How does neuroplasticity work? A large amount of research focuses on this question. Scientists are certain that the brain continually adjusts and reorganizes. In fact, while studying monkeys, they found that the neuronal connections in many brain regions appear to be organized differently each time they are examined! While it remains uncertain at this writing (April 2003) whether reorganization in the adult brain involves the formation of new neural connections, existing neural pathways that are inactive or used for other purposes do show the ability to take over and carry out functions lost to degeneration. Understanding the brain's ability to dynamically reorganize itself helps scientists understand how patients sometimes recover brain functions damaged by injury or disease.
Brain Reorganization
Genes are certainly not the only factor determining how our brain develops and forms its inner connections. Conditions in our environment, such as social interactions, challenging experiences and even fresh air can play a crucial role in brain cell survival and the formation of connections. Just as the brain changes in response to environmental conditions, it can also change and rearrange in response to injury or disease. Commonly, these rearrangements involve changes in the connection between linked nerve cells, or neurons, in the brain. Brain reorganization takes place by mechanisms such as "axonal sprouting", where undamaged axons grow new nerve endings to reconnect the neurons, whose links were severed through damage. Undamaged axons can also sprout nerve endings and connect with other undamaged nerve cells, thus making new links and new neural pathways to accomplish what was a damaged function. For example, although each brain hemisphere has its own tasks, if one brain hemisphere is damaged, the intact hemisphere can sometimes take over some of the functions of the damaged one. Flexible and capable of such adaptation, the brain compensates for damage in effect by reorganizing and forming new connections between intact neurons.
New connections can form at an amazing speed, but in order to reconnect, the neurons need to be stimulated through activity. In one study, researchers damaged a small brain area in several monkeys, which resulted in the loss of particular hand movements. Due to the lack of hand activity, even the neurons surrounding the damaged brain area withered, resulting in further impairment of hand movements. These observations confirm the notion that it is important to provide stimulation to neurons in order for them to remain active and form new connections, promoting rehabilitation.
Unfortunately, this same brain reorganization may sometimes contribute to the symptoms of disease or impairment. For example, people who are deaf sometimes suffer from a continual ringing in their ears, which may be the result of the rewiring of brain cells starved for sound. It is important to stimulate the neurons in just the right way for them to form beneficial new connections. By better understanding how the brain reorganizes itself, we can better learn how this task can be accomplished.
Strategies for Promoting Brain Reorganization
A first key principle of neuroplasticity is this: brain activity promotes brain reorganization. In other words, "brain workouts" help the brain reorganize connections more quickly and stimulate reorganization when the brain is not capable of reorganizing on its own. Even simple brain exercises such as presenting oneself with challenging intellectual environments, interacting in social situations, or getting involved in physical activities will boost the general growth of connections. However, generalized stimulation may not be very helpful for rebuilding a specific damaged area of the brain.
Another way to promote neuronal connections in the brain has been learned from efforts to help stroke patients. Studies show that drugs that increase the availability of the hormone norepinephrine help in the rehabilitation of movement loss. These drugs stimulate or provoke the synapses of the nerve cells, making them more capable of forming new connections. Because they can be costly and have unintended side effects, drugs alone may not be the optimal approach to rehabilitation. However, drugs may well be beneficial when used in conjunction with a third approach: physical or rehabilitation therapy.
Building on the principle that neuronal activity promotes new connections, rehabilitation therapy attempts to stimulate particular neurons that have not been active for some time. Here the goal is to promote selective self-repair and reorganization through specific motor activity. Because brain reorganization generally becomes more difficult as we age (for reasons not yet fully understood), a damaged adult brain needs a specific "neuroplasticity jump-start" to rebuild. For example, practicing a particular movement over and over-referred to in the literatures as “constraint-induced movement-based therapy”-helps your brain form and strengthen the connections necessary for that movement. Thus in Germany, seven patients who had lost the ability to walk was placed on a treadmill with a parachute and harness. They were given as much physical support as possible, but the treadmill forced the movement of their legs. By the end of therapy, this forced movement enabled some of the intact neurons in the damaged area of the brain to form new connections, which in turn enabled three of the patients to walk independently and another three to walk with supervision.
An important aspect of rehabilitation therapy is timing. If a person who has suffered from brain damage does not practice a lost movement, the damaged neurons-as well as surrounding neurons-are starved of stimulation and will be unable to reconnect. However, research on non-human animals indicates that if an injured limb is used immediately after the brain area has been damaged, damage to the brain actually increases. To be successful, rehabilitation must wait a week or two. By the second week, use of the injured limb stimulates damaged connections that would otherwise atrophy without input. Yet, a particular movement can be practiced too much. If practiced millions of times per month over years, for example, the pattern of connections can grow so much that it inhibits or "squeezes out" other patterns of connection, resulting in the inability to perform other movements. In short, rehabilitation therapy can indeed take advantage of the brain's natural flexibility for forming new neural connections; however, this is a delicate process that must be done carefully and under professional guidance.
The Limits of Innate Brain Plasticity
Neuroplasticity enables the brain to compensate for damage, but sometimes an area of the brain is so extensively damaged that its natural ability to reorganize is insufficient to regain the lost function. In the case of Huntington's Disease and other diseases that cause neuronal death, the death of many cells may render the brain unable to reorganize corrective connections. In order to have a chance of repair, a certain (as yet unknown) number of neurons must remain intact. Thus, if a highly specialized brain "circuit" is completely destroyed, the associated mental function may be lost. Currently there is no way of determining with certainty whether a lost function can be recovered. However, there is another source of hope. Recent research (discussed in the next section) has shown that the brain can sometimes generate new neurons, not simply new connections, and that these new neurons can sometimes "migrate" within the brain. This raises the possibility that, under certain conditions, new neurons could migrate to damaged areas, form new connections, and restore some or all lost functions. It is too early to tell for sure: we still have much to learn about neuroplasticity!
Neurons and Neurogenises
Billions of tree-shaped nerve cells make up the human brain. Neurons are produced through a process called neurogenises, which begins during the third week of development in humans. Nerve cells develop at an average rate of 250,000 per minute during the prenatal period, but by birth, the process of neurogenises has largely ceased. (To read more about neurons, click here.)
A widely held belief is that neurons, unlike other cells, cannot reproduce after the first few years of life. This would mean that neurons that are destroyed couldn't be replaced. However, recent research suggests that this belief is not supported by evidence. In 1999, production of new neurons was discovered in the neocortex of adult primates. Also in 1999, researchers at the Salk Institute in San Diego, California discovered neurogenises occurring in the brains of adult humans, including in a 72-year-old adult. In this study, researchers used a chemical marker to identify new neurons and observed neurogenises in the hippocampal region, a brain region that controls certain types of memory.
This research indicates that neurogenises may well continue to occur throughout the human life span, although it occurs less rapidly in adults. Many of the new neurons that form in adults die almost immediately, but evidence suggests that some cells that are able to integrate themselves into the existing web of neural connections. Other researchers have also found definitive evidence that the brain does not stop producing new neurons after the "critical period" of development; the brain has been shown to generate new neurons from stem cells in select regions of the brain.
Research in the area of neurogenises has resulted in an exciting recent discovery bearing on Huntington's Disease. By studying post-mortem brains of people with HD, researchers at the University of Auckland in New Zealand found evidence suggesting that HD-affected brains produce new neurons throughout the course of the disease. Moreover, there is a correlation between the rate of neurogenises and the severity of the illness. The brains of individuals at the most severe stages of HD showed the most neurogenises. It appears that the brain is attempting to compensate for the neural damage resulting from the disease. Unfortunately, however, brains damaged by HD seem to be unable to generate new neurons quickly enough to replace the dying ones. Another problem may be that the new neurons are unable to migrate to the areas where they are needed.
Neuronal Growth Factors
The discovery of neurogenises in the brain of adult humans, including those suffering from HD, has spurred an investigation of how to influence neural development as well as how to replace dying cells with new ones. In an attempt to increase the production of new neurons, scientists are experimenting with neuronal growth factors. Growth factors have been successful at stimulating stem cells to produce new neurons. (To read more about stem cells, click here.) One possibility is to use the growth factors with a patient's own brain tissue to generate new cells. However, these new lab-produced neurons would need to be transplanted safely and effectively into the brain of the patient, which could prove very difficult. Ideally, the growth factor could be produced directly in the damaged area, stimulating neuronal growth in the damaged area. Two scientists at the Salk Institute in San Diego, California, Fred Gage and Mark Tuszynski, experimented with this possibility. They removed skin cells from rats with severed spinal cords and added new genes to the cells, which caused them to produce neuronal growth factors. They let the cells multiply and then implanted the daughter cells into the damaged areas. The rats were able to regrow neurons and regain some of their lost function, a very promising finding.
The future for people with brain damage may likely involve some combination of rehabilitation therapy, drug therapy, and possibly, the transplantation of new brain cells into the damaged brain area. Unfortunately, the use of new neurons and growth factors for treatment is not yet ready for clinical use. Scientists need to learn more about how the process of neurogenises is controlled and how to successfully integrate the new neurons into the existing brain circuitry. As research continues, there is growing hope that science will discover a safe and effective way to guide the process of neuronal growth in order to repair areas of the brain that are damaged by injury or disease.
Future Research
Scientists continue to investigate the workings of neuroplasticity and continue to ask how best to encourage this natural process of reorganization? Studies confirm that an active lifestyle maintains brain function; thus, new research aims to develop lifestyle behaviors and medications that could improve normal brain development as well as repair damaged brains. Complementing this area of research, some scientists are exploring the ability of an especially stimulating environment to boost reorganization and repair damage. Research also continues in the treatment of diseases such as HD and Parkinson's with cell transplantation in conjunction with physical therapy (To read more about cell transplantation, click here.)
Another technique called Transcranial Magnetic Stimulation (TMS) may soon be very helpful for guiding the process of brain reorganization; however, this technique requires more study before it is deemed safe and ready for clinical use. Scientists have used TMS to modify the process of reorganization to enhance the benefits of "rewiring". TMS consists of a wire coil that produces a magnetic field, which surrounds the head and produces an electrical current in nearby regions of the brain. The electrical current is used to stimulate areas of the brain that will benefit from input, and to prevent stimulation of brain regions where the formation of new connections is not beneficial. The ability to focus brain reorganization could bring about more rapid and more successful recoveries from damage to brain areas.
