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Isochronicity in neural networks
Mental Synthesis theory:
• the mechanism of imagining novel objects
involves temporal SYNCHRONIZATION
of independent neuronal ensembles.
Synchronization
no enhanced
connections
Asynchronously
firing neuronal
ensembles
Perceived as
two different
objects
Synchronously
firing neuronal
ensembles
Perceived as
one morphed
image
The lateral prefrontal cortex as a puppeteer
PFC
Puppeteer
Puppets in the
posterior cortex
Synchronization
Mental
Synthesis
• Remarkably, the volume of
Brodmann area 10
(frontopolar cortex) is nearly
200% as large as expected
for a primate brain of our
size.
• Neuronal density in human
Brodmann area 10 was
around half of that of other
primates  Brodmann area
10 in humans has a
significantly greater portion
of its volume dedicated to
connections between
neurons
• Conclusion: Humans’
Brodmann area 10 is nearly
200% as large as expected
for a primate brain of our
size and that increase in size
is due to greater number of
connections and
myelination
2. Mental Synthesis Hardware
Puppeteer
Puppets
Synchronous
connections
• The Mental Synthesis
theory predicts that to
synchronize neuronal
ensembles dispersed
throughout the
posterior cortex, the
prefrontal cortex must
rely on synchronous
connections to those
areas.
• Without a mechanism that could equalize transit times, the
signal from the prefrontal cortex would arrive to its targets in the
posterior cortex at different times.
• This synchronization mechanism poses a serious challenge
that every human needs to solve during development:
• These connections must be fine-tuned to become synchronous.
• Only vertebrates have myelin.
• In unmyelinated axons, the
conduction velocity is proportional
to the square root of the axon
diameter. To have a conduction
velocity that is 10 times faster, the
diameter of an unmyelinated axon
needs to be 100 times larger.
• Accordingly, invertebrates often
solve the problem of fast connection
by using axons with large diameters.
For example, squid giant axons
which mediate its escape response
have a diameter of up to 1mm,
which is about 1000 times greater
than the diameter of a typical
vertebrate axon (normally only 1µm
in diameter).
• The stellate ganglion is connected to
axons distributed throughout the
mantle. The action potential reaches
the muscles throughout the mantle
simultaneously.
The result is that the muscles contract
synchronously, rapidly closing the
mantle, and forcing water out of the
mantle cavity. Water is expelled
through the siphon, producing a jet
action.
• HOW can action potentials reach the
muscles throughout the mantle
simultaneously?
• The longer the distance the thicker
the axon. Thicker axons allow for
faster conduction.
In vertebrates conduction velocity is regulated by myelin
• In the vertebrate brain,
increasing the axonal
diameter is an inferior
option since it is packed
with a large number of
neurons  myelination
• Conduction velocity in
myelinated fibers can be
100 times faster than
conduction velocity in
unmyelinated fibers
• Nearly all neurons in the
human brain are
myelinated
• The fastest axons have up
to 160 layers of myelin
• Myelin occupies nearly
half of the human brain
Fast conduction
velocity
Slow conduction
velocity
Greater differential myelination
Slower
conduction
velocity
Faster
conduction
velocity
Slower
conduction
velocity
Faster
conduction
velocity
Faster
conduction
velocity
Faster
conduction
velocity
More myelin ->
faster conduction
velocity
Less myelin ->
slower conduction
velocity
• Hypothesis: myelination of the PFC connections is the primary factor
producing uniform conduction time throughout the cortex and enabling
precise (milliseconds) control of the posterior cortex by the PFC
Hypothesis: myelination is the primary
factor producing uniform conduction time
EXPERIMENTAL EVIDENCE:
1. In the cat retina, axons from peripheral regions
have a greater conduction velocity than
axons from neurons at the center of the
retina to assure simultaneous arrival of
impulses in the brain (Stanford LR, 1987).
2. Experiments in rats show that myelination is the
primary factor producing uniform conduction
time (to within 1ms) in connections between
the inferior olive nucleus in the medulla and the
cerebellar cortex, despite wide variation in axon
length (Sugihara I, 1993; Lang EJ, 2003 – JC2).
3. Isochronous activation of groups of cells
distributed in distant cortical locations has been
shown in the visual cortex (Gray et al., 1989)
and even between the two hemispheres of the
brain (Engel et al., 1991).
inferior
olive
nucleus
cerebellar
cortex
EXPERIMENTAL EVIDENCE (continued):
4. In the cerebral cortex, the layer V pyramidal neurons in the
ventral temporal lobe innervate various subcortical regions.
Chomiak and colleagues showed that isochronous action
potential delivery to target regions located in the ipsilateral
hemisphere is based on the differential conduction velocity in
each fiber branch (Chomiak T, 2008). Chomiak’s observation on
isochronicity is best explained by differential myelination (Kimura
F, 2009 – JC1).
5. The amygdala connections to the perirhinal cortex play an
important role in establishing fear memory. While the perirhinal
cortex is an elongated structure, the small nucleus of the lateral
amygdala is isochronically connected with a large portion of the
perirhinal cortex (Pelletier JG, 2002).
6. Neurons in the thalamus send axons to a wide area of the
somatosensory cortex through different trajectories of various
travelling lengths. Nevertheless, action potentials in the thalamic
neurons arrive almost simultaneously at each target cortical
neuron. This isochronicity (to within 2ms) is achieved by changing
the conduction velocity within the individual axons by differential
myelination (Salami M, 2003 – JC1).
Conclusion
•
•
•
David J. Linden (“The Accidental Mind):
“The brain is not elegantly designed by
any means: it is a cobbled-together mess,
which, amazingly, and in spite of its
shortcomings, manages to perform a
number of very impressive functions. But
while its overall function is impressive, its
design is not.”
Many structures are elongated and
therefore located at various distances
from the source of information.
To vote on a particular issue, neurons have
to synchronize. Synchronization is only
possible, if the conduction time is uniform.
• Fumitaka Kimura and Chiaki Itami: “myelination plays
a major role in creating isochronicity. In other words,
myelination is not merely insulation among
neighboring cells, but is a method of regulating the
timing of postsynaptic activations” (Kimura F, 2009).
More myelin ->
faster conduction
velocity
Less myelin ->
slower conduction
velocity
• It is, in fact, possible that myelination is the primary factor producing
uniform conduction time throughout the cortex
Assuming myelination is producing uniform
conduction time,
How does the brain know
how much myelin each fiber needs?
• Genetic instructions alone are
inadequate to specify the optimal
conduction velocity in every fiber.
• Therefore, synchronous connections
are likely established in an experiencedependent manner.
• Examples?
• Nearly all neuronal connection are
experience-dependent to some degree.
•
•
•
•
Myelination is nearly completed by birth in most species in which the young are relatively
mature and mobile from the moment of birth, such as wild mice and horses.
In humans, myelination is delayed considerably. Few fibers are myelinated at birth and some
brain regions continue myelination well into mid-life.
The prefrontal cortex region is the last region to complete myelination. Myelination of fibers
that connect the prefrontal cortex to other cortical areas does not reach full maturation until
the third decade of life or later.
Myelination in humans is delayed for years and therefore has significant potential to be
experience-dependent!
• In humans, myelination normally increases
with age and with years of education
Experimental evidence of the role of
experience in myelination:
1. Rats: The number of myelin-forming cells in the visual cortex of
rats increases by 30% when the rats are raised in an environment
that is enriched by additional play objects and social interaction
(Szeligo F, 1997).
2. Human infants: early experiences increase myelination in the
frontal lobes in parallel with improved performance on cognitive
tests (Als H, 2004).
3. On the contrary, children suffering from abuse and neglect show
on average a 17% reduction in myelination of the corpus
callosum, the structure comprised of connections between the
neurons of the left and the right hemispheres of the brain
(Teicher MH, 2004).
4. Extensive piano practicing in childhood is accompanied by
increased myelination of axons involved in musical performance
(Bengtsson SL, 2005): the white matter thickening increases
proportionately to the number of hours each subject had
practiced the instrument.
Conclusions
• Isochronicity in at least some neuronal networks
seems to be achieved via differential myelination
and myelination may be experience-dependent.
• Considering the many variables affecting conduction delays in an
adult brain, genetic instruction alone would seem inadequate to
specify the optimal conduction velocity in every axon.
• Neuronal ensembles encoding physical objects are located in the
posterior sensory cortex, however the process of synchronization
is executed by the prefrontal cortex .
• The only way the prefrontal cortex could be capable of
synchronizing ensembles of neurons distributed over the large
area of the posterior sensory cortex is if the prefrontal cortex had
isochronous connections to those cortical areas.
• Therefore isochronicity is expected to develop in an experiencedependent manner via differential myelination during the limited
period of prefrontal cortex plasticity
What experience might be involved in
the development of mental synthesis?
• What system do we, humans, use to
manipulate mental images stored in our
memory into infinite number
of novel mental pictures?
• SYNTACTIC LANGUAGE (internal or external).
• We converse with ourselves and each other
and in the process create an infinite number of
novel mental images.
• Might the syntactic language be that very
mechanism that provides the training necessary
for the development of mental synthesis?
• If the answer to this question is “yes,”
then it might be expected that the lack of
syntactic language during the sensitive period
of prefrontal cortex plasticity would result in an
underdevelopment of mental synthesis.
Linguistically deprived children
Feral children:
1. Genie, 1970
(Curtiss S, 1977)
2. Victor of Aveyron (1797)
(Itard, 1962)
Deaf linguistic isolates :
3. E.M. (Grimshaw GM, 1998)
4. Chelsea (Curtiss S, 1988)
5. Maria and Marcus (Morford J, 2003)
6. I.C. (Hyde DC, 2011)
7. Three adolescents (Ramírez NF, 2012)
• Rescued after puberty.
• Tested after many years
of rehabilitation.
• Can learn many
new words.
• Linguistic isolates do
not understand
complex syntax.
• Linguistic isolates do
not understand spatial
prepositions such as in,
on, under, over, beside,
behind, in front.
Normally children use
syntactic language to
fine-tune their connections
Easily
synchronize
independent
neuronal
ensembles
Linguistically deprived children
end up with asynchronous
connections
Unable
to synchronize
neuronal
ensembles
• Use of infinite syntactic language with
prepositions and verb tenses during critical
period seems to provide vital training for normal
brain development and mental synthesis
acquisition.
Syntactic
language
Asynchronous
connections
Synchronous
connections
• Genie (55 min):
https://www.youtube.com/watch?v=hmdycJQ
i4QA