X-Message-Number: 14506
From: Eugene Leitl <>
Date: Wed, 20 Sep 2000 01:42:28 -0700 (PDT)
Subject: Scienceweek: ON BRAIN PLASTICITY AND STROKE

6. NEUROBIOLOGY:
ON BRAIN PLASTICITY AND STROKE
In human brain research, the term "plasticity" refers to the
ability of various regions of the brain to assume specific
functions as the result of experience, and also the ability of
various regions of the brain to assume the functions of other
regions that are damaged by disease or trauma ("adaptive
plasticity"). Important questions concerning the biological basis
of plasticity are a) What are the neural mechanisms responsible
for plasticity? and b) What are the conditions which limit
plasticity? Until recently, the primary source of evidence in
this field was "anecdotal" -- evidence from individual clinical
cases. That has changed: during the past decade, numerous studies
have been carried out using non-invasive methods to monitor
ongoing localized brain activity in conscious subjects, and
evidence concerning plasticity and other characteristics of human
brain function is rapidly mounting.
... ... N.P. Azari and R.J. Seitz (Heinrich Heine University, DE)
present a review of current research in brain plasticity and
recovery from stroke, the authors making the following points:
     1) When a particular neural network is damaged, as often
happens in a stroke, the system fails and function is initially
lost because no other neurons in the brain are "wired" to do the
task formerly performed by the damaged network. The result may be
paralysis or the loss of speech or the inability to comprehend
speech or any one of a number of actions. But many people who
have suffered a stroke regain some or most of the lost functions
after a brief recovery period, sometimes in a matter of weeks.
     2) The capacity of the brain to reorganize itself -- its
"plasticity" -- in the process of learning a task is perhaps the
most interesting phenomenon that distinguishes the nervous system
from all other tissues in the body. The plasticity of the brain
appears to be greatest when we are young (from infancy through
early adolescence), a time when many of the neural pathways that
will be used for the acquisition of language and motor skills are
formed. But our ability to learn new languages and new skills as
adults indicates that the brain retains a certain level of
plasticity throughout our lives (although our potential for
learning new languages and skills may be decreased).
     3) Many studies have shown that stroke patients require time
to regain function. During this time, the brain is evidently
sorting out how it might compensate for the damaged neurons, and
the subsequent process of neural recovery appears to occur in
several stages:
... ... a) Initially there is a passive tissue response in the
first few hours and days following brain-tissue injury. This
passive response involves the reperfusion of tissue deprived of
blood-oxygen (ischemic tissue) and cessation of *inflammatory
processes produced by brain damage. This leads to a regression of
dysfunction associated with the temporary "shock" to the neurons
in the vicinity of the lesion. Medical interventions that
facilitate these early recovery processes determine the extent to
which recovery will proceed to the subsequent stages.
... ... b) In the days and weeks following a stroke, the brain
begins active processes of recovery involving adaptive
plasticity. In the early stages, this may include intra-system
pathways, if any have survived undamaged, pathways that normally
play a mere supporting role in the undamaged brain. Since such
pathways have previously been involved in the task, only task
relearning is necessary, and this may explain why recovery is
sometimes seen within a few weeks following a stroke.
... ... c) But if there is complete damage to a neural system,
the brain may still have the capacity to recruit an alternative
brain system, one not generally activated for the task by normal
subjects. In such instances, the alternative system is naive to
the task, so that the patient must relearn the task more or less
completely. This requires more time, and evidence concerning
alternative system pathways was until recently unavailable.
     4) The authors conclude: "The existence of distinct stages
in the recovery process has only become evident through the use
of *functional imaging techniques. As the technology develops, we
have little doubt that we will come to appreciate progressively
finer aspects of adaptive plasticity and its role in a patient's
recovery from brain lesions such as stroke."
-----------
N.P. Azari and R.J. Seitz: Brain plasticity and recovery from
stroke.
(American Scientist Sep/Oct 2000 88:426)
-----------
Text Notes:
... ... *inflammatory processes: In general, an "inflammatory
change" is a response of tissues to irritation or injury. The
response involves a dynamic complex of cellular and chemical
reactions that occur in the affected blood vessels and adjacent
tissues.
... ... *functional imaging techniques: The two main functional
brain imaging techniques are *functional magnetic resonance
imaging (fMRI) and *positron-emission tomography (PET).
... ... *functional magnetic resonance imaging (fMRI): We must
first distinguish between magnetic resonance imaging (MRI) and
"functional" magnetic resonance imaging (fMRI) as applied to the
brain. The former is essentially a technique for examining
morphology, while the latter is a technique for examining
activity of brain tissue. Both techniques involve computerized
analysis of data. In general, MRI involves magnetic coils
producing a static magnetic field parallel to the long axis of
the patient or subject, combined with inner concentric magnetic
coils producing a static magnetic field perpendicular to the long
axis. A radio-frequency coil specifically designed for the head
perturbs the static fields to generate a magnetic resonance
image. The interaction physics in this technique is that between
the magnetic fields and atomic nuclei in brain tissue. "Sliced"
views can be obtained from any angle, and the resolution is quite
high and on the order of millimeters for current magnetic field
strengths of 1.5 tesla. Functional magnetic resonance imaging
(fMRI), the variant of MRI discussed here, is based on the fact
that oxyhemoglobin, the oxygen-carrying form of hemoglobin, has a
different magnetic resonance signal than deoxyhemoglobin, the
oxygen-depleted form of hemoglobin. Activated brain areas utilize
more oxygen, which transiently decreases the levels of
oxyhemoglobin and increases the levels of deoxyhemoglobin, and
within seconds the brain microvasculature responds to the local
change by increasing the flow of oxygen-rich blood into the
active area. This local response thus leads to an increase in the
oxyhemoglobin-deoxyhemoglobin ratio, which forms the basis for
the fMRI signal in this technique. Because of its high spatial
resolution (millimeters) and high temporal resolution (seconds)
compared to other imaging techniques, fMRI is now the technology
of choice for studies of the functional architecture of the human
brain.
... ... *positron-emission tomography (PET): This is a technique
for producing cross-sectional images of the body after ingestion
and systemic distribution of safely metabolized positron-emitting
agents. The images are essentially functional or metabolic, since
the ingested agents are metabolized in various tissues.
Fluorodeoxyglucose and H(sub2)O(sup15) are common agents used for
cerebral applications, and in cerebral applications of central
importance to the technique is the fact that changes in the
cellular activity of the brains of normal, awake humans and
unanesthetized laboratory animals are invariably accompanied by
changes in local blood flow and also changes in oxygen
consumption.
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Summary & Notes by SCIENCE-WEEK http://scienceweek.com 22Sep00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
EVIDENCE OF CROSS-MODAL PLASTICITY IN BLIND HUMANS
In neurobiology, the term "plasticity" is the name given to the
capacity of neural tissue to adjust to change. One variant of
this concerns the dependence of the "wiring" of the nervous
system on its input. Another variant concerns the degree to which
one region can under certain conditions assume the function of
another region. Plasticity does not occur everywhere in the
nervous system, but it is often evident in the cerebral cortex of
the brain, the cortex being the thin layer of cells apparently
responsible for higher analysis of sensory input, language,
ideation, and other so-called higher functions lumped together in
the category "cognitive processes". Last week Leonardo G. Cohen
et al (11 authors at 4 installations in US, AR, JP) reported the
results of studies of cross-modal plasticity in blind humans.
These studies involved non-invasive interference with cortical
activity by applying transient magnetic stimulation from outside
the skull. It has been demonstrated that such stimulation can
affect brain activity, and in this study the apparatus threshold
for stimulation of the motor cortex was first determined, and
then transient magnetic stimulation 10% above that threshold
applied to the occipital lobes of the brain through the overlying
skull to interfere with electrical activity in the visual cortex.
The experiments involved various location and procedural
controls, and also a group of sighted individuals. Essentially,
what was found is that in people blind from an early age, the
visual cortex is apparently involved in somato-sensory function
(fingertip reading of individual Braille characters), while the
same is not true for sighted subjects.
-----------
QY: L. G. Cohen 
(Nature 11 Sep 97) (Science-Week 26 Sep 97)
-------------------
Related Background:
BRAIN PLASTICITY IN CHILDREN AFTER HEMISPHERECTOMY
Epilepsy is a term unhappily applied to several dozen different
seizure disorders, their commonality being central nervous system
seizures rather than identical pathological processes causing the
seizures. From a neurophysiological standpoint, a seizure is the
end result of a massive discharge of nerve cells, often the motor
neuron pathways that activate muscle cells. Seizures can be
produced by various central nervous system infections, metabolic
disturbances, toxic agents, cerebral oxygen deficiency, expanding
brain lesions, cerebral trauma, cerebral hemorrhage, and so on.
In general, any physiological event or series of events that
produces a wide disruption of central nervous system activity has
the potential for production of seizures of one sort or another.
Most patients who for reasons known (symptomatic epilepsies) or
unknown (idiopathic epilepsies) are chronically subjected to
seizures can be helped with various pharmacological agents such
as phenytoin or cloneazepam, but 10% to 20% of patients have
seizures that cannot be managed by drugs. If the seizures are due
to a specific damaged locus in the brain (the "epileptic focus"),
the recourse for these patients, if the locus can be determined,
is surgery. What is done is to completely remove the epileptic
focus, sometimes an area no larger than a small coin, and if the
surgery is successful the cure is immediate and permanent. There
are cases, however, in which the affected part of the brain is
quite large, the seizures completely unmanageable, and the only
recourse is radical surgery. Since severe chronic epilepsy due to
brain lesions is usually first diagnosed in young children, it is
such children who are the usual patients in radical brain surgery
for epilepsy. The most radical and fairly common procedure is
hemispherectomy, removal of an entire half of the brain, and the
most remarkable aspect of this is that when the surgical
procedure is successful, not only are the seizures eliminated,
but the child can function as well or almost as well as any other
child. It is an example of a phenomenon well-known to
neurobiologists called "brain plasticity", the ability of the
brain to recover the function of a damaged or removed region by
assignment of the function to an undamaged location. The language
area of the brain, for example, is often considered to be fixed
on the left side of the brain by genetics, but in truth it is not
so fixed, and if the left side of the brain is removed at an
early age, the right side of the brain will quickly develop a
language center and there will be little functional impairment.
In a recent publication, Eileen P.G. Vining (Johns Hopkins
University, Baltimore MD US) reports the progress of 54 children
who underwent hemispherectomy for recurrent severe epileptic
seizures. The majority of the patients were seizure-free
following surgery, no longer needed drugs, and many of the
patients are now in school. One of the most significant facts
about the human brain is that its histological development
continues at least until adolescence, and the dynamism of this
histological development is what is responsible for its
remarkable plasticity.
-----------
QY: E. Vining, Johns Hopkins University (410) 516-8171
(Pediatrics August 1997) (Science-Week 22 Aug 97)
For more information: http://scienceweek.com/swfr.htm

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