The nervous system appears conservative in its use of mechanisms related to behavioral change. If neuroscientists wish to change the brain, as after injury or disease, then they should look for treatments that will produce plastic changes related to learning, memory, and other behaviors.

Recall that H. M. failed to recover his lost memory capacities, even after 55 years of practice in trying to remember information. Relearning simply was not possible for H. M. He had lost the requisite neural structures. But other people do show some recovery.

An average person would probably say that the recovery process after brain trauma requires the injured person to relearn lost skills, whether walking, talking, or using the fingers. But what exactly does recovery entail? Partial recovery of function is common after brain injury, but a person with brain trauma or brain disease has lost neurons. The brain may be missing structures critical for relearning or remembering.

Donna started dancing when she was 4 years old, and she was a natural. By the time she finished high school, she had the training and skill necessary to apprentice with and later join a major dance company. Donna remembers vividly the day she was chosen to dance a leading role in The Nutcracker. She had marveled at the costumes as she watched the popular Christmas ballet as a child, and now she would dance in those costumes!

The births of two children interrupted her career as a dancer, but Donna never lost the interest. In 1968, when both her children were in school, she began dancing again with a local company. To her amazement, she could still perform most of the movements, although she was rusty on the choreography of the classical dances that she had once memorized so meticulously. Nonetheless, she quickly relearned. In retrospect, she should not have been so surprised, because she had always had an excellent memory.

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One evening in 1990, while on a bicycle ride, a drunk driver struck Donna. She was wearing a helmet but received a brain-damaging blow to the head—a traumatic brain injury, or TBI. She was comatose for several weeks. As she regained consciousness, she was confused and had difficulty talking to and understanding others. Her memory was very poor; spatial disorientation meant she often got lost; she endured various motor disturbances; and she had difficulty recognizing anyone but her family and closest friends.

Over the ensuing 10 months, Donna regained most of her motor abilities and language skills, and her spatial abilities improved significantly. Nonetheless, she was short-tempered and easily frustrated by the slowness of her recovery, symptoms typical of people with brain trauma. She had periods of depression.

Donna also found herself prone to inexplicable surges of panic when doing simple things. On one occasion early in her rehabilitation, she was shopping in a large supermarket and became overwhelmed by the number of salad dressing choices. She ran from the store, and only after she sat outside and calmed herself could she go back inside to continue shopping.

Two years later, Donna was dancing once again, but now she found learning and remembering new steps difficult. Her emotions were still unstable, which put a strain on her family, but her episodes of frustration and temper outbursts grew far less frequent. A year later, they were gone, and her life was not obviously different from that of other middle-aged women.

Even so, some cognitive changes persisted. Donna seemed unable to remember the names or faces of new people she met. She lost concentration if background distractions such as a television or a radio playing intruded. She could not dance as she had before her injury, but she did work at it diligently. Her balance on sudden turns gave her the most difficulty. Rather than risk falling, she retired from her life’s first love.

Donna’s case demonstrates the human brain’s capacity for continuously changing its structure and ultimately its function throughout a lifetime. From what we have learned in this chapter, we can identify three ways in which Donna could recover from her brain injury: she could learn new ways to solve problems, she could reorganize the brain to do more with less, and she could generate new neurons to produce new neural circuits. We briefly examine each possibility.

Cats that lose a leg quickly learn to compensate for the missing limb and once again become mobile. They show recovery of function: the limb is gone, but behavior has changed to compensate. This simplest solution to recovery from brain injury we call the three-legged cat solution.

A similar explanation can account for many instances of apparent recovery of function after TBI. Imagine that a right-handed person has a stroke that costs her the use of her right hand and arm. Unable to write with the affected limb, she switches to her left hand. Such behavioral compensation presupposes that some nervous system changes underlie this new skill.

A second way to recover from brain damage is for the brain to form new connections that allow it to do more with less. This change is most easily accomplished by processes similar to those we considered for other forms of plasticity. The brain changes its neural connections to overcome the loss.

Without some intervention, recovery from most brain injuries is relatively modest. Recovery can increase significantly if the person engages in behavioral, pharmacological, or brain-stimulation therapy that encourages the brain to make new connections.

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Behavioral therapy—speech therapy, physiotherapy, and music therapy are examples—presumably increases brain activity, which facilitates neural changes. In a pharmacological intervention, the patient takes a drug, such as nerve growth factor, known to influence brain plasticity. When NGF is given to animals with strokes that damaged the motor cortex, their motor functions improve (Experiment 14-4). The behavioral changes correlate with a dramatic increase in dendritic branching and spine density in the remaining intact motor regions. The morphological changes correlate with improved motor functions, such as reaching with the forelimb to obtain food, as illustrated in Experiment 14-2 (Kolb, Cote, et al., 1997). But because brain tissue is still missing, recovery is by no means complete.

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In principle, we might expect that any drug that stimulates the growth of new connections would help people recover from brain injury. However, that neural growth must occur in brain regions that can influence a lost function. A drug that stimulates synaptic growth on cells in the visual cortex, for example, would not enhance recovery of hand use. The visual neurons play no direct role in moving the hand.

A third strategy to generate new neural circuits uses either deep brain stimulation (DBS) or direct electrical stimulation of perilesional regions. The goal of electrical stimulation is to directly increase activity in remaining parts of specific damaged neural networks. In DBS, it is to put the brain into a more plastic (trainable) state so that rehabilitation therapies work better. Both strategies are in preliminary clinical trials.

The third strategy a patient like Donna could pursue is to generate new neurons to produce new neural circuits. The idea that brain tissue could be transplanted from one animal to another goes back a century. The evidence is good that tissue transplanted from fetal brains will grow and form some connections in the new brain.

Unfortunately, in contrast with transplanted hearts or livers, transplanted brain tissue functions poorly. The procedure seems most suited to conditions in which a small number of functional cells are required, as in the replacement of dopamine-producing cells in Parkinson disease or in the replacement of suprachiasmatic cells to restore circadian rhythms.

By 2004, dopamine-producing cells had been surgically transplanted into the striata of many Parkinson patients. Although the disease has not been reversed, some patients, especially the younger ones, have shown functional gains that justify the procedure. Nonetheless, ethical issues will remain as long as the tissue is taken from aborted human fetuses.

Adult stem cells offer a second way to replace lost neurons. Investigators know that the brain is capable of making neurons in adulthood. The challenge is to get the brain to do so after an injury. Brent Reynolds and Sam Weiss (1992) made the first breakthrough in this research.

Cells lining the ventricles of adult mice were removed and placed in a culture medium. The researchers demonstrated that if the correct trophic factors are added, the cells begin to divide and can produce new neurons and glia. Furthermore, if the trophic factors—particularly epidermal growth factor (EGF)—are infused into the ventricle of a living animal, the subventricular zone generates cells that migrate into the striatum and eventually differentiate into neurons and glia.

In principle, it ought to be possible to use trophic factors to stimulate the subventricular zone to generate new cells in the injured brain. If these new cells were to migrate to the site of injury and essentially regenerate the lost area, as shown in Figure 14-26, then it might be possible to restore at least some lost function. Not all lost behaviors could be restored, however, because the new neurons would have to establish the same connections with the rest of the brain that the lost neurons once had.

This task would be daunting: connections would have to be formed in an adult brain that already has billions of connections. Nonetheless, such a treatment might someday be feasible. Cocktails of trophic factors are effective in stimulating neurogenesis in the subventricular zone after brain injury. For example, in Figure 14-26, and many differentiated into immature neurons.

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Although they did not integrate well into the existing brain, the new cells influenced behavior and led to functional improvement (Kolb et al., 2007). The mechanism of influence is poorly understood. The new neurons apparently had some trophic influence on the surrounding uninjured cortex. Preliminary clinical trials with humans are under way and so far show no ill effects in volunteers.

Recovery from Brain Injury

Before you continue, check your understanding.

Question 1

Question 2

Question 3

Question 4

Answers appear in the Self Test section of the book.