an ALS Hypothesis - extended to all 'abnormal' neural atrophy

kenneth Collins kpaulc at earthlink.net
Wed Feb 2 19:21:18 EST 2000


dag.stenberg at helsinki.nospam.fi wrote:
> 
> kenneth Collins <kpaulc at earthlink.net> wrote:
> > > > >> the Hypothesis:
> > > I had not earlier been able to find this among the over-long lines.
> > my fault, as explained at the top of this post. i apologize for the
> > unnecessary difficulty my failure imposed upon you.
> 
> No worries about the difficulty, but the fact was that I never saw that
> there was a hypothesis, because the entire message consisted of three
> or four superlines...
> 
> > one must put-things-together. the lesion alters cerebellar function,
> > which results in abnormal motor-system dynamics,
> 
> Please, do not even try to explain the pathology in ALS through the
> cerebellum. It does not work, lower motor symptoms could NOT occur that
> way.

i'm sorry, what you say is False.

in ALS, there's relatively-large atrophy in motor cortex. that atrophy
is precisely-correlated with both upper and lower motor neuron atrophy,
in exactly the way that i've discussed in the preceding msgs of this
thread.

it's all integrated by chained activation-dependence. if motor cortex
'shuts-down', then, to the degree of that, lower motor neuron activation
is diminished. if lower motor neuron activation is diminished, the
normal trophic dynamics that maintain the robustness of the lower motor
neurons is, commensurately, diminished.

where the cerebellum enters into the picture is, as was discussed in the
hypothesis that i've described, 'because' (in the hypothesis; due to a
'lesion') there has developed a deficit in type II synchronization
within motor activation.

as the cerebellum performs its =normal= powerful TD E/I-minimization
function, it will attempt to eliminate all activation pertaining to the
desynchronized 'state'. but, since the TD E/I(up) (activation
randomness) that the cerebellum is acting upon is interjected by the
lesioned tissue, no matter what the cerebellum does, it will not, in
fact, be able to successfully eliminate the relative randomness.

the cerebellum will, however, persist in its =normal= functionality,
which includes the elimination of such 'randomness' (TD E/I(up) within
ongoing activation 'states'.

the atrophy of motor cortex results from this 'never-ending-struggle' of
the cerebellum to eliminate 'randomness'.

because its functioning is driven by a TD E/I(up)-interjecting =lesion=,
the net result of the cerebellum's functioning is the gradual
'shutting-down' of motor cortex.

which is exactly what is correlated with the observed degeneration of
motor cortex.

it's important to realize that, in all of these 'degeneration' dynamics,
almost everything is functioning =normally=.

the problem results from the 'fact' (in the hypothesis) that there's
aberrent TD E/I(up) being interjected into the, otherwise, integrated
and =normal= dynamics.

the =normal= function produces the degeneration because the aberrant TD
E/I(up) is being interjected by 'lesioned' tissue, and it, therefore,
escapes normal TD E/I-minimization.

but since this cannot-be-minimized TD E/I(up) exists within the
supersystem, the TD E/I-minimization that does occur actually 'eats' the
rest of the correlated motor functionality.

the "lesion's" non-minimizable TD E/I(up) is 'the squeaky-wheel' that
gets all of the cerebellum's TD E/I-minimization 'attention', but since
the 'lesioned' tissue is 'lesioned', it's TD E/I(up) interjection cannot
be acted-upon by the cerebellum's powerful TD E/I-minimization dynamics.

the cerebellum's powerful TD E/I-minimization dynamics, nevertheless, do
occur =normally= with the net result being that all that's normal,
elsewhere within the correlated motor functionality (and probably
non-motor functionality, too; hence 'dementia') is abnormally TD
E/I-minimized, while the cerebellar TD E/I-minimization dynamics
'attempt' to rid the supersystem of the TD E/I that's being interjected
by the 'lesioned' tissue.

it's somewhat  akin to the way a 'nuclear' chain-reaction occurs. an
'instability' is established within the fissionable material, and, if
the control rods are withdrawn, it runs its course.

in the hypothesis i've been discussing, interjection of non-minimizable
TD E/I(up) by the 'lesioned' tissue is analogous to the withdrawal of
the control rods (which i understand tends to be meaningless if one
doesn't comprehend nuclear chain reactions, so what's another analogy
that i can invoke?)

spurious 'events' in a computer's random access memory... this example
is 'inadequate' because, lacking intrinsic TD E/I-minimization
mechanisms (within traditional computer architecture) the spurious
activity in RAM quickly brings the computer to a halt. so what's a
better analogy?

the MD-80 plane crash yesterday. the stabilizer problem is analogous to
the nervous system 'lesion'. the pilots tried desperately to correct for
the malfunction induced by the stabilizer failure, but because the
failure of the stabilizer =separated= the stabilizer's functionality
from the rest of the plane's controlable dynamics, the efforts of the
pilots 'only' led to the deterioration of the functionality of the
remaining control systems. 

[an asside TO THE AVIATION AUTHORITIES: i've been analyzing plane crash
dynamics for years, and have converged upon a 'core' set of things that
might be of some use with respect to in-flight failure. this analysis
focusses upon the alterations of flight configurations that 'surround'
the instances of failure (such as this stabilizer failure). the
underpinning rationale derives in the fact that it's relatively-obvious
that in-flight reconfiguration, probably most-significantly power-down,
as was apparently the case with this MD-80 yesterday, is a
failure-precipitation factor. so, it =might= be possible, in some
instances of in-flight failure, to 'reverse' the failure by reversing
the in-flight reconfiguration. if the failure was precipitated by
power-down, then power-up. of course, if there's a mechanical failure
that 'locks-up' control mechanisms, it can be the case that reversing
the failure-precipitating flight reconfiguration will be to no avail.
but since these events are so catostrophic, why not explore the
possibility, which is sort of like 'kicking a fender', while one's
riding one's bike, to get the fender to stop rubbing on the tire. of
course, reversing a power-down leaves the plane powered-up, which
creates landing problems. these could be addressed via a carrier-type
arresting apparatus that replaces the cable and hook with a net that's
activated during landing emergencies. this setup would allow planes to
touch-down at full-power, maximizing the functionality of control
systems that remain effective. (before such safety apparatus could be
installed, if reversing the failure-precipitating dynamics works, it
would, at least, allow pilots to fly and 'ditch' closer to rescue.) i
=understand= that this discussion, itself, has a lot of possible
points-of-failure, but trying anything is better than 'abandoning' folks
in the air, no? so why not, at least, explore the possibility of doing
the 'reverse' thing? if it works, train pilots to attempt it when all
else fails. sorry about having do do this, here. it's a long-shot, but
it is a possibility, so i had to put it 'out-there' so that Engineers,
and other folks responsible for flight safety, can consider it, explore,
implement/reject it.]

anyway, back to Neuroscience.

> 
> > because, the
> > interminable TD E/I(up) condition that the lesion interjects prevents
> > normal achievment of 'type II synchronization" (as evidences in ALS
> > fasciculations and fibrilations.
> 
> Can't see that. The fasciculations and fibrillations are not due to
> disturbed coordination, but to denervation, which dissolves the motor
> units plus induces muscle membrane hypersensitivity. The spasticity is
> another thing altogether.

we disagree, Dag. try to follow the cbl discussion. =if= a lesion
interjects aberrant non-minimizable TD E/I(up), fasciculations and
fibrilations will, =NECESSARILY=, result.

i've explained how such lact of type II synchronization further results
in 'excito toxic' motor neuron degeneration.

> 
> > the late onset of respiratory functionality ...
> 
> The pathology seems to ascend in a rostral direction. Your explanation
> is too complicated, and all of it, illustrated by the citation below,
> seems totally hopelessly untrue.

i stand on what i posted. the nervous system is Complex, especially when
one ventures forth into the brain stem.

> > in other words, the demise of the motor neurons results in an =actual=
> > 're-engineering['] of the neural topology of the brain stem, and, as a
> > result, the relationship between the respiratory nucs of the brain 
> > stem with respect to TD E/I-minimization becomes rewired, and what 
> > remains of the supersystem 'blindly' 'seeks-out', and 'attacks' the 
> > 'normal' respiratory functionality as a TD E/I(up)-condition, which 
> > results in the aberrant 'shutting-down of respiratory functionality.
> 
> > > How would you diagnose the disease 35+ years before outbreak?
> 
> > =iff= there's anything to the hypothesis that i've been discussing,
> > contemporary 'scanning' methods would disclose the aberrant TD
> > E/I-minimization 'struggle', through which, what has been considered 
> > to be the disease condition, is generated (precipitated). and 
> > sensitive versions of those scanning methods should be able disclose 
> > the TD E/I(up)-generating 'lesion' location. of course, all such work 
> > can only occur with respect to deviations from a background database 
> > that tracks 'normal' (average) activation 'states'. building this
> > background-comparison database would, itself, be a major undertaking,
> > but would definitely, itself, become o font of useful insight.
> 
> Yeah, you earlier asked for a scanning method do discriminate excitatory
> from inhibitory activity.

i, earlier, =described= how such could be achieved in a thread titled
"Differential Analysis".

> We are not there yet. Actually imaging
> techniques do not seem to be moving in that direction at all. I have
> been impressed lately by proton imaging of lactic acid accumulation, but
> even that does not take us anywhere in a TD I/E direction.
> 
> > so, in it, i've kept my word about advancing the Science.
> 
> Er - I think that is still a very premature conclusion, sorry.

forgive me. my read is that you've not followed my discussion, which i
can take down to much-greater detail, and upon which i stand.

> As I mentioned some time last year, I had a boss who had a 
> all-encompassing 'neurodarwinist' theory (not Edelman, who also proposed 
> another neurodarwinist theory). Unfortunately, all my former boss's 
> theorizing has never advanced science at all, whereas actual measuring 
> has during the same decades advanced neuroscience hugely.

please, your former 'boss' and i are distinct entities, Dag.

this discussion has been worthwhile for me because it's disclosed the
actual costs inherent in what has been the Censorship of NDT's stuff.

i mean no 'offense'. just the opposite.

K. P. Collins




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