Neuroplasticity of brain

Dr Anuradha
• Neuroplasticity is the brain’s capacity to
continue growing and evolving in response to
life experiences.
• Plasticity is the capacity to be shaped, molded,
or altered; neuroplasticity, then, is the ability
for the brain to adapt or change over time, by
creating new neurons and building new
networks.
• One of the most intriguing questions in
behavioral neuroscience concerns the manner in
which the nervous system can modify its organization
and ultimately its function throughout an individual's
lifetime, a property that is often referred to as
plasticity.
• The capacity to change is a fundamental characteristic
of nervous systems and can be seen in even the
simplest of organisms, such as the tiny worm C.
elegans, whose nervous system has only 302 cells.
• When the nervous system changes, there is often a
correlated change in behavior or psychological
function.
• This behavioral change is known by names such as learning,
memory, addiction, maturation, and recovery. Thus, for
example, when people learn new motor skills, such as in
playing a musical instrument,
• there are plastic changes in the structure of cells in the
nervous system that underlie the motor skills. If the plastic
changes are somehow prevented from occurring, the motor
learning does not occur.
• Although psychologists have assumed that the nervous
system is especially sensitive to experience during
development, it is only recently that they have begun to
appreciate the potential for plastic changes in the adult brain.
• Understanding brain plasticity is obviously of considerable
interest both because it provides a window to understanding
the development of the brain and behavior and because it
allows insight into the causes of normal and abnormal
behavior.
• The underlying assumption of studies of brain and
behavioral plasticity is that if behavior changes, there
must be some change in organization or properties of
the neural circuitry that produces the behavior.
• Conversely, if neural networks are changed by
experience, there must be some corresponding change
in the functions mediated by those networks.
• For the investigator interested in understanding the
factors that can change brain circuits, and ultimately
behavior, a major challenge is to find and to quantify the
change
• brain plasticity is a common term used by
neuroscientists, referring to the brain's ability to
change at any age – for better or worse.
• As you would imagine, this flexibility plays an
incredibly important role in our brain development
(or decline) and in shaping our distinct
personalities.
• The science of neuroplasticity and the brain is the
basis of our clinically proven brain training
exercises.
• Brain plasticity science is the study of a physical
process. Gray matter can actually shrink or thicken;
neural connections can be forged and refined or
weakened and severed. Changes in the physical
brain manifest as changes in our abilities.
• For example, each time we learn a new dance
step, it reflects a change in our physical brains:
new "wires" (neural pathways) that give
instructions to our bodies on how to perform the
step
• Each time we forget someone's name, it also
reflects brain change— "wires“ that once
connected to the memory have been
degraded, or even severed. As these examples
show, changes in the brain can result in
improved skills (a new dance step) or a
weakening of skills (a forgotten name).
• Often, people think of childhood and young
adulthood as a time of brain growth—the
young person constantly learns new things,
embarks on new adventures, shows an
inquisitive and explorative spirit.
• Conversely, older adulthood is often seen as a
time of cognitive decline, with people
becoming more forgetful, less inclined to seek
new experiences, more "set in their ways".
• But what recent research has shown is that under the
right circumstances, the power of brain plasticity can
help adult minds grow.
• Although certain brain machinery tends to decline with
age, there are steps people can take to tap into plasticity
and reinvigorate that machinery.
• We just have to keep our brains fit with a series of
targeted brain plasticity exercises.
• Similarly, people suffering from a variety of cognitive
conditions—from schizophrenia to "chemo brain"—may
be able to retrain their brains to healthier function.
• The key—and the challenge—lies in identifying what
brain mechanisms to target, and how to exercise them
effectively.
• Neuroplasticity and the Senses
One of the important findings of recent neuroplasticity
research is the discovery of how closely our senses are
connected to memory and cognition.
• Because of their interdependence, a weakness in one is
often related to—or even the cause of—a weakness in the
other. For example, we all know that Alzheimer's patients
slowly lose their memories.
• One way this manifests is that they eat less food. Why? As
it turns out, visual deficits are also a part of Alzheimer's.
People eat less because they can't see the food as well. (For
more on this, see Alice Cronin-Golomb's article on brain
plasticity and Alzheimers) Another example is in normal
age-related cognitive changes
• As we grow older, we get more forgetful and
distracted in large part because our brain does
not process what we hear, see, and feel as
well as it once did.
• The result is that we can't store images of our
experiences as clearly, and so have trouble
using them and recalling them later.
• Non-invasive Treatment
One of the most attractive features of plasticity-based
therapies is that they are drug free. They rely on retraining the
brain through repetitious, challenging activity.
• Certainly there are conditions that require medications, and
thank goodness science has made such incredible forward
leaps in providing them.
• But in an era when people take more and more medications,
with more and more side effects and interactions,
• it is exciting to think that the next great breakthrough in
health might come from a less invasive source.
• The Plasticity Revolution
The growing understanding of and interest in brain
plasticity is driving a revolution in brain health and
science to measure how the brain changes.
• In addition to the work being done at Positive
Science, scientists and brain plasticity luminaries at
institutions around the globe are beginning to look
to plasticity-based therapies for treating a wide
spectrum of other cognitive problems.
• Ultimately, brain-plasticity based programs might help
schizophrenics improve their symptoms and live more
normal lives. Musicians stricken with focal dystonia might
learn to play again, without pain. People with mild
cognitive impairment or early-stage Alzheimer's might
halt the progression of their disease.
• Cancer patients whose ability to function has been
impeded by the lasting cognitive effects of chemotherapy
treatment might find their old selves again.
• Stroke or traumatic brain injury victims may relearn skills
they thought were lost forever. The list goes on.
• Exercising the Brain in Daily Life
Scientifically designed plasticity-based programs
target specific brain machinery to improve
function.
• On our own, are unlikely to find ways to exercise
that machinery as efficiently as with a clinically
proven program like BrainHQ.
• But there are science-based guidelines for choosing
daily activities that are likely to engage the brain
for positive change
• In the late 1800s, Camillo Golgi invented
a technique for staining a random subset of
neurons (1-5%) so that the cell bodies and the
dendritic trees of individual cells can be
visualized (Fig. 1).
• The dendrites of a cell function as the
scaffolding for synapses, much as tree
branches provide a location for leaves to grow
and be exposed to sunlight.
 FACTORS AFFECTING BRAIN PLASTICITY
• . Until recently, the impact of these neuropsychological experiments was
surprisingly limited, in part because the environmental treatments were perceived
as extreme and thus not characteristic of events experienced by the normal brain.
It has become clear, however, not only that synaptic organization is changed by
experience, but also that the scope of factors that can do this is much more
extensive than anyone had anticipated. Factors that are now known to affect
neuronal structure and behavior include the following:
•
• experience (both pre- and postnatal)
• psychoactive drugs (e.g., amphetamine, morphine)
• gonadal hormones (e.g., estrogen, testosterone)

• anti-inflammatory agents (e.g., COX-2 inhibitors)

• growth factors (e.g., nerve growth factor)
• dietary factors (e.g., vitamin and mineral supplements)
• genetic factors (e.g., strain differences, genetically modified mice)
• disease (e.g., Parkinson’s disease, schizophrenia, epilepsy, stroke)
• stress
• brain injury and disease
• It is generally assumed that experiences early in life have
different effects on behavior than similar experiences later in life. The
reason for this difference is not understood, however. To investigate
this question, we placed animals in complex environments either as
juveniles, in adulthood, or in senescence (Kolb, Gibb, & Gorny, 2003).

• Thus, like many investigators before us, we found that the length of
dendrites and the density of synapses were increased in neurons in the
motor and sensory cortical regions in adult and aged animals housed
in a complex environment (relative to a standard lab cage).
• In contrast, animals placed in the same environment as juveniles
showed an increase in dendritic length but a decrease in spine density.
In other words, the same environmental manipulation had
qualitatively different effects on the organization of neuronal circuitry
in juveniles than in adults.
• Psychoactive Drugs
• Many people who take stimulant drugs like nicotine,
amphetamine, or cocaine do so for their potent psychoactive
effects. The long-term behavioral consequences of abusing
such psychoactive drugs are now well documented, but much
less is known about how repeated exposure to these drugs
alters the nervous system.
• One experimental demonstration of a very persistent form of
drug experience-dependent plasticity is known as behavioral
sensitization. For example, if a rat is given a small dose of
amphetamine, it initially will show a small increase in motor
activity (e.g., locomotion, rearing).
 Other Factors
• All of the factors that are conceptually similar to the two
examples that we just discussed. For instance, brain injury
disrupts the synaptic organization of the brain, and when there is
functional improvement after the injury, there is a correlated
reorganization of neural circuits (e.g., Kolb, 1995).
• But not all factors act the same way across the brain. For
instance, estrogen stimulates synapse formation in some
structures but reduces synapse number in other structures (e.g.,
Kolb, Forgie, Gibb, Gorny, & Rowntree, 1998), a pattern of change
that can also be seen with some psychoactive drugs, such as
morphine.

• In sum, it now appears that virtually any manipulation that

produces an enduring change in behavior leaves an anatomical
footprint in the brain.
• In sum, the structure of the brain is constantly
changing in response to an unexpectedly wide range
of experiential factors.
• Understanding how the brain changes and the rules
governing these changes is important not only for
understanding both normal and abnormal behavior,
• but also for designing treatments for behavioral and
psychological disorders ranging from addiction to
stroke.
• case studies of patients with neurodegenerative
disorders or after traumatic brain injury have
reported about violent and antisocial behavior,
impulsivity, and inability to inhibit responses after
damage to the orbitofrontal cortex
• . For example the dramatic case of Phineas Cage, a
railroad worker, who had an iron bar driven through
the orbito-frontal cortex as a result of an explosion .
After the accident he became belligerent, socially
inappropriate, unrealistic, and impersistent.
• The Vietnam Head Injury Study (VHIS) found that
subjects with lesions limited to the frontal lobes
tended to show about 10% more aggressive and
violent behaviors compared with patients with
nonfrontal head injury and controls without head
injury .
• Furthermore, persons with frontal network
damage acquired before the age of 8 have also
been reported to have adult histories of recurrent
impulsive, aggressive, and antisocial behavior .
• Moreover, reports have found higher rates of
antisocial behavior in patients with
frontotemporal dementia, even when
compared with equally cognitively impaired
patients with Alzheimer's disease .
• Morphometric neuroimaging studies of
aggressive and violent subjects have
consistently found frontal lobe abnormalities .
• However, to date the structural MRI literature
produced inconsistent results regarding the
volume size abnormalities in aggressive and
violent patients, with most studies finding
reduced volumes of frontal structures in
violent patients
• Any time there is damage to the cell body, the result is cell
death. If there is damage to the axon, death is not certain.
• Anterograde degeneration – Breakdown of an axon from
the point of damage back toward the terminal button
• Retrograde degeneration – Breakdown of an axon from
the point of damage back toward the cell body
• Chromatolysis – Retrograde degeneration can spread
toward cell body
• Transneuronal degeneration – Spreads to neighboring
cells
• Neuron regeneration
• Neuron regeneration will occur in the Peripheral Nervous System
(PNS), but not the CNS (brain and spinal cord). And in the PNS, even if
neurons do regenerate, there is no guarantee that they will connect.
Just because the potential is there, it does not mean that things will
“hook up” correctly.
• Why no regeneration in the Central Nervous System?
• No glycoproteins – Growth-promoting glycoproteins are present in
the PNS only.
– Laminin and fibronectin – Necessary for development of growth
cone/neuron
– Oligodendrocytes – Glycoproteins that inhibit growth are present in the
CNS. Remember, oligodendrocytes are a type of CNS glial cell responsible for
forming myelin sheath. Schwann cells do this in the PNS.
• This is seen in transplant studies. When
transplant a PNS cells to the CNS, they do not
regrow.
• When there is transplant of CNS cells to PNS,
they can regrow.
• Therefore, the ability for these cells to
regenerate is dependent on the cellular
environment.
• Studies have found that Brilliant Blue G
dye (found in M&Ms) may be beneficial in
reducing inflammation, swelling and the
formation of scar tissue following a spinal cord
injury, allowing more time for treatments.
• Unfortunately, one of the side effects of Brilliant
Blue G is that it turns you blue, as seen in this rat.
Testing is still in progress to determine if this
treatment can be used effectively in humans.
• Lesions on spinal cord… Looking for drugs that
encourage regeneration by neutralizing
growth-inhibiting proteins (MAG and No-Go).
• Today, we are able to recover some functions,
but they are reflexive in nature and happen at
the level of the spinal cord, not the brain.
• For example, increases in stride length versus
limb placement (picking up a limb in response
to sensory input).
• his is demonstrated when a paraplegic’s body’s is suspended
(body weight supported) and placed on a treadmill using
Lokomat system.
• This activates a reflex as if you are falling, causing you to step
forward. With practice, this can be refined, so steps do not
appear so robotic.
• Today, advances in technology have led to robotic
exoskeletons that make it possible for some paraplegics to
walk again.
• A sensor is placed on the body that reads signals from the
brain transmitted to the nerves, that then activate the
exoskeleton to move as desired.
• Neural reorganization
• Collateral sprouting is when a neighboring cell and
move in and form new cell connections, fill vacant
cell receptor sites.
• You see things like Mirror Box Treatments
for Phantom Limb Pain, the visual input allows
people to feel relaxation.
• The parts of the brain that process the missing limb
are still being activated, where are they getting
their information from?
• Neuroregeneration involves synthesizing new
neurons and connections, providing extra
resources in the long term to replace those
damaged by the injury, and achieving a lasting
functional recovery.
• Therefore, by understanding the factors that
affect neuroregeneration and plasticity, we
can combine their advantages and develop
rehabilitation techniques.
• Rehabilitation training methods, coordinated
with pharmacological interventions and/or
electrical stimulation, contributes to a precise,
holistic treatment plan that achieves functional
recovery from nervous system injuries.
• Furthermore, these techniques are not limited
to limb movement, as other functions lost as a
result of brain injury, such as speech, can also be
recovered with an appropriate training program.
• Current treatment options available after injury to the
CNS are limited, often consisting of palliative care .
• The reasons for these limited options are due to both
the intracellular and extracellular factors within the
CNS that hinder regeneration.
• This review investigates the physiological reactions to
injuries to the nervous system and attempts by the
system to recover to its prior functional state.
• By comparing the differences in the PNS and CNS, we
can help elucidate these mechanisms.
• Neuroregeneration and plasticity changes occur first at
the regional level in an attempt to revive immediate
function and bridge the short-term requirements of the
nervous system.
• While this is occurring, the lengthy process of restoring
function with greater permanence occurs at a cellular
level.
• When these processes are combined with rehabilitation
techniques , a synergistic effect leads to the functional
recovery of nervous system injuries sustained in the
field.
• THE END