Neuro Science  

 

 

 

 

 

Neuroplaciticity

 

I think you know of the meaning of 'Neuro' in this word. Then, what does 'placiticity' mean ? Following is definitions of 'placiticity' from a few web dictionaries.

  • the quality of being easily shaped or molded.
  • the quality of being soft enough to be changed into a new shape
  • the quality or state of being plastic

Extending this definition of 'placiticity' to the term 'neuroplaciticity', you may come up with your own definition for the term. Among the many different definition I can google, following seems to be one of the best described one to me. It is the definition from Britanica written as below.

    Neuroplaciticity is the capacity of neurons and neural networks in the brain to change their connections and behaviour in response to new information, sensory stimulation, development, damage, or dysfunction.

Even without this kind of formal/dry definition, if you think of 'plastic' comparing to the hard materials like rocks, steel etc, you may have some intuition poping up in your mind, that intuition (whatever it is) would be the right definition.

 

Neuroplacity is the process or capability by which a neuron or a circuit of neuron 'changes' to perform various functions. This placiticity can be considered at various different levels. Sometimes it would indicates a specific part within single neuron (e.g, change of the numbers or forms of synapses), sometimes it may indicates the certain neural pathways which are involving huge amount of neurons and other supporting cells.

 

In early days of neuroscience research, we thought that our nerveous system gets fixed once we passed a certain developmental phase (i.e, a certain age in our life) but with recent researches we have been getting more and more evidence that our nerveous system is not that solid / fixed system and it continue to change to create new functions (e.g, learn new things and skills) and in some cases it changes its pathways to compensate the regions that had been damaged.

 

 

 

Lifetime plan for development

 

Before I dive into the details of Neuroplaciticity, I want to introduce you an interesting plot that I got from a World Science Festival YouTube video.

 

Image Source : The Nuts and Bolts of Better Brains: Harnessing the Power of Neuroplasticity - World Science Festival

 

As implied in the plot, there are a few points to note

  • At the time of birth, the development of our brain is far from being complete. We are born with bare minimume of brain development
  • Most of high level brain development occurs for very long period after birth. What's happening at the level of neuron changes and pathway changes happening in this period can be good topics for neuroplaciticity because neruons, its synaptic link with neighbouring neuron and forming / enhancing various neural pathways.
  • Even though brain system for Sensory and Motor/Language completes relatively early stages in our life span, higher level cognitive function start developing from birth and continue to develop almost throughout the whole life.

 

 

 

Good News and Bad News

 

This is to set a proper expectation about the neurotransmitter. I don't like you to have too much expectation or too much disappointment,

 

There is both good news and bad news about the neuroplaciticity. When I was learning about nervous system (almost 40 years ago/1980s), it was generally believed that nervous system (especially the nervous system in higher animal) stops development only upto a certain age. So if you have any damages in nervous system after a specific age, it can never be recovered. However more and more researches shows that it is not the case. Those research shows that the nerve system development is an ongoing process spanning almost whole period of our life and can heal many types of the damages in various different ways. This is obviously a Good News.

 

However, you'd better not expect too much about this capability. The new development of nervous system does not work for every regions of nervous system. There are some part or functions of the nervous system that cannot be recovered once it get damaged. This is a bad news (at least not a good news). In addition, the capability of neuroplaciticity varies (usually get weaker) as we ages. This is definitely a bad news for the aging people including me.

 

 

 

How neuroplaticity works ?

 

Now let's look into the details of how neuroplaciticiy works (i.e, the mechanism of neuroplaciticity). Roughly speaking the neuroplaciticity happens at the two different level, structural and functional level. However, the border line between function and structural placiticity is not always clear cut. For example, if a neuroplacity happens by enhancing the synaptic connectibity between presynapse and post synapse and this enhancement happens by putting more neurotransmitter receptors on the cell membrane of the postsynaptic neuron, would you call this as a functional level placiticity ? or structural level placiticity ?  You may call it as structural level placiticity if you observe cell membrane structure, but you may call it as functional level placiticity if you just observe electrical relationship between presynapse and post synapse without looking into the micro structural changes. So you may see a little bit of different categorization of functional and structural placiticiy depending on which text / articles you read.

 

Regardless of whether you call it as structural or functional, I would suggest you to get familiar with basic terminology for individual mechanism. I think Long Term Potentiation, Long Term Depression and Synaptic Pruning would be what you may hear or read from almost every text or videos/lectures dealing with neuroplaciticity.

 

 

Long Term Potentiation (LTP)

 

Long Term Potentiation is a phenomena where a synaptic response gets higher than regular cases when the same synapse is stimulated repeatedly. This is considered as the most fundamental phenomena for synaptic placiticity. It is often interprested as the first step for momory formation.

 

There are so many researches and evidences showing LTP and now would be one of the best established facts about synaptic placiticy (especially related to memory formation). One of the research/evidence is shown below. This experiment is done with neurons in Hipocampus.

 

Image Source : Long-Term Synaptic Potentiation

 

[A] shows the illustration of test setup. You see the two pathways : Pathway 1 and Pathay 2. In these pathways, two different neuronal axons are stimulated by stimulus electrode : Stimulus 1 and Stimuls 2. The researcher used the two pathways for the comparative purpose. Pathway 1 shows long term potentiation and Pathway 2 does not. Before the measurement shown in the graph, the presynaptic neuron in Pathway 1 was stimulated multiple times (a high frequency sequence of stimulus pulse from Stimulus 1 electrode) and the presynaptic neuron in Pathway 2 was not stimulated.

[B] Shows the comparative plots measured at 'Record' electrode (post synaptic cell) when the same size of stimulus is applied by stimulus 1 and stimulus 2. As you may notice, The response for Pathway 1 (the pathway stimulated before the test) is much stronger than the case of Pathway 2 (the pathway with no previous stimulus).

 

Following is the my own illustration of LTP. I hope this would better illustrate the concept.

 

< Synaptic response with LTP >

 

< Synaptic response with NO LTP >

 

NOTE :  This video shows very clearly on how LTP is tested and measured : What Memories Are Made Of

 

There are many other examples of neuronal pathways showing LTP. As you may notice, most of them are from Hippocampus (CA), Sensory system (visual and auditory system). This is from a paper in 2004 and I am pretty sure that much more diverse cases has been researched by now.

 

< Pathways support LTP >

: The source of this list is [ Long-Term Potentiation and Memory - PHYSIOLOGICAL REVIEWS - 2004]

  • Auditory thalamus → amygdala
  • Entorhinal cortex → dentate gyrus
  • Mossy fibers → CA3
  • Commissural fibers → CA3
  • Schaffer collaterals → CA1
  • Hippocampus (CA1) → subiculum
  • Hippocampus (CA1) → prefrontal cortex
  • Subiculum → prefrontal cortex
  • Thalamus → layer IV cortex
  • Mesocortical thalamic nucleus → medial prefrontal cortex
  • Cortico-cortical pathways
    • Layer I → layer V
    • Layer II → layer V
    • Layer II/III → layer IV
  • Cortex → striatum
  • Dorsolateral geniculate nucleus → visual cortex
  • Parallel fiber → Purkinje neuron

 

 

Long Term Depression (LTD)

 

Long Term Depression is a kind of opposite concept of LTP explained in previous section. In the synapse showing LTD, if you apply a sequence of stimulus at a presynaptic neuron, the potential measured at the post synpatic cell get smaller as shown in the following plot.

 

 

The potential shown in 0~15 min indicates the reference potential measured at the 'record' electrode. The range shows the meaured potential when a sequence of consecutive stimulus (once per second). As you see, the response is gradually decreases. And the with a brief break, stimulus is applied and the measured reponse (measured voltage) gets much lower than normal as shown in the range from 30 and later.

 

Following is my own representation of the concept of LDP. I hope this would be easier for me to understand.

 

 

 

Denervation supersensitivity

 

As you may notice from the terminology, it is about the fact that some neuron get supersensitive (to the same input signal). Why do they become supersensitive ?  It happens when some of corticol neurons are lost. Due to this neuron loss, a signal path to which the lost neuro used to belong gets disconnected(i.e, denervated). In order to compensate this, the post-synaptic membrane develop more receptors for neurotransmitters leading to super sensitivity for the post synaptic neuron (refer to this article).

  • This was reported to a skeletal muscle which lost some of nuerons connected to the muscle fiber (see this paper)
  • This doesn't mean that any kind of neuronal damage can be compenstated by the supersensitivity. If the amount of the damage is greater than a certain range, the neural path would get contracted which is called degenerative contranction (see this paper).

 

 

Synaptic Strengthening

:

Synaptic strength is an indicator showing how strong potential (voltage or current) at post synaptic neuron when a stimulus is applied to the presynaptic neuron. You may take it as the ratio of output to input. For example, in LTP you can say the synaptic strength got increased and in LTD you can say the synaptic strength got decreased.

Synaptic Strengthening is any mechanism (or structural change) that increase the synaptic strength.

 

 

Synaptic Pruning

 

In gardening (horticulture), pruning means cutting off (trimming) unused/not-useful branches. Same applies to Synaptic Pruning. Synaptic Pruning means removing synapses which are not used.

 

This usually observed in some part of mammalian brain during the early stage of brain development. As shown in the image below, the number of synapsis continuosly increases from embryonic stages through a certain ages. But from a certain ages, only those synapsis which recieves stimulus remains and others (non-used) synapses gets removed (i.e, gets pruned).

 

Image Source : Synaptic Formation - BioNinja

 

< Examples of Synaptic Pruning >

 

Follwoings are some of the examples of synaptic prunning.

    Human Brain Development : Overall number of synapsis in human brain vary over the developmental cycle as summarized below based on What Is Synaptic Pruning?

    • Early emborynic stage to 2 years : New neurons and synapses are formed at an extremely high rate
    • Ages 2 to 10 years : the number of synapses drops dramatically (i.e, synaptic pruning happens rapidly)
    • Adolescence : Synaptic pruning continues but not as fast as before
    • Early adulthood : Synaptic pruning continues mostly in the prefrontal cortex of the brain and seems to stop in the late 20s

     

    Visual Cortex Development : The number of synapses peaks around 8 month of age and they start getting pruned as the baby gets more visual inputs and adapts to the visual environment.

 

 

< Medical conditions associated with Pruning >

 

There some medical conditions associated with unusual level of synaptic pruning. Followings are some of the examples even though most of these conditions and its association with synaptic prunning is at still early stages of research.

 

NOTE : These examples implies that there would be some link between these medical condition and Synaptic pruning. It does not mean that synaptic pruning is the direct and only root cause.

    Schizophrenia : There is some theory that schizophrenic brain is caused by over pruning which is caused by genetic mutations that affects the synaptic pruning processes. (What Is Synaptic Pruning?)

    Brains of individuals with schizophrenia, for example, have fewer synapses than normal. Some researchers have hypothesized that excess synaptic pruning could trigger the disease—likely during the active period of synapse elimination in adolescence, which coincides with the typical onset of schizophrenia.(How synaptic pruning shapes neural wiring during development and, possibly, in disease).

    Note : Even though over pruning is observed in cortex of the brain of schizophrenia, some research shows that a specific part of hippocampus shows more dendritic spikes in schizonphrenia patient than control group (Discovering Neurobiology for Psychosis)

     

    Autism : There are some researches hiting that Autism is associated with under-pruning. (What Is Synaptic Pruning?)

    Note : Under-pruning may imply that higher connectivity. But this can be observed differently (in some case observed contradictory) based on various factors like 'local vs global' brain region or developmental stages etc (Network Neuroscience of Autism)

     

    Savant Ability/Syndrome : It is also considered that Savant syndrome is associated with under-pruning as in the case of autism. This may explain the fact that Savant syndrom is much more prevalent in autistic population than in general population. (Synaptic growth, synesthesia & savant abilities)

 

 

Adult neurogenesis

 

Neurogenesis is a process of generating new functional neurons from precursor cells. So 'Adult Neurogenesis' is a processing of generating new functional neurons from 'adult' precursor cells. Why 'Adult Neurogensis' is so sopecial ? It is because it had long been thought that this kinds of neurogenesis happens only in emborionic or prenatal stages in higher animal like mammalian. But recent study shows that this kind of neurogenesis happens throughout the whole life in some restricted area of nervous system (Note the keyword 'restricted area' meaning that unfortunately not every area of nervous system can undergo neurogenesis when it reaches a certain point in life).

Since the first evidence of adult neurogenesis in Hippocampus of a rat brain, many other cases of adult neurogenesis was observed among various animals (refer to this paper)

 

 

Equipotentiality

 

Equipotentiality is a capacity of neural system in which normal functioning part (intact part) of the system to carry out the functionality of a damaged part to make the overall neural system function as normal. This theory was postulated at early memory research. Some scientists make small lesions on various locations of brain (rat brain) and check if the lesion cause any memory loss. The result showed that those small lesions (damages) does not cause any visible problems wherever you make unless the amount of the legion (damage) reaches considerably large area. This result lead to a few hypothesis as follows.

  • Memory is not localized, it is globally distrubed all over the brain. ==> This hypothesis was contradicted by the case of H.M and others shows that a certain part of the brain region (localized region) cause serious memory loss / memory formation.
  • The functionality of a damaged part can be compensated by the intact part to make overall functionality work normally. This is the theory of Equipontentiality. I saw some of the papers supporting this theory, but I am not sure if this theory has been accepted as a well established fact or not.

I want to introduce a little bit different way of defining Equipotentiality which is defined in What is Neuroplasticity? A Simplified Guide as follows : (I personally like this definition since it fits better for the term 'equal' in the term equipotentiality.

    All parts are equivalent for the mediation of function within a given cortical association area. Thus, each portion of any given region can encode or produce the behaviour usually controlled by the entire region. Thus, the remaining are compenstates for incomplte damage within a zone.

 

 

Vicariation

 

Vicariation sounds mouthfull to me and I have no idea on what it would literally mean. Even googling I haven't find any definition that sounds clear to me.  One of the definition that I think is best fit for me is :

    The separate occurrence of corresponding species in corresponding but separate environments, divided by a natural barrier; i.e., similar species have evolved independently in similar environments (from this source)

Still not so clear to me. In other words, Vacriation refers to the process by which one brain area or system can compensate for the loss or damage of another brain area or system. I think it would be clearer if I see some cases of examples as listed below. I got these examples from chatGPT.

  • After a stroke, an individual may experience paralysis on one side of their body. In response, the brain may compensate by increasing the strength of connections between the undamaged brain areas that control the non-paralyzed side of the body. This can allow the individual to regain some degree of control over their movements.
  • After a traumatic brain injury, an individual may experience problems with memory and learning. In response, the brain may develop new connections between brain areas that are involved in these functions, allowing the individual to compensate for the damaged areas.
  • In individuals with hearing loss, the brain may compensate by increasing the strength of connections between brain areas that are involved in processing visual information, such as from sign language or lip reading. This can allow the individual to maintain or improve their communication abilities.
  • In individuals with vision loss, the brain may compensate by increasing the strength of connections between brain areas that are involved in processing auditory and tactile information. This can allow the individual to maintain or improve their ability to navigate and interact with the world.

 

 

 

Diaschisis

 

Diaschisis refers to a temporary decrease in function of a particular brain region as a result of damage or injury to a connected area. As mentioned, Diaschisis is usually temporary symptom and it gradually recover to normal in most cases. For now, exact mechanism behind Diachisis is largely in mystery and require further researches, it is believed that synaptic changes or neurotransmitters are involved in this symptom.

There are some examples of Diaschsis as follows.

  • Temporary decrease of a brain functions after stroke : This can result in a variety of symptoms, such as weakness or paralysis on one side of the body, difficulty speaking or understanding language, and changes in vision or other sensory functions. This symptom may recover to normal as the decreased functionality is recovered directly or other brain area start compensating the decreased functionalities.
  • Temporary descrease of a brain function after brain surgery (e.g, removing brain tumer) : The regions around the removed part (the tumor region) may suffer from the decrease of function. This can lead to changes in cognitive function, such as difficulty with memory or attention, as well as changes in sensory or motor function
  • Temporary descrease of a brain function after concussion : You may suffer from a temporary decrease in function, leading to symptoms such as headache, dizziness, and difficulty with memory and concentration. But in most case you would recover to normal as time goes on.

 

 

 

Nature of Neuroplacitity

 

 

How plasticity varies on Age

 

In general, neuroplaciticity occurs more actively in young ages, especially within a few years after the birth.

 

 

Neuroplaciticy continues in life time

 

Even though neuroplaciticiy happens more actively in young ages in general, it happens throughout the whole life.

Especially the neurons involved in learning, experience, and memory formation would happen relatively actively even in adult ages.

In some cases when a part of brain is damaged (e.g, stroke), healthy part of the brain would take over the functionality of the damaged part.

 

 

Neuroplaciticy is NOT the cure for all

 

Even though Neuroplaciticy is ongoing process throughout lifetime and some of damaged part can be compensated by some other part of the brain, it is important to know that neuroplaciticity is not a solution for every problem.  You should consider the possible restriction of neuroplaciticity as follows : 

  • Some part of the brain does not show the placiticity
  • Even though some damage can be compensated by other part of the brain, the damage may not get fully recovered if the scope of the damage is very wide.

 

 

 

Examples of Neuroplaciticity

 

There has been wide range of researchs about neuroplaciticy. In this section, I want to introduce some of the most popular (widely mentioned in many lectures) examples of these researches.

 

 

Structural changes in Hippocampi of Taxi Driver

 

This would be an example that are most frequently mentioned in lectures and videos as an evidence showing that neuroplaciticity really happens. It is about the research from London Taxi driver. Comparing to other jobs, Taxi driver would use more of the brain parts that are associated with figuring out geographical maps and memories about those facts.

The conclusion of this research can be summarized as below : (If you are interested in further details, check out the original paper linked at the bottom of the image).

  • There are not meaningful difference in terms of overall volumn of Hippocampus
  • posterior part of Hippocampus of those taxi drivers are developed more than others (control group). ==> Since there is no significant difference in overall volumn of hippocampus, this indicates some other parts of the Hippocampus of taxi driver would be smaller than control group. In conclusion, anterior part of Hippocampus of taxi driver is smaller than the case of control group.
  • the degree of development of posterior Hippocampus of the taxi driver gets higher as their experience as taxi driver gets longer

 

The subjects in this research are as follows. One thing you may notice is that all of them are adults with a few years of experience as a taxi driver. This would be a good indicator that the placiticity happens even during the adulthood

  • mean age 44 years; range 32–62 years
  • licensed London taxi drivers for more than 1.5 years
  • The average time spent training to be a taxi driver before passing the licensing tests fully (i.e., time on The Knowledge) was 2 years

The brain image evidence showing that the taxi driver shows higher development in a specific area of Hippocampus is as follows.

  • Significantly increased gray matter volume was found in the brains of taxi drivers compared with those of controls in only two brain regions, namely the right and the left hippocampi as shown in a and b.
  • No differences were observed elsewhere in the brain.
  • The increase in hippocampal gray matter volume was focal and limited to the posterior hippocampus bilaterally

 

Following plot shows the volumn changes of three different parts of Hippocampus of taxi drivers. It can be summarized as below :

  • Anterior part of Hippocampus : In this area, the volumn size in taxi driver is smaller than the control group. The difference is even greater in the hippocampus in left hemisphere comparing to the case of right hemisphere.
  • Body part of Hippocampus : There are small difference between taxi driver and control group, but not much meanigfully different.
  • Posterior part of Hippocampus : The volum size of the hippocampus in tax driver is larger than the case of control group. ==> absolute different may not look such a big difference comparing to the body part, but if you take the ratio of the difference it is greater (statistically meaningful) than the case of the body part.

 

Following plot shows the correlation between the volum increase of posterior Hippocampus and the length of experience month of tax drivers. The conclusion is that the volum of posterial Hippocampus increases over time whereas the anterial Hippocampus volume decreases over time.

 

Image Source : Navigation-related structural change in the hippocampi of taxi drivers - PNAS (2000)

 

 

Second Language Aquisition

 

First language acquisition (learning the mother tungue) is intrinsic part of the brain and the development for this would be done for almost everybody, but the second langauge aquision is mostly done by active learning.

The pioneering research on this area was published in Nature in 2004 as stated below :

    Humans have a unique ability to learn more than one language — a skill that is thought to be mediated by functional (rather than structural) plastic changes in the brain1. Here we show that learning a second language increases the density of grey matter in the left inferior parietal cortex and that the degree of structural reorganization in this region is modulated by the proficiency attained and the age at acquisition. This relation between grey-matter density and performance may represent a general principle of brain organization.

NOTE : Grey matter is the part formed by bundles of cell body parts of neurons. High density of Grey matter would imply the more number of cell body or more synaptic connections among neurons.

 

Image Source : Structural plasticity in the bilingual brain  - Nature (2004)

 

[a] shows the location of brain area that shows the increased grey matter density from the aquision of the second language.

[b] shows the relationship between the preficiency in second language and Gray matter density. You would notice that the grey matter density increases as the proficiency of the second languate (i.e, gray matter density is proportional to the proficiency in the second language)

[c] shows the relationship between the age at the acquisition of the second language and Gray matter density. You would notice that the earliear you learn the second language, the higher grey matter density is (i.e, gray matter density is anti-proportional to the the age at the aquision of the second language)

 

 

Compenstation of Visual Impairment

 

This paper shows the case of neuroplaciticity where visual cortex area of those persons who has vision imparment. In these patient, the visual cortex would not process visual information/stimulus since they are visually impaired. Then the area for the visual cortex remain unused at all for those patients ? According to this review paper, the area of visual cortex still active but it mainly used for processing other sensory inputs instead of processing visual input.

 

Following image shows how the visual cortex are of the visually impared person are utilized for other purpose. Pay attention to color code when you compare each of the image (A,B,C). [A] shows the cortex area for visual processing in Healthy person. [B] shows the area that are involved in language comprehension and semantic processed. [C] shows the cortex functionality in Visually Impaired person. You would notice that large prtions of visual cortex is replaced by green and blue colors indicating language comprehension and semantic processes and the yellow/orange are shrinked greatly.

Image Source : Neuroplasticity in visual impairments - Neurology International (2018)

 

 

Following image shows another aspect of how the visual cortex are of the visually impared person are utilized for other purpose.  [A] shows the case of visual cortex development in healthy indivisual. At the birth, the visual cortex would have synapsis not only for Vision processing but also for processing other inputs like hearing (audition), touch (Tact) and Smell (olfactory). Of course, the vision processing is main functionality of this cortex area but there are some of synapsis associated other functionality (e.g, hearing, touch, smell etc). As the individual experience various visual inputs after birth, synapsis for hearing / touch / smell gets inhibited and eventually get removed.

[B] shows the case of visual cortex development (placiticity) for the indivisuals with visual imparement. Since these individual does not get any visual stimulus, the synapses for vision processing would get degenerated (removed) and the remaining functionality (like hearing, touching, smell etc) would get more developed. Since the indivisuals with the impairment from the birth has more of the synapses for hearing, touching, smell comparing to the individual with the impairment at later age, the indivisuals with the imparment from the birth shows stronger placiticity (i.e, developing other functionality at the visual cortex) comparing to the other cases.

Image Source : Neuroplasticity in visual impairments - Neurology International (2018)

 

Some of the bullets that would give you a little bit further details from this papar are listed below :

  • The neural networks reorganization in neuroplasticity in blind patients is a compensatory form of visual deprivation, mainly with the increased sensitivity to touch, smell and hearing
  • Cortical thickness is related to neuroplasticity, differently between congenital and late blind. the visual cortex of early blind are thicker than the late blind and non-blind. The congenital visual impairment has a greater cortical thickness in areas associated with vision, while those with late blind have little or no cortical surface reduction. ==> The reason why the peron with visual imparment at congenital period (i.e, at the time of birth) would be because they haven't gone through the process of eliminating non-functional synapses which is caused by visual input during the early developmental stages (especially 2-4 month after birth) in healthy individuals. ==> Since the indivisual with visual imparement at early stage has more (diverse) functional synapses, they shows increased placiticity comparing to those with the imparement at later ages.
  • the occipital cortex participates in the tactile, auditory and olfactory functions improvement.
  • brain plasticity depends on the age of vision loss and can occur basically in two ways: cross-plasticity and multimodal

 

 

Brain Changes with Braille Learning

 

 

 

Image Source : Brain plasticity dynamics during tactile Braille learning in sighted subjects: Multi-contrast MRI approach - NeuroImage (2021)

 

 

 

YouTube

 

 

 

Reference