Continuing Education Activity
Neuroplasticity, also known as neural plasticity or brain plasticity, is a process that involves adaptive structural and functional changes to the brain. It 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 after injuries, such as a stroke or traumatic brain injury (TBI). This activity describes neuroplasticity, the evaluation and management of neuroplasticity, and reviews the role of the interprofessional team in improving care for patients.
Objectives:
Summarize the treatment considerations for patients with a stroke that utilize neuroplasticity.
Describe the classic imaging findings associated with diaschisis.
Identify the risk factors associated with poor synaptic plasticity.
Explain the importance of collaboration and communication amongst the interprofessional team to enhance the delivery of care for patients with stroke as it relates to neuroplasticity.
Access free multiple choice questions on this topic.
Introduction
Neuroplasticity, also known as neural plasticity or brain plasticity, is a process that involves adaptive structural and functional changes to the brain. A good definition is “the ability of the nervous system to change its activity in response to intrinsic or extrinsic stimuli by reorganizing its structure, functions, or connections.”[1] Clinically, it is the process of brain changes after injury, such as a stroke or traumatic brain injury (TBI). These changes can either be beneficial (restoration of function after injury), neutral (no change), or negative (can have pathological consequences).
Neuroplasticity can be broken down into two major mechanisms:
Neuronal regeneration/collateral sprouting: This includes concepts such as synaptic plasticity and neurogenesis.
Functional reorganization: This includes concepts such as equipotentiality, vicariation, and diaschisis
The first mention of the term plasticity in regards to the nervous system was by William James in 1890.[2] However, the term neural plasticity is credited to Jerzy Konorski in 1948[1] and was popularized by Donald Hebb in 1949.[3]
Issues of Concern
Plasticity after injury: Neuroplasticity is a complicated process that is still being elucidated; however, the concept can be applied in the setting of injury to the brain. Neuroplasticity is traditionally thought of as occurring in 3 phases or epochs.[4][5]
First 48 hours: Depending on the mechanism of the injury (such as stroke or TBI), there is initial damage that cumulates as cell death with the loss of certain cortical pathways associated with the lost neurons. The brain attempts to use secondary neuronal networks to maintain function.
[4]The following weeks: Recruitment of support cells occurs in this period as the cortical pathways shift from inhibitory to excitatory. Synaptic plasticity and new connections are made during this period.
[4]Weeks to months afterward: The brain continues to remodel itself via axonal sprouting and further reorganization around the damage.
[4]
Mechanisms of Neuroplasticity
1) Neuronal Regeneration/Collateral Sprouting
Synaptic plasticity: Synaptic plasticity is the ability to make experience-dependent long-lasting changes in the strength of neuronal connections.[1] This is best expressed with the concept of long-term potentiation. First discovered in 1973 by Bliss and Lomo[6] while studying the rabbit hippocampus, repetitive stimulation of presynaptic fibers resulted in high responses of granule cells of postsynaptic neurons.[7] As the postsynaptic potential continued for a much longer time than expected, they termed this long-term potentiation. What is theorized to occur is that when the presynaptic neuron stimulates the postsynaptic neuron, the postsynaptic neuron responds by adding more neurotransmitter receptors, which lowers the threshold that is needed to be stimulated by the presynaptic neuron. This enhances the synapse over time in accordance with the idea by Konorski and Hebb. Synaptic plasticity can be positively influenced by several things, including, but not exclusively, exercise, the environment, repetition of tasks, motivation, neuromodulators (such as dopamine), and medications/drugs.[8][9][10][11][12] Aging and neurodegenerative diseases have been associated with a decrease of neuromodulators and may contribute to a reduction in the ability of synaptic plasticity.[13] The theory of synaptic plasticity has also grown to include more of the evolving complexity of synaptic communication.[1]
These include:
Spike-timing-dependent plasticity (STDP): This incorporates the timing of action potentials generated by presynaptic and postsynaptic neurons to explain how some synapses are strengthened and others are weakened.
Metaplasticity: This broadens the concept to include networks and involves the activity-dependent changes in synapses and how they respond.
Homeostatic plasticity: Mechanisms that maintain homeostasis of the synaptic network over time.
As research continues to grow, these concepts will flesh out more of how synaptic plasticity can influence learning and aid in regaining function in the brain.
Adult neurogenesis: Adult neurogenesis is the concept that the brain continues to make new neurons. Studies by Ramon Cajal had failed to find any evidence of new neuron development in adults, which led to his ‘harsh decree’ that there were no new neurons after the development of the brain stopped.[14] This view continued until Josef Altman was able to find evidence of neurogenesis in adult rats.[14] Since then, neurogenesis has been able to be discovered in birds and other small mammals. It has not been convincingly demonstrated in humans.[15]
There have been two proposed sites of adult neurogenesis in humans, one in the olfactory bulb and the other in the hippocampus. Studies using specific biomarkers associated with developing neurons have been used to support the idea of adult neurogenesis in humans. These biomarkers are complicated as they have also been found in immature neurons, cells that can be found in the human brain that are not newborn nor migrating cells.[15] Coupled with no evidence of a recognizable niche-like structure on histological examination (something seen in other species that exhibit adult neurogenesis), the evidence is inconclusive. More specific biomarkers will most likely need to be developed to identify newborn neurons from immature neurons to elucidate what role they may play in the plasticity of the brain.[15]
2) Functional Reorganization
Equipotentiality and vicariation: Equipotentiality is the concept that when one area of the brain is damaged, the opposing side of the brain would be able to sustain the lost function. This concept stretches back at least to Galen, which was a way to explain why the brain appeared ‘twinned.’ This ‘redundancy theory’ remained until famed researchers such as Pierre Paul Broca demonstrated that unilateral lesions to an area of the left side of the brain caused loss of speech, even though the opposing side was intact. Broca postulated that the relearning of certain functions, such as speech, were easier for a child than if an adult suffered loss. This concept morphed into equipotentiality, meaning that if the damage occurred very early, then the brain has the potential to be able to overtake lost functions.[16]
This is slightly different from the thought of vicariation, which is that the brain can reorganize other portions of the brain to overtake functions that they were not intended to. Broca developed this theory after seeing that some of his patients had a sparing of function even though they had damage to the left hemisphere.[16] In the strictest sense, vicariation is when a part of the brain overtakes a new and unrelated function. With the advent of advanced imaging techniques, it has been shown that neither theory is quite correct.
Graveline, Mikulis, Crawley, and Hwang were able to show that after a hemispherectomy (where one-half of the cerebral cortex is removed, typically due to intractable seizures at a young age), the brain can reorganize the remaining half to restore lost function.[17] Using functional magnetic resonance imaging (MRI), they were able to show that the remaining supplemental motor and sensory areas were able to be reorganized to take over the function of the affected side.[17] Jaillard et al.[18] were able to demonstrate similar findings in 4 adult patients who had had an ischemic stroke of their right primary motor cortex. By performing serial functional MRI, they were able to show that the brain was able to show increased activity initially in the bilateral premotor cortex, which shifted over time to the right hemisphere supplemental motor cortex.[18] These clinical examples highlight that the brain uses both equipotentiality and vicariation.
Diaschisis: Diaschisis is a concept that damage to one part of the brain could cause a loss of function in another area due to some connected pathway.[19] Constantin von Monakow proposed this concept in an attempt to explain why some people lost specific functions (such as speech) but did not have a lesion in the area of the brain thought to supply that function.[20]
An example of this is the hypoperfusion of the ipsilateral thalamus after an acute middle cerebral artery (MCA) stroke. The thalamus, which receives its blood supply from branches of the posterior cerebral artery and a branch of the posterior communicating artery, should be unaffected during an ipsilateral MCA ischemic stroke. Surprisingly, in approximately 20% of acute MCA strokes, there is noted hypoperfusion of the ipsilateral thalamus upon computed tomography (CT) perfusion imaging.[21] Other studies have shown that the incidence increases in the subacute and chronic phases of stroke up to 86%, and while the cause is still unknown, a predominant theory is that there is disinhibition from the loss of gamma-aminobutyric acid (GABA-energic) neurons that leads to a combination of neurotoxicity and retrograde degeneration.[21] While this phenomenon has been noted, it has not been shown to influence any major clinical outcomes at this time.
The concept of diaschisis has broadened over time and is used to explain several different concepts about the functional connections of the brain and what ensues when damage occurs. While these are discussed by Carrera and Tononi,[19] a brief explanation is given:
Diaschisis ‘at rest’: The classic von Monakow type such as ipsilateral thalamic hypoperfusion in MCA stroke.
Functional diaschisis: This is when an area of diaschisis is found when another part of the brain is activated. An example of this is when lesions affected the putamen, when given a functional task of their ipsilateral hand, causes hypoactivation of the ipsilateral cerebellums, which had no signs of hypoactivation at rest. Dynamic diaschisis can also be used and has been used when areas of the brain can be both hypoactive and hyperactive, depending on the task.
Connectional diaschisis: This is when a loss of a part of the brain forces the rerouting of information. This has been seen in rat models where subcortical lesions can cause a decrease in interhemispheric connectivity of the motor strips.
[22]Connectome diaschisis: As advanced imaging has shown the vast complexity of connections between neurons, a map can be generated, called a connectome. This map shows clusters of high connected nodes, which are then linked by a limited number of nodes (hubs). If damage is done to a hub, this can cause much more severe damage than a non-hub node.
As we learn more about the functional connections of the brain, the concept and role of diaschisis will continue to evolve and change.
Clinical Significance
Neuroplasticity, the process of structural and functional changes to the brain after internal or external insult, is an encompassing term that includes multiple different processes. Synaptic plasticity, functional reorganization, and diaschisis demonstrate unique processes that the brain utilizes in response to damage and the restoration of function. As research continues exploring the functional connections in the brain and what influences those connections, we will be able to develop more targeted therapies to help the brain regain function more quickly and more completely.
Clinically, several treatment options can be used to help guide neuroplasticity in restoring function and treating unwanted symptoms. An example is mirror therapy, a technique used in phantom limb pain. In a basic premise, the patent uses a mirror to cover their amputation and focuses on watching their intact limb perform activities while imaging that both limbs are performing the same activity. This has been shown to have increased activation and functional connectivity in the frontoparietal network.[11]
One of the most studied rehabilitation techniques is constraint-induced movement therapy (CIMT). Used in patients with a stroke, the premise is that by constraining the functional limb, the affected limb is engaged in repetitive task practice and behavioral shaping. Using functional magnetic resonance imaging (fMRI) technology, patients who engage in this therapy have been shown to have increased activity in their contralateral premotor and secondary somatosensory cortex in association with improved function.[23]
While therapies can be used to help guide neuroplasticity, multiple medications can also be used to influence brain healing. These include selective serotonin reuptake inhibitors (SSRIs) like fluoxetine, serotonin and noradrenergic reuptake inhibitors (SNRIs) like duloxetine, cholinergic agonists such as donepezil, glutaminergic partial antagonists like amantadine, and several others.[12] Amantadine has been shown to improve recovery in patients in a minimally conscious or vegetative state after a severe TBI.[24] Amantadine has also been shown to have an increase in left prefrontal cortex activation in association with improved cognitive functioning in patients with chronic TBI.[25] As research continues, we will be able to utilize pharmacological treatments further to help guide the brain back to health.
Maladaptive plasticity: While neuroplasticity can be beneficial (i.e., restoring function), it can also be harmful. Maladaptive plasticity is when a connection that is made in the brain produces aberrant or negative symptoms. This can be seen in the examples of use-dependent dystonia (writer’s cramp) and phantom limb pain.[9] Both of these examples have shown abnormal primary sensory cortex changes in association with painful symptoms.
Lastly, a great deal of research has been focused on influencing neuroplasticity through the modification of environmental factors. Music therapy has been shown to influence neuroplasticity positively. It has been shown to improve cognition and other executive functions.[26][27] Exercise has been shown to improve episodic memory and processing speed in addition to decrease age-related atrophy of the hippocampus.[28] A healthy diet has also been shown to be helpful for this. Different dietary supplements are being studied to see if they could help trigger neuroplasticity. Lastly, reducing stress and avoiding sleep deprivation have been shown to be helpful to improve memory, attention span, and other domains of cognition.[29][30]
Enhancing Healthcare Team Outcomes
An interprofessional team approach involving neurologists, physiatrists, therapists, nurses, and other health professionals involved in patients receiving rehabilitation after neurological injury will provide the best outcomes for patients; however, literature is limited in evaluating this care approach.[31] An interprofessional team will be able to identify the most appropriate treatment options to utilize neuroplasticity. Collaboration, shared decision-making, and communication are key for good outcomes. The interprofessional care provided to the patient must use an integrated care pathway combined with an evidence-based approach to planning and evaluation of all activities. While gaining in use, telerehabilitation still needs more research to determine its effect on the brain and healing.[31] This can help leverage technology to utilize telemedicine as part of a comprehensive team approach to patient care. [Level 5]
