Muscle tension control and Parkinson's disease

[From Bruce Abbott (971222.1710 EST)]

Bill Powers (971222.1249 MST) --

Bruce Abbott (971222.1135 EST)

Put me in the latter category, if by "nothing more and physics and
chemistry," you do not mean to exclude the nervous system's organization.

I do mean to exclude it. Organization, I think, has to be considered
separately from physics and chemistry. It doesn't obey the same laws.

Yes, we can talk about organization apart from the substrate of which it is
"composed." An amplifier is an amplifier apart from whether it is made of
silicon and electron-conducting wires or brass and water-conducting pipes,
and in some sense they are the "same" amplifier if their flow-diagrams are
the same.

There may also be damage to the "wiring" of the brain which may create
biochemical imbalances even though the individual undamaged components are
regulating properly. A nice example is Parkinson's disease: Neurons in the
brainstem that carry signals to the basal ganglia (motor centers in the
brain) begin to die (for reasons not yet known). These neurons release the
neurotransmitter dopamine at synapses in the basal ganglia, where the
dopamine serves an inhibitory function. When the loss of neurons crosses a
threshold, the motor tremors and muscular rigidity that are characteristic
of Parkinson's disease begin to develop, because the loss of inhibition in
the basal ganglia effectively raises the gain in the motor system to the
point of oscillation.

I'm not convinced that inhibition is anything special -- it's just a
negative sign on a signal, isn't it? I've heard the above description
before, and while it sounds plausible, I don't see any reason to believe it.

Do you see any reason _not_ to believe it? This is one hypothesis, and I
believe it has empirical support (although I am not "up" on this particular
line of research). Is there some reason you do not _want_ to believe it?
This involves part of the motor system; what sort of changes in a system
controlling muscle tensions (tonus) would you expect to produce excess
tension and oscillation?

...it is well to remember that this "user and controller" of this
hardware is composed of that hardware. ...
The distinction seems to be one of the hardware itself (the
physical arrangement of matter) and the dynamically changing signals and
states flowing through the hardware as determined through time by its
organization and its inputs.

That will do. Also, before Rick reminds you, in a closed-loop system it's
somewhat difficult to say what "determines" what, since the inputs are also
partly outputs. And the organization has its roots in billions of years of
evolution; it's somewhat futile to speak of "determination" when almost all
of the critical factors are unknown. I don't see why we have to subscribe
to any article of faith on this matter. Why not just say we don't know?

I think you're getting unnecessarily picky here. When I say "as determined
through time by its organization and its inputs," I do not mean to exclude
any feedback loops, and I certainly do not mean to imply linear causation.
I am simply making the usual scientific assumption, which is that the whole
machine is not acting capriciously, but according to its organization and
the conditions acting upon and within it at any given present moment. To
put it perhaps more starkly, La Mettrie and I assert that it operates
strictly as permitted by physics. You are quite free, of course, to make
your own assumptions, or not make them.

Treatment with L-DOPA, a precursor of dopamine,
increases the synthesis of dopamine in the remaining neurons by supplying
more raw material (circumventing the neuron's normal regulation of dopamine
synthesis rate); thus larger than normal amounts of dopamine are released
into the basal ganglia with each impulse, increasing the inhibition there
and bringing about more normal motor function. (Unfortunately, as neurons
continue to die, dosages must be increased, and eventually a point is
reached at which there are no longer sufficient neurons left to do the job.)

Again, very plausible, but does anyone know that this is what is actually
happening?

Of course. The biochemical pathways for dopamine synthesis within the
neuron are well known. The rate of production of dopamine from L-DOPA
within the neuron is rate-limited by the availability of L-DOPA; by
increasing L-DOPA levels, you increase the amount of dopamine synthesized,
and the amount released per action potential. The effects of dopamine
release on the basal ganglia have been explored and characterized by
physiologists. (There has been a lot of progress in brain physiology in
recent years.)

As I understand them, psychoactive substances do not act by altering the
body's biochemical state, but by directly altering activities in the brain.

I don't follow you here. Don't they alter the activities in the brain by
altering the biochemical state of certain parts of the brain?

I was thinking of the body as that which is not brain. The brain's
biochemistry is rather well isolated from that of the body.

O.K. Then I agree, so long as you do not include hormones produced in the
"body" as part of what the brain is isolated from. (I'm sure you don't.)

By the way, I recently saw a program on cable (I don't remember which one)
showing remarkable _immediate_ relief from the symptoms of Parkinson's
disease, which involved brain surgery to interrupt certain pathways in the
basal ganglia (I don't know which ones). It's a case of creating new damage
to offset the overactivity produced by the loss of inhibition via dopamine.
The result of the surgery was amazing, although of course it does not
actually fix the real problem. As a result, patients do not have to take
L-DOPA, which produces unwanted side-effects as it boosts dopamine levels in
other parts of the brain where this boosting is not needed. Parkinson's
disease would make a great subject for a control-system analysis (and I
suspect that physiologists have already conducted such an analysis).

Regards,

Bruce

[From Bill Powers (971222.1715 MST)]

Bruce Abbott (971222.1710 EST)--

I do mean to exclude it. Organization, I think, has to be considered
separately from physics and chemistry. It doesn't obey the same laws.

Yes, we can talk about organization apart from the substrate of which it is
"composed." An amplifier is an amplifier apart from whether it is made of
silicon and electron-conducting wires or brass and water-conducting pipes,
and in some sense they are the "same" amplifier if their flow-diagrams are
the same.

That's what I'm talking about.

I'm not convinced that inhibition is anything special -- it's just a
negative sign on a signal, isn't it? I've heard the above description
before, and while it sounds plausible, I don't see any reason to believe it.

Do you see any reason _not_ to believe it?

I don't disbelieve it. But until someone works out the whole system design,
I won't believe it, either. It's just a possibility.

This is one hypothesis, and I
believe it has empirical support (although I am not "up" on this particular
line of research). Is there some reason you do not _want_ to believe it?
This involves part of the motor system; what sort of changes in a system
controlling muscle tensions (tonus) would you expect to produce excess
tension and oscillation?

Loss of feedback; loss of damping; excess gain; increased delay; instabiity
in local feedback loops; positive feedback through parastic paths. A good
deal depends on whether the synaptic connections are nonlinear. There could
be other control systems attempting to compensate for the loss of the
neurons by increasing the gain, or the affected systems, interacting with
the dynamics of other control systems, could make the combined system
unstable. About all that seems well-established is that increasing L-DOPA
has a beneficial effect (although not in all individuals). It would be nice
to know what is making those neurons die.

...it is well to remember that this "user and controller" of this
hardware is composed of that hardware. ...
The distinction seems to be one of the hardware itself (the
physical arrangement of matter) and the dynamically changing signals and
states flowing through the hardware as determined through time by its
organization and its inputs.

That will do. Also, before Rick reminds you, in a closed-loop system it's
somewhat difficult to say what "determines" what, since the inputs are also
partly outputs. And the organization has its roots in billions of years of
evolution; it's somewhat futile to speak of "determination" when almost all
of the critical factors are unknown. I don't see why we have to subscribe
to any article of faith on this matter. Why not just say we don't know?

I think you're getting unnecessarily picky here. When I say "as determined
through time by its organization and its inputs," I do not mean to exclude
any feedback loops, and I certainly do not mean to imply linear causation.
I am simply making the usual scientific assumption, which is that the whole
machine is not acting capriciously, but according to its organization and
the conditions acting upon and within it at any given present moment. To
put it perhaps more starkly, La Mettrie and I assert that it operates
strictly as permitted by physics. You are quite free, of course, to make
your own assumptions, or not make them.

There's that word again, "capriciously." Of course if you'll allow that
some behaviors can arise strictly as a result of internal organization,
without the need for inputs (other than unpatterned energy), I'd be more
inclined to agree.

I'd have to disagree with you and your friend about physics "permitting"
anything. Physics is a model. Nature permits what it permits; physics
attempts to describe what that is. I presume there is still something left
for physics to discover.

Treatment with L-DOPA, a precursor of dopamine,
increases the synthesis of dopamine in the remaining neurons by supplying
more raw material (circumventing the neuron's normal regulation of
dopamine
synthesis rate); thus larger than normal amounts of dopamine are released
into the basal ganglia with each impulse, increasing the inhibition there
and bringing about more normal motor function. (Unfortunately, as neurons
continue to die, dosages must be increased, and eventually a point is
reached at which there are no longer sufficient neurons left to do the
job.)

Again, very plausible, but does anyone know that this is what is actually
happening?

Of course. The biochemical pathways for dopamine synthesis within the
neuron are well known. The rate of production of dopamine from L-DOPA
within the neuron is rate-limited by the availability of L-DOPA; by
increasing L-DOPA levels, you increase the amount of dopamine synthesized,
and the amount released per action potential. The effects of dopamine
release on the basal ganglia have been explored and characterized by
physiologists. (There has been a lot of progress in brain physiology in
recent years.)

I'm sure all that is true. But why would increasing inhibition restore more
normal motor function? That part of the explanation seems to be rather vague.

By the way, I recently saw a program on cable (I don't remember which one)
showing remarkable _immediate_ relief from the symptoms of Parkinson's
disease, which involved brain surgery to interrupt certain pathways in the
basal ganglia (I don't know which ones). It's a case of creating new damage
to offset the overactivity produced by the loss of inhibition via dopamine.

I don't understand words like "overactivity." Loss of inhibition of WHAT?
There are all sort of loose ends dangling here. I don't think I'm forced to
believe anything about this yet. Maybe all the information I'm looking for
is there in the literature, but I don't know what's there.

Best,

Bill P.

[From Tim Carey (971223.11.15)]

[From Bruce Abbott (971222.1710 EST)]

other parts of the brain where this boosting is not needed. Parkinson's
disease would make a great subject for a control-system analysis (and I
suspect that physiologists have already conducted such an analysis).

I couldn't agree more Bruce. This demonstrates what I've been trying to say
in the drug conversation. In a text I have called Fundamentals of Human
Neuropsychology (Kolb & Whishaw, 1990) they report that "partial remission
of Parkinson's disease may also occur in response to interesting and
activating situations" and they recount "an incident in whcih a
parkinsonian patient leaped from his wheelchair at the seaside and rushed
into the breakers to save a drowning man, only to fall back into his chair
immediately afterward and become inactive again." Could this possibly be
some kind of control process :wink: ???

I think this is an area that is _screaming_ out for PCT research. Come to
think of it I think _every_ area of psychological research is screaming out
for PCT methodology.

Cheers,

Tim

[From Bruce Gregory (971222.21.25 EST)]

Bill Powers (971222.1715 MST)]

There are all sort of loose ends dangling here. I don't think I'm forced to
believe anything about this yet. Maybe all the information I'm looking for
is there in the literature, but I don't know what's there.

At last, something we can all agree on.

Bruce