Most.

Productive.

Time.

For.

This.

Kind of.

Work.

We're going.

To.

Work receptive networkers.

Muscles that will.

Really help the organize
in a way that when.

You're awake.

For.

Years we're very we're
all regulated you know.

So with that I think that the detail
which was here with us there's room for.

Growth Thank you Mark.

Thank you for that kind of introduction
and thank you everybody for

braving the storms to be here this
morning but it's a bright object.

It's a little intimidating to give
a talk to your own colleagues but

we can do here this is actually
pretty much a brand new talk so.

You know if anything along the way isn't
all that clear or just raise your hand I'm

happy to keep it in informal anyway.

We know that the spinal cord has
intrinsic motor capacities it contains

pattern generating networks which can.

Regulate stepping as well as other
kinds of rhythmic behaviors it also has

circuits and neural circuits that arise
from receptor isn't muscles skin and

joints and so forth which are involved
in the regulation of posture and

balance both during quiet standing and
movement.

And.

All of these circuits are of course
very closely integrated with

activity of the brain stem in the brain
but it's a particular particularly

interesting to focus on the intrinsic
motor capacity is the spinal cord because

unfortunately there are individuals
who have spinal cord injury and

so until we find a way to
completely regenerate the spinal.

Board after spinal cord injury
which is a long long way off.

The approach to rehabilitating patients
with spinal cord injury has to

depend on a deep understanding of
these intrinsic motor capacities so

that's what we're going
to talk about today so

we're still kind of in the infancy of
understanding the details of these

circuits they've been worked out in
great detail and lobsters and crabs and

other invertebrate animals mammals
seem to be particularly difficult to.

Intractable to to get to so
you can sort of reap report on

some some progress in this light I want to
frame the question about the involvement

appropriate Cept of circuits that is those
circuits that arise from muscle receptor

is predominately muscle spindles and
golgi tendon organs.

I want to frame a question
in the following way and

that is Is Spinal circuitry modular and
the reason for

framing it in this particular way is
that most of the classical descriptions

of spinal circuitry provides us with
a modular model of how it works and

this is of course a reductionist.

Approach.

Because if you can understand how a single
module works then it's just a matter of

adding more modules and then you've got
the whole system easy well it's not so

easy because it's a modular system you're
having to pass the buck of coordination

to some other level in the central nervous
system and what we're trying to argue here

is that actually a lot of the coordination
takes place right there in the spinal cord

so just to give you the classical
view which will provide a little

bit of introduction for those of you or
who are not familiar with this field

this is a classic textbook picture of
spinal circuitry that you find and

this is the latest edition of candle
Schwartz just soul and others.

Probably the most famous neuroscience
textbook for medical stoop.

In the world and basically.

You have here a muscle with a stretch
receptor in it called a muscle spend zero

and that feeds back to the spinal cord and
so we have the muscle itself which we can

call the agonist we have another muscle
which we call a sinner just which

does similar things maybe
not identical things but

similar things and
I'll get to that in a little bit and

then another muscle that has the opposite
action called the antagonist and this

little circuit was first proposed by David
Lloyd in one thousand nine hundred six and

it's called the MIO tatic unit and
it's sort of a unitary idea

of how the sponsor could operate and
basically it's pretty nifty because if you

perturb the elbow joint all of these
pathways the excited Torrie pathways from

this muscle spindle back to the agonist
Center just and the inhibitory pathways

to the antagonist all conspire together
to resist that perturbation it all adds

up to resistance to the probation so
it's a very nice idea and

it was sort of the cornerstone of
our thinking for many many years.

Unfortunately it's it's very flawed but

we'll get to that in a little bit so
that's the my attack unit concept and

it's still pretty much taught to medical
students and graduate students today as

being one of the building
blocks of the spinal cord.

Another another building block is the as
follows there's another receptor in

muscles called the Goldie tendon organ
which have in serious connections between

the muscle and the tendon these golgi
tendon organs measure muscular forces

whereas the muscle spindle measure
measures the lengths of our muscles and.

Tendons organs there are afferent
to go back to the spinal cord and

they have more complicated connections
in the spinal cord and under many

conditions these connections tend to be
inhibitory rather than excite atory and.

The explanation for the function
of these pathways isn't quite so

clear cut as it is for the supposedly for

the muscle spindles but
to give you some idea of the complexity.

The Goldy tenor organ circuits which
are inhibitory under many conditions

under some conditions for particularly
during locomotion scratching and

other rhythmic behaviors some of these
one be afferent pathways switch from

an inhibitory pathway to an excited to a
pathway and they actually excite the motor

neurons causing a positive force feedback
loop and one of the one of the challenges

is to understand how these inhibitory
pathways in excited Torrie pathways are.

Are integrated and
intermix during natural movements.

A third kind of modular model of
the spinal cord is this one proposed

by James help in one thousand nine hundred
two and explicated more completely

in one thousand nine hundred nine he
happened to be my thesis advisor so

I had to talk about this of course.

What he said was Well we've got some
muscle spindles measuring the length and

tenor organs measuring force but
where's the integration between these

two what do they do as an integrated set
most neuroscience textbooks tend to talk

about these pathways as if they were two
separate things and that continues to

the present where he made a very very
astute observation he said well if you

combine excite a Tory length feedback
from muscle spindle receptor

gather with inhibitory feedback from golgi
tendon organs measuring muscular force

then you end up with a negative feedback
control system which regulates not length

not force but the relationship
between the two change in force over

a change in like this stiffness so
what he did is propose by POTUS is called

the stiffness regulation hypothesis in
which he said that the function of these.

If ways is to regulate muscular
stiffness by integrating length and

force feed back together now this
model also turned out to be incorrect.

But we were left of this very powerful
idea that length and force feedback

can be integrated at the level of
the spinal cord to regulate stiffness and

what I'm going to try to convince you is
that this regulation of stiffness does not

take place at the level of a single muscle
as implied by this original version

of the of the hypothesis that
the regulation of stiffness takes place at

a more integrated level the level
of the use of the intact limb.

OK so.

Here's the problem with
these simple models

as I said before the idea of a modular
system is that all the integration

has to take place somewhere else so
you kind of passing the buck but

in the first place the musculoskeletal
system is not modular itself the system

which is being regulated by these pathways
and here are some of the reasons why that

muscular skeletal system is not modular
it's not the simple sort of center just

antagonist system that I had that I
showed you in the beginning with the.

Unit.

Take the biceps femoris muscle and
the cat.

This muscle crosses the hip crosses
the name it has fibers that extend

all along here or
through fashion and tendon and.

It provides coupling across the hip
joint and the need joint It also is not

shown here it has fashion which connects
the these muscles to the ankle as well so

that muscle is actually working at
several different joints all at once.

The other thing is that this muscle is
because it's on the lateral side of

the leg tends to to rotate
the the shank outward.

I didn't do that very well
did I tend to do that.

And it's count.

Part the semi tend to notice muscle in the
medial side tends to do the opposite so

this muscle in the semi tendon
Gnosis are both agonists and

synergy and antagonist the same
time there are synergistic for

knee flexion and
antagonistic for knee rotation.

So what do we do that how do we squeeze
that into them I tell you no concept so

because muscles are multi
articular multi axis and

have fascial connections which
makes them have transmit forces in

other places than is accounted for
by tendons.

Joints throughout the limb are have this
goal last a coupling because MUST muscles

have a school lasting properties the other
reason why the system is not modular

is that of course limb
Segment seven inertia and

therefore the movement of any one limb
segments going to give rise to movements

of neighboring limbs segments
by inertial coupling like like

like this I'm not using my
wrist muscles to do this right.

So we have this problem of inner segmental
dynamics when we're doing something very

ballistic and very rapid how do we gain
control over our multi segment of limbs so

is the interesting mental dynamics to
not interfere not only is there inertial

coupling but that inertial coupling is
non-uniform because these big the big mass

of thought I hear next to the smaller
shank in this little itty bitty foot here

means that the inertial properties
are going to be changing with respect to

position on the limb and we're going to
get to that a little bit later with some

of Mark's work that I'm going to reflate
mention just one thing on fashion This is

Victoria stall she was a Ph D. student in
biomedical engineering that work me it or

thesis now is a post-doctoral fellow and

Randy Trumbo as laboratory
at Emory she actually.

She actually interfered with the fashion
between these muscles and the Kal can you.

Some showed not only that there was a loss
of acceleration of the ankle joint but

surprisingly found that
the animal this is a a disservice

cat this is an animal that's been
rendered permanently comatose by removing

part of its brain actually most of the
brain which is involved in consciousness

these animals walk very nicely on a on a
treadmill when you start the treadmill and

you can do invasive experiments on them
without worrying about the ethical

concerns because the animal cannot
suffer at all she found that the.

This is a tracing of the During the step
cycle of the foot's going back and

forth and sort of a little elliptical
shape when you cut the fashion different

stages the the limb sort
of loses control and

starts going all over the place so
fashion is really an important thing and

adds to our story that the muscular
skeletal system is not modular that

is forces are transmitted
widely throughout the limb.

Spinal circuits aren't modular either and
in fact.

As I said before if spinal
circuits were modular they would

contribute little to coordination.

This is actually been known since
the one nine hundred fifty S. were and

surge on Echols Nobel Prize winner and his
daughter and unders Lundberg did a series

of made wrote a series of classic
papers which are widely quoted but

very seldom discussed in
any detail they pretty much

demolished the my attack unit concept by
saying when you actually look at the at

the way feedback from muscles is
distributed within the spinal cord it

does not conform to that simple model of
the Maya tatic unit and I I won't drag you

through the details I promise because
we only have a few more minutes.

So that was the first and we've known
that actually for a long time but

this work is as I said widely quoted but
very seldom discussed right into our

modern conception of what's going on as
a side note here I want to remark that.

Very.

Talented push doctoral fellow of mine
named Young he Chang That was at Emory

who's now an associate professor
in Applied Physiology.

Did some experiments in my
laboratory at Emory where he.

We were asking a particular question and
the experiments turned out not to be.

Well we couldn't answer the question
with experiments we did and

we didn't neither of us won the bet.

So he came over to Georgia Tech and
sat on the data for a year and

then came up with this really fantastic
idea that he could use the data for

which is that the control of multi
segmented limbs is hierarchical task or

limb level variables like total
limb length limb angle so

what the whole limb is
doing during movement.

Are controlled at the expense of local or

joint level variables like
the movements of individual joint So

when you're walking through one
an animal or humans walking along.

The trajectory of the limb as a whole is
maintained very very reliably from step

to step but there's a lot of variation
in what individual joints are doing.

Presumably correcting some sort of
internal disturbances in order to keep

the task little variables that implies
there's some kind of local mechanisms of

coordination and we think those local
mechanisms are within the spinal cord so

for all of these reasons we thought it
would be best to try to reinvest to

reinvestigate the question
of such a spinal circuitry.

So.

Moving back in time a little bit two
of my grad students Stephen who's by

the way an electrical engineering graduate
of Georgia Tech he did a master's in

electrical engineering here the Ph D. with
me and then went on to medical school and

is now social professor at
University of Nebraska and

Ronny will make an engineer from the
Netherlands who did his thesis with me and

is now a practicing engineer and Marietta.

These two.

These two then students did
some remarkable studies

which they took this do serve
at Cat preparation again they

because we could do invasive procedures
on these animals without the risk of.

Of ethical considerations the animal was
personally comatose again they descended

out the tendons of individual muscles and
attach them to stretching devices and

by stretching these muscles in different
combinations they could figure out by

recording the forced responses they could
figure out how these muscles talk talk

to each other through pro perceptive
pathways and one what they discovered and

this is sort of an anatomical rendition
what they discovered is that in agreement

with the work of Eccles that all that
go to ten or organs in muscles and

the muscle let's say would take
this muscle here one of the.

Quadriceps group would go to ten
organs in this muscle colored and

sort of mustard yellow and the green.

The ten organs project not only to
neighboring muscles but also muscles down

lower down in the limb and
vice versa so they found that.

Force feedback from go to ten organs as
widely distributed through the limb is not

localized and not modular.

This serve to extend and confirm
the the results of Eccles at all but

it did something very important the work
of Eccles the experiments of vehicles were

performed in animals that were deeply
anesthetized was sodium pentobarbital So

these animals had the spinal cord
essentially asleep in these experiments

and so what Echols did was essential kind
of electrophysiological Anatomy what these

experiments did was to say when there's
active force production in muscles or

working on the spinal cord is alive and

well that the same findings
from Eccles were still.

Still a political and
they were able to document.

How these pathways change their activity
with respect to the different forces and

lengths in the muscle and
I won't go into that in detail here so

this is a kind of it gives you kind of
an intuitive idea that these pathways

from the gold eternal games
are widely distributed but

this isn't particularly this is a nice
sort of anatomical illustration but

what we were really interested in doing
was trying to find a more quantitative and

more comprehensive way of expressing.

What how these pathways were distributed
in relationship to the anatomy of the limb

and so these four individuals
came into the picture.

Starting with this guy over here John
Henry Lawrence the third with my first

graduate student at Emory biomedical
engineer from Brown University he.

What we decided to do is to do
a quantitative analysis of the anatomy of

the limb by trying to understand how
muscles produce torques about different

joints and John did a very nice
thesis where he documented the torque

contributions of different muscles in that
cross the ankle joint of the of the cat

in a full three dimensional model
showing that there were muscles that

synergistic and antagonistic relationships
are not as simple as it was once thought

then I had an another very talented
post-doctoral fellow named

Tom Burkholder now associate professor
in the School of Life physiology.

Who came along from.

Rick Libras lab and.

What Tom and I decided to do was
what I decided that Tom might

be interested in doing because
because he's the guy with the skills.

Was to actually build a computational
model of the feline hind limb one that

included all of the all of the anatomy and
all of the mechanical properties

the inertial properties and
the whole should bang.

Once we had a computational model of the
hind limb of the muscular skeletal system

then we could start to test hypotheses.

About.

What these different proprioceptive
pathways would do to the coordination of

the limb and this is a process which is
still ongoing we're not there yet but

I want to give you sort of
an update on where we are.

Tom then got a job here at dreaded SEC and
he started working with

Dr King and
they expanded the model further.

And put it onto a more
user friendly platform and

then Tom had a graduate student named
Nate Bunder send who just left my lab

as a post doc and
to take a job in industry and

Nate has sort of taken the this
muscular skill to modeling too to

its present level of sophistication which
is it's considerable He also had help of

a number of other students in the in the
TNG laboratory Lucas Mackay Jeff Bingham.

Hung on for example.

And he produced a platform called
neuro mechanic which is this

really complete model of the of the feline
hind limb and actually has gone on to

model other beasts as well
including human human subject so

I'm not going to be able to go through
a detailed description of this model nor

mechanic but we one thing we
extracted from this model became very

useful in trying to understand
the relationship between the mechanics

of the of the musculoskeletal system on
one hand and the organization appropriate

Cept of circuits on the other
hand see how they interact and

so because this model contains a lot
of more from metric information

that is where the different muscles attach
to different points on the skeleton.

We were able to.

To come up with a a way of quantifying
the mechanical relationships between

muscles and the limb and this method is
actually the brainchild of Tom Burkholder.

These anatomical diagrams are nice but

they don't really get you to what we
want to get so what Tom said to us look

we've got the hind limb of the cat
it's the model has a is a seven degree

of freedom model that has three
degrees of freedom at the hip.

Two degrees of freedom at the knee and
two degrees of freedom at the ankle.

So what you do is you construct
a seven dimensional space.

And the moment arm of each of the thirty
one muscles that we used in our model

the moment arms of each one of
those muscles could be expressed

as a vector in that seven
dimensional space OK.

Then what you do is you take
the angle between a given

pair of vectors and that tells you how
anatomically similar those muscles

are if they're actually pulling in
the same direction they're called.

Highly synergistic if
they put if they point

in opposite directions they're called
You can call them highly antagonistic

if they're right angles they're really
neither Center just nor antagonists and

when you go through this pairwise
computation of these of these angles.

You get the following beautiful matrix
which you can make you can use for

tiles on your bathroom floor
whatever you'd like to do.

So all of the thirty one muscles are
placed all are here on the two axes and

each one of these cells provides
the mechanical relationship between those

muscles in this term so we have
the red ones are the agonist ones and

the blue ones are our antagonists and
so that.

It's our representation of the anatomy
of the hind limb essentially and

you can see we're not going to go
through all this in detail of course but

what you can see is lined
up along the diagonal

are the big synergistic groups let's say
these muscles up here are the triceps or

a groups these muscles here at
the in the in the shank down here

we've got the quadriceps groups these big
knee extensors up here and so on and so

forth so these are all lined up as and
as agonistic muscles and

you might wonder what all this is about
the order in which the muscles were listed

here on this matrix were determined by a
cluster analysis of based on similarity So

which muscles were most similar to each
other and by doing that cluster analysis

it actually automatically determined the
order in which these muscles were listed

so everything was nicely lined up so
you expect to see lots of red here and

lots of blue out here which is kind
of what you'd expect although.

It's not exactly.

If this were if the Maya tatic unit
concept were actually the way things

worked these the anatomy would be
just all red here and all blue here.

In very distinct little sort
of little columns like that.

But you can see there's some blue here in
the middle and some of these blue areas

down here are much wider than you would
expect from the my attack unit model so

just take my word for it this this
matrix here sort of shows you that.

The the anatomy that the model is
based on is is a little deficient

Now if we take that this
mechanical matrix and show and

paired up with a matrix describing the
distribution of feedback from muscle spend

all pathways which is shown here it's
exactly the same the same axes but now.

Colors represent
the connections due to muscle

spindle receptors remember the my tactic
unit concept was muscle spindle and

one muscle excites itself and
center just inhibits in its antagonists So

if the Maya tatic unit concept were
the way things worked you'd see all red

here and you'd see lots of blue down here.

We're obviously we're we're not going to
talk about some great detail just wanted

to point out a couple things
there are some interesting.

Interesting connections here like this
one and these down here which represent

excited Torrie connections
between muscles that either.

Work at different joints and
the muscle where them and

those are located that that does not.

That's not consistent with the my ticket
model and in some cases they work at

these connections are between muscles
that span different joints so

this kind of documents the extent
to which the model is a political

You'll notice also that the distribution
of length feedback is a little bit

more circumscribed than the distribution
of these antagonistic areas here

a lot of these blue areas here represent
mechanical relationships of muscles

that work at about different joints where
is the muscle spent all pathways which

actually is a little bit consistent with
my unit tend to be a little bit more

circumspect circumscribed but
in general are not consistent and

then finally.

This is the matrix identifying
the distribution of force related feedback

from Goldie ten or organs again compared
with the mechanical Matrix over here

we can see a couple of interesting
features first of all the finding

of inhibitory force feedback seems to
correspond with those inhibitory regions

linking muscles that work about different.

Joints which is a more quantitative way of
expressing what I showed you in the some

of the day diagrams that this inhibitory
force feedback seems to be distributed

widely throughout the limb also within
muscles that have similar actions we find

inhibitory force feedback among some
of those muscles too so one of the.

One of the goals here is then to try
to understand these pathways and

again it's a little bit beyond the scope
of this lecture to go into this in

in detail but
this is getting sort of on the way so

I'm just going to sort of tie up where
we are with this part of the talk.

But I just going back over the take
home message is so mechanical and

neural circuits of the motor system or
are distributed they're not modular That's

the first big conclusion the neural
circuits if they're regulating stiffness

and all show you some of the evidence for
that and in a second.

Are not regulating stiffness
on a muscle by muscle or

even by unit my tatic unit basis
their regulating stiffness

on the basis of the entire limb because
of these widely distributed pathways.

In support of these ideas and

one of the one of the predictions was that
this widely distributed HIV atory force

feedback would help us solve the problem
of these inner segmental dynamics and

in fact patients with a condition known
as large fiber sensory neuropathy who

actually lose the sensory feedback from
these muscle receptor as well as skin and

in other places have great difficulty
with Enter segmental dynamics they

cannot control the coordination of their
joints no matter how hard they try or

how hard they concentrate so
this is actually.

Very nice evidence in favor of
this idea that the distributed

properties of the muscular
skeletal system.

Are matched and
regulated by a distributed set of

purpose of pathways in the spinal cord and
this said we are now in the process of

incorporating the patterns of force
feedback and length feedback that I just

showed you on those two major cities
of incorporating those pathways

into the neural mechanic model and then
we can do experiments on the model and

test different ways that these pathways
might be distributed in order to see

what the implications they are for
whole in function any questions

this point because I'm going to jump
into a slightly different topic now.

OK yeah.

Yes

but they would but they are not the
feedback circuits are not symmetrically

distributed right.

That's right exactly yeah actually
Amy brings up an interesting point

that the that mechanical matrix
I showed you is symmetrical.

The feedback is distributed nonsymmetrical
which actually raises some interesting.

Issues with how.

How a whole multi segmented limb how
its properties can be regulated.

The technical the technical idea I'm
getting at is that if you have a multi

segmented limb with a bunch of muscles
connected to it every which way and

there's no feedback at all
that system will behave in and

her only springlike way.

If you have a symmetrical neural
feedback there is a POS there

is the possibility that that system
is non springlike non-conservative

That's a technical term
is nonzero curl and

under those conditions there may it
may have some special properties which

are not conducive to movement and
posture it turns out that actually

there are some cases where nonzero
curl is actually consistent.

And actually a paper by and
they understand has actually.

Talked about that in some detail but

anyway so
there's the symmetry business anyway.

Yeah but.

Yes.

Yes So

in the human you can't do the sort of
experiments we do in the animals right so.

Investigators This is a huge a long
history of work on the human in which in.

Stead of you know pulling on muscles and
we depend

on doing a kind of you can electrically
stimulate nerves in such a way as to

activate some of these pathways and
then you can do sort of conditioning test

combinations in order to to
to measure the interactions

among different muscles somewhat to the
way we had and the the wiring diagram so

to speak that comes out of
the human is somewhat different and

seems to be more consistent with
by people are by people posture

However the basic the basic
patterns are actually quite similar

the problem with those experiments is that
when you electrically stimulate muscles

you're activating these receptors in non
physiological ways which you always have

to consider that they're you're not seeing
the accurate picture but there are there

is some correspondence and in fact a cat
which has been the experimental model for

these kinds of studies for over one
hundred years actually is remarkably close

to the human despite the fact that
it's a Quadrupeds and that we are

bipeds.

Right.

Right there is there is sort
of a dearth of information on

these same questions in the primate.

For historical reasons.

I guess I guess it was it was
decided that there was so much

relevant information from the cat there
Miles would just go right to the human and

see what to do so there isn't a not a lot
of information on the non-human primate.

OK so.

Really quickly because we're.

By.

We're saying is that the the feedback
from a given muscle is not only

distributed back to that same muscle it's
distributed widely to other muscles so

whatever it's regulating must be
relevant to the entire structure and

not on an individual basis OK so.

So I want to get back to this question we
talked about the fact that these pathways

from spittles internal organs might be
combined in the spinal cord to regulate

stiffness of the limb What's
the evidence for that OK so

how do you actually do
experiments to probe that well.

According to this difference regulation
model as I said before limbs differences

Turman by the balance of length and
force feedback one experiment we can do is

knocking out length feedback and
it turns out that.

A colleague of mine Timothy
cope discovered that if you

if you cut on your personal nerve going
to a muscle and immediately repair it and

wait about nine months the nerve
grows back into the muscle

the muscle becomes powerful again it can
exert just as much force as the before but

this is the length feedback from that
muscle is permanently disrupted and

not there so people have had transaction
injuries and repairs surgical repairs

often have great difficulty with
dexterity not because of the fact they

can exert forces it's because they don't
have the the sensory feedback from

those muscles the chemist's the Asia to
execute those finally find movements so

we can knock out length feedback force
feedback is more difficult to knock out so

the way we study force feedback
is to see how it's modulating

by under different tasks and
we'll get to that in a second.

So if you actually re innervate
the triceps eery muscles in in a cat.

And allow the the animal to recover and

in a social colony and
have a great time for for a year.

The more.

One finds that the reduction in
length feedback that accompanies

re innervation.

Results in a loss of knee and
ankle joint stiffness so

this is the kinematics of
of walking in an animal.

Walking down a ramp and it's really pretty
simple one when the animal puts its

weight on the leg this is all the stance
phase the the the knee and the ankle

give a little bit when the animal puts its
weight on those on those on that limb and

then the two joints extend pushing
the animal off from the to

the rest of the the stance face
after the reenter of ation these

muscles are now capable of producing every
bit as much force as they did before but

now look what happens now
the yield is prolonged and

sort of stays there through
the entire step cycle so.

There is a profound loss of ankle joint
stiffness after this re innervation

procedure which says that the pathways for
muscle specials must be important in

increasing the stiff and
regulating the stiffness of the limb.

The.

To go it trying to test
the the the role of force feedback

from tendon organs in a limb stiffness
is somewhat more difficult because

we don't have a simple
way of knocking it out.

But here's a couple of ideas that we've
been pursuing that might have to do with

how this these pathways
might be involved in.

In task specificity so
one idea is we said that

force feedback is widely distributed
through the limb let's say the force

feedback was focused more on the distal
musculature that is the distal muscles

were more subject to force feedback
coming from elsewhere in the limb now.

I mean that the the compliance
of the distal limb joints

should be joints not segments
would be would be reduced.

And that might be useful when you're
interacting with the outside world because

when we when we interact with the outside
world either by stepping on the ground or

hitting a wall.

Some compliance is desirable and those
joints that are right at the interface

point would be the ones that we would
want to have the compliance control but

there's another argument there for
doing something like jumping or

running really quickly we run
into this problem of inertial

disparity between the different
limb segments so.

If you are running really rapidly or
jumping down from onto the floor it's

those poor little old distal joints
that are attached to the light.

Low inertia limb segments are going
to be taking the brunt of the of

the of the interaction so
we might actually want to have

inhibition going more from distill the
proximal in order to help compensate for

that non-uniform distribution of inertia
these are just two ideas that we've been

we've been kicking around the idea is that
we might have a gradient of force feedback

either from distill the proximal or

proximal to distill the might be
useful for different tasks and

Kyla Ross was actually a student.

Steve Doris and mine.

She was in the first class of biomedical
engineering students at Georgia Tech and

Emory right because very
first class you know.

And so Kyla did some experiments
my lab and she used the locomotive

to serve a cat preparation I was
talking about before and she.

This diagram just shows the different
muscle groups as the quadriceps group

these big knee for

extensors appear the triceps eery again
the ones down here in the shank and these.

Controlling the toes and we can
summarize her findings by saying that

during slow walking on the treadmill
that the force feedback which is

shown by all of these arrows was
strongest from proximal to distil.

Sort of.

So under those conditions it seemed to
favor that first hypothesis that under

some conditions a proximal to
distil gradient of force feedback

would be more desirable we still haven't
gotten to the stiffness part yet but

at least that that's a good start the red
ellipse here just refers to the fact and

I've been sort of hiding this a little
bit but I did mention at the beginning.

These particular muscles here also
showed a transition from inhibitory

force feedback to excite atory force
feedback so under these conditions the two

kinds of force feedback were code
co-existing and I won't go into that

in any more detail unless you would
like to discuss it during discussion.

So Mark is a champion of
this other idea right.

And that is that again referring to
the fact that there is a disk disparity in

mass of the different
segments of the limb.

What Mark has been doing is noticing that
in our last few years of experiments

actually going way back to bias or and
woman's work is that in some of these

animal preparations and these preparations
are reasonably consistent but

they do vary in terms of what which
pathways seem to be active different

times and we can see patterns
both of those distal to Proxima

one proximal to distil gradient
patterns in different preparations and

what Mark is trying to do is actually
two to document those to find out

what the patterns are do they
correspond to those two kinds.

Of gradients and
to see what would what happened.

Trying to design experiments
to to see what would happen or

under conditions where the animal
might take advantage of this distal

to proximal gradient of force feedback.

Again I'd love to spend more time
on each one of these topics but

I need to move along here finally.

Here in neon C. is a graduate
student in Applied Physiology says

she's a physician from Pakistan
who's doing her thesis here and

she is collaborating with Dr Dean on
how and it was eminent researcher at

the University of Louisville who
studies spinal cord injury in cats she

does partial spinal cord injuries on
these animals so they're actually.

Able to move quite well and
take care of themselves.

But what she finds is they
fail on certain motor tasks or

they don't perform as well as an animal
without the spinal cord injury and

that gives her a way of evaluating
the different treatments that she is using

that involve the promotion of
regeneration of the spinal cord and also.

The use of drugs to prevent
scar tissue from forming and

so Arum is actually just completed
her thesis experiments and

she has she found the following spinal
Hemi section force feedback is greatly

amplified it's much much more powerful
than in any of our control experiments and

it's strongly polarized from a distal
to from distilled to proximal

Regardless every single animal seems to be
hey that same way so after a spinal cord

injury it seems that this force feedback
system is greatly distorted and

this may account for
the the the problems of balance and

stability of these animals as I said
they actually can manage quite well if

you see them walk across the floor
they may look reasonably normal.

Little a little a little shaky Maybe but
if you put them on an unstable surface

they have more trouble
than than normal animal so

we think that this greatly exaggerated
force feedback may be part of the problem.

Finally the last last little bit
here in the last couple of minutes

Ginger got show was a post-doctoral
fellow in my laboratory as now its

associate professor at
Penn State University.

And she was interested in and

the vestibular system and I won't
go through this again in detail but

we had observed that animals walking or we

famous scientists Judy Smith from U.C.L.A.
had observed in and

her colleagues had observed that
when animals are walking uphill or

downhill they use a completely different
pattern of muscle activation pattern

so something in the spinal cord
has to change in order for

the animal to adopt these different these
these different patterns too because

the physics of walking uphill and the
walking down hill are entirely different

basically when you're walking uphill use
your extensor muscles for propulsion when

you're walking down hill you turn those
propelling extensor muscles off and

you use your flex your muscles as brakes
so you kind of switch the role of

different muscles and
what Ginger managed to find was that.

Combining the the feedback
from the vestibular system.

And feedback from the afferent muscle
spindle efforts in the neck there

is generated a body orientation signal
which automatically causes the switch and

these patterns of of movement now
what does this have to do with and

all of that that I've been talking
about well we predicted that.

During the downhill look in motion you my.

I want to have an ample somewhat
amplified inhibitory force

feedback particularly focused on
the distal joints in order to use your

muscles more as brakes than
as propelling devices so

my senior grad student Chris total
embarked on a series of experiments to

use the same experimental
paradigm as Ginger head used for

her locomotion studies to see if if
an animal was in the so-called downhill

vs uphill mode whether the stiffness
of the limb would be affected and

if the stiffness of the limb were affected
what are the underlying mechanisms and

in short he connected the limbs of
these animals to a robotic system

which perturbed the limb and different
directions and we could measure endpoint

stiffness which is represented by this
ellipse here he measured both the sagittal

plane ellipse which is in the plane
of the screen and the horizontal.

Directions of stiffness which
are perpendicular to the screen and

what he found was indeed that in
the downhill condition the animals indeed

showed a reduced stiffness both in
the saddle and the horizontal plane and

I won't show you the data because it take
too much time he also found using those

muscle stretching experiments that I
talked about earlier that in fact this

reduction in stiffness was correlated with
increased inhibitory force feedback so

we think that this force feedback
system is very very important in.

In the regulation of limit can exceed
the final thing I want to mention is that.

Gareth venison who was a student of
Steve the worse he's not here and

mine who is a an engineer.

Who is actually designing a micro lecture
to Ray that fits on a muscle that

can be used for stimulation and recording
of that muscle and this is for rebuilt.

Purposes no words to provide
more strength of contraction and

muscles and
patients who are either weak or paralyzed.

Alison clear is a master of science and
prosthetics and orthotics student and for

her capstone research project she's
working with Gareth to test whether

electrical stimulation of
muscles also produces normal or

natural inhibitory force feedback to
other muscles to see that if you put such

a device into a patient it would actually
restore some of the normal pro precept of

pathways that we have so
conclusions part to.

Remove all of length feedback reduces
joint stiffness modulation of force

feedback may be an important mechanism for
regulating limb stiffness and

the postural dysfunction after partial
spinal cord injury results in part from

the amplification of
inhibitory force feedback.

This work has been supported
by mainly three grants

spanning one thousand nine
hundred three to the present.

I have a number of colleagues that
have really helped with this.

Tech support from these two individuals
Alex Bragg was a and B. Ph D.

student now a practicing neurologist at
at Emory who actually wrote some really

important software for us and a whole host
of students that I didn't mention during

the talk Thank you.

Thank you.

He's done

silent.

Right well this.

That's a it's a really great question and

so the question is does the the actual
slope that you're walking up and

down change so a couple things
to say about that first of all.

Yes In journalist Miss
experiments she was actually a.

Co-worker above Gregor's.

They showed that putting
animals on different slopes and

they did use different
slopes that the changes in

coordination of muscles
actually was somewhat.

Proportional to the slope but there are
obviously are some behavioral distances

differences cats will hold their heads in
different orientations if it's a really

steep slope they may tend to look down the
slope if it's only a slight downslope they

tend to keep their heads more level and
these have profound implications for

the sensory feedback that's coming
back the other thing I want to say is

this is a cat quadrupeds is a great.

Animal to study this particular behavior
and so you know you might say well what

what relevance does this have to
humans because humans are by pads and

we walk up and down hill we don't
we don't go like this right so it

turns out that we actually do changed our
trunk posture slightly want to go up and

down hill and a student Bob Gregor's
Andrea Lay who is an engineering

student here Georgia Tech showed
that when humans are walking up and

down hills of different slopes
in different directions of slope

that the muscular activation patterns
that we see in the human are actually

remarkably similar to those in the cat and
it probably comes about because there

are slight changes in trunk posture which
engage the same sensory mechanisms of so

on the cat and Ginger is actually
follow that up at Penn State so

this may be more than
you wanted to know but.

OK Well thank you very much OK.

So what.

No.

They're not they're taught I can
list a whole host of basic concepts

which are basically outmoded like the
upper motor neuron syndrome is one of them

the class my reflex is another one my
tactic unit is still being taught as

a bastion of I mean this is
what you do that yeah right so.

I hope that this.

Case is.

One of yours.

Well I think only start making more
progress on treating spinal cord injury

and things like that the information will
become updated in the clinic I hope.

Thanks.