Neuroplasticity

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Introduction

Before understanding Neuroplasticity, it is necessary to understand the term; 'plasticity'. 'Plasticity is the ability of any structure weak enough to change by an external stimulus, however strong enough not to mould at a once'. In addition, the nervous tissue in the human brain is allocated with a tremendous capacity of plasticity.

Neuroplasticity or brain plasticity is defined as the ability of the nervous system to change its activity in response to intrinsic or extrinsic stimuli by reorganizing its structure, functions, or connections. A fundamental property of neurons is their ability to modify the strength and efficacy of synaptic transmission through a diverse number of activity-dependent mechanisms, typically referred to as synaptic plasticity. The brief video below outlines the principles of Neuroplasticity.

It was once believed that the brain stopped developing after the first few years of life, it was thought that it was only during the early "critical period" as a young child that connections formed between the brains nerve cells which then remained fixed in place as we age. As such it was considered that only young brains were 'plastic' and thus able to form new connections. Because of this belief, scientists also thought that if a particular area of the adult brain was damaged, the nerve cells could not form new connections or regenerate, and the functions controlled by that area of the brain would be permanently lost. In the book "Principle of Psychology" written over 100 years ago, William James presented the first theory of neuroplasticity, suggesting that the human brain is capable of reorganizing. It was not until 1948 when the term Neuroplasticity was first used by a Polish Neuroscientist named Jerzy Konorski, who suggested that over time neurons that had 'coincidental activation due to the vicinity to the firing neuron would after time create plastic changes in the brain'.  But it was not until the mid to latter half of the 20th century, following a wide range of research which showed that many aspects of the brain remain changeable even into adulthood, that the term Neuroplasticity came to prominence. Neuroplasticity, also referred to as brain plasticity, is a term used to describe changes to the brain that happen throughout the lifespan in response to new experiences. Latest research shows that brain development and behaviour are guided by a basic genetic blueprint, in addition to a range of experiences and all that shapes the emerging brain. Even prenatal events could be a factor in the modification of neuronal connections. This notion contrasted with the previous scientific consensus that the brain develops during a critical period in early childhood then remains relatively unchangeable afterwards. Definitions A wide range of definitions exist in relation to the term neuroplasticity, some of which look at noral development but others looking more specifically in relation to damage to the central nervous system. 'The ability of the brain to change in structure or function in response to experience'.   'The capacity of the nervous system for adaptation or regeneration after trauma' . 'The ability of the Central Nervous System to undergo structural and functional change in response to new experiences'.  Overview Information in the brain is transmitted from neuron to neuron through specialized connections called synapses. A synapse between two neurons is made up of presynaptic and postsynaptic terminals, which are separated by a synaptic cleft. The presynaptic terminal is filled with small vesicles containing chemical neurotransmitters, and the postsynaptic terminal consists of receptors specific for these neurochemicals. Neurons carry information in the form of an electrical impulse called an action potential that is initiated at the cell body and travels down the axon. At the synapse, an action potential causes the voltage-dependent release of neurotransmitter-filled vesicles, thereby converting an electrical impulse into a chemical signal. Neurotransmitters diffuse across the synaptic cleft, where they bind to receptors and generate an electrical signal in the postsynaptic neuron. The postsynaptic cell will then, in turn, fire an action potential if the sum of all its synapses reaches an electrical threshold for firing. Since a neuron can receive synapses from many different presynaptic cells, each cell is able to integrate information from varied sources before passing along the information in the form of an electrical code. The ability of neurons to modify the strength of existing synapses, as well as form new synaptic connections, is called neuroplasticity. Defined in this way, neuroplasticity includes changes in strength of mature synaptic connections, as well as the formation and elimination of synapses in adult and developing brains. This encompasses a vast field of research, and similar processes may also occur at peripheral synapses, where much of the pioneering studies on synaptic transmission first took place. In addition, neuroplasticity includes the regrowth (or sprouting) of new synaptic connections following central nervous system injury. The human brain is now considered to be a highly dynamic and constantly reorganizing system capable of being shaped and reshaped across an entire lifespan. It is believed that every experience alters the brain’s organization at some level. Neuroplasticity refers to the lifelong capacity of the brain to change and rewire itself in response to the stimulation of learning and experience. Neurogenesis is the ability to create new neurons and connections between neurons throughout a lifetime. As we age, the rate of change in the brain, or neuroplasticity, declines but does not come to a halt. In addition, we now know that new neurons can appear in certain parts of the brain up until the day we die. The more you engage neuroplasticity. As you practice and repeat each movement over and over, the new neural connections( new pathways) in your brain get stronger and stronger.

'Plasticity Hypothesis'

This plasticity hypothesis is based on the activity of the nerve impulses and the subsequent changes happening in the nerve fibres at the cortical level. Firstly, a nerve impulse leads to functional transformation in the cortical network by carrying out excitability of the nerve fibres. Furthermore, this functional transformation enhances plastic changes in the nervous system leading to neuroplasticity

Main phenomena of neuroplasticity:

‘’Functional changes leads to structural changes’’

A change could be temporal(functional) or spatial(structural). A temporal change is further divided into short-term and long term change. Besides, a spatial change takes place either at synapses, within neurons or within glial cells. Furthermore, functional changes take place at individual neurons. Following sequences such as excitatory postsynaptic potential, synapse strengthening, long-term potentiation and long term depression takes place at an individual neuron. Besides, structural changes take in the population of the neurons. These changes are related to changes in the dendritic arbor, spine density, synapse number, synapse size, axonal arboru, receptor density, unmasking, pruning, cortical representation, structural thickness and grey matter density.

Mechanism of functional changes

(a)  Denervation supersensitivity:

This phenomenon occurs when cortical neurons are lost. Due to damaged neurons, there are no nerve signals passing across these neurons. Thus, to compensate this, the post-synaptic membrane develops more receptors for neurotransmitters to pass nerve signal. This phenomenon of increased receptors at postthe -synaptic membrane leads to super-sensitivity in its denervation stage.

(b)  Long-term potentiation

In this phenomenon, at a postsynaptic membrane, there occurs a release of a small amount of glutamate. Furthermore, this glutamate binds to receptors present over the membrane. This leads to stimulation of AMPA (alpha amino-3-hydroxy-5-mether 4-isoxazole propionic acid) receptors that allows influx of sodium (Na+) into the post-synaptic membrane. In addition, magnesium ions are released which subsequently blocks NMDA (N-methyl D-aspartate) receptors. Overall, this process leads to further release of glutamate over the pos-synaptic membrane. Therefore, more sodium ions enter into the post-synaptic membrane increasing the positive charge. Furthermore, this event leads to expelling of magnesium ions from the NMDA receptors, which allows more calcium influx into the post-synaptic cells. All this leads to activation of ‘Protein Kinase C and Calmodulin Kinase’, which causes the addition of more AMPA receptors over the pos-synaptic membrane. This leads to further stimulation of post-synaptic membrane to release more glutamate which enhances ‘strengthening of the synapse and thus potentiation has occurred’

Properties of Long term potentiation

(i) Cooperativity: A presynaptic membrane should reach to a threshold to produce an impulse

(ii) Specificity: Long term potentiation can only be generated at one particular synaptic junction. However, the adjacent which is not activated cannot show long term potentiation

(iii) Associativity: There is a connection between the two adjacent synapses. In which stronger stimulus at one synapse can lead to the generation of impulse at a weaker synapse

(c)  Long-term Depression

This long term depression follows the low-frequency stimulation of the post-synaptic membrane. In this process, the release of glutamate over the post-synaptic membrane leads to a lower level of depolarisation. This slow gradual stimulus leads to the passage of calcium through NMDA receptors, which gradually builds up the number of calcium ions at the receptor site. This process leads to activation of the ‘Phosphatases’ protein, which further dephosphorylates the substrate to maintain AMPA receptors to carry out generation or stimulation of the post-synaptic membrane. Therefore, leading to the generation of ‘Weaker post-synaptic response’

(d) Synaptic strengthening

In this process, there occur structural changes in the synapse to facilitate neurotransmission. Basically this works on the ‘Hebbs Postulate’ in which coordinated activity of a presynaptic terminal and a postsynaptic membrane would make the synaptic connection stronger (‘Hebbian plasticity).

Mechanism of structural changes

Functional changes in the brain cortex facilitate structural changes. Furthermore, structural changes include sprouting and pruning, Sprouting generally includes increase in synapse number, size, spine density, receptor density, dendritic arbour and axonal arbour density.

Experience and brain plasticity

Changes in the brain can occur due to a variety of stimulus. Kolb et al., state that there are three main types of plasticity that shape the developing brain:

• Experience-independent plasticity is pretty much everything that happens with the brain during the prenatal developmental phase. Neuronal connections and brain formation are processes driven by complex genetic instructions. There is so much going on at this stage of brain development: neurons that fire together, make some structures stronger and parts of the brain more prominent than others, whereas those that do not sync very well together die out. And because all those neuronal losses could harm the brain nature came up with a solution for that - overproduction of neurons. That is why a due course of life we have most of our neurons when we are the youngest and then gradually start losing grey material.
• Experience-expectant plasticity which is independent of external factors helps the neurons to connect to each other independent of other processes. An example is the formation of the retinal ganglion. Axons coming from the retina, initially are sending axonal branches for both eyes but in due course, each branch has its own neurons. The axons of each branch fire together and create neuronal network independent of those in the other eye.
• Experience-dependent plasticity can be seen throughout the life of every animal. Brain changes when different situations occur: moving to new territory, when learning problems or suffer from injury. Those are the daily challenges for all living creatures which could either increase or decrease synapse numbers and make some brain areas bigger than others.

Plasticity is a hugely experience-dependent event, especially experience which occur in early stages of life and is expected that this type of experience will have long-lasting effects. The plasticity of the brain in its whole complex manner can be summarised in one sentence: "Neurons that fire together, wire together".

Learning is the key to neural adaptation. Plasticity is the mechanism for encoding, the changing of behaviours, and both implicit and explicit learning

Physiotherapy - Clinical Implications

Neuroplasticity is also a phenomenon that aids brain recovery after the damage produced by events like stroke or traumatic injury. This ability to manipulate specific neuronal pathways and synapses has important implications for physiotherapeutic clinical interventions that will improve health. Promising therapies like specific exercise training, cognitive training and neuropharmacology are all based on our current understanding of brain plasticity (currently the subject of intense research for different pathologies). A better understanding of the mechanisms governing neuroplasticity after brain damage or nerve lesion will help improve the patient's quality of life.

Physical neurorehabilitation can enhance brain and neuromuscular adaptation. PT for neurological patients is a comprehensive process that intends to teach, guide, and promote brain plasticity, thus reducing the threats for any functional and cognitive variations

Neuroplastic specific techniques in physiotherapy include

• Motor Learning
• Biofeedback
• Task Analysis and Task-Specific Training
• Neurodevelopmental treatment (Bobath)
• Constraint Induced Movement Therapy
• Proprioceptive Neuromuscular Facilitation (PNF) see the section in this link

The below briefly outlines the principles of neuroplasticity in relation to Physiotherapy.

A 2019 study into the role of neuroplasticity in Rehabilitation noted that "Rehabilitation plays a role in adaptive plasticity and motor recovery in subjects after CVA where through locomotion training and neurostimulation techniques". This improves mobility through cortical reorganisation. Cognitive functions also improved with the addition of aerobic fitness and video games. Thus rehabilitation that is dedicated to promoting wellbeing and health stimulates advantageous neuroplastic changes in the brain, promoting functional improvement.

A 2017 study into MaLT - Combined Motor and Language Therapy Tool for Brain Injury Patients Using Kinect, looked at a pilot multidisciplinary computer-based therapy tool for motor and language rehabilitation following brain injury. Although rehabilitation services are becoming increasingly multidisciplinary and "integrated", treatment for language and motor functions often occurs in isolation. Thus, behavioural therapies which promote neural reorganisation and neuronal regrowth do not reflect the high intersystem connectivity of the neurologically intact brain. This project uses the Kinect sensor to develop an integrated motor and language rehabilitation therapy tool, capable of providing cost-effective, long-term, high dosage rehabilitation in the home setting. In conclusion, it noted that motion sensor technology can be successfully combined with a language therapy task to target both upper limb and linguistic impairment in patients following brain injury. The initial studies on stroke survivors have demonstrated that the combined therapy approach is viable and the outputs of this study will inform planned larger-scale future trials.

Conclusion

Recent advances in rehabilitation techniques have produced better functional outcomes in age-related neurological conditions. With more of the world’s population surviving longer, individuals often face age-related neurology disorders and decline of function that can affect lifestyle and well-being. Neuroplasticity can be manipulated in both the healthy and diseased brain. Utilising the brains' ability to create and lay down new pathways the physiotherapist can play a big role in rehabilitation and improved quality of life.

Resources

Presentations

• Neuro Recovery & the Foundation for Rehabilitation - Neuroplasticity. Presentation by Jacqui Ancliffe, Senior Physiotherapist at the Royal Perth Hospital. (presentation slides)
  

• Neuroplasticity, Motor Learning and it's Application in Rehabilitation. Presentation by Frank Hyland, Vice President Rehabilitation Services and Hospital Administrator at Good Shepard Rehabilitation.
  http://www.goodshepherdrehab.org/sites/goodshepherdrehab.org/files/images/1_NeuroPlasticiy_2013.pdf

• Basic Knowledge - A Movement Therapy Perspective
  The learning incentives of this slidepool are to understand the neural principles underlying neurorehabilitation, to deepen the knowledge of the key factors which influence recovery and to learn how new technologies can improve therapy by utilizing these key factors.
  http://www.iisartonline.org/fileadmin/education/education_material/sp1_basic_knowlegde_movement_perspective.pptm

Books

• The Brain that Changes Itself 
  Dr.Doidge is a Canadian Psychiatrist, Psychologist, and best selling author of 'The Brain that Changes Itself' (2007). The book covers the field of neuroplasticity. Doidge does a great job of explaining the practical modern application for the field of Neuroplasticity. For people interested in neuroplasticity he gives us this list of words that we may come across that also relate to the field of neuroplasticity cognitive neurorehabilitation, neurorehabilitation, neurorehab, cognitive rehab, experience-based plasticity, neuroplasticity, neural plasticity, neuronal plasticity, brain plasticity, and plasticity.

Podcasts 

• Neuroplasticity: How the Brain Heals. Norman Doidge talks about the implications of neuroplasticity and his new book 'The Brain's Way of Healing', and from San Jose in California Ian Sample gives a roundup of key issues discussed at the annual meeting of the American Association for the Advancement of Science. 
  https://www.theguardian.com/science/audio/2015/feb/20/aaas-neuroscience-neuroplasticity-how-the-brain-heals

• Brain Science. Hosted by Dr. Ginger Campbell. Dr. Campbell's podcasts have inteviews from leading researchers on the cutting edges of their respected fields.The podcast are great for learning the latest advances and trends in neuroscience including information on neuroplastisicity. 
  https://brainsciencepodcast.squarespace.com/bsp/?category=Brain+Plasticity

• Imaging and Stimulating Brain Plasticity. Professor Heidi Johansen-Berg gives her inaugural lecture as head of the Plasticity Group at the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB).
  https://podcasts.ox.ac.uk/keywords/neuroplasticity

• Neuroplasticity and Genetic Variation Physical Therapy Discussion Podcast. Authors Cameron Mang and Lara Boyd join Steven Wolf and moderator James Carey to discuss the role of aerobic exercise in enhancing neuroplasticity and how genetic variation can affect the response of a patient to poststroke rehabilitation. The group also discusses the amount and intensity of exercise needed to increase BDNF secretion and the future directions for research. http://ptjournal.apta.org/content/ptjournal/suppl/2013/11/21/ptj.20130053.DC1/ptj_201312_discussion_neuroplasticity.mp3