Arches. Photo by Daniel Chia
HOPES: Huntington's Outreach Project for Education, at Stanford
Jun
26
2010

Neuroplasticity

Scientists once thought that the brain stopped developing after the first few years of life. They thought that connections formed between the brain’s nerve cells during an early “critical period” and then were fixed in place as we age. If connections between neurons developed only during the first few years of life, then only young brains would be “plastic” and thus able to form new connections. (To learn more about neurons, click here.)

cells controls

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. However, new research on animals and humans has overturned this mistaken old view: today we recognize that the brain continues to reorganize itself by forming new neural connections throughout life. This phenomenon, called neuroplasticity, allows the neurons in the brain to compensate for injury and adjust their activity in response to new situations or changes in their environment.

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! Existing neural pathways that are inactive or used for other purposes show the ability to take over and carry out functions lost to degeneration, and there is evidence that reorganization in the adult brain can even involve the formation of new neural connections. 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.  The brain can also respond to a deficiency in one type of sensory input by enhancing the processing of other sensory inputs.  In blind individuals, for instance, areas of the cortex normally assigned to visual processing can adapt to process completely different sensory inputs, such as hearing or touch.

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 literature 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 were 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 Neurogenesis^

Billions of tree-shaped nerve cells make up the human brain. Neurons are produced through a process called neurogenesis, 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 neurogenesis 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 neurogenesis 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 neurogenesis in the hippocampal region, a brain region that controls certain types of memory.

This research indicates that neurogenesis 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 neurogenesis 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 neurogenesis and the severity of the illness. The brains of individuals at the most severe stages of HD showed the most neurogenesis. 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.

Other studies have shown that neuroplasticity in response to environmental stimulation can delay the onset and progression of HD symptoms in mice.  Scientists are currently searching for molecular targets that could imitate this effect in humans.

Neuronal Growth Factors^

The discovery of neurogenesis 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 neurogenesis 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.

If you are interested in other areas of ongoing research related to Huntington’s Disease, click here.

For Further Reading^

  1. Changeux, J. (Trans. Dr. Laurence Garey). “Neuronal Man: The Biology of the Mind”. New York: Pantheon Books, 1985. p. 282.
    This book presents a comprehensible, clear explanation of complex theories on the brain as well the author’s own theory on the concept of the “mind”. (Not directly related to HD.)
  2. Eliot, L. “What’s Going On in There? How the Brain and Mind Develop in the First Five Years of Life”. New York: Bantam Books, 1999. p. 23-27.
    This book focuses on brain development and how to optimize brain development in children during the first five years. (Not directly related to HD.)
  3. Martin, Ernst. NCCR Neuro-Research-Projects. Project 8 – In-Vivo Functional Analysis of Brain Plasticity. http://www.nccr-neuro.ethz.ch/resp8.html
    A short proposal for future neuroplasticity research focusing on a comparison of two types of neuroplasticity, the neuroplasticity in the developing brains of children and reparatory neuroplasticity (Not directly related to HD.)
  4. National Institute of Neurological Disorders and Stroke. Transcranial Magnetic Stimulation Enhances Short-Term Brain Plasticity: Finding Suggests Ways to Improve Recovery from Neurological Disorders.
    (Indirectly related to HD.)
  5. http://www.ninds.nih.gov/news_and_events/pressrelease_tms_012998.htm?format=printable
    A press release presenting Transcranial Magnetic Stimulation, which may soon be used to guide the process of brain reorganization in a non-invasive way. (Not directly related to HD.)
  6. New York Times on the web. Science/Health, August 28, 2001. Therapies Push Injured Brains and Spinal Cords Into New Paths.
    This article describes new rehabilitation therapies, which promote brain reorganizing. Currently, these therapies are being used to treat patients who have suffered from strokes, individuals with cerebral palsy, and paraplegics. (Indirectly related to HD.)
  7. Ornstein, R. and Thompson, R.F. (ill. David Macaulay). “The Amazing Brain”. Boston: Houghton Mifflin Company, 1984. p. 38, 68-69, 168-169.
    An easy to read book which explains brain basics: the functions of its many parts and how the parts communicate via neurons and synapses. (Not directly related to HD.).
  8. Pinel, J. Biopsychology: Hot Topics. Neurogenesis in the Adult Human Brain. http://www.abacon.com/pinel/hot_sept.html
    This clear and concise article describes the recent discovery of neurogenesis in the adult human brain. It also provides links to articles regarding this discovery, which appeared in scientific journals. (Not directly related to HD.)
  9. Rately, J.J. “A User’s Guide to the Brain: Perception Attention and the Four Theaters of the Brain”. New York: Vintage Books, 2001. p. 167-171.
    A basic description of the functions of the brain. There is only a short section on the brain’s ability to repair itself. (Not directly related to HD.)
  10. Roberts, I.H. “Mind Sculpture: Unlocking Your Brain’s Untapped Potential”. NewYork: Fromm International, 1999. p. 90-110.
    The focus of this entire book is how to enhance ones brain capabilities. “Invisible mending” is how the author refers to neuroplasticity. Techniques that can be used to stimulate brain reorganization are discussed as well as factors that limit the brain’s natural reparatory ability. (Indirectly related to HD.)
  11. Travis, J. “Slow Brain Repair Seen in Huntinton’s.” Science News. 2002. Vol. 162 (21). p. 334.
    This brief article summarizes the exciting finding that neurogenesis occurs in the brains of individuals suffering from HD.
  12. Society for Neuroscience. Brain Briefings. Brain Rehabilitation, Exercise and the Brain, Brain Plasticity, Language Processing and Reading, Brain Work-outs, Brain Reorganization. http://web.sfn.org/content/Publications/BrainBriefings
    These brief articles describe brain reorganization and techniques that may prompt reorganization. (Not directly related to HD.)
  13. Wallenberg Neuroscience Center, Restorative Neurology. Brain Plasticity. http://www.wnc.lu.se/restoneu.html
    This short article is a presentation of what the Wallenberg Neuroscience Center hopes to accomplish in the area of brain plasticity. The aim of the research at this center is to develop new therapies based on cell transplantation to treat diseases such as Parkinson’s Disease and Huntington’s Disease.

-K. Hammond 8-28-02