PLASTICITY IN THE CNS-LEARNING FROM EXPERIENCE

PLASTICITY IN THE CNS­LEARNING FROM EXPERIENCE

The third principle of this chapter stated that the CNS responds to experi­ence by learning—that is, it reorganizes some of its neurochemistry and connections so that the experience is remembered. It is very important to understand that this plasticity is a broad concept. Not only does the CNS remember events that are consciously experienced, but it also changes in response to all sorts of signals, such as the constant presence of drugs.

The most familiar plasticity in the CNS is the simple remembering of experiences—faces, odors, names, classroom lectures, and lots more. The neurobiological mechanisms through which this kind of learning hap­pens are not completely understood, but we have some clues. One import­ant site of learning appears to be the synapse.

As discussed, synapses of nerve cells are quite complex, and there is extensive biochemical machinery in both the presynaptic and the post-synaptic areas. We think memory is built one synapse at a time: some synapses that are stimulated repeatedly change how they function (learn) and maintain that change for a long time. 'There is an electrical manifesta­tion of this learning that scientists call long-term potentiation (ITP). It is a long-lasting strengthening (potentiation) of the electrical signal between two neurons that occurs when the synapse between them is stimulated.

We're not sure how this happens, but it is likely through a series of bio­chemical changes in how the first neuron releases its neurotransmitter and/or in how the second neuron responds to the neurotransmitter. On the presynaptic side, a synapse could be strengthened by increasing the number of presynaptic terminals, by releasing more transmitters from the same number of terminals, or by a reduction in transmitter removal. On the postsynaptic side, strengthening could occur with an increase in the number of receptors, a change in the functional properties of the receptors, a change in how well the postsynaptic site is coupled to the remainder of the neuron, or a change in the biochemistry of the postsyn­aptic neuron. There is scientific controversy about the true mechanisms of um and the issue may not be clear for a number of years.

Almost every neuron can modify many aspects of its function to adapt to new conditions—by making more or less neurotransmitter, by chang­ing the number of receptors on the surface of its cells, by changing the number of molecules responsible for the passage of the electrical stimu­lus down the axon, and so forth. If a neural circuit is being overstimu­lated, it can reduce the stimulation by removing some of the receptors for the neurotransmitter stimulating it. Therefore, even if the neural cir­cuit is being sent lots of signals, they don't get through. Alternatively, if a neural circuit is receiving much less stimulation than usual, it can adapt by becoming more sensitive to each stimulus. This is how the brain stays

in balance.

This type of biochemical plasticity goes on all the time and is part of normal brain function. However, these same changes can cause abnormal brain function. For example, we think that the tremendous mood changes in depression might result from changing numbers of neurotransmitter receptors following changing stimulation of specific neurons in the brain. If neurons and synapses learn, do they also forget? The answer appears to be yes. We just described how stimulating a neural pathway in a certain way can cause it to "learn" to respond to stimulation differently. Stimulat­ing it in another way (slowly, and for a long time) can cause a process called depotentiation, which appears to be the opposite of long-term potentiation. Why is this interesting? Depotentiation could be quite important because it may represent the synaptic equivalent of amnesia. Depotentiation can be produced by prolonged slow activity or by very strong high-frequency activity, like that which occurs in seizures. It may be a protective mechanism by which the CNS prevents a seizure or brain trauma from encoding new information into the circuits. Again, it is almost certainly under the control of cell-signaling pathways and thus

could be manipulated by drugs.

This gradual change in the electrical strength of a connection seems subtle, but it makes intuitive sense that memories could form in this way. Can the brain actually change physically? We used to think that once a person was mature, the brain didn't change anymore. However, more and more research shows that actual changes in the shapes of neurons also can happen in response to earlier experiences. We know that the shape of certain neurons in the brain changes when different hormones become available. For example, at least in animals, treating them with hormones can stimulate the production of little protuberances, or "spines," on the dendrites of neurons. Other research has shown that synapses actually remodel themselves over time after different levels of activity. So, connec­tions actually get lost or remade. For example, prolonged stress seems to actually shrink the dendrite on neurons, perhaps explaining the cognitive difficulties people encounter during prolonged stressful periods.

It has been known for a long time that this happened in lower animals. For example, as songbirds learn new songs, the structure of certain parts of their brains changes. It was once thought that the brains of mammals did not have this type of structural plasticity. However, more recent stud­ies have shown similar changes in rats, and scientists think that they

probably occur in all mammals.

The most exciting recent development in neuronal plasticity is our understanding that the brain can actually make new neurons. This pro­cess, called neurogenesis, was long thought to occur mostly during prena­tal development, but now we find that it is happening in adult humans. Neurogenesis results from the conversion of neural stem cells into func­tional neurons. The rate of conversion seems to increase in response to injury or other pathologies and decrease in response to chronic stress. As with most neuroscience research, the data come primarily from animal experiments, usually rats, and as always, relevance to humans needs to be established.

There have been some intriguing findings regarding the effects of drugs on neurogenesis in animals. It appears that depression reduces neurogen­esis and subsequent treatment with antidepressants restores it. More rele­vant to this book, the laboratory of Fulton Crews at the University of North Carolina has made the startling discovery that binge exposure to alcohol dramatically suppresses rat neurogenesis, particularly in the ado­lescent forebrain, which is a brain area in rapid development. The poten­tial implications of this are enormous, because adolescents tend to be binge drinkers. Is this behavior impairing their brain development? What other drugs affect these processes? Does this really happen in humans? These questions should and will be answered by future research, but for now they alert us to the possibility that drug abuse could have profound effects on teenage brain development

Approaches to Wives

Approaches to Wives

In our experience with this population, wives of the clients were perhaps the most willing participants of all family members. For the most part, if the IP would cooperate, his wife was easy to bring in. For whatever reasons, they just did not give us much trouble, and some-times even helped us recruit their husbands' parents.* The only exceptions to this were cases in which the wife and the IP's family of origin were openly antagonistic toward each other. In such instances our research design dictated that we concentrate on involving the family of origin (since they, but not the wife, were required to attend the evaluation session), and bring the wife in after treatment began.

THE NONBLAM1NG MESSAGE

When these families are approached they often feel frightened, de-fensive, and guilty. At some level they know they are to a great extent to blame for the problems of the IP. Thus they are ready to hear blaming from the therapist. They anticipate it, and often attempt to deny or avoid the blame they fear the therapist will place on them by diverting it to external influences such as peers, the neighborhood, or the treatment program. The therapist's task is to get beyond this stumbling block and reduce resistance arising from fear of blame.

Principle 10: The therapist must approach the family with a rationale for treatment that is nonpejorative, nonjudgmental, and which in no way blames them for the problem. This requires skill. Some responsibility is being ascribed to the family by the very fact that they are being asked to become involved. There is an implicit message that the family has not resolved something with one of its members. Consequently, the therapist must approach them in a nonconfronting way, which gets them off the hook, thereby re-ducing resistance and making them more amenable to hearing what he has to say. Our experience is consonant with that of Vaglum's" that family members should not be treated as -patients,- but as "healthy- people who, themselves, are without problems. Under no circumstances should the therapist become involved in a struggle with the family over whether they are the problem or not. Instead, he should allow them to become acquainted with him in order to remove mystery and fear; if they sense that he is both genuinely concerned

and not out to put them on the "hot seat,- they will be more agreeable to his requests.

Vignette 12. In this case the therapist (Jerry I. Kleiman) underscored the parents' martyrdom, talking about all they had been through and how their son never listened to them. He emphasized repeatedly that the son did these things despite "all they had done so far." He empathized with the father's plight—nobody listened to him, people kept secrets from him—and told him it was time for this to stop. He talked to the parents as victims, telling them that there was a need for them to be in control of the situation.

Principle 11: Primary focus should be on helping the index patient rather than the family. This approach stems from the work of Haley, and is described in Chapter 6. It has also been applied by others with these families."' '8" Again, the emphasis is on joining the parents in helping their son to "be the kind of person he can be.- To the extent that the therapist ever takes a blaming stance, it would be in this context. He might join the parents in mildly blaming the IP for the problem. Alternatively, he could state, -No one is to blame.- Or, he might emphasize how difficult it is to get off drugs, and, -Your son needs all the help he can get." The family is then redefined as a group that can help the IP, rather than one that causes his problem. Vignette /3. In this family the therapist (Jerry I. Kleiman) empathized and shared with them. He got them to admit that with all they had done so far, they had not been able to help. He suggested that maybe this was an opportunity for them to teach their son what the world is all about.

Vignette 14. The therapist (Jerry I. Kleiman) talked to the father about his goals for his son. The discussion had a kind of "reparenting" flavor, as the father talked about his lack of success both with his son and in general. Kleiman suggested that perhaps this program would give him a chance to succeed in a new way.

Principle 12: The rationale for family treatment should be pre-sented in such a way that, in order to oppose it, family members would have to state openly that they want the index patient to remain symptomatic. While not necessarily easy to do, succeeding at this task can greatly facilitate the recruiting effort. If nothing else, the family may come in to disprove an implication that they do not want change. It sometimes helps to begin by -ascribing noble intentions- to the family (see Chapter 6): -Of course, your goal is to see him straighten out.- In fact, the therapist ought to operate under the assumption that the family wants to help and desires to see the IP get better. He has to believe that, in the end, the parents really do not want a drug addict for a son. If he implies that they do want an addicted son, he will have a battle on his hands. If he is able to avoid such an altercation, the therapist can instead proceed with establishing his case for family treatment, using strategies of the sort described in other sections.