Plasticity

PLASTICITY

Overall, then, it should be clear that the brain—indeed, the entire nervous system— contains many distinct regions. Each region has its own job to do, and so we can under-stand the nervous system only by keeping track of the various parts—where each is, what it does, and how each contributes to a person’s overall functioning.

But there’s one more layer of complexity that we need to confront, because the functioning and arrangement of the brain can change during our lifetimes. Neurons can change their pattern of connections—so that, in effect, the brain gets new “wiring.” And there is increasing evidence that the brain can grow new neurons in certain circumstances. These changes are fascinating on their own—but they also hold out a promise of enormous importance: Perhaps we can harness this potential for change in order to repair the brain when it has been damaged through injury or disease. Let’s look at the nature of brain plasticity—the brain’s capacity to alter its structure and function.

Changes in Neuronal Connections

Each day brings us new experiences, and through them we learn new facts, acquire new skills, and gain new perspectives. Our reactions to the world—indeed, our entire personalities—evolve as we acquire knowledge, maturity, and maybe even wisdom. These various changes all correspond to changes in the nervous system, making it clear that the nervous system must somehow be plastic—subject to alteration.

In  fact,  the  nervous  system’s  plasticity  takes  many  different  forms.  Among  other options, individual neurons can alter their “output”—that is, can change the amount of  neurotransmitter they release. On the “input” side, neurons can also change how sensitive they are to neurotransmitters by literally gaining new receptors. Both of these alterations  play  a  pivotal  role  in  learning,  and  we’ll  return  to  these  mechanisms.

Neurons  can also create entirely  new connections, producing new synapse in response to new patterns of stimulation. The changes in this case seem to take place largely on the dendrites of postsynaptic cells. The dendrites grow ne dendritic spines—little knobs attached to the surface of the dendrites (Figure 3.38; Kolb, Gibb, & Robinson, 2003; Moser, 1999; Woolf, 1998). These spines are the “receiving stations” for  most  synapses; so  growing  more  spines  almost  certainly  means  that, as  learning proceeds, the neuron is gaining new synapses—new points of communication with its cellular neighbors.

Cortical Reorganization

Plasticity in the nervous system can also lead to larger-scale changes in the brain’s archi-tecture. In one study, investigators trained monkeys to respond in one way if they heard a certain musical pitch and in another way if they heard a slightly different pitch (Recanzone, Schreiner, & Merzenich, 1993). We know from other evidence that—just as in humans—the monkeys’ projection areas for sounds are organized in maps; different sites on the monkey’s cortex are responsive to different frequencies of sound. After train-ing, though, the map of the monkey’s auditory projection area was reorganized, so that much more cortical area was now devoted to the frequencies emphasized during training.

Can the same plasticity be demonstrated in humans? One research team used neu-roimaging to examine the somatosensory projection areas in a group of highly trained musicians, all of whom played string instruments; a comparison group consisted of nonmusicians (Elbert, Pantev, Wienbruch, Rockstroh, & Taub, 1995). The results showed that in the musicians’ brains, more cortical area was dedicated to the represen-tation of input from the fingers—suggesting that because of their instrumental training, the musicians’ brains had been reorganized to devote more tissue to skills essential for their playing.

A related result comes from a study of London cabdrivers. These drivers need sophis-ticated navigation skills to find their way around London, and they become more and more skillful as they gain experience. This skill, in turn, is reflected directly in their brain structure: Studies show that these cabdrivers have enlarged hippocampi—and the hippocampus, you’ll recall, is a brain structure crucial for navigation. Further, the more years of cab-driving experience an individual had, the greater the degree of hip-pocampal enlargement (E. Maguire et al., 2000).

Even more evidence comes from research with the blind. In one study, investigators used neuroimaging to compare the brain activity in blind and sighted research partici-pants who were exploring a surface with their fingertips (Sadato et al., 1996). The sighted participants showed the expected pattern of increased activity in somato-sensory areas as they felt the target surface. In contrast, during this task the blind participants showed increased activity in the visual cortex. Apparently, for these individ-uals, this brain area had taken on a new job. No longer occupied with visual informa-tion, this area of cortex had shifted to the entirely new task of processing information from the fingertips (also see Kauffman et al., 2002).

Thus it seems that the brain is plastic both at the microscopic level, where it involves changes in how neurons communicate with each other, and at a much grander level. If a person receives a lot of practice in a task, more brain tissue is recruited for the task—presumably because the tissue has been “reassigned” from some other task. Likewise, sensory cortex that was initially sensitive to one modality can apparently be reassigned to an entirely different modality.

New Neurons

The last form of plasticity we’ll look at has been controversial because a long-held doctrine in neuroscience was that, at birth, the brain has all the neurons it will ever have. As a result, plasticity during the organism’s lifetime must be due to changes in these neurons. However, neuroscientists have been expressing reservations about this doctrine for years (e.g., Ramón y Cajal, 1913), and it turns out that those reservations were justified. There is now clear evidence that new neurons continue to develop throughout an organism’s lifetime and that this growth is promoted by learning and enriched experience (Eriksson et al., 1998).

The evidence suggests, however, that neurogenesis—the birth of new neurons—is very slow in the adult human brain; and it seems that most of these new neurons don’t survive for long (Scharfman & Hen, 2007; Shors, 2009). It’s also unclear whether neu-rogenesis occurs in all parts of the adult brain—and, in particular, whether it occurs in the cerebral cortex (Bhardwaj et al. 2006). If it doesn’t, this may be a regard in which humans are different from many other species.

In some ways, these results seem backwards. One would think that the creation of new neurons would allow flexibility for the organism and so would contribute to learning— and therefore would be most prominent in species (including humans!) that are capable of especially sophisticated learning. Yet it seems that we may be the species for which cor-tical neurogenesis is least likely. What explains this pattern? One hypothesis is that human intellectual capacities depend on our being able to accumulate knowledge, building on things we have already learned. This in turn may require some degree of biological stabil-ity in the brain, so that we do not lose the skills and knowledge we’ve already acquired. For this purpose, we may need a permanent population of cortical neurons—and this means not introducing new neurons. From this perspective, the absence of neuronal growthmight limit our flexibility; but it might nonetheless be a good thing, helping to sustain long-term retention of complex knowledge (Rakic, 2006; Scharfman & Hen, 2007).

Repairing Damage to the Nervous System

Notice, then, that plasticity has its advantages and disadvantages. On the positive side, plasticity makes it possible to “rewire” the nervous system in response to new informa-tion and new experience. On the negative side, plasticity may in some circumstances undermine the stability of a pattern of neural connections and thus may be disruptive. So perhaps it’s not surprising that different species have evolved to have different degrees of plasticity, with the pattern presumably dependent on that species’ need for flexibility or for longer-term retention.

There’s one arena, though, in which plasticity is certainly desirable: If the nervous system is damaged through injury or disease, the effects can be disastrous. It would be wonderful, therefore, if the nervous system could repair itself by growing new neurons or reestablishing new connections. This sort of self-repair is often possible in the peripheral nervous system; there, neurons can regenerate their axons even after the original axon has been severed. Unfortunately, this sort of regrowth after damage seems not to occur in humans’ central nervous system, and here, once nerve fibers are dam-aged, they generally stay damaged. (For some of the mechanisms blocking this self-repair, see W.-Y.Kim & Snider, 2008.)

Is there some way, however, to use the processes of plasticity observed in healthy brains to restore damaged brains? If so, we might be able to repair the damage created by injury—such as the spinal injury suf-fered by actor Christopher Reeve, well known for his role in the Superman movies (Figure 3.39). After his injury, Reeve spent the rest of his life paralyzed but devoted his energy and talent to encouraging research on spinal cord injuries and other nerve damage. A means of restoring damaged brains might also give hope to those suffering from Alzheimer’s dis-ease or Parkinson’s disease, both of which involve the destruc-tion of brain tissue (Figure 3.40).

Researchers are actively exploring these issues; some of their efforts are focused on encouraging the growth of new neurons (e.g., W.-Y. Kim & Snider, 2008), and other research

is seeking to implant new tissue into the brain in order to replace the damaged cells. Some of the most exciting work, however, is in a third category and involves a mix of implanting tissue and encouraging growth. Specifically, this effort involves implanting, into an area of damage, the same sorts of stem cells that are responsible for building the nervous system in the first place. Stem cells are, in general, cells that are found in early stages of an organ-ism’s development and that have not yet begun to specialize or differentiate in any way. The idea in using these cells is that we would not be replacing the damaged brain tissue directly. Instead, the stem cells would, once in place, serve as precursors of the cells the brain needs—so the brain could, in effect, grow its own replacements.

Preliminary studies in animals suggest that when stem cells are injected into a patch of neurons, the cells are—as we would hope—induced to turn into healthy neurons just like their neighbors, taking the same shape, producing the same neurotransmitters, and filling in for dead neurons (Holm et al., 2001; Isacson, 1999; Philips et al., 2001; Sawamoto et al., 2001). Thus it seems plausible that stem-cell therapy may provide a means of treatment for various forms of brain injury—and so far the results have been quite encouraging (Kondziolka et al., 2000; Veizovic, Beech, Stroemer, Watson, & Hodges, 2001). In one remarkable study, researchers inserted human stem cells into the damaged spines of laboratory rats. The rats, which had been paralyzed at the study’s start, recovered well enough so that they could walk again (Cizkova et al., 2007).

Research in this domain continues. In early 2009, the U.S. Food and Drug Administration gave permission for the first clinical trials for stem-cell therapy in humans who had suffered spinal cord injury. However, the progress of research in this arena has been slow—largely due to an ethical debate over where the stem cells usually come from. As part of a fertility treatment, a woman’s ova are sometimes removed, fertilized in a labo-ratory, and allowed to develop into large masses of cells. One of these masses is then placed back into the woman in hopes that it will implant in the uterus and develop into a normal pregnancy. The other masses—the ones not implanted—were for many years the main sources for stem cells, and there lies the problem: In principle, these other masses might also have been implanted and might also have developed into a human fetus. On that basis, some people have argued that use of these cells for any other purpose is essen-tially a form of abortion and thus is unacceptable to anyone who opposes abortion.

This issue led President George W. Bush to limit the use of federal research money for studies relying on embryonic stem cells. Early in 2009, President Barack Obama reversed that policy—so we can now expect the pace of research to accelerate. Meanwhile, investigators are also seeking to develop alternative sources of stem cells; this may allow us to avoid the ethical debate altogether. One way or another, stem cell research is certain to continue; and in light of the evidence so far, this research holds enormous promise for treating—and perhaps reversing—a range of profoundly dis-abling diseases as well as helping people who have suffered tragic injuries.