Advancing Basic Science for Humanity
The Fantastic Plastic Brain
WHY DOES A CHILD TEND TO HAVE A BRAIN LIKE A SPONGE, while an older adult tends to have a brain more like a sieve? What changes in our brains as we get older and how do those changes affect our ability to learn, develop new skills and abilities, and recover from brain injury?
Recent research is beginning to answer these fundamental questions by exploring the plasticity of the adult brain—its ability to readily be shaped by experience. Contrary to the common assumption that you can’t teach an old dog new tricks, there is increasingly strong evidence that the adult human brain is remarkably malleable and capable of new feats even in the last decades of life, but it might need a little extra prodding to bring its plasticity into play. Researchers report that new experiences can trigger major physical changes in the brain within just a few days, and that certain conditions can accelerate this physical, chemical and functional remodeling of the brain.
To explore these startling new findings and what they mean for the treatment of brain disorders, brain injuries, learning as an adult, and the aging brain, The Kavli Foundation brought together three experts in brain plasticity:
- Randy Bruno, PhD, Assistant Professor of Neuroscience and member of the Kavli Institute for Brain Science at Columbia University. Dr. Bruno conducts basic research aimed at understanding how experience causes structural changes in the brain.
- Michael Merzenich, PhD, Emeritus Professor at the Keck Center for Integrative Neurosciences at the University of California, San Francisco, co-founder and Chief Scientific Officer of Posit Science, which develops brain-training software and therapies, and Director/Founder of the Brain Plasticity Institute. Dr. Merzenich was elected to the National Academy of Sciences in 1999 and to the Academy’s Institute of Medicine in 2009, both in recognition of his pioneering research on brain plasticity.
- Randy Nudo, PhD, Director of the Landon Center on Aging and Professor in the Department of Molecular and Integrative Physiology at the University of Kansas. He is principal investigator of a long-term National Institutes of Health-funded project to study neural mechanisms of functional recovery after stroke. Dr. Nudo was selected by the National Institute for Neurological Disorders and Stroke for the prestigious Javits Investigator Award in Neuroscience.
These experts held a far-ranging and fascinating discussion exploring why children can learn an instrument faster than adults, what helps the brain recover from injury, how to prevent declines in brain function linked to aging, and how brain training can help people with autism, schizophrenia, dyslexia, and other developmental brain disorders.
The following roundtable discussion has been edited by the participants.
THE KAVLI FOUNDATION (TKF): Dr. Merzenich, your research shows that there is a critical period early in life in which we readily absorb and process information from our environment, in contrast to adulthood, when we only learn new information the brain judges as beneficial. Can you tell us what exactly is happening physically and functionally in the brain that underlies the critical period and its aftermath?
Michael Merzenich (Credit: UCSF)
MICHAEL MERZENICH: During the critical period, all that’s required to drive changes in the brain is exposure to the physical world. With that exposure, the brain competitively sorts information coming in, and refines its responses to it by creating selective, coordinated networks of neurons. Such neuronal organization enables the brain to respond efficiently and effectively to the environmental stimuli it encounters. Once that organization is achieved, the brain releases growth factors and other compounds that cause a complex series of changes that bring the brain out of the critical period.
TKF: At this point, how does the brain process new information?
MICHAEL MERZENICH: After the closure of the critical period, the older brain is still plastic and remains plastic to the end of life, but it is not plastically remodeled continuously and automatically in response to environmental stimuli as it was during the critical period. So-called “adult plasticity” – which actually begins in early childhood -- only occurs when the brain is excited in particular, specific behavioral contexts. Rather marvelously, the older brain only permits change when it judges that change to be important, rewarding or good for it.
TKF: How long does the critical period last in the human brain?
RANDY NUDO: There’s not one critical period. Different parts of the brain have different critical periods and they last different periods of time. It depends on the area of the brain and the type of function.
MICHAEL MERZENICH: There are waves of maturation that occur in the brain that determine the ages of onset and the durations of the critical periods for each brain sector. The first areas to mature are the parts of the brain that process elementary visual, tactile and sound information -- the critical periods for these sectors are closed in the normal child by the end of the first year of life. But the higher thinking and action control parts of the brain have critical periods that can be open into your late teens or early twenties.
Randy Nudo (Credit:University of Kansas)
RANDY NUDO: Brain injury amplifies the whole process of anatomical rewiring and alters the normal connection pattern. The injured brain is not simply a brain with a hole in it. It’s a completely rewired system. Brain areas that normally don’t have any direct connections can sprout them after injury. A lot of experts in brain injury think the first several weeks after injury is a window of special opportunity. Normal brains are plastic throughout life, but because the growth processes are being turned on so robustly during those first several weeks after injury, that may be a special time to retune the system. The proliferative growth of connections (synapses) between neurons and their pruning that we see in early brain development may be repeated after brain injury. The environmental or behavioral control of the experiences of the injured individual may shape how well his or her brain recovers from the injury.
TKF: Why are brain injuries so notoriously difficult to recover from?
RANDY NUDO: It depends on how big the injury is. Spared areas of the brain can rewire themselves and become like the injured or lost portions of the brain. But if you have a massive stroke, it’s hard for the remaining brain tissue to bridge that major loss of tissue.
TKF: What have we learned about the plasticity of the adult brain that can help people recover from brain injury?
RANDY NUDO: Just simple repetitive movement may not be as effective as a type of movement that is constantly challenging the limits of what someone can do. The most robust recovery occurs with interventions that challenge one’s skills to some degree. Sports athletes know this inherently, but it’s now being applied to rehabilitation.
TKF: It’s my understanding that if people have strokes that impair their ability to move their right arms, they are no longer allowed to rely on their left arms. Instead, often the functional arm is restrained so they are forced to relearn how to use the arm affected by their stroke. Is this done so that they sprout new connections in the brain that will restore movement in the right arm?
RANDY NUDO: Yes, our brains tend to want to do whatever is the easiest solution—it’s easier to use your functional limb and compensate with that limb. But in certain cases it may be more functional and efficient to relearn with that impaired limb. The constraint-induced movement therapy trial demonstrated that even years after stroke, individuals who had this therapy did better, and there are changes in the brains of those individuals that reflect their functional improvements. The only caveat is that this therapy has only been shown to be effective so far in people with mild to moderate stroke damage. If you don’t have enough of the brain substrate for that impaired limb, you can’t have plasticity to the degree that’s required for skilled movements.
Randy Bruno (Credit: Columbia University)
RANDY BRUNO: This issue of use dependence is borne out very clearly in the basic science literature. We showed that when the rat is not using some kind of sensory organ—its whiskers, for example—its brain connections that process information from that organ will be lost because of the ongoing plasticity.
RANDY BRUNO: We used to think that the brain was completely formed by development and its basic structure didn’t change much in adults, but as research went on we discovered that wasn’t true, at least in the cerebral cortex (Many of us focus on the cortex because it is involved in the sophisticated processing and thinking tasks that make us fundamentally human.) We now know that an underlying portion of the brain called the thalamus, which feeds the cortex information from our senses, is also remarkably plastic. Using new research techniques on rats, our lab found that the neuronal connections bridging the thalamus to the cortex are massively plastic—they grow and retract rather rapidly in only a few days in response to different sensations we expose the rat to.
TKF: Can you expand on this by talking about your latest findings?
RANDY BRUNO: When we deprived rats of their normal pattern of sensory information by cutting their whiskers, the brain connections responsible for transmitting that information from the thalamus to the cortex seemed to whither. But when we put rats in an enriched environment where they received much more sensory stimulation than typical, those connections sprouted and grew. The rapidity of this growth is really striking—it happens within just three days, which is something nobody in the past thought was possible. Those kinds of rapid physical changes also probably occur in other parts of the brain as well. Growth and pruning of neuronal connections are opposing processes happening all the time, with our experiences altering the balance of these two.
MICHAEL MERZENICH: In our experiments in adult rats, changes only occurred when the animal was attentive within a rewarded learning environment. When we train the animals to improve their behavioral capabilities under near-optimal contextual conditions, we can drive easily recordable functional and physical changes in the cerebral cortex within a day or two. By contrast, little or no change is induced by the passive exposure of an animal to many days of stimulation with thousands of the same stimuli applied in training.
TKF: So if the adult brain is plastic, there should be nothing preventing an adult from learning a new skill or ability, right?
RANDY BRUNO: Once the critical period is over, our brains continue to be shaped by experience and we continue to learn new skills, although it’s not really clear if that requires more effort than it would in a child. There are certainly changes that occur in our brains during adulthood that might affect our ability to learn, but there are also external factors that affect our learning of new skills. For example, adults don’t necessarily have the time to engage in a lot of the repetitive practice that they need to improve in a skill. But the more experience we’re exposed to, the more synapses we’re going to build in our brains, and that will enable our learning.
RANDY NUDO: There is no evidence that there is any part of the adult brain that is not plastic. But studies indicate that some aspects of musical training, such as the ability to perceive temporal patterns, require the brain to be trained during early developmental periods when its primed for certain types of stimuli. For other aspects of musical development, such as the ability to perceive and repeat a sequence of tones, it’s irrelevant whether you’ve had that experience and training early in life.
TKF: In addition to the importance of creating new synapses when learning new skills, doesn’t it matter how “cleanly” the synaptic wiring is created? As we get older we accumulate so much information in our brains, I would imagine our synaptic wiring gets rather messy, which could dampen the speed we’re able to process new information.
RANDY BRUNO: There’s some biological evidence for this. As you encode more information into some network of neurons, eventually, adding new information into the network can corrupt the information you already have there. The more mature or older brain may have to learn a bit slower in order to preserve the information that’s already there. It bears a lot on whether you can ever learn something as well as someone who started young.
TKF: So can you?
RANDY BRUNO: There are clear advantages to getting the brain wired up in the right fashion early in development, but still there are a number of Olympic medalists who didn’t begin their sport until they were well into their twenties. Maybe we learn a bit slower, but with persistent training and practice we can overcome this limitation or lack of advantage we didn’t get early on.
RANDY BRUNO: Yes, but your nervous system has to be careful about maintaining the roads and tunnels you already have. This is still something that people are actively researching.
TKF: What about the brain’s actual performance—how high a level of mastery can you achieve with training as an adult?
MICHAEL MERZENICH: I know a woman who didn’t begin to paint until she was in her 60’s, yet ended her life as a professional painter of high quality. We are capable of remarkable brain changes contributing to the development of remarkable new abilities at any stage of life. Still, I often wonder how far this woman might have gone if she had mastered and elaborated the physical and aesthetic abilities that supported her painting when she was a child or young adult. There’s no doubt you can acquire new abilities and continuously improve them as an adult learner, but that doesn’t mean that you’ll reach the level of mastery or the complete neurological powers that you would have had if you had started at a younger age.
MICHAEL MERZENICH:There are also people who are able to effectively acquire a new language with a high level of fluency in adulthood, but they are less efficient at doing so than a child, in part because by the time they begin learning that second language, their native language has dramatically altered, and now dominates their physical and functional brain.
The many branches of a neuron (seen in blue) as well as its long extensions (seen in red) enable numerous connections to several layers of other neurons in the brain. (Discrete groupings of these neurons are seen in white.) The sprouting or pruning back of these extensions happen within days in response to sensory stimuli, new research reveals. (Credit: Bruno Lab, Columbia University)
TKF: Could you expand on that?
MICHAEL MERZENICH: When you learn a second language as a child, you actually integrate the structure of the second language into a phonemic and syntactic library that encompasses both your native tongue and the second language. But when you learn a second language as an adult, there is so much competitive power generated by the heavy weight of the first language experience that the brain actually creates a second structural representation for language number two that struggles to compete with the deeply embedded representations of language number one. In language and in other domains, you pay the price of historic weights of experience that have created very reliable and, in many ways, automatic actions in your brain. You have to override these automatic actions to learn that second language. Of course the effort and intensity with which you undertake to learn that second language–establishing the optimal contextual conditions for driving brain plasticity in your adult brain– will also affect your ability to learn it.
TKF: My daughter and I are learning the pedal harp, and I find I progress much slower than she does. She started harp lessons at the same time as me, but at the age of 11. Why is she learning at a faster rate than me?
MICHAEL MERZENICH: I have done several studies to try to understand why adults are frustrated by what they are trying to accomplish, and it almost always comes back to the influences of their earlier neurological histories, and the platform from which their brains are operating given those histories. For example, it is probable that in your practice on the harp, you did not go back to the most elemental stages of learning, unlike your daughter. You likely initiated work on the instrument based on a platform of your other musical experiences, and have done a poorer job than your daughter of establishing all of the elementary skills or abilities that support proficient musicianship. Your daughter’s brain began closer to the beginning. It has probably done a much more complete job of modifying itself to more fully master the elemental abilities that more strongly support highest level abilities.
TKF: But I do the same basic practice exercises that she does.
MICHAEL MERZENICH: More practice may not help without going back to the beginning and going through the full set of skills and refining them progressively in the right order. You may lack elemental skills related to the control of movement or some aspects of listening that won’t improve simply by repetitively plucking the harp strings. For example, most people that have trouble remembering, think they can improve their memory just by practicing remembering. But there are a lot of basic skills that underlie a good memory, such as listening skills, that may need practice instead.
RANDY NUDO: There’s a loss of synaptic connections that increases with age and virtually everything that makes us who we are is encoded in those synapses—when we learn something or hold on to a memory, it’s encoded across many different synapses. Synaptic loss occurs differentially in different brain areas and is subject to different environmental influences. You will see behavioral evidence first in those structures that require the most computational power. That might explain the loss of memory seen in older people, even in those who don’t have some disorder like Alzheimer’s disease.
MICHAEL MERZENICH: We’ve compared the brains of animals near the end of life to those in the prime of life, looking at about 20 main categories of brain operations in the cerebral cortex. These categories included processing speed, state of myelination, coordination of activity across the brain as well as within local neuronal networks, synaptic connectivity, and the distribution of cell receptors for various neurotransmitters, among others. In all these categories, the younger brain was the better brain.
TKF: What causes that decline in brain function in the elderly?
MICHAEL MERZENICH: When we’re older, we spend most of the day operating automatically using skills and abilities that we developed in early life. The actual quantity of new learning and the use of our bodies and brains in novel ways is attenuated, and we’re not doing the kind of practicing that keeps our brains in good shape. We avoid challenges, surprises and problems. To cite one of innumerable examples, we pave the world so that every footfall is certain. In the natural environment, every footfall is uncertain and leads to a little bit of visual slip and balancing to correct that. A little bit of refined movement occurs with almost every step. We forego millions of such little practice moments every year. We’re also not paying much attention to any details anymore. The average person can’t describe the details of the street they live on. Because the brain hasn’t been learning, its learning machinery is down regulated.
TKF: All sorts of “brain aerobics” have been offered as a way to counter age-related decline in brain function. Is there any validity to the notion that if we do a crossword puzzle everyday or some other mentally challenging task, we’ll keep our brains in good shape?
RANDY BRUNO: The key is to be actively engaged in a task and that there be meaningful elaboration on the information taken in at higher levels in order to maintain associations between different pieces of information. Such active engagement, as opposed to passive acquisition of what we experience with our senses, may enhance changes in the brain.
This is an image of a neuron within a living animal that reveals its numerous thread-like branches where it receives connections from other neurons. (Credit: Bruno Lab, Columbia University)
MICHAEL MERZENICH: In the rat, we could sharply reverse all of the brain deficits linked to aging with training. We have extended these studies to the human, and up to this point, everything that we could change physically and functionally in the rat has been shown to be reversible in the human brain. I should point out, however, that these human studies are still not complete. Probably with the right training all these declines can be substantially improved in the elderly, but there’s a misunderstanding of what you need to do to drive changes that would be helpful or corrective. For example, people often assume that practicing a lost ability will contribute to the maintenance of or the improvement of that ability. I might practice remembering, for example, by doing my daily crossword puzzle, thinking that it might help sustain my memory. In fact, there is little evidence that this form of brain exercise has any significant benefit.
TKF: What will help?
MICHAEL MERZENICH: As Randy said, don’t receive information passively. Reconnect with your physical environment and actively pay attention to its details--reconstruct them mentally. Engage in activities that challenge your basic abilities. These activities may be learning a new language or instrument.
TKF: It sounds like you’re suggesting we act like kids again.
MICHAEL MERZENICH: Yes, it’s doing what is stressed in mindfulness training, which tells you to act like a kid again in how you are absorbing information from the environment. Just being connected to the physical world that you are moving and operating in is really important. Many individuals can benefit from spending time at a brain gym website like our BrainHQ site. But if you live your life appropriately, you probably do not have to go to a brain gym, just like if you are appropriately physically exercising, you would have relatively little need to go to a physical gym.
TKF: How are you putting what you know about brain plasticity to work in treating brain developmental disorders, such as autism, Down’s syndrome and dyslexia?
MICHAEL MERZENICH: You can drive large-scale corrective changes by substantially recovering the kind of brain changes that would have occurred if the child had gone through a more normal brain development in early childhood. You have to reconstitute the fundamental abilities that are going to support the complex behaviors. We’ve had big impacts in training children with dyslexia, social conduct disorders, and mild to moderate autism, following this approach.
MICHAEL MERZENICH: No. The brain is plastic for life. Our animal and human studies have shown that there are no age-related effects for children between about 6 and 18, in the training of individuals with developmental disorders. The fundamental thing that determines how much they will improve is the level of their initial impairment, but not their age. We also have training programs that have improved the functioning of people with schizophrenia, bipolar disease, and major depression. We have published about 35 controlled trials and each show the same thing--the training drives physical and functional changes in the brain that lead to behavioral improvements. In a number of these studies, corrective physical brain changes have paralleled those behavioral recoveries.
RANDY BRUNO: I have to caution that there are great challenges with developmental disorders. People who have autism or Down’s syndrome have had these disorders for their entire lives, so the brain may not have developed some of the required wiring to do its work properly.
MICHAEL MERZENICH: Some of the genes involved in autism, Down’s syndrome and other pervasive developmental disorders do affect learning itself, so they can impact and may compromise the brain’s plasticity to some degree. It may take more effort or additional pharmacological treatments to drive a correction in some people with these disorders. But in most of these individuals, there is no indication that their brains are any less plastic than those of normal individuals.
TKF: This has been a fascinating discussion. I have one last question for Dr. Merzenich—do you have any training programs that can help an adult learn the harp?
MICHAEL MERZENICH: No one has taken on that challenge up to this date, but that would be a fun thing to think about. Look on the bright side -- your daughter could become wonderfully accomplished at the harp, especially if she’s motivated by the energy with which you are competing with her!
- July 2012