is looking at the left side of the brain.
This is the rear of the brain where the occipital lobes are,
where V1 is.
And on the side or temporal cortex,
you have the auditory fields, including
A1 or primary auditory cortex.
And we'll talk, at least touch upon a little bit,
toward the end of the course the human auditory-- primary
auditory cortical field is right here on the superior surface
of the superior temporal gyrus.
And just near it, it could be called an auditory association
area, is an area called Wernicke's area
that's very important in processing of language.
And of course, connected with that
is the Broca's area, which is another important language
center, in the dominant hemisphere at least, of humans.
So we'll touch upon that at the very end of the course.
And we'll also have a special topic called bat echolocation,
how bats use their auditory sense to navigate around
the world at night even without their vision.
And finally, at the very last class period before the review
sessions, we'll all go over for a tour of the research lab
where I work at the Massachusetts Eye and Ear
Infirmary.
So it's across the Longfellow Bridge right at the end
there where the arrow is.
And we'll have some demonstrations there.
I think last year we had a demonstration
on single-unit recording from an awake animal that's
listening to sound.
We had measurements from humans of the so-called otoacoustic
emissions.
These are sounds that can be detected
in the ear canal with a very sensitive microphone.
They're used in tests of hearing.
And I also think we had a discussion
of imaging of the auditory system.
And of course, if you've ever listened to an MRI machine,
it's sort of described sometimes as being
as loud as being inside a washing machine.
And it's very challenging for people
that image subjects who are listening
to especially very low-level sounds
when there's all this background noise coming from the imaging
machine.
So there's some special things that
are done to minimize the noise coming
from the imager in auditory studies.