The term neuroplasticity is derived from the Greek word "plastikos" meaning "to form".

Neuroplasficity refers
to structural and functional changes in the brain that are brought about by training and experience. The brain is
the organ that is designed to change in response to experience. At birth, each neuron has 7500 connections.
These increase rapidly in the first 2 years of life until the synaptic connections are double that of adult brain.
This is followed by pruning of synapses through the process of apoptosis or programmed cell death.

This plasticity of the brain is also maximal during the critical periods. Critical period is a maturational time
period during which some crucial experience will have its peak effect on development or learning resulting in
normal behavior attuned to the particular environment to which the organism has been exposed. If the organism
is not exposed to this experience until after this time period, the same experience will have only a reduced effect
or in extreme cases may have no effect at all. After the critical period, the brain may never again show the same
ability to make big changes in neuronal connectivity. For eg. the critical period for the development of the visual
cortex in children with acquired amblyopia is up to 7 yr, and similarly, a cochlear implant for early deafness has
maximal effectiveness within the first 7 yr of life. The critical period for natural language acquisition is the first
6 yrs of life and thereafter, the innate ability to acquire language declines gradually and after 12 yrs, it slows
down dramatically. Children whose caregivers talk to them regularly display good language skills and well
organized language brain systems.

Plasticity of the brain is maximal in the first few years of life, but continues at a reduced rate throughout life. It
is more in certain parts of the brain compared to other parts and more in certain periods of life than in others.
This explains the fact that children are able to recover from head injury much better than adults and recovery of
functions is more complete.

There are four major types of plasticity in children. These four types are adaptive, impaired, excessive and
plasticity which make the brain vulnerable to injury or becomes the 'Achilles heel" of the developing brain.
Adaptive plasticity refers to changes in neuronal circuitry that enhances a special skill with practice allowing the
brain to adapt or compensate for injuries or changes in sensory output. One of the known examples of this type
is the reorganization of connection in the visual cortex with acquired amblyopia due to strabismus. Selection'of
visual input in one eye leads to the loss of cortical synaptic connection in the other eye. The therapy of patching
the opposite eye leads to improvement of vision if it is done during the period of visual plasticity which is the
first decade of life. A similar period of maximum plasticity for recovery of auditory cortex is within the first
seven years of life. It is for this reason that cochlear implants is most effective if it is done before this period.
Impaired plasticity refers to situation in which genetic or acquired disorders disrupt molecular plasticity
pathways. One of the examples of this is Fragile X syndrome which is due to defect Fragile Mental retardation
protein which binds the RNA within synapses and regulates activity dependent protein translation.
Similarly disorders of transcription are seen in Rhett's, Coffin-Lowry and other syndrome

Excessive plasticity in the developing brain can lead to disability through reorganization of new maladaptive
neuronal circuits that cause neurological disorders as partial seizures following mesial temporal sclerosis or
focal dystonia. Plasticity becomes the brain's Achilles heel in situations like status epilepticus when excitatory
mechanism becomes over stimulated resulting in excitotoxic neuronal damage.

( Neuroplasticity in Children)
Neuroplasticity can be broadly defined as the ability of the nervous system to respond to intrinsic and extrinsic stimuli by
reorganizing its structure, function and connections; can be described at many levels, from molecular to cellular to systems
to behaviour; and can occur during development, in response to the environment, in support of learning, in response to
disease, or in relation to therapy. Such plasticity can be viewed as adaptive when associated with a gain in function (Cohen
et al., 1997) or as maladaptive when associated with negative consequences such as loss of function or increased injury,
points illustrated by animal models and some human studies (Nudo, 2006). )harnesing)

Developmental neuroplasticity is a complex genetically encoded, time-dependent and sequenced maturational process that is closely
regulated by intrinsic homeostatic mechanisms and is influenced by extrinsic environmental experiences. Developmental neuroplasticity is
an inclusive term that involves fundamental changes in neurogenesis, neuronal cell migration, synapse formation and structural and
functional neuronal networks specialization leading to behavioral acquisition of motor and non-motor developmental milestones and
adaptation to a constantly changing environment through learning and memory
Adaptive plasticity: reorganization that promotes or improves adaptive function
The long standing notion that the developing brain has an intrinsically greater capacity for plasticity compared to the adult brain stems from
many clinical observations pertaining to children's enhanced capacity for learning and memory as evident by their ability to learn a second
language more efficiently,71,72 easy acquisition of complex motor skills as seen in early musical practice73 and capacity to recover from
major brain injuries as exemplified by the capacity to recover gross motor skills after hemispherectomy

Reactive plasticity following sensory deprivation or CNS insult

An important form of plasticity is activity-dependent plasticity following chronic sensory deprivation or brain injury. It is well established
that infants born with bilateral congenital deafness undergo auditory cortex reorganization and visual cross-modal compensatory plasticity.

What we know about critical and sensitive periods in the developing brain
The original description of critical periods came from the 1960e70s experiments of early monocular deprivation in kittens by Nobel Prize
Laureates Hubel and Wiesel. They showed that visual deprivation during a certain time window of young brain development leads to
alteration in visual cortex networks.174,175 They deemed that visual experience during that period is “critical” for normal neural circuit
development and that restoration of normal visual experience after that period does not remediate the abnormal circuits. Subsequently, with
better understanding of developmental neurobiology, the broader concept of sensitive periods emerged and was defined as the time
window(s) during which the effect of experience on brain development is unusually profound and can strongly modulate the neural circuits.

during critical periods, are committed to a single pattern of connectivity that is largely established by the genetic blueprint and that pattern is
consolidated by the presence of a preferred stimulus, so the absence of that stimulus leads to permanently abnormal connections. during
sensitive periods, the neural circuits are highly “motivated to change” and have geneticallyencoded multiple potential connection patterns to
select from and can commit to one pattern or the other based on the stimulus. So in the absence of the preferred stimulus, the network is still
“open for change” once the stimulus is reintroduced, although this capacity decreases with age. Therefore, all critical periods are sensitive
periods but not all sensitive periods are critical periods. For insightful reading, please refer to Knudsen. The term ‘critical period’ has
been described at multiple levels and in different regions of the nervous system. For example, there are critical periods for neurogenesis and
cell migration during which an insult to the brain can lead to malformations. Similarly, critical periods for synaptic plasticity, experience
dependent local and large scale network wiring, and even the onset of the spectrum of higher cognitive functions and behaviors have been
described

So, can the onset of a critical or sensitive period be “traced” clinically? With advances in electrophysiological and neuroimaging techniques,
we are closer than ever to precisely decode online the “language of neural communication” via means of EEG/MEG, resting state and
functional connectivity fMRI and PET.

Unique childhood plasticity has been demonstrated particularly in the areas of vision, audition, motor, and
language abilities. It is clear, for example, that lesions such as therapeutic hemispherectomy or stroke are
handled better in childhood than at later ages. Perhaps the best known example of compensatory plasticity
could be seen in the observation that the functional effects of strabismus (squint) in the infant are different from
that in the adults. In infancy, strabismus causes suppression of the image from the squinting eye, whereas in
adults squint causes persistent double vision, a disabling symptom.
Surgical correction with preservation of vision is possible up to the age of 7 years. A similar period for maximal
plasticity for auditory cortex has been defined within the first 7 years of life in children fitted with cochlear
implants for early deafness. These observations have led to the hope that treatment of cognitive or behavior
disturbance during the childhood years might be more effective in reshaping trajectories of early development
either to normalize or compensate for earlier abnormalities.

MECHANISMS IN PLASTICITY
The molecular mechanisms in developmental as well as adaptive/compensatory plasticity are still largely
unknown. Much of the brain development is assumed to require modification of gene expression and protein
production. repetitive activation (in response to external stimuli) of excitatory synapses increases the synaptic
strength through a phenomenon called long-term potentiation (LTP) in many brain regions that are crucial in
learning and memory. This process in which synaptic connections are refined requires localized increase in
intracellular calcium in dendritic spines, which is typically achieved via the activation of the NMDA subtype of
glutamate receptor and is modulated further by activation of AMPA subtype of glutamate receptors. Persistent
coincident firing of neurons leads to calcium entry through NMDA receptors into post-synaptic neurons and
release of trophic factors that support synaptic connections. The activity of the excitatory glutamatergic neurons
is also modulated by inhibitory interneurons which use the major neurotransmitter GABA and also provide an
important inhibitory signal for the development of neural networks. Recent studies suggest that
the neurotrophin BDNF influences the GABA release by promoting the mobilization of presynaptic calcium
channels near the vesicle release site

( Brain Neuroplasticity in Healthy)

Plasticity during development can also be adaptive or maladaptive. Two cardinal examples of adaptive plasticity in relation
to development are the age-dependent recovery of language and motor functions following hemispherectomy for intractable
epilepsy and the ability to benefit from a cochlear implant in early childhood. After hemispherectomy, the shift of language
and motor functions to the non-removed hemisphere is remarkable, but highly dependent on age, with the greatest potential
for reorganization seen in children under 6 years of age. interpretation of such plasticity measures must bear in mind that
they arise in the setting of an atypical brain at baseline. Congenitally deaf children appear to benefit most from cochlear
implants within the first 3.5 years of life, a time during which the central auditory pathways show maximal plasticity. Recent
research shows that the latency of the early (P1) component of the cortical auditory evoked potential falls within the normal
range for age among children who receive an implant by 3.5 years of age. In contrast, those who receive implants after 7
years of age show abnormal cortical responses even years after receiving the implant

(HARNESING)
Principle of Neuroplasticity Intervention Strategies Factors that Support Neuroplasticity
Timing Early intervention is key. Plasticity is greater in childhood.
For learning to occur, the child must attend to the
Attention Model “in the moment” feedback to child and caregiver.
activity.
Sufficient stimulation is needed to create the long
Infants and toddlers learn best in familiar contexts with
Stimulation term potentiation in synapses that creates durable
familiar people.
memory
The type of stimulation affects the outcome of the
Specificity Identify regularly occurring routines. stimulation (e.g., visual processing practice improves
visual processing, but not auditory processing).
With challenging behaviors, determine the function of the
Sustain attention and activation of targeted skills,
Reward behavior and then teach an alternative and more
thereby improving learning.
appropriate social communicative behavior.
Embed intervention into everyday activities and Repetition is essential for strengthening knowledge
Repetition
interactions. and skills.
Recommended 25 hours per week in which the child is Sufficient intensity is needed to create change in the
Intensity
actively and productively engaged in meaningful activities. brain.
Utilize a team approach that includes caregivers in all Sufficient duration of stimulation is needed to create
Duration
aspects of intervention planning and implementation. change and maintain knowledge and skills.

Little research has been conducted on the verbal skill development in populations of children with autism below the age of 3.
НeorLes related to neuroplasticity and brain development before the age of 3 lend support the notion of critical periods
during which cortical circuits in the brain are refned by experience [13-15]. One responsibility of clinicians is to provide
stimulation that will produce positive structural and chemical changes in the brain to positively alter the clinical
manifestation of ASD. Considerable improvements in the communication skills of young children with autism can be
attributed to early intervention provided before the age of 4 and the involvement of caregivers and practitioners in the
intervention process. Research suggests that intervention beginning before age 3 yields greater positive outcomes as
compared to intervention starting after 5 years of age

( Neuroplasticity and Young Children with Autism)

TyPES of NEuRoPlASTICITy
Neuroplasticity is a general term, defning the fact that the brain changes, recognizing the need for further
defnition of the term. We distinguish structural from functional neuroplasticity.
a) Structural neuroplasticity
Synaptic plasticity refers to changes in the strength between neurons (synapses), chemical or electric meeting
points between brain cells. Synaptic plasticity is a general term, and the name itself has no meaning other that
something changed within the synapse, but can include many specifc processes such as long-term changes in the
number of receptors for certain neurotransmitters, or changes where some proteins are being synthetized more
within the cell.
Synaptogenesis refers to formation and ftting of synapse or group of synapses into a neural circuit (13).
Structural plasticity is a normal marking of fetal neurons during brain development and is called developmental
plasticity, including neurogenesis and neuronal migration.
Neuronal migration is a process in which neurons travel from their ‘place of birth’ in fetal ventricular or
subventricular zone, towards their fnal position in the cortex.
During development, brain areas become specialized for certain tasks such as processing signals form the
surrounding areas through sensory receptors. For example, in occipital brain area, the fourth layer of cortex
hypertrophies in order to receive signals from the visual pathway (14).
Neurogenesis is formation of new neurons. It is a process which mainly takes place during brain development,
even though in the last decade neurogenesis was found in adult brain as well. On the other hand, neuronal death
occurs throughout life, due to brain damage or programmed cell death. Other forms of structural neuroplasticity
include changes in white or gray matter density which can be visualized by magnetic resonance.
b) functional neuroplasticity
Functional neuroplasticity depends upon two basic processes, learning and memory. Tey also represent a special
type of neural and synaptic plasticity, based on certain types of synaptic plasticity causing permanent changes in
synaptic effectiveness (15). During learning and memory permanent changes occur in synaptic relationships
between neurons due to structural adjustments or intracellular biochemical processes.

( Neuroplasticity)
Normal sensory experience is necessary for normal development. An important component
in the development of sensory systems is the concept of a sensitive or critical period. The
critical period is the time during development when neural connections are forming and the
system is most vulnerable to the damaging effects of abnormal sensory input. In the visual
system, faulty visual input, such as from a central cataract or strabismus, if not corrected
before the end of the critical period, can result in permanent visual deficits, including
functional blindness. Once a child is beyond the critical period, the visual deficit can remain
permanent, even if the original source of the abnormal visual experience is corrected.

The critical period in visual development involves the first six years of life, although the first
two or three years are most crucial. The critical period in audition is less well defined, but
appears to last longer

SENSORY PLASTICITY
How can we “prime” the
Brain to learn?
1.  Practice
2.  Exercise
3.  Sleep
Exercise Enhances…
•  Blood Flow
•  Blood Vessel Formation
•  Cerebral White and Grey Matter
Exercise Enhances…
•  Neuron and Synapse Growth
•  Neural Growth Factors
•  Neurotransmitters