Behavioral disorders afflict millions every year. The National Institute for Mental Disorders estimates that in a given year about one in four people in the United States has a diagnosable behavioral disorder, and nearly half of the population does over their lifetime. Only a minority receive treatment of any kind, and even fewer receive treatment from a mental health specialist. Large-scale surveys of neurological disorders show a similar pattern of prevalence. Together, behavioral, psychiatric, and neurological disorders are the leading cause of disability after age 15. Behavioral disorders, traditionally classified as social, psychological, psychiatric, and neurological, reflect the assessment and treatment roles different professional groups play. As understanding of brain function increases, the lines between behavioral disorders are blurring.

Epidemiologists study disease distribution and causes in human populations and help define and assess behavioral disorders of three general types—psychoses, mood, and affect. Various professional organizations classify disorders differently, for example, as in Table 16-3.

The first set of criteria for diagnoses in psychiatry was developed in 1972. Since that time, three parallel sets of criteria have gained prominence, and new versions appear periodically. One is the most recent edition of the World Health Organization’s International Classification of Diseases (ICD-10); another, the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM). The newest, launched by the National Institutes of Mental Health, is the Research Domain Criteria (RDoC). With this new classification system, NIMH is looking to transform behavioral diagnoses by incorporating genetics, imaging, and cognitive science, among other levels of information.

In addition, the Society for Clinical Psychology provides a list of psychological disorders, their symptoms, and a summary of psychological treatments. The National Institute of Neurological Disorders and Stroke provides a list of neurological disorders, including their symptoms, treatments, and any clinical trials that are investigating treatments. Classification systems organize knowledge about disorders and their treatments and are useful for decision making in such institutions as insurance companies, courts, and schools.

Table 16-3 summarizes the classification scheme used currently in the DSM-5. As with any attempt to classify psychiatric disorders, the DSM is to some extent arbitrary and unavoidably depends on prevailing cultural views. A good example is the social definition of sexual behavior viewed as abnormal. At its inception, the DSM listed homosexual behavior as pathological but has omitted it since 1980. With evidence solidifying around a neural basis for the spectrum of gender identity, a similar fate will likely befall the DSM category gender dysphoria.

Each revision of any classification system reflects new perspectives. For example, the DSM-5 labels all forms of autism as autism spectrum disorder (ASD) and most forms of schizophrenia as schizophrenia spectrum disorder. Classifying broad ranges of conditions as one simplifies diagnosis but draws criticism for its associated loss of descriptive power and a perceived difficulty in obtaining treatment sensitive to the severity of particular symptoms.

Among the continually emerging means of searching for indicators of behavioral disorders, genetics and brain imaging, including MRI and PET, stand out. Although these tools are not currently used clinically, they are increasingly used both to classify disorders and to monitor treatment effectiveness. But to be useful, imaging test resolution, for example, must be sensitive enough to detect unique features of brain disorders and specific enough to rule out similar conditions. This sets a high bar, because many behavioral disorders display similar abnormalities. Enlarged ventricles, indicating a loss of brain cells, may appear in schizophrenia, Alzheimer disease, alcoholism, or head trauma, for example.

Nonetheless, imaging technology is shedding new light on behavioral disturbances. Imaging the brain structure, connections, and chemistry of subjects with childhood-onset schizophrenia, for example, suggests that the condition begins in utero and is characterized by excessive pruning of short-distance cortical connections (Rao et al., 2015). Cortical maps derived by Judith Rapoport and coworkers (2012) reveal that between the ages of 13 and 18, children who developed schizophrenia showed a remarkable loss of gray matter in the cerebral cortex (Figure 16-2). An earlier study by the same group found changes in the quantity of growth factors that influence brain development and a delayed growth rate in white matter—on the order of 2 percent per year—in children with schizophrenia compared with healthy children (Gogtay et al., 2008).

Abnormalities found throughout the brain vary by functional region and correlate with the onset of behavioral disturbances characteristic of schizophrenia. Not all disorders show such obvious loss of tissue but may show abnormal blood flow or metabolism that can be detected by either fMRI or PET. The PET images in Figure 16-3 illustrate metabolic changes in adult-onset schizophrenia. The scan on the left reveals an obvious abnormality in prefrontal cortex activity compared with the scan on the right, from an adult who does not have schizophrenia. Note that the prefrontal area does not show loss of gray matter in the MRI study of early-onset schizophrenia reproduced in Figure 16-2. Therefore, it is likely that the two diseases have different origins.

Combining behavioral diagnoses with genetic analysis and neuroimaging will move practitioners beyond symptom checklists to objective medical diagnoses. Imaging analyses will help target treatments to reduce the severity of such serious disorders as schizophrenia and Alzheimer disease. Current imaging techniques do not detect all brain pathology. It is not whether a gene is present or absent but whether that gene is or is not expressed that is relevant to its effects. The challenge lies in improving current techniques and in developing others that can identify subtler nervous system abnormalities.

Classification systems such as taxonomy, the branch of biology that groups organisms according to their common characteristics and relationships, have advanced our knowledge of brain structure and function. Likewise, classifications of behavioral disorders produced by the behavioral sciences have advanced understanding. Yet classification systems have their critics. One criticism is that “just because you name a disorder does not mean it exists.” Another is that changing societal views result in the inclusion or exclusion of disorders, as with sexual relationships other than heterosexuality.

Naming disorders becomes problematic as well. The term idiot once designated a person with a low IQ score. When the term became pejorative, it was replaced with the term retarded. That term then became pejorative, and the DSM-5 now uses the term intellectual disability. Nevertheless, just as genetics has clarified taxonomic relationships among animals, our growing understanding of brain function and genetics likely will clarify the taxonomy of behavioral disorders. The NIMH’s Research Domain Criteria project, for example, is one response to criticisms of broad behavioral classifications such as those used in the DSM-5.

An inclusive list of brain and behavioral disorders would number in the thousands, including, on the organic side, genetic and developmental disorders, infectious diseases, nervous system injuries, and degenerative dementias. Behavioral disorders would include PTSD among the anxiety-related disorders. Abnormalities may also appear via imbalances in biochemical organization or nervous system operation. Biochemical abnormalities include disordered proteins in cell membrane channels, low or high neuroreceptor numbers, and low or high numbers of molecules, especially neurotransmitters or hormones. Each disorder may be associated with various structural changes, congenital abnormality of neurons or glia, and neuronal death.

The ultimate goal for behavioral neuroscientists lies in applying their knowledge to generate treatments that can restore a disordered brain to a range of healthy functioning. This goal is daunting because the first task is so difficult: learning what causes a particular behavioral disturbance. Few behavioral disorders have a cause as simple as PKU does. Most, like schizophrenia, are complex. A more achievable goal is to make small advances by improving current treatments, to develop new treatments, and to analyze disease causes. Available treatments, while extensive, fall into four general categories:

Neurosurgical Treatments

Neurosurgical manipulation of the nervous system is largely reparative, as when tumors are removed or arteriovenous (AV) malformations corrected. Typically, such neurosurgical interventions are successful. Advances include improved imaging of a target for surgery—as the surgery takes place—and methods that allow diseased tissue to be destroyed without opening the skull. For example, radiosurgery uses energy, such as X-rays directed from different sources to converge on a target and destroy abnormal cells. The x-rays lack the energy to damage healthy cells through which they pass: tissue is destroyed only where multiple beams converge.

Treatment for Parkinson disease entails inactivating brain regions that produce tremors and regions participating in the production of muscular rigidity that impairs movement. An electrode is placed in the motor thalamus and an electric current used to damage neurons responsible for producing the unwanted effects. Alternatively, in deep brain stimulation (DBS), an electrode fixed in place in the globus pallidus or subthalamic nucleus is connected to an external electrical stimulator that the patient can activate (Figure 16-4). The stimulation can inactivate cells responsible for unwanted effects and so restore more normal movement (Knight et al., 2015).

DBS is also used experimentally to treat traumatic brain injury (TBI) and behavioral dysfunctions such as obsessive-compulsive disorder (OCD) and major depression (Cleary et al., 2015). Electrodes implanted in the brain are well tolerated and remain effective for several years. Electrical stimulation can have an activating effect and so relieve depression or compulsive behaviors. Stimulation may also make brain tissue more plastic and receptive to other treatments. During stimulation, patients can learn more effective thought and behavioral patterns. For many conditions, DBS remains an experimental option of last resort. It is not a permanent cure: when the stimulation stops, beneficial effects are reduced; hence the importance of coupling DBS with cognitive-behavioral therapy.

Another highly experimental neurosurgical strategy draws on the fixed sequence of prenatal brain development from cell division and cell differentiation to cell migration and synaptogenesis. If a brain region is functioning abnormally or if it is diseased or dead, as occurs in TBI or after a stroke, it should be possible to return this region to the embryonic state and regrow a healthy region. The use of so-called induced neurogenesis has a science fiction ring but may someday be feasible. In laboratory rats, for example, stem cells can be induced by neurotrophic factors to generate new cells that can migrate to the site of an injury.

In the 1980s, neurosurgeons experimented with implanting fetal stem cells in adult brains. Success was limited due to difficulties in cell placement and connections and rejection by the patient’s immune system. Another restorative idea comes from the discovery that multipotent stem cells in other body regions, such as bone marrow and skin, appear capable of manufacturing neural stem cells. Indeed, using appropriate manipulations, any cell can potentially be returned to a stem cell state. The advantage is that the patient’s own cells are not rejected by the immune system.

If people’s own multipotent stem cells prove practical for generating neural stem cells, it should be possible to extract stem cells, place them in a special culture medium to generate thousands or millions of cells, and place these stem cells in the damaged brain. The cells would be instructed to differentiate appropriately and develop the correct connections. Stem cell transplantation is taken seriously today as a potential treatment for disorders such as TBI and stroke, but it remains largely at an investigative stage (Savitz, 2015).

Electrophysiological Treatments

Treating the mind by treating the body is an ancient notion. In the 1930s, researchers used insulin to lower blood sugar and produce seizures as a treatment for depression. By the 1950s, insulin therapy had been replaced by electroconvulsive therapy (ECT), the first electrical brain stimulation treatment.

ECT was developed as a treatment for otherwise untreatable depression, and although its mode of action was not understood, it did prove useful. Although rarely used today, ECT sometimes remains the only treatment that works for people with severe depression. One reason may be that it stimulates the production of a variety of neurotrophic factors, especially BDNF (brain-derived neurotrophic factor), that in turn restore inactive cells to a more active mode.

Problems with ECT include the massive convulsions electrical stimulation causes. Large doses of medication are normally required to prevent them. ECT also leads to memory loss, a symptom that can be troublesome with repeated treatments. A noninvasive technique, transcranial magnetic stimulation (TMS), uses magnetic rather than electrical stimulation. Magnetic stimulation can be applied to a localized brain region. Anesthesia is not necessary. TMS is an FDA-approved treatment for depression. Clinical applications, reviewed in Research Focus 16-2, Treating Behavioral Disorders with Transcranial Magnetic Stimulation, are growing.

Pharmacological Treatments

Several accidental discoveries, beginning in the 1950s, led to a pharmacological revolution in the treatment of behavioral disorders:

The power of psychoactive drugs to change disordered behavior revolutionized the pharmaceutical industry. The central goal is developing drugs that can act as magic bullets to correct the chemical imbalances found in various disorders. Research is directed toward making drugs more selective in targeting specific disorders while producing fewer side effects. Both goals have proved difficult to achieve.

Pharmacological treatments have significant downsides. Acute and chronic side effects top the list, and long-term use may cause new problems. Consider a person who receives antidepressant medication. The drug may ease the depression but it may also produce unwanted side effects, including decreased sexual desire, fatigue, and sleep disturbance. The last two effects may also interfere with cognitive functioning.

Thus, although a medication may be useful for getting a person out of a depressed state, it may produce other symptoms that are themselves disturbing and may complicate recovery. Furthermore, in depression related to a person’s life events, a drug does not provide the behavioral tools needed to cope with an adverse situation. Some psychologists say, “A pill is not a skill.”

Negative side effects of drug treatments are evident in many people whose schizophrenia is being treated with neuroleptics. Antipsychotic drugs act on the mesolimbic dopamine system, which affects motivation, among other functions. The side effect emerges because the drugs also act on the nigrostriatal dopaminergic system, which controls movement. Patients who take neuroleptics also eventually develop motor disturbances. Tardive dyskinesia, an inability to stop the tongue, hands, or other body parts from moving, is a motor symptom of long-term neuroleptic administration. Side effects of movement disorders can persist after the psychoactive medication has been stopped. Taking drugs for behavioral disorders, then, does carry risk. Rather than magic bullets, these medications often act like shotguns.

Despite their drawbacks, drugs do prove beneficial for many people. Improved drug chemistry will reduce side effects, as will improved delivery modes that bring a drug to a target system with minimal effects on other systems. One improved delivery system uses nanoparticles called liposomes, biosynthetic molecules 1 to 100 nm (nanometers, or billionths of a meter) in size. One natural biological nanoparticle, with a radius of about 40 nm, is the synaptic vesicle that houses a neurotransmitter for delivery into the cell’s extracellular space. Liposomes consisting of a synthetic vesicle with a homing peptide on the surface can, in principle, be constructed to carry a drug across the blood–brain barrier and deliver it to specified types of neuron or glial cells within the nervous system.

Behavioral Treatments

Treatments for behavioral disorders need not be direct biological or medical interventions. Just as the brain can alter behavior, behavior can alter the brain. Behavioral treatments focus on key environmental factors that influence how a person acts. As behavior changes in response to treatment, the brain is affected as well.

An example is treatment for generalized anxiety disorders attributed to chronic stress. People who endure a persistently high anxiety level often engage in maladaptive behaviors to reduce it. While they require immediate treatment with antianxiety medication, long-term treatment entails changing their behavior. Generalized anxiety disorder is not simply a problem of abnormal brain activity but also of experiential and social factors that fundamentally alter the person’s perception of the world.

Perhaps you are thinking that behavioral treatments may help somewhat in treating brain dysfunction, but the real solution must lie in altering brain activity. Since every aspect of behavior is the product of brain activity, behavioral treatments do act by changing brain function. If people can change how they think and feel about themselves or some aspect of their lives, this change has taken place because talking about their problems or resolving a problem alters how their brain functions. In a sense then, a behavioral treatment is a biological intervention. Behavioral treatments may sometimes be helped along by drug treatments that make the brain more receptive to change through behavioral therapy. In this way, drug treatments and behavioral treatments have synergistic effects, each helping the other to be more effective.

Your behavior is a product of all your learning and social experiences. An obvious approach to developing a treatment is to re-create a learning environment that replaces a maladaptive behavior with an adaptive behavior. Thus, the various approaches to behavioral treatment use principles derived from experiment-based learning theory. Following is a sampling of these approaches.

BEHAVIOR MODIFICATION Behavioral therapies apply well-established learning principles to eliminate unwanted behaviors. Therapists apply principles developed in studying learning by reinforcement in laboratory settings, including operant and classical conditioning. For example, if a person is debilitated by a fear of insects, rather than looking for inner causes, the behavioral therapist tries to replace the maladaptive behaviors with more constructive ways of behaving. These might include training the patient to relax while systematically exposing him to unthreatening insects (butterflies) followed by gradual exposure to more threatening insects (bees). This form of habituation (adaption to a repeatedly presented stimulus) is called systematic desensitization.

COGNITIVE THERAPY Cognitive therapy operates from the perspective that thoughts intervene between events and emotions. Consider responses to losing a job. One thought could be, I’m a loser, life is hopeless. An alternative thought is, The job was a dead end. The boss did me a favor. The former cognition might lead to depression, whereas the latter would not. Cognitive therapies challenge a person’s self-defeating attitudes and assumptions and are important for people with brain injury too, because it is easy for people to think that they are crazy or stupid after brain injury. Equally if not more powerful is cognitive-behavioral therapy, discussed in Section 16-4.

NEUROPSYCHOLOGICAL THERAPY If a relative or friend had a stroke and became aphasic, you would expect him or her to attend speech therapy—a behavioral treatment for an injured brain. The logic in speech therapy is that by practicing (relearning) the basic components of speech and language, the patient should be able to regain at least some lost function. The same logic can apply to other types of behavioral disorders, whether motor or cognitive.

Therapies for cognitive disorders resulting from brain trauma or dysfunction aim to retrain people in the fundamental cognitive processes they have lost. Although cognitive therapy seems as logical as speech therapy after a stroke, cognitive therapy assumes that we know what fundamental elements of cognitive activity are meaningful to the brain. Cognitive scientists are far from understanding these elements well enough to generate optimal therapies. Still, neuropsychologists are developing neurocognitive programs that can improve functional outcomes following TBI and stroke (Mateer & Sira, 2006; Sohlberg & Mateer, 1989). Treatment effectiveness can be improved with computer-based tools and follow-up therapy.

EMOTIONAL THERAPY In the 1920s, Sigmund Freud developed the idea that talking about emotional problems enables people to gain insights into the causes of the problems and serves as treatment too. Talk cures and other forms of psychological intervention may be broadly categorized as psychotherapies.

Since Freud’s time, many ideas have been put forth about the best type of therapy for emotional disorders. Key here is that for many disorders, whether neurological or psychiatric, medical treatments are not effective unless patients also receive psychotherapy. Indeed, the only effective treatment in many cases lies in addressing the unwanted behaviors directly—in acquiring the skill rather than taking the pill.

Consider a 25-year-old woman pursuing a promising career as a musician who suffered a traumatic brain injury in an automobile accident. After the accident, she found that she was unable to read music. Not surprisingly, she soon became depressed. Part of her therapy required her to confront her disabling cognitive loss by talking about it rather than by simply stewing over it. Only when she pursued psychotherapy did she begin to recover from her intense depression.

For many people with emotional impairments resulting from brain disease or trauma, the most effective treatment for depression or anxiety is helping them adjust by encouraging them to talk about their difficulties. Group therapy provides such encouragement and is standard treatment in brain injury rehabilitation units.

PHYSICAL ACTIVITY AND MUSIC AS THERAPY Exercise and music have positive effects on peoples’ attitudes, emotional well-being, and brain function. Physical exercise demands visual control of movement. Music affects arousal and activates the motor and premotor cortex. Listening to music can improve gait in Parkinson and stroke patients and reduce pain post surgery. Learning to play a musical instrument likewise is beneficial therapy (François et al., 2015). Singing, a useful adjunct to rehabilitative speech therapy, enhances the ability to enunciate. Physical activity, including dancing and playing sports, combined with other therapies, improves well-being and counteracts the effects of depression.

REAL-TIME FMRI Using this behavior-modification technique, individuals learn to change their behavior by controlling their own brain activation patterns. Real-time fMRI was first used to treat intractable pain, which produces a characteristic brain activity pattern (deCharms, 2008). The researchers proposed that if subjects could see their brain activity via fMRI in real time as they felt pain, they could be trained to reduce the neural activity and lessen their pain. Real-time fMRI (rt-fMRI) uses a form of operant conditioning in which the gradual modification of a participant’s behavior increases the probability of reward.

Think of rt-fMRI as a form of neural plasticity in which the individual learns new strategies, guided by brain activation information. When subjects decrease brain activation in regions associated with pain, they report decreased pain perception. Conversely, through learning to increase brain activation in these regions, they would be able to increase their pain—although it seems unlikely that this ability would be much cultivated! An actual potential application of rt-fMRI is in monitoring brain activation when treatment for disorders occurs in the context of behavioral therapy. Patients need not be consciously aware of the therapy’s objectives: induced brain changes, whether conscious or unconscious, can prove beneficial (Birbaumer et al., 2013).

VIRTUAL REALITY THERAPY The principle behind VR therapy is that patients enter or interact with a virtual world displayed on a computer screen or through goggles. One example is the Virtual Iraq and Afghanistan Simulation described in Research Focus 16-1. The participant can experience sights, sounds, even smells that mimic situations related to acquiring the behavioral disorder, in this case PTSD. In modified VR therapy a patient interacts as a character in a computer game. Winning the game necessitates making adaptive choices; maladaptive choices result in losing the game (Shin et al., 2015).

Classifying and Treating Brain and Behavioral Disorders

Before you continue, check your understanding.

Question 1

Question 2

Question 3

Question 4

Question 5

Question 6

Question 7

Answers appear in the Self Test section of the book.