Can someone help with a powerpoint

blteeyesv8041n

biopsychology_8e_ch05.pdf

Home >Psychology homework help >Can someone help with a powerpoint

The Research Methods

of Biopsychology Understanding What Biopsychologists Do

PART ONE Methods of Studying the

Nervous System

5.1 Methods of Visualizing and Stimulating

the Living Human Brain

5.2 Recording Human Psychophysiological

Activity

5.3 Invasive Physiological Research Methods

5.4 Pharmacological Research Methods

5.5 Genetic Engineering

PART TWO Behavioral Research Methods

of Biopsychology

5.6 Neuropsychological Testing

5.7 Behavioral Methods of Cognitive Neuroscience

5.8 Biopsychological Paradigms of Animal Behavior

5 IS

B N

0- 55

8- 78

57 1-

Of course, he was upset that his brain had deteriorated so badly, but he sensed that his neurosurgeon was secretly pleased: “We won’t have to try to save the nerve; we’ll just cut it.”

There was one last test. The skin of his right cheek was lightly pricked while the EEG responses of his somatosen- sory cortex were recorded from his scalp. “This is just to establish a baseline for the surgery,” it was explained. “One main risk of removing tumors on the auditory- vestibular cranial nerve (VIII) is damaging the facial cra- nial nerve (VII), and that would make the right side of your face sag. So during the surgery, electrodes will be in- serted in your cheek, and your cheek will be repeatedly stimulated with tiny electrical pulses. The cortical re- sponses will be recorded and fed into a loudspeaker so that the surgeon can immediately hear changes in the ac- tivity if his scalpel starts to stray into the area.”

As Professor P. was driving home, his mind wandered from his own plight to his day at the hospital. “Quite in- teresting,” he thought to himself. There were biopsychol- ogists everywhere, doing biopsychological things. In all three labs he had visited, there were people who began their training as biopsychologists.

Two weeks later, Professor P. was rolled into the prepa- ration room. “Sorry to do this, Professor P., you were one of my favorite instructors,” the nurse said, as she inserted a large needle into Professor P.’s face and left it there.

Professor P. didn’t mind; he was barely conscious. He did not know that he wouldn’t regain consciousness for several days—at which point he would be incapable of talking, eating, or even breathing.

Don’t forget Professor P.; you will learn more about his case in Chapter 10. For now, this case has demonstrated to you that many of the research methods of biopsychology are also used in clinical settings (see Matthews, Honey, & Bullmore, 2006). Let’s move on to the methods themselves.

PART ONE

METHODS OF STUDYING THE NERVOUS SYSTEM

5.1 Methods of Visualizing and Stimulating the Living Human Brain

Prior to the early 1970s, biopsychological research was impeded by the inability to obtain images of the organ of primary interest: the living human brain. Conventional

C hapters 1 and 2 introduced you to the general inter- ests, ideas, and approaches that characterize biopsychology. In Chapters 3 and 4, your introduc-

tion to biopsychology was temporarily curtailed while background material in neuroanatomy, neurophysiology, and neurochemistry was presented. This chapter gets down to the nitty-gritty of biopsychology; it describes the specific day-to-day activities of the biopsychology labora- tory. It is intended to prepare you for later chapters and to sharpen your understanding of biopsychology by describ- ing how biopsychologists do their research.

The organization of this chapter reflects biopsychol- ogy’s intrinsic duality. The chapter has two major parts: One deals with methods of studying the nervous system, and the other deals with methods of studying behavior.

As you read through this chapter, you should keep in mind that most of the methods that are used to study the human brain are also used for clinical purposes, for either diagnosis or treatment. The case of Professor P. makes this point.

The Ironic Case of Professor P.

Two weeks before his brain surgery, Professor P. reported to the hospital for a series of tests. What amazed Professor P. most about these tests was how familiar they seemed. No,

Professor P. was not a psychic; he was a behavioral neuroscientist, and he was struck by how similar the tests performed

on him were to the tests he had seen in his department. Professor P. had a brain tumor on his right auditory-

vestibular cranial nerve (cranial nerve VIII; see Appen- dices III and IV), and he had to have it excised (cut out). First, Professor P.’s auditory abilities were assessed by measuring his ability to detect sounds of various volumes and pitches and then by measuring the magnitude of the EEG signals evoked in his auditory cortex by clicks in his right ear.

Next, Professor P.’s vestibular function (balance) was tested by injecting cold water into his ear.

“Do you feel anything, Professor P.?” “Well, a cold ear.” “Nothing else?” “No.” So colder and colder water was tried with no effect until

the final, coldest test was conducted. “Ah, that feels weird,” said Professor P. “It’s kind of like the bed is tipping.”

The results of the tests were bad, or good, depending on your perspective. Professor P.’s hearing in his right ear was poor, and his right vestibular nerve was barely functioning. “At the temperatures we flushed down there, most people would have been on their hands and knees puking their guts out,” said the medical technician. Professor P. smiled at the technical terminology.

102 Chapter 5 ■ The Research Methods of Biopsychology

Clinical Clinical Implications Implications

IS B

N 0-558-78571-9

One contrast X-ray technique, cerebral angiography, uses the infusion of a radio-opaque dye into a cerebral artery to visualize the cerebral circulatory system during X-ray photography (see Figure 5.1). Cerebral angiograms are most useful for

localizing vascu- lar damage, but the displacement of blood vessels from their normal position also can indicate the loca- tion of a tumor.

X-Ray Computed Tomography

In the early 1970s, the study of the living human brain was revolution- ized by the introduction of com- puted tomography. Computed tomography (CT) is a computer- assisted X-ray procedure that can be used to visualize the brain and other internal structures of the living body. During cerebral computed tomography, the neurological pa- tient lies with his or her head posi- tioned in the center of a large cylinder, as depicted in Figure 5.2.

1035.1 ■ Methods of Visualizing and Stimulating the Living Human Brain

X-ray photography is next to useless for this purpose. When an X-ray photograph is taken, an X-ray beam is passed through an object and then onto a photographic

plate. Each of the molecules through which the beam passes absorbs some of the radiation; thus, only the un-

absorbed portions of the beam reach the photographic plate. X-ray photography is therefore effective in charac- terizing internal structures that differ substantially from their surroundings in the degree to which they absorb X-rays—for example, a revolver in a suitcase full of clothes or a bone in flesh. However, by the time an X-ray beam has passed through the numerous overlapping structures of the brain, which differ only slightly from one another in their ability to absorb X-rays, it carries little information about the structures through which it has passed.

Contrast X-Rays

Although conventional X-ray photography is not useful for visualizing the brain, contrast X-ray techniques are. Contrast X-ray techniques involve injecting into one com- partment of the body a substance that absorbs X-rays either less than or more than the surrounding tissue. The injected substance then heightens the contrast between the compart- ment and the surrounding tissue during X-ray photography.

X-ray source X-ray detector Horizontal CT scans

Three-dimensional reconstruction

FIGURE 5.2 Computed tomogra- phy (CT) uses X-rays to create a CT scan of the brain.

FIGURE 5.1 A cerebral angiogram of a healthy subject.

Clinical Clinical Implications Implications

Watch Brain Imaging www.mypsychlab.com

IS B

N 0-

55 8-

78 57

1- 9

104 Chapter 5 ■ The Research Methods of Biopsychology

On one side of the cylinder is an X-ray tube that projects an X-ray beam through the head to an X-ray detector mounted on the other side. The X-ray tube and detector automatically rotate around the head of the patient at one level of the brain, taking many individual X-ray photographs as they rotate. The meager information in each X-ray photograph is combined by a computer to generate a CT scan of one horizontal sec- tion of the brain. Then, the X-ray tube and detector are moved along the axis of the patient’s body to another level of the brain, and the process is repeated. Scans of eight or nine horizontal brain sections are typically obtained from a pa- tient; combined, they provide a three-dimensional represen- tation of the brain.

Magnetic Resonance Imaging

The success of computed tomography stimulated the de- velopment of other techniques for obtaining images of the inside of the living body. Among these techniques is magnetic resonance imaging (MRI)—a procedure in which high-resolution images are constructed from the measurement of waves that hydrogen atoms emit when they are activated by radio-frequency waves in a magnetic field. MRI provides clearer images of the brain than does CT. A color-coded two-dimensional MRI scan of the mid- sagittal brain is presented in Figure 5.3.

In addition to providing relatively high spatial resolu- tion (the ability to detect and represent differences in spatial location), MRI can produce images in three dimen-

sions. Figure 5.4 is a three-dimensional MRI scan. Figure 5.5 shows two-dimen- sional MRI scans of a patient with a grow- ing tumor.

Positron Emission Tomography

Positron emission tomography (PET) was the first brain- imaging technique to provide images of brain activity (functional brain images) rather than images of brain struc- ture (structural brain images). In one common version of PET, radioactive 2-deoxyglucose (2-DG) is injected into the patient’s carotid artery (an artery of the neck that feeds the ipsilateral cerebral hemisphere). Because of its simi- larity to glucose, the primary metabolic fuel of the brain, 2-deoxyglucose is rapidly taken up by active (energy- consuming) cells. However, unlike glucose, 2-deoxyglucose cannot be metabolized; it therefore accumulates in active neurons—or in associated astrocytes (Barros, Porras, & Bittner, 2005)—until it is gradually broken down. Each PET scan is an image of the levels of radioactivity (indicated by color coding) in various parts of one horizontal level of the brain. Thus, if a PET scan is taken of a patient who engages in an activity such as reading for about 30 seconds after the 2-DG injection, the resulting scan will indicate the areas at that brain level that were most active during the 30 seconds of activity (see Figure 5.6).

Notice from Figure 5.6 that PET scans are not really images of the brain. Each PET scan is merely a colored map of the amount of radioactivity in each of the tiny

FIGURE 5.3 A color-enhanced midsagittal MRI scan.

FIGURE 5.4 Structural MRI can be used to provide three- dimensional images of the entire brain. (Courtesy of Bruce Foster and Robert Hare, University of British Columbia.)

Clinical Clinical Implications Implications

IS B

N 0-558-78571-9

cubic voxels (volume pixels) that compose the scan. Ex- actly how each voxel maps onto a particular brain struc- ture can be estimated only by superimposing the scan on a brain image.

Functional MRI

MRI technology has been used to produce functional im- ages of the brain. Indeed, functional MRI has become the most influential tool of cognitive neuroscience (Poldrack, 2008) and is now widely used for medical diagnosis (Holdsworth & Bammer, 2008).

Functional MRI (fMRI) produce images representing the increase in oxygen flow in the blood to active areas of the brain. Functional MRI is possible because of two at- tributes of oxygenated blood (see Raichle & Mintun, 2006). First, active areas of the brain take up more oxy- genated blood than they need for their energy require- ments, and thus oxygenated blood accumulates in active areas of the brain. Second, oxygenated blood has mag- netic properties (oxygen influences the effect of magnetic fields on iron in the blood). The signal recorded by fMRI is called the BOLD signal (the blood-oxygen-level- dependent signal).

Functional MRI has four advantages over PET: (1) Nothing has to be injected into the subject; (2) it provides both structural and functional information in the same image; (3) its spatial resolution is better; and (4) it can be used to produce three-dimensional images of activity over the entire brain. Functional MRIs are shown in Figure 5.7.

1055.1 ■ Methods of Visualizing and Stimulating the Living Human Brain

Tumor shortly after radiotherapy

Same tumor several weeks later

FIGURE 5.5 Structural MRI can also be used to provide two-dimensional images of brain slices. The MRI scan on the left shows a tumor shortly after radiotherapy, and the MRI scan on the right shows the same tumor several weeks later—clearly, the tumor has continued to grow. Ventricles are outlined in yellow; the tumor is outlined in red. (Based on Calmon et al., 1998; courtesy of Neil Roberts, University of Liverpool.)

FIGURE 5.6 A series of PET scans. Each scan is a horizontal section recorded during a different cognitive or perceptual task. Areas of high activity are indicated by reds and yellows. For example, notice the high level of activity in the visual cortex of the occipital lobe when the subject scanned a visual display. (From “Positron Tomography: Human Brain Function and Biochemistry” by Michael E. Phelps and John C. Mazziotta, Science, 228 [9701], May 17, 1985, p. 804. Copyright 1985 by the AAAS. Reprinted by permission. Courtesy of Drs. Michael E. Phelps and John Mazziotta, UCLA School of Medicine.)

IS B

N 0-

55 8-

78 57

1- 9

It is important not to be unduly swayed by the impres- siveness of fMRI images and technology. The images are often presented—particularly in the popular press or gen- eral textbooks—as if they are pictures of human neural activity. They aren’t: They are images of the BOLD signal, and the relation between the BOLD signal and neural activity is proving to be complex and variable (see Bar- tels, Logothetis, & Moutoussis, 2008; Ekstrom et al., 2009; Goense & Logothetis, 2008; Shmuel & Leopold, 2009; Zhang et al., 2009). Furthermore, fMRI technol- ogy is too slow to capture many neural responses—it takes 2 or 3 seconds to create an fMRI image, and many

neural responses, such as action potentials, occur in mil- liseconds (see Dobbs, 2005; Poldrack, 2008).

Magnetoencephalography

Another technique that is used to monitor the brain ac- tivity of human subjects is magnetoencephalography (MEG). MEG measures changes in magnetic fields on the surface of the scalp that are produced by changes in un- derlying patterns of neural activity. Its major advantage over fMRI is its temporal resolution; it can record fast changes in neural activity.

106 Chapter 5 ■ The Research Methods of Biopsychology

FIGURE 5.7 Functional magnetic resonance images (fMRIs). These images illustrate the areas of cortex that became more active when the subjects observed strings of letters and were asked to specify which strings were words; in the control condition, subjects viewed strings of asterisks (Kiehl et al., 1999). Thesis fMRIs illustrate surface activity; but images of sections through the brain can also be displayed. (Courtesy of Kent Kiehl and Peter Liddle, Department of Psychiatry, University of British Columbia.)

IS B

N 0-558-78571-9

Transcranial Magnetic Stimulation

PET, fMRI, and magnetoencephalography have allowed cognitive neuroscientists to create images of the activity of the human brain. But these methods all have the same weakness: They can be used to show a correlation between brain activity and cognitive activity, but they can’t prove that the brain activity caused the cognitive activity (Ror- den & Karnath, 2004; Sack, 2006). For example, a brain- imaging technique may show that the cingulate cortex becomes active when subjects view disturbing photo- graphs, but it can’t prove that the cingulate activity causes the emotional experience—there are many other explana- tions. One way of supporting the hypothesis that the cin- gulate cortex is an area for emotional experience would be to assess emotional experience in people lacking a func- tional cingulate cortex—for example, by studying patients with cingulate damage or studying healthy patients whose cingulate cortex has somehow been “turned off.” Transcra- nial magnetic stimulation is a way of accomplishing this.

Transcranial magnetic stimulation (TMS) is a tech- nique for affecting the activity in an area of the cortex by creating a magnetic field under a coil positioned next to the skull (see Fitzpatrick & Rothman, 2000; Pascual- Leone, Walsh, & Rothwell, 2000). In effect, the magnetic stimulation temporarily turns off part of the brain while the effects of the disruption on cognition and behavior are assessed. Although there are still fundamental ques- tions about safety, depth of effect, and mechanisms of neural disruption (see Allen et al., 2007; Bestmann, 2007; Wagner, Valero-Cabre, & Pascual-Leone, 2007), TMS is often employed to circumvent the difficulty that brain- imaging studies have in determining causation.

5.2 Recording Human Psychophysiological Activity

The preceding section introduced you to functional brain imaging, the cornerstone of cognitive neuroscience re- search. This section deals with psychophysiological recording methods (methods of recording physiological activity from the surface of the human body). Five of the most widely studied psychophysiological measures are described: one measure of brain activity (the scalp EEG), two measures of somatic nervous system activity (muscle tension and eye movement), and two measures of autonomic nervous sys- tem activity (skin conductance and cardiovascular activity).

Scalp Electroencephalography

The electroencephalogram (EEG) is a measure of the gross electrical activity of the brain. It is recorded through large electrodes by a device called an electroencephalograph (EEG machine), and the technique is called electroen- cephalography. In EEG studies of human subjects, each

channel of EEG activity is usually recorded from disk- shaped electrodes, about half the size of a dime, which are taped to the scalp.

The scalp EEG signal re- flects the sum of electrical events throughout the head. These events include action potentials and postsynaptic potentials, as well as electrical signals from the skin, muscles, blood, and eyes. Thus, the utility of the scalp EEG does not lie in its ability to provide an unclouded view of neural activity. Its value as a research and diagnostic tool rests on the fact that some EEG wave forms are associated with particular states of consciousness or particular types of cerebral pathology (e.g., epilepsy). For example, alpha waves are regular, 8- to 12-per-sec- ond, high-amplitude waves that are associated with relaxed wakefulness. A few examples of EEG wave forms and their psychological correlates are presented in Figure 5.8.

Because EEG signals decrease in amplitude as they spread from their source, a comparison of signals recorded from various sites on the scalp can sometimes indicate the origin of particular waves. This is why it is usual to record EEG activity from many sites simultaneously.

Psychophysiologists are often more interested in the EEG waves that accompany certain psychological events than they are in the background EEG signal. These ac- companying EEG waves are generally referred to as event- related potentials (ERPs). One commonly studied type of event-related potential is the sensory evoked potential—the change in the cortical EEG signal that is elicited by the momentary presentation of a sensory

1075.2 ■ Recording Human Psychophysiological Activity

1 second

Deep sleep

Asleep

Relaxed

Aroused

Alpha waves

FIGURE 5.8 Some typical electroencephalograms and their psy- chological correlates.

Watch Visit to a Cognitive Neuroscience Laboratory www.mypsychlab.com

IS B

N 0-

55 8-

78 57

1- 9

stimulus. As Figure 5.9 illustrates, the cortical EEG that follows a sensory stimulus has two compo- nents: the response to the stimulus (the signal) and the ongoing back- ground EEG activity (the noise). The signal is the part of any recording that is of interest; the noise is the part that isn’t. The problem in recording sensory evoked potentials is that the noise of the background EEG is often so great that the sensory evoked po- tential is masked. Measuring a sensory evoked potential can be like detecting a whisper at a rock concert.

A method used to reduce the noise of the background EEG is signal averaging. First, a subject’s response to a stimulus, such as a click, is recorded many—let’s say 1,000—times. Then, a computer identifies the millivolt value of each of the 1,000 traces at its starting point (i.e., at the click) and calculates the mean of these 1,000 scores. Next, it considers the value of each of the 1,000 traces 1 millisec- ond (msec) from its start, for example, and calculates the mean of these values. It repeats this process at the 2-msec mark, the 3-msec mark, and so on. When these averages are plotted, the average response evoked by the click is more apparent, because the random background EEG is canceled out by the averaging. See Figure 5.9, which illus- trates the averaging of an auditory evoked potential.

The analysis of average evoked potentials (AEPs) fo- cuses on the various waves in the averaged signal. Each wave is characterized by its direction, positive or nega- tive, and by its latency. For example, the P300 wave illus- trated in Figure 5.10 is the positive wave that occurs about 300 milliseconds after a momentary stimulus that has meaning for the subject (e.g., a stimulus to which the subject must respond)—see Friedman, Cycowicz, and Gaeta (2001). In contrast, the portions of an evoked potential recorded in the first few milliseconds after a stimulus are not influenced by the meaning of the stim- ulus for the subject. These small waves are called far- field potentials because, although they are recorded from the scalp, they originate far away in the sensory nu- clei of the brain stem.

Although electroencephalography scores high on tem- poral resolution, it initially failed miserably on spatial resolution. With conventional electroencephalographic procedures, one can only roughly estimate the source of a particular signal. However, newer techniques employing

108 Chapter 5 ■ The Research Methods of Biopsychology

Average background EEG

Average evoked potential Click

1-second segments of background EEG

1-second segments of EEG with evoked potential

FIGURE 5.9 The averaging of an auditory evoked potential. Averaging increases the signal-to-noise ratio.

Time (milliseconds)

Meaningful click 200 400 600

Far-field potentials

P300

FIGURE 5.10 An average auditory evoked potential. Notice the P300 wave. This wave occurs only if the stimulus has meaning for the subject; in this case, the click signals the imminent deliv- ery of a reward. By convention, positive EEG waves are always shown as downward deflections.

IS B

N 0-558-78571-9

sophisticated computer software and many electrodes can accurately locate the source of signals. The spatial resolu- tion of these techniques is sufficient to enable the amplitude of evoked EEG signals recorded on the cortex to be color- coded and plotted on the surface of a three-dimensional MRI scan (Gevins et al., 1995). This useful marriage of tech- niques is illustrated in Figure 5.11.

Muscle Tension

Each skeletal muscle is composed of millions of threadlike muscle fibers. Each muscle fiber contracts in an all-or- none fashion when activated by the motor neuron that in- nervates it. At any given time, a few fibers in each resting muscle are likely to be contracting, thus maintaining the overall tone (tension) of the muscle. Movement results when a large number of fibers contract at the same time.

In everyday language, anxious people are commonly referred to as “tense.” This usage acknowledges the fact that anxious, or otherwise aroused, individuals typically

display high resting levels of tension in their muscles. This is why psychophysiologists are interested in this measure; they use it as an indicator of psychological arousal.

Electromyography is the usual procedure for measur- ing muscle tension. The resulting record is called an electromyogram (EMG). EMG activity is usually recorded between two electrodes taped to the surface of the skin over the muscle of interest. An EMG record is presented in Figure 5.12. You will notice from this figure that the main correlate of an increase in muscle contraction is an increase in the amplitude of the raw EMG signal, which reflects the number of muscle fibers contracting at any one time.

Most psychophysiologists do not work with raw EMG signals; they convert them to a more workable form. The raw signal is fed into a computer that calculates the total amount of EMG spiking per unit of time—in consecutive 0.1-second intervals, for example. The integrated signal (i.e., the total EMG activity per unit of time) is then plot- ted. The result is a smooth curve, the amplitude of which is a simple, continuous measure of the level of muscle tension (see Figure 5.12).

Eye Movement

The electrophysiological technique for recording eye move- ments is called electrooculography, and the resulting record is called an electrooculogram (EOG). Electrooculography is

1095.2 ■ Recording Human Psychophysiological Activity

FIGURE 5.11 The marriage of electroencephalography and magnetic resonance imaging: The distribution of EEG signals can be represented on a structural cerebral MRI. Plotted in this illustration is the distribution of theta waves recorded while the subjects worked on a memory task. The highest incidence of theta waves (indicated by red in the three-dimensional MRI of the dorsal brain surface and by blue on the midsagittal section) occurred in the anterior cingulate cortex. (Courtesy of Alan Gevins, EEG Systems Laboratory & SAM Technology, San Francisco.)

FIGURE 5.12 The relation between a raw EMG signal and its integrated version. The subject tensed the muscle beneath the electrodes and then gradually relaxed it.

Integrated EMG signal

Raw EMG signal

IS B

N 0-

55 8-

78 57

1- 9

modern psychophysiologists were not the first to recog- nize the relationship between cardiovascular activity and emotion. The cardiovascular system has two parts: the blood vessels and the heart. It is a system for distrib- uting oxygen and nutrients to the tissues of the body, removing metabolic wastes, and transmitting chemical messages. Three different measures of cardiovascular ac- tivity are frequently employed in psychophysiological research: heart rate, arterial blood pressure, and local blood volume.

Heart Rate The electrical signal that is associated with each heartbeat can be recorded through electrodes placed on the chest. The recording is called an electro- cardiogram (abbreviated either ECG, for obvious rea- sons, or EKG, from the original German). The average resting heart rate of a healthy adult is about 70 beats per minute, but it increases abruptly at the sound, or thought, of a dental drill.

Blood Pressure Measuring arterial blood pressure in- volves two independent measurements: a measurement of the peak pressure during the periods of heart contraction, the systoles, and a measurement of the minimum pressure during the periods of relaxation, the diastoles. Blood pres- sure is usually expressed as a ratio of systolic over diastolic blood pressure in millimeters of mercury (mmHg). The normal resting blood pressure for an adult is about 130/70 mmHg. A chronic blood pressure of more than 140/90 mmHg is viewed as a serious health hazard and is called hypertension.

You have likely had your blood pressure measured with a sphygmomanometer—a crude device composed of a hollow cuff, a rubber bulb for inflating it, and a pressure gauge for measuring the pressure in the cuff (sphygmos means “pulse”). More reliable, fully automated methods are used in research.

Blood Volume Changes in the volume of blood in par- ticular parts of the body are associated with psychological events. The best-known example of such a change is the engorgement of the genitals that is associated with sexual arousal in both males and females. Plethysmography refers to the various techniques for measuring changes in the volume of blood in a particular part of the body (plethysmos means “an enlargement”).

One method of measuring these changes is to record the volume of the target tissue by wrapping a strain gauge around it. Although this method has utility in measuring blood flow in fingers or similarly shaped or- gans, the possibilities for employing it are somewhat limited. Another plethysmographic method is to shine a light through the tissue under investigation and to measure the amount of the light that is absorbed by it. The more blood there is in a structure, the more light it will absorb.

110 Chapter 5 ■ The Research Methods of Biopsychology

Electrooculograms of the subject as she scanned a circle

FIGURE 5.13 The typical placement of electrodes around the eye for electrooculography. The two electrooculogram traces were recorded as the subject scanned a circle.

based on the fact that there is a steady potential difference between the front (positive) and back (negative) of the eyeball. Because of this steady potential, when the eye moves, a change in the electrical potential between elec- trodes placed around the eye can be recorded. It is usual to record EOG activity between two electrodes placed on each side of the eye to measure its horizontal movements and between two electrodes placed above and below the eye to measure its vertical movements (see Figure 5.13).

Skin Conductance

Emotional thoughts and experiences are associated with in- creases in the ability of the skin to conduct electricity. The two most commonly employed indexes of electrodermal ac- tivity are the skin conductance level (SCL) and the skin conductance response (SCR). The SCL is a measure of the background level of skin conductance that is associated with a particular situation, whereas the SCR is a measure of the transient changes in skin conductance that are associ- ated with discrete experiences.

The physiological bases of skin conductance changes are not fully understood, but there is considerable evidence im- plicating the sweat glands. Although the main function of sweat glands is to cool the body, these glands tend to be- come active in emotional situations. Sweat glands are dis- tributed over most of the body surface; but, as you are almost certainly aware, those of the hands, feet, armpits, and forehead are particularly responsive to emotional stimuli.

Cardiovascular Activity

The presence in our language of phrases such as chicken- hearted, white with fear, and blushing bride indicates that

IS B

N 0-558-78571-9

5.3 Invasive Physiological Research Methods

We turn now from a consideration of the noninvasive tech- niques employed in research on living human brains to a consideration of more direct techniques, which are com- monly employed in biopsychological studies of laboratory animals. Most physiological techniques used in biopsycho- logical research on laboratory animals fall into one of three categories: lesion methods, electrical stimulation methods, and invasive recording methods. Each of these three meth- ods is discussed in this section of the chapter, but we begin with a description of stereotaxic surgery.

Stereotaxic Surgery

Stereotaxic surgery is the first step in many biopsycholog- ical experiments. Stereotaxic surgery is the means by which

experimental devices are precisely positioned in the depths of the brain. Two things are required in stereotaxic surgery: an atlas to provide directions to the target site and an instrument for getting there.

The stereotaxic atlas is used to locate brain structures in much the same way that a geographic atlas is used to locate geographic landmarks. There is, however, one im- portant difference. In contrast to the surface of the earth, which has only two dimensions, the brain has three. Accordingly, the brain is represented in a stereotaxic atlas by a series of individual maps, one per page, each repre- senting the structure of a single, two-dimensional frontal brain slice. In stereotaxic atlases, all distances are given in millimeters from a designated reference point. In some rat atlases, the reference point is bregma—the point on the top of the skull where two of the major sutures (seams in the skull) intersect.

The stereotaxic instrument has two parts: a head holder, which firmly holds each subject’s brain in the prescribed position and orientation; and an electrode holder, which holds the device to be inserted. A system

of precision gears allows the electrode holder to be moved in three dimen- sions: anterior–posterior, dorsal–ventral, and lateral–medial. The implantation by stereotaxic surgery of an electrode in the amygdala of a rat is illustrated in Figure 5.14.

Lesion Methods

Those of you with an unrelenting drive to dismantle objects to see how they work will appreciate the lesion meth- ods. In those methods, a part of the brain is removed, damaged, or de- stroyed; then, the behavior of the sub- ject is carefully assessed in an effort to determine the functions of the le- sioned structure. Four types of lesions are discussed here: aspiration lesions, radio-frequency lesions, knife cuts, and cryogenic blockade.

Aspiration Lesions When a lesion is to be made in an area of cortical tis- sue that is accessible to the eyes and in- struments of the surgeon, aspiration is frequently the method of choice. The

1115.3 ■ Invasive Physiological Research Methods

7 6 5 4 3 2 1 0 1 2 3 4 5 6 7

0 1 2 3 4 5 6 7 8 9

Amygdala

Bregma

Electrode connector

Electrode

Bregma 2.8

1 2 3 4 5 6 7 8 9 10

6 5 4 3 2 1 0 1 2 3 4 5 6 7

1 The atlas indicates that the amygdala target site is 2.8 mm posterior to bregma, 4.5 mm lateral, and 8.5 mm ventral.

2 A hole is drilled 2.8 mm posterior to bregma and 4.5 mm lateral to it. Then, the electrode holder is positioned over the hole, and the electrode is lowered 8.5 mm through the hole.

3 The electrode is anchored to the skull with several stainless steel screws and dental acrylic that is allowed to harden around the electrode connector.

FIGURE 5.14 Stereotaxic surgery: implanting an electrode in the rat amygdala.

IS B

N 0-

55 8-

78 57

1- 9

cortical tissue is drawn off by suction through a fine- tipped handheld glass pipette. Because the underlying white matter is slightly more resistant to suction than the cortical tissue itself, a skilled surgeon can delicately peel off the layers of cortical tissue from the surface of the brain, leaving the underlying white matter and major blood vessels undamaged.

Radio-Frequency Lesions Small subcortical lesions are commonly made by passing radio-frequency current (high-frequency current) through the target tissue from the tip of a stereotaxically positioned electrode. The heat from the current destroys the tissue. The size and shape of the lesion are determined by the duration and intensity of the current and the configuration of the electrode tip.

Knife Cuts Sectioning (cutting) is used to eliminate conduction in a nerve or tract. A tiny, well-placed cut can unambiguously accomplish this task without producing extensive damage to surrounding tissue. How does one insert a knife into the brain to make a cut without severely damaging the overlying tissue? One method is depicted in Figure 5.15.

Cryogenic Blockade An alternative to destructive lesions is cryogenic blockade. When coolant is pumped through an implanted cryoprobe, such as the one depicted in Figure 5.16, neurons near the tip are cooled until they stop firing. The temperature is maintained above the freezing level, so there is no structural damage. Then, when the tissue is allowed to warm up, normal neural activity returns. A cryogenic blockade is functionally sim- ilar to a lesion in that it eliminates the contribution of a particular area of the brain to the ongoing behavior of the subject. This is why cryogenic blockades are sometimes referred to as reversible lesions. Reversible lesions can also be produced with microinjections into the brain of local anesthetics such as lidocaine (see Floresco, Seamans, & Phillips, 1997).

Interpreting Lesion Effects Before you leave this section on lesions, a word of caution is in order. Lesion effects are deceptively difficult to interpret. Because the structures of the brain are small, convoluted, and tightly packed together, even a highly skilled surgeon cannot completely destroy a structure without produc- ing significant damage to adjacent structures. There is, however, an un- fortunate tendency to lose sight of this fact when interpreting lesion studies—see the dis- cussion of the hippocampus and memory in Chapter 11. For example, a lesion that leaves major portions of the amygdala intact and damages an assortment of neigh- boring structures comes to be thought of simplistically as an amygdala lesion. Such an apparently harmless ab- straction can be misleading in two ways. If you believe that all lesions referred to as “amygdala lesions” include damage to no other brain structure, you may incor- rectly attribute all of their behavioral effects to amyg- dala damage; conversely, if you believe that all lesions referred to as “amygdala lesions” include the entire amygdala, you may incorrectly conclude that the amyg- dala does not participate in behaviors uninfluenced by the lesion.

112 Chapter 5 ■ The Research Methods of Biopsychology

FIGURE 5.15 A device for performing subcortical knife cuts. The device is stereotaxically positioned in the brain; then, the blade swings out to make the cut, Here, the anterior commis- sure is being sectioned.

Thinking CreativelyThinking Creatively

IS B

N 0-558-78571-9

Bilateral and Unilateral Lesions As a general principle—but one with several notable exceptions—the behavioral effects of unilateral lesions (lesions restricted to one half of the brain) are much milder than those of symmetrical bilateral lesions (lesions involving both sides of the brain), particularly in nonhuman species. Indeed, behavioral effects of unilateral lesions to some brain struc- tures can be difficult to detect. As a result, most experi- mental studies of lesion effects are studies of bilateral, rather than unilateral, lesions.

Electrical Stimulation

Clues about the function of a neural structure can be obtained by stimulating it electrically. Electrical brain stimulation is usually delivered across the two tips of a

bipolar electrode—two insulated wires wound tightly together and cut at the end. Weak pulses of current pro- duce an immediate increase in the firing of neurons near the tip of the electrode.

Electrical stimulation of the brain is an important biopsychological research tool because it often has behav- ioral effects, usually opposite to those produced by a le- sion to the same site. It can elicit a number of behavioral sequences, including eating, drinking, attacking, copulat- ing, and sleeping. The particular behavioral response that is elicited depends on the location of the electrode tip, the parameters of the current, and the test environment in which the stimulation is administered.

Invasive Electrophysiological Recording Methods

This section describes four invasive electrophysiological recording methods: intracellular unit recording, extracel- lular unit recording, multiple-unit recording, and invasive EEG recording. See Figure 5.17 on page 114 for an example of each method.

Intracellular Unit Recording A method whose find- ings were discussed at length in Chapter 4, intracellular unit recording, provides a moment-by-moment record of the graded fluctuations in one neuron’s membrane poten- tial. Most experiments using this recording procedure are performed on chemically immobilized animals because it is next to impossible to keep the tip of a microelectrode positioned inside a neuron of a freely moving animal.

Extracellular Unit Recording It is possible to record the action potentials of a neuron through a microelectrode whose tip is positioned in the extracellular fluid next to it— each time the neuron fires, there is an electrical disturbance and a blip is recorded at the electrode tip. Accordingly, extracellular unit recording provides a record of the firing of a neuron but no information about the neuron’s membrane potential. It is difficult to record extracellularly from a sin- gle neuron in a freely moving animal without the electrode tip shifting away from the neuron, but it can be accom- plished with special flexible microelectrodes that can shift slightly with the brain. Initially, extracellular unit recording involved recording from one neuron at a time, each at the tip of a separately implanted electrode. However, it is now possible to simultaneously record extracellular signals from up to about 100 neurons by analyzing the correlations among the signals picked up through several different elec- trodes implanted in the same general area (e.g., Nicolelis & Ribeiro, 2006).

Multiple-Unit Recording In multiple-unit recording, the electrode tip is much larger than that of a microelectrode; thus, it picks up signals from many neurons, and slight shifts in its position due to movement of the subject have little

1135.3 ■ Invasive Physiological Research Methods

FIGURE 5.16 A cryoprobe. The cryoprobe is implanted in the brain; then the brain area at the uninsulated tip of the cryoprobe is cooled while the effects on behavior are assessed. Cryoprobes are slender so that they can be implanted in the brain without causing substantial damage; they are typically constructed of hypodermic tubing of two gauges.

IS B

N 0-

55 8-

78 57

1- 9

effect on the overall signal. The many action potentials picked up by the electrode are fed into an integrating circuit, which adds them together. A multiple-unit recording is a graph of the total number of recorded action potentials per unit of time (e.g., per 0.1 second).

recording from it using surgical and electrical methods. In this section, you will learn how psychopharmacologists manipulate and record from the brain using chemical methods.

The major research strategy of psychopharmacology is to administer drugs that either increase or decrease the effects of particular neurotransmitters and to observe the behavioral consequences. You learned in Chapter 4 how agonists and antagonists affect neurotransmitter systems. Described here are routes of drug administration, methods of using chemicals to make selective brain le- sions, methods of measuring the chemical activity of the brain that are particularly useful in biopsychologi- cal research, and methods for locating neurotransmitter systems.

Routes of Drug Administration

In most psychopharmacological experiments, drugs are administered in one of the following ways: (1) They are fed to the subject; (2) they are injected through a tube

114 Chapter 5 ■ The Research Methods of Biopsychology

An extracellular microelectrode records the electrical disturbance that is created each time an adjacent neuron fires.

V o

lt a g

e (m

il li

vo lt

s )

0.1 0.2 0.3 0.4 0.5

An Extracellular Unit Recording

Seconds

M e

m b

ra n

e P

o te

n ti

a l

(m il

li vo

lt s

)

An intracellular microelectrode records the membrane potential from one neuron as it fires.

1 2 3 4 5

An Intracellular Unit Recording

Milliseconds

A small electrode records the action potentials of many nearby neurons. These are added up and plotted. In this example, firing in the area of the electrode tip gradually declined and then suddenly increased.

N u

m b

e r

o f

A c

ti o

n P

o te

n ti

a ls

(p e

r m

il li

s e

c o

n d

)

0.1 0.2 0.3 0.4 0.5 SecondsSeconds

A Multiple-Unit Recording

A large implanted electrode picks up general changes in electrical brain activity. The EEG signal is not related to neural firing in any obvious way.

V o

lt a g

e (m

ic ro

vo lt

s )

An Invasive EEG Recording

1 2 3 4 5 Milliseconds

FIGURE 5.17 Four methods of recording electrical activity of the nervous system.

Invasive EEG Recording In laboratory animals, EEG signals are recorded through large implanted electrodes rather than through scalp electrodes. Cortical EEG signals are frequently recorded through stainless steel skull screws, whereas subcortical EEG signals are typically recorded through stereotaxically implanted wire electrodes.

5.4 Pharmacological Research Methods

In the preceding section, you learned how physiological psychologists study the brain by manipulating it and

IS B

N 0-558-78571-9

into the stomach (intragastrically); or (3) they are injected hypodermically into the peritoneal cavity of the abdomen (intraperitoneally, IP), into a large muscle (intramuscularly, IM), into the fatty tissue beneath the skin (subcutaneously, SC), or into a large surface vein (intravenously, IV). A prob- lem with these peripheral routes of administration is that many drugs do not readily pass through the blood–brain barrier. To overcome this problem, drugs can be admin- istered in small amounts through a fine, hollow tube, called a cannula, that has been stereotaxically implanted in the brain.

Selective Chemical Lesions

The effects of surgical, electrolytic, and cryogenic le- sions are frequently difficult to interpret because they affect all neurons in the target area. In some cases, it is possible to make more selective lesions by injecting neurotoxins (neural poisons) that have an affinity for certain components of the nervous system. There are many selective neurotoxins. For example, when either kainic acid or ibotenic acid is administered by microin- jection, it is preferentially taken up by cell bodies at the tip of the cannula and destroys those neurons, while leaving neurons with axons passing through the area largely unscathed.

Another widely used selective neurotoxin is 6-hydroxy- dopamine (6-OHDA). It is taken up by only those neurons that release the neurotransmitter norepinephrine or dopamine, and it leaves other neurons at the injection site undamaged.

Measuring Chemical Activity of the Brain

There are many procedures for measuring the chemical activity of the brains of laboratory animals. Two tech- niques that have proved particularly useful in biopsycho- logical research are the 2-deoxyglucose technique and cerebral dialysis.

The 2-Deoxyglucose Technique The 2-deoxyglucose (2-DG) technique entails placing an animal that has been injected with radioactive 2-DG in a test situation in which it engages in the activity of interest. Because 2-DG is sim- ilar in structure to glucose—the brain’s main source of energy—neurons active during the test absorb it at a high rate but do not metabolize it. Then the subject is killed, and its brain is removed and sliced. The slices are then subjected to autoradiography; they are coated with a photographic emulsion, stored in the dark for a few days, and then developed much like film. Areas of the brain that absorbed high levels of the radioactive 2-DG during the test appear as black spots on the slides. The density of the spots in various regions of the brain can then be color-coded (see Figure 5.18).

Cerebral Dialysis Cerebral dialysis is a method of measuring the extracellular concentration of specific neu- rochemicals in behaving animals (see Robinson & Justice, 1991)—most other techniques for measuring neurochem- icals require that the animals be killed so that tissue can be extracted. Cerebral dialysis involves the implantation in the brain of a fine tube with a short semipermeable sec- tion. The semipermeable section is positioned in the brain structure of interest so that extracellular chemicals from

the structure will diffuse into the tube. Once in the tube, they can be collected for freezing, storage, and later analysis; or they can be carried in solution directly to a chromatograph (a device for measuring the chemical constituents of liquids or gases).

1155.4 ■ Pharmacological Research Methods

FIGURE 5.18 The 2-deoxyglucose tech- nique. The accumulation of radioactivity is shown in three frontal sections taken from the brain of a Richardson’s ground squirrel. The subject was injected with radioactive 2-deoxyglucose; then, for 45 minutes, it viewed brightly illuminated black and white stripes through its left eye while its right eye was covered. Because the ground squirrel visual system is largely crossed, most of the radioactivity accumulated in the visual struc- tures of the right hemisphere (the hemisphere on your right). (Courtesy of Rod Cooper, Department of Psychology, University of Calgary.)

IS B

N 0-

55 8-

78 57

1- 9

Locating Neurotransmitters and Receptors in the Brain

A key step in trying to understand the psychological func- tion of a particular neurotransmitter or receptor is finding out where it is located in the brain. Two of the techniques available for this purpose are immunocytochemistry and in situ hybridization. Each involves exposing brain slices to a labeled ligand of the molecule under investigation (the ligand of a molecule is another molecule that binds to it).

Immunocytochemistry When a foreign protein (an antigen) is injected into an animal, the animal’s body creates antibodies that bind to it and help the body remove or de- stroy it; this is known as the body’s immune reaction. Neu- rochemists have created stocks of antibodies to the brain’s peptide neurotransmitters (neuropeptides; see Chapter 4) and their receptors. Immunocytochemistry is a procedure for locating particular neuroproteins in the brain by label- ing their antibodies with a dye or radioactive element and then exposing slices of brain tissue to the labeled antibodies. Regions of dye or radioactivity accumulation in the brain slices mark the locations of the target neuroprotein.

Because all enzymes are proteins and because only those neurons that release a particular neurotransmitter are likely to contain all the enzymes required for its synthesis, im- munocytochemistry can be used to locate neurotransmit- ters by binding to their enzymes. This is done by exposing brain slices to labeled antibodies that bind to enzymes lo- cated in only those neurons that contain the neurotrans- mitter of interest (see Figure 5.19).

In Situ Hybridization Another technique for locat- ing peptides and other proteins in the brain is in situ hybridization. This technique takes advantage of the fact that all peptides and proteins are transcribed from sequences of nucleotide bases on strands of messenger RNA (see Chapter 2).

The nucleotide base sequences that direct the synthesis of many neuroproteins have been identified, and hybrid strands of mRNA with the complementary base se- quences have been artificially created. In situ hybridiza- tion (see Figure 5.20) involves the following steps. First, hybrid RNA strands with the base sequence complemen- tary to that of the mRNA that directs the synthesis of the target neuroprotein are obtained. Next, the hybrid RNA strands are labeled with a dye or radioactive element. Finally, the brain slices are exposed to the labeled hybrid RNA strands; they bind to the complementary mRNA strands, marking the location of neurons that release the target neuroprotein.

5.5 Genetic Engineering

Genetics is a science that has made amazing progress in the last two decades, and biopsychologists are reaping the benefits. Modern genetic methods are now widely used in biopsychological research, which just a few years ago would have seemed like science fiction.

Gene Knockout Techniques

Gene knockout techniques are procedures for creating organisms that lack a particular gene under investigation (see Eisener-Dorman, Lawrence, & Bolivar, 2008). Mice (the favored mammalian subjects of genetic research) that are the products of gene knockout techniques are re- ferred to as knockout mice. (This term often makes me

116 Chapter 5 ■ The Research Methods of Biopsychology

FIGURE 5.19 Immunocyto- chemistry. This section through a rat’s substantia nigra reveals dopaminergic neurons that have taken up the antibody for tyro- sine hydroxylase, the enzyme that converts tyrosine to L-dopa. (Courtesy of Mark Klitenick and Chris Fibiger, Department of Psychiatry, University of British Columbia.)

IS B

N 0-558-78571-9

smile, as images of little mice with boxing gloves flit through my mind.)

Many gene knockout studies have been conducted to clarify the neural mechanisms of behavior. For example, Ruby and colleagues (2002) and Hattar and colleagues (2003) used melanopsin knockout mice (mice in whom the gene for the synthesis of melanopsin has been deleted) to study the role of melanopsin in regulating the light–dark cycles that control circadian (about 24 hours) rhythms of bodily function—for example, daily cycles of sleep, eating, and body temperature. Melanopsin is a protein found in some neurons in the mammalian retina (the receptive layer of the eye), and it had been implicated in the control of cir- cadian ryhythms by light because many of the neurons containing melanopsin project to the circadian clock mechanism in the hypothalamus. Knockout of the gene for synthesizing melanopsin reduced, but did not eliminate, the responses of the clock mechanism to changes in light, and it impaired, but did not eliminate, the ability of mice to adjust their circadian rhythms in response to changes in the light–dark cycle. Thus, melansopsin appears to con- tribute to the control of circadian rhythms by light, but it is not the only factor.

This type of result is typical of gene knockout studies of behavior: Many genes have been discovered that con- tribute to particular behaviors, but invariably other

mechanisms are involved. It may be tempting to think that each behav- ior is controlled by a single gene,

but the reality is much more complex. Each behavior is controlled by many genes interacting with one another and with experience.

Gene Replacement Techniques

It is now possible to replace one gene with another. Gene replacement techniques have created interesting possi- bilities for research and therapy. Pathological genes from human cells can be inserted in other animals such as mice—mice that contain the genetic material of another species are called transgenic mice. For example, Shen and colleagues (2008) created transgenic mice by inserting a defective human gene that had been found to be associ- ated with schizophrenia in a Scottish family with a partic- ularly high incidence of the disorder. The transgenic mice displayed a variety of cerebral abnormalities (e.g., re- duced cerebral cortex and enlarged ventricles) and abnor- mal behaviors reminiscent of human schizophrenia, confirming that the defective gene was a causal factor in the familial schizophrenia of the Scottish family.

In another gene replacement technique, a gene is replaced with one that is identical except for the addition of a few bases that can act as a switch, turning the gene off or on in response to particular chemicals. The chem- icals can then be used to activate or suppress the gene at a particular point in development. Treating neurological disease by replacing faulty genes in patients suffering from genetic disorders is an exciting, but as yet unreal- ized, goal.

Fantastic Fluorescence and the Brainbow

Green fluorescent protein (GFP) is a protein that exhibits bright green fluorescence when exposed to blue light. First isolated by Shimomura, Johnson, and Saiga (1962), from a species of jellyfish found off the west coast of North America, GFP is currently stimulating advances in many fields of biological research. Martin Chalfie, Osamu Shimomura, and Roger Y. Tsien were awarded the 2008 Nobel Prize in chemistry for its discovery and study.

The utility of GFP as a research tool in the biological sciences could not be realized until its gene was identi- fied and cloned in the early 1990s. The general strategy is to activate the GFP gene in only the particular cells under investigation so that they can readily be visual- ized. This can be accomplished in two ways: by inserting the GFP gene in only the target cells or by introducing the GFP gene in all cells of the subject but expressing the gene in only the target cells. Chalfie and colleagues (1994) were the first to use GFP to visualize neurons. They introduced the GFP gene into a small transparent roundworm, Caenorhabditis elegans, in an area of its chromosomes that controls the development of touch receptor neurons. Figure 5.21 on page 118 shows the glowing touch receptor neurons. The GFP gene has now been expressed in the cells of many plant and animal species, including humans.

1175.5 ■ Genetic Engineering

Thinking CreativelyThinking Creatively

Clinical Clinical Implications Implications

Evolutiona Evolutionary Perspective Perspective

FIGURE 5.20 In situ hybridization. This color-coded frontal section through a rat brain reveals high concentrations of mRNA expression for an endorphin in the striatum (in red and yellow). (Courtesy of Ningning Guo and Chris Fibiger, Department of Psychiatry, University of British Columbia.)

IS B

N 0-

55 8-

78 57

1- 9

Livet and colleagues took the very useful GFP tech- nique one step further—one big step. First, Tsien (1998) found that making minor alterations to the GFP gene resulted in the synthesis of proteins that fluoresced in different colors. Livet and colleagues (2007) then in- troduced the mutated genes for cyan, yellow, and blue fluorescent proteins into the genomes of developing mice in such a way that they were expressed in develop- ing neurons. Each neuron produced different amounts of the three proteins, giving it a distinctive color—in the

same way that a color printer can make any color by mixing only three colored inks in differing propor-

tions. Because each neuron was labeled with its own distinctive color, the pathways of neural axons could be traced to their destinations through the cellular morass. This technique has been dubbed brainbow for obvious reasons—see Figure 5.22.

118 Chapter 5 ■ The Research Methods of Biopsychology

The research methods of biopsychology illustrate a psy-

chological disorder suffered by many scientists. I call it

“unabbreviaphobia”—the fear of leaving any term unab-

breviated. To determine whether you have mastered Part

One of this chapter and are ready for Part Two, supply the

full term for each of the following abbreviations. The

correct answers are provided at the end of the exercise.

Before proceeding, review material related to your

incorrect answers and omissions.

1. CT: __________________________________________

2. MRI: _________________________________________

3. PET: _________________________________________

4. 2-DG: ________________________________________

5. fMRI: _______________________________________

6. MEG: _______________________________________

7. TMS: _______________________________________

8. EEG: _______________________________________

9. ERP: ________________________________________

10. AEP: _______________________________________

11. EMG: _______________________________________

12. EOG: _______________________________________

13. SCL: _______________________________________

14. SCR: _______________________________________

15. ECG: _______________________________________

16. EKG: _______________________________________

17. IP: _________________________________________

18. IM: ________________________________________

19. IV: ________________________________________

20. SC: ________________________________________

21. 6-OHDA: ____________________________________

22. GFP: _______________________________________ Scan Your Brainanswers: (1) computed tomography, (2) magnetic resonance

imaging, (3) positron emission tomography, (4) 2-deoxyglucose, (5) functional

MRI, (6) magnetoencephalography, (7) transcranial magnetic stimulation,

(8) electroencephalogram, (9) event-related potential, (10) average evoked

potential, (11) electromyogram, (12) electrooculogram, (13) skin

conductance level, (14) skin conductance response, (15) electrocardiogram,

(16) electrocardiogram, (17) intraperitoneal, (18) intramuscular,

(19) intravenous, (20) subcutaneous, (21) 6-hydroxydopamine, (22) green

fluorescent protein.

PART TWO BEHAVIORAL RESEARCH METHODS OF BIOPSYCHOLOGY

We turn now from methods used by biopsychologists to study the nervous system to those that deal with the behavioral side of biopsychology. Because of the inherent invisibility of neural activity, the primary objective of the methods used in its investigation is to render the unob- servable observable. In contrast, the major objectives of behavioral research methods are to control, to simplify, and to objectify.

A single set of procedures developed for the investiga- tion of a particular behavioral phenomenon is commonly referred to as a behavioral paradigm. Each behavioral paradigm normally comprises a method for producing the behavioral phenomenon under investigation and a method for objectively measuring it.

Thinking CreativelyThinking Creatively

FIGURE 5.21 Touch receptor neurons of the transparent Caenorhabditis elegans labeled by green fluorescent protein.

IS B

N 0-558-78571-9

5.6 Neuropsychological Testing

A patient suspected of suffering from some sort of nervous system dysfunction is usually referred to a neurologist, who assesses simple sensory and motor functions. More subtle

changes in perceptual, emotional, moti- vational, or cognitive functions are the domain of the neuropsychologist.

Because neuropsychological testing is so time con- suming, it is typically prescribed for only a small por- tion of brain-damaged patients. This is unfortunate; the results of neuropsychological testing can help brain- damaged patients in three important ways: (1) by assist- ing in the diagnosis of neural disorders, particularly in cases in which brain imaging, EEG, and neurological testing have proved equivocal; (2) by serving as a basis for counseling and caring for the patients; and (3) by pro- viding a basis for objectively evaluating the effectiveness of the treatment and the seriousness of its side effects.

Modern Approach to Neuropsychological Testing

The nature of neuropsychological testing has changed radically since the 1950s (see Stuss & Levine, 2002). In- deed, the dominant approach to psychological testing has evolved through three distinct phases: the single-test approach, the standardized-test-battery approach, and the

ful, in large part because no single test could be devel- oped that would be sensitive to all the varied and com- plex psychological symptoms that could potentially occur in a brain-damaged patient.

Standardized-Test-Battery Approach The standard- ized-test-battery approach to neuropsychological testing grew out of the failures of the single-test approach, and by the 1960s, it was predominant. The objective stayed the same—to identify brain-damaged patients—but the test- ing involved standardized batteries (sets) of tests rather than a single test. The most widely used standardized test battery has been the Halstead-Reitan Neuropsychological Test Battery. The Halstead-Reitan is a set of tests that tend to be performed poorly by brain-damaged patients in re- lation to other patients or healthy control subjects; the scores on each test are added together to form a single ag- gregate score. An aggregate score below the designated cutoff leads to a diagnosis of brain damage. The standard- ized-test-battery approach has proved only marginally successful; standardized test batteries discriminate effec- tively between neurological patients and healthy patients, but they are not so good at discriminating between neu- rological patients and psychiatric patients.

The Customized-Test-Battery Approach The cus- tomized-test-battery approach began to be used routinely in a few elite neuropsychological research institutions in the 1960s. This approach proved highly successful in re- search, and it soon spread to clinical practice. It now pre- dominates in both the research laboratory and the

1195.6 ■ Neuropsychological Testing

Clinical Clinical Implications Implications

FIGURE 5.22 With the research technique called brainbow, each neuron is labeled with a different color, facilitating neuron tracing.

modern customized-test-bat- tery approach.

Single-Test Approach Be- fore the 1950s, the few exist- ing neuropsychological tests were designed to detect the presence of brain damage; in particular, the goal of these early tests was to discriminate between patients with psy- chological problems resulting from structural brain damage and those with psychological problems resulting from func- tional, rather than structural, changes to the brain. This approach proved unsuccess-

IS B

N 0-

55 8-

78 57

1- 9

neurological ward (see Lezak, 1997; Strub & Black, 1997).

The objective of current neuropsychological testing is not merely to identify patients with brain damage; the ob- jective is to characterize the nature of the psychological deficits of each brain-damaged patient. So how does the customized-test-battery approach to neuropsychological testing work? It usually begins in the same way for all pa- tients: with a common battery of tests selected by the neu- ropsychologist to provide an indication of the general nature of the neuropsychological symptoms. Then, depend- ing on the results of the common test battery, the neuropsy- chologist selects a series of tests customized to each patient in an effort to characterize in more detail the general symp- toms revealed by the common battery. For example, if the results of the test battery indicated that a patient had a memory problem, subsequent tests would include those de- signed to reveal the specific nature of the memory problem.

The tests used in the customized-test-battery approach differ in three respects from earlier tests. First, the newer tests are specifically designed to measure aspects of psy- chological function that have been spotlighted by modern theories and data. For example, modern theories, and the evidence on which they are based, suggest that the mech- anisms of short-term and long-term memory are totally different; thus, the testing of patients with memory prob- lems virtually always involves specific tests of both short- term and long-term memory. Second, the interpretation of the test results often does not rest entirely on how well the patient does; unlike early neuropsychological tests, currently used tests often require the neuropsychologist to assess the cognitive strategy that the patient employs in performing the test. Brain damage often changes the strat- egy that a neuropsychological patient uses to perform a test without lowering the overall score. Third, the cus- tomized-test-battery approach requires more skill and knowledge on the part of the neuropsychologist to select just the right battery of tests to expose a patient’s deficits and to identify qualitative differences in cognitive strategy.

Tests of the Common Neuropsychological Test Battery

Because the customized-test-battery approach to neu- ropsychological testing typically involves two phases—a

battery of general tests given to all pa- tients followed by a series of specific tests customized to each patient—the

following examples of neurological tests are presented in two subsections. First are some tests that are often admin- istered as part of the initial common test battery, and second are some tests that might be used by a neuropsy- chologist to investigate in more depth particular prob- lems revealed by the common battery.

Intelligence Although the overall intelligence quotient (IQ) is a notoriously poor measure of brain damage, a test

120 Chapter 5 ■ The Research Methods of Biopsychology

of general intelligence is nearly always included in the battery of neuropsychological tests routinely given to all patients. Many neuropsychological assessments begin with the Wechsler Adult Intelligence Scale (WAIS), first published in 1955 and standardized in 1981 on a sample of 1,880 U.S. citizens between 16 and 71. The WAIS is often the first test because knowing a pa- tient’s IQ can help a neuropsychologist interpret the re- sults of subsequent tests. Also, a skilled neuropsychologist can sometimes draw inferences about a patient’s neu- ropsychological dysfunction from the pattern of deficits on the 15 subtests of the WAIS. For example, low scores on subtests of verbal ability tend to be associated with left hemisphere damage, whereas right hemisphere damage tends to reduce scores on performance subtests. The 11 original subtests of the WAIS are described in Table 5.1.

Memory One weakness of the WAIS is that it often fails to detect memory deficits, despite including subtests specifically designed to test memory function. For exam- ple, the information subtest of the WAIS assesses memory for general knowledge (e.g., “Who is Queen Elizabeth?”), and the digit span subtest (the most widely used test of short-term memory) identifies the longest sequence of random digits that a patient can repeat correctly 50% of the time; most people have a digit span of 7. However, these two forms of memory are among the least likely to be disrupted by brain damage—patients with seriously dis- turbed memories often show no deficits on either the information or the digit span subtest. Be that as it may, memory problems rarely escape unnoticed; they are often reported by the patient or the family of the patient.

Language If a neuropsychological patient has taken the WAIS, deficits in the use of language can be inferred from a low aggregate score on the verbal subtests. A pa- tient who has not taken the WAIS can be quickly screened for language-related deficits with the token test. Twenty tokens of two different shapes (squares and circles), two different sizes (large and small), and five different colors (white, black, yellow, green, and red) are placed on a table in front of the subject. The test begins with the examiner reading simple instructions—for example, “Touch a red square”—and the subject trying to follow them. Then, the test progresses to more difficult instructions, such as “Touch the small, red circle and then the large, green square.” Finally, the subject is asked to read the instruc- tions aloud and follow them.

Language Lateralization It is usual for one hemi- sphere to participate more than the other in language- related activities. In most people, the left hemisphere is dominant for language, but in some, the right hemisphere

Clinical Clinical Implications Implications

Watch Robert Sternberg on Intelligence www.mypsychlab.com

Simulate Digit Span www.mypsychlab.com

IS B

N 0-558-78571-9

is dominant (see Chapter 16). A test of language lateral- ization is often included in the common test battery because knowing which hemisphere is dominant for lan- guage is often useful in interpreting the results of other tests. Furthermore, a test of language lateralization is virtually always given to patients before any surgery that might encroach on the cortical language areas. The results are used to plan the surgery, trying to avoid the language areas if possible.

There are two widely used tests of language lateraliza- tion. The sodium amytal test (Wada, 1949) is one, and the dichotic listening test (Kimura, 1973) is the other.

The sodium amytal test involves injecting the anes- thetic sodium amytal into either the left or right carotid artery in the neck. This temporarily anesthetizes the ipsilateral (same-side) hemisphere while leaving the contralateral (opposite-side) hemisphere largely unaffected. Several tests of language function are quickly administered while the ipsilateral hemisphere is anesthetized. Later, the process is repeated for the other side of the brain. When the injection is on the side dominant for language, the patient is completely mute for about 2 minutes. When the injection is on the nondominant side, there are only a few minor speech problems. Because the sodium amytal test is invasive, it can be administered only for medical reasons— usually to determine the dominant language hemisphere prior to brain surgery.

In the standard version of the dichotic listening test, se- quences of spoken digits are presented to subjects through stereo headphones. Three digits are presented to one ear at the same time that three different digits are presented to the other ear. Then the subjects are asked to report as many of the six digits as they can. Kimura (1973) found that sub- jects correctly report more of the digits heard by the ear contralateral to their dominant hemisphere for language, as determined by the sodium amytal test.

Tests of Specific Neuropsychological Function

Following analysis of the results of a neuropsychological patient’s performance on the common test battery, the neuropsychologist selects a series of spe- cific tests to clarify the nature of the general problems exposed by the com- mon battery. There are thousands of tests that might be selected. This section describes a few of them and men- tions some of the considerations that might influence their selection.

Memory Following the discovery of memory impair- ment by the common test battery, at least four fundamen- tal questions about the memory impairment must be answered (see Chapter 11): (1) Does the memory im- pairment involve short-term memory, long-term memory, or both? (2) Are any deficits in long-term memory anterograde (affecting the retention of things learned after the damage), retrograde (affecting the retention of things learned before the damage), or both? (3) Do any deficits in long-term memory involve semantic memory (memory for knowledge of the world) or episodic memory (memory for personal experiences)? (4) Are any deficits in long- term memory deficits of explicit memory (memories of which the patient is aware and can thus express verbally), implicit memory (memories that are demonstrated by the

1215.6 ■ Neuropsychological Testing

Clinical Clinical Implications Implications

TABLE 5.1 The 11 Original Subtests of the Wechsler

Adult Intelligence Scale (WAIS)

Verbal Subtests

Information Read to the subject are 29 questions of

general information—for example “Who is the president of

the United States?”

Digit Span Three digits are read to the subject at 1-second

intervals, and the subject is asked to repeat them in the

same order. Two trials are given at three digits, four digits,

five digits, and so on until the subject fails both trials at

one level.

Vocabulary The subject is asked to define a list of 35

words that range in difficulty.

Arithmetic The subject is presented with 14 arithmetic

questions and must answer them without the benefit of

pencil and paper.

Comprehension The subject is asked 16 questions that test

the ability to understand general principles—for example,

why should people vote?

Similarities The subject is presented with pairs of items

and is asked to explain how the items in each pair are

similar.

Performance Subtests

Picture Completion The subject must identify the

important part missing from 20 drawings—for example, a

drawing of a squirrel with no tail.

Picture Arrangement The subject is presented with

10 sets of cartoon drawings and is asked to arrange each

set so that it tells a sensible story.

Block Design The subject is presented with blocks that are

red on two sides, white on two sides, and half red and half

white on the other two. The subject is shown pictures of

nine patterns and is asked to duplicate them by arranging

the blocks appropriately.

Object Assembly The subject is asked to put together the

pieces of four simple jigsaw puzzles to form familiar

objects.

Digit Symbol The subject is presented with a key that

matches each of a series of symbols with a different digit.

On the same page is a series of digits and the subject is

given 90 seconds to write the correct symbol, according to

the key, next to as many digits as possible.

IS B

N 0-

55 8-

78 57

1- 9

improved performance of the patient without the patient being conscious of them), or both?

Many amnesic patients display severe deficits in ex- plicit memory with no deficits at all in implicit memory (Curran & Schacter, 1997). Repetition priming tests have proven instrumental in the assessment and study of this pattern. Patients are first shown a list of words and asked to study them; they are not asked to remember them. Then, at a later time, they are asked to complete a list of word fragments, many of which are fragments of words from the initial list. For example, if “purple” had been in the initial test, “pu_p_ _” could be one of the test word fragments. Amnesic patients often complete the frag- ments as well as healthy control subjects. But—and this is the really important part—they often have no conscious memory of any of the words in the initial list or even of ever having seen the list. In other words, they display good implicit memory of experiences without explicit memories of them.

Language If a neuropsychological patient turns out to have language-related deficits on the common test bat- tery, a complex series of tests is administered to clarify the nature of the problem (see Chapter 16). For example, if a patient has a speech problem, it may be one of three fundamentally different problems: problems of phonology (the rules governing the sounds of the language), prob- lems of syntax (the grammar of the language), or prob- lems of semantics (the meaning of the language). Because brain-damaged patients may have one of these problems but not the others, it is imperative that the testing of all neuropsychological patients with speech problems in- clude tests of each of these three capacities (Saffran, 1997).

Reading aloud can be disrupted in different ways by brain damage, and follow-up tests must be employed that can differentiate between the different patterns of disrup- tion (Coslett, 1997). Some dyslexic patients (those with reading problems) remember the rules of pronunciation but have difficulties pronouncing words that do not follow these rules, words such as come and tongue, whose pronun- ciation must be remembered. Other dyslexic patients pro- nounce simple familiar words based on memory but have lost the ability to apply the rules of pronunciation—they cannot pronounce nonwords such as trapple or fleeming.

Frontal-Lobe Function

Injuries to the frontal lobes are common, and the Wisconsin Card Sorting Test (see Figure 5.23) is a com- ponent of many customized test batteries because per- formance on it is sensitive to frontal-lobe damage (see Eling, Derckx, & Maes, 2008). On each Wisconsin card is either one symbol or two, three, or four identical symbols. The symbols are all either triangles, stars, circles, or crosses; and they are all either red, green, yellow, or blue.

At the beginning of the test, the patient is confronted with four stimulus cards that differ from one another in the form, color, and number of symbols they display. The task is to correctly sort cards from a deck into piles in front of the stimulus cards. However, the patient does not know whether to sort by form, by color, or by number. The pa- tient begins by guessing and is told after each card has been sorted whether it was sorted correctly or incorrectly. At first, the task is to learn to sort by color. But as soon as the patient makes several consecutive correct responses, the sorting principle is changed to shape or number with- out any indication other than the fact that responses based on color become incorrect. Thereafter, each time the pa- tient learns a new sorting principle, the principle is changed.

Patients with damage to their frontal lobes often con- tinue to sort on the basis of one sorting principle for 100 or more trials after it has become incorrect (Demakis, 2003). They seem to have great difficulty learning and remembering that previously appropriate guidelines for

122 Chapter 5 ■ The Research Methods of Biopsychology

FIGURE 5.23 The Wisconsin Card Sorting Test. This woman is just starting the test. If she places the first card in front of the stimulus card with the three green circles, she is sorting on the basis of color. She must guess until she can learn which principle—color, shape, or number—should guide her sorting. After she has placed a card she is told whether or not her placement is correct.

IS B

N 0-558-78571-9

Raichle, 1994). Let me illustrate this technique with an example from a PET study of single-word processing by Petersen and colleagues (1988). Petersen and his col- leagues were interested in locating the parts of the brain that enable a subject to make a word association (to re- spond to a printed word by saying a related word). You might think this would be an easy task to accomplish by having a subject perform a word-association task while a PET image of the subject’s brain is recorded. The problem with this approach is that many parts of the brain that would be active during the test period would have noth- ing to do with the constituent cognitive process of form- ing a word association; much of the activity recorded would be associated with other processes such as seeing the words, reading the words, and speaking. The paired- image subtraction technique was developed to deal with this problem.

The paired-image subtraction technique involves obtaining PET or fMRI images during several different cognitive tasks. Ideally, the tasks are designed so that pairs of them differ from each other in terms of only a single constituent cognitive process. Then, the brain ac- tivity associated with that process can be estimated by

subtracting the activity in the image as- sociated with one of the two tasks from the activity in the image associated with the other. For example, in one of the tasks in the study by Petersen and col- leagues, subjects spent a minute reading aloud printed nouns as they appeared on a screen; in another, they observed the same nouns on the screen but re- sponded to each of them by saying aloud an associated verb (e.g., truck— drive). Then, Petersen and his colleagues subtracted the activity in the images that they recorded during the two tasks to obtain a difference image. The difference image illustrated the areas of the brain that were specifically involved in the constituent cognitive process of forming the word association; the activity associ- ated with fixating on the screen, seeing the nouns, saying the words, and so on was eliminated by the subtraction (see Figure 5.24).

Interpretation of difference images is complicated by the fact that there is sub- stantial brain activity when human sub- jects sit quietly and let their minds wander—this level of activity has been termed the brain’s default mode (Raichle, 2010). The brain structures that are typi- cally active in the default mode are collec- tively referred to as the default mode network, which comprises medial and

FIGURE 5.24 The paired-image subtraction technique, which is commonly em- ployed in cognitive neuroscience. Here we see that the brain of a subject is generally active when the subject looks at a flickering checkerboard pattern (visual stimulation condition). However, if the activity that occurred when the subject stared at a blank screen (control situation) is subtracted, it becomes apparent that the perception of the flashing checkerboard pattern was associated with an increase in activity that was largely restricted to the occipital lobe. The individual difference images of five subjects were averaged to produce the mean difference image. (PET scans courtesy of Marcus Raichle, Mallinckrodt Institute of Radiology, Washington University Medical Center.)

effective behavior are no longer appropriate, a problem called perseveration.

5.7 Behavioral Methods of Cognitive Neuroscience

Cognitive neuroscience is predicated on two related as- sumptions. The first premise is that each complex cognitive process results from the combined activity of simple cogni- tive processes called constituent cognitive processes. The second premise is that each constituent cognitive process is mediated by neural activity in a particular area of the brain. One of the main goals of cognitive neuroscience is to iden- tify the parts of the brain that mediate various constituent cognitive processes.

With the central role played by PET and fMRI in cutting- edge cognitive neuroscience research, the paired-image subtraction technique has become one of the key behav- ioral research methods in such research (see Posner &

1235.7 ■ Behavioral Methods of Cognitive Neuroscience

IS B

N 0-

55 8-

78 57

1- 9

lateral parietal cortex, medial frontal cortex, and lateral temporal cortex. See Figure 5.25.

Another difficulty in using PET and fMRI to locate constituent cognitive processes results from the noise as- sociated with random cerebral events that occur during the test—for example, thinking about a sudden pang of hunger, noticing a fly on the screen, or wondering whether the test will last much longer (see Mason et al., 2007). The noise created by such events can be signifi- cantly reduced with a technique discussed earlier in this chapter: signal averaging. By averaging the difference im- ages obtained from repetitions of the same tests, the re- searchers can greatly increase the signal-to-noise ratio. It is standard practice to average the images obtained from several subjects; the resulting mean (averaged) difference image emphasizes areas of activity that are common to most of the subjects and deemphasizes areas of activity that are peculiar to a few of them (see Figure 5.24). How-

ever, this averaging procedure can lead to a serious problem: If two subjects had specific but different

patterns of cortical activity, the average image derived from the two would reveal little about either. Because people differ substantially from one another in the corti-

cal localization of cognitive abilities, this is a serious problem (see Haynes & Rees, 2006). Moreover, the area of cor-

tex that controls a particular ability can change in an in- dividual as a result of experience.

5.8 Biopsychological Paradigms of Animal Behavior

Noteworthy examples of the behavioral paradigms used to study the biopsychology of laboratory species are provided here under three headings: (1) paradigms for the assess- ment of species-common behaviors, (2) traditional condi- tioning paradigms, and (3) seminatural animal learning paradigms. In each case, the focus is on methods used to study the behavior of the laboratory rat, the most common subject of biopsychological research.

Paradigms for Assessment of Species-Common Behaviors

Many of the behavioral paradigms that are used in biopsychological research are used to study species- common behaviors. Species-common behaviors are those that are displayed by virtually all members of a species, or at least by all those of the same age and sex. Commonly studied species-common behaviors include grooming, swimming, eating, drinking, copulating, fighting, and nest building. Described here are the open- field test, tests of aggressive and defensive behavior, and tests of sexual behavior.

124 Chapter 5 ■ The Research Methods of Biopsychology

Medial parietal cortex

Lateral parietal cortex

Medial prefrontal cortexLateral

temporal cortex

Medial prefrontal cortex

Midsagittal view of right hemisphere Lateral view of right hemisphere

FIGURE 5.25 The default mode network: areas of the brain in which activity is commonly recorded by functional brain imaging techniques when the mind wanders.

Thinking CreativelyThinking Creatively

NeNeuroplasticityroplasticity ISB N

0-558-78571-9

Open-Field Test In the open-field test, the subject is placed in a large, barren chamber, and its activity is recorded (see Brooks & Dunnett, 2009). It is usual to measure general activity either with an automated activity recorder or by drawing lines on the floor of the chamber and counting the number of line-crossings during the test. It is also common in the open-field test to count the number of boluses (pieces of excrement) that were dropped by an animal during the test. Low activity scores and high bolus counts are fre- quently used as indicators of fearfulness. Fearful rats are highly thigmotaxic; that is, they rarely venture away from the walls of the test chamber and rarely engage in such ac- tivities as rearing and grooming. Rats are often fearful when they are first placed in a strange open field, but this fearful- ness usually declines with repeated exposure to the same open field.

Tests of Aggressive and Defensive Behavior Typical patterns of aggressive and defensive behavior can be ob- served and measured during combative encounters between the dominant male rat of an established colony and a smaller male intruder (see Blanchard & Blanchard, 1988). This is called the colony-intruder paradigm. The behaviors of the dominant male are considered to be aggressive and those of the hapless intruder defensive. The dominant male of the colony (the alpha male) moves sideways toward the intruder, with its hair erect. When it nears the intruder, it tries to push the intruder off balance and to deliver bites to its back and flanks. The defender tries to protect its back and flanks by rearing up on its hind legs and pushing the at- tacker away with its forepaws or by rolling onto its back. Thus, piloerection, lateral approach, and flank- and back- biting indicate conspecific aggression in the rat; freezing, boxing (rearing and pushing away), and rolling over indi- cate defensiveness.

Some tests of rat defensive behavior assess reactivity to the experimenter rather than to another rat. For example, it is common to rate the resistance of a rat to being picked up—no resistance being the lowest category and biting the highest—and to use the score as one measure of de- fensiveness (Kalynchuk et al., 1997).

The elevated plus maze, a four-armed, plus-sign-shaped maze that is typically mounted 50 centimeters above the floor, is a test of defensiveness that is commonly used to study in rats the anxiolytic (anxiety-reducing) effects of

drugs. Two of the arms of the maze have sides, and two do not. The meas- ure of defensiveness, or anxiety, is the

proportion of time the rats spend in the protected closed arms rather than on the exposed arms. Many established anxiolytic drugs significantly increase the proportion of time that rats spend on the open arms (see Pellow et al., 1985), and, conversely, many new drugs that prove to be ef- fective in reducing rats’ defensiveness on the maze often turn out to be effective in the treatment of human anxiety.

Tests of Sexual Behavior Most attempts to study the physiological bases of rat sexual behavior have focused on the copulatory act itself. The male mounts the female from behind and clasps her hindquarters. If the female is receptive, she responds by assuming the posture called lordosis; that is, she sticks her hindquarters in the air, she bends her back in a U, and she deflects her tail to the side. During some mounts, the male inserts his penis into the female’s vagina; this act is called intromission. After in- tromission, the male dismounts by jumping backwards. He then returns a few seconds later to mount and intro- mit once again. Following about 10 such cycles of mount- ing, intromitting, and dismounting, the male mounts, intromits, and ejaculates (ejects his sperm).

Three common measures of male rat sexual behavior are the number of mounts required to achieve intromis- sion, the number of intromissions required to achieve ejaculation, and the interval between ejaculation and the reinitiation of mounting. The most common measure of female rat sexual behavior is the lordosis quotient (the proportion of mounts that elicit lordosis).

Traditional Conditioning Paradigms

Learning paradigms play a major role in biopsychological research for three reasons. The first is that learning is a phe- nomenon of primary interest to psychologists. The second is that learning paradigms provide an effective technology for producing and controlling animal behavior. Because animals cannot follow instructions from the experimenter, it is often necessary to train them to behave in a fashion consistent with the goals of the experiment. The third rea- son is that it is possible to infer much about the sensory, motor, motivational, and cognitive state of an animal from its ability to learn and perform various responses.

If you have taken a previous course in psychology, you will likely be familiar with the Pavlovian and operant con- ditioning paradigms. In the Pavlovian conditioning par- adigm, the experimenter pairs an initially neutral stimulus called a conditional stimulus (e.g., a tone or a light) with an unconditional stimulus (e.g., meat powder)—a stimu- lus that elicits an unconditional (reflexive) response (e.g., salivation). As a result of these pairings, the conditional stimulus eventually acquires the capacity, when adminis- tered alone, to elicit a conditional response (e.g., salivation)— a response that is often, but not always, similar to the unconditional response.

In the operant conditioning paradigm, the rate at which a particular voluntary response (such as a lever press) is emitted is increased by reinforcement or de- creased by punishment. One of the most widely used operant conditioning paradigms in biopsychology is the self-stimulation paradigm. In the self-stimulation paradigm, animals press a lever to deliver electrical stimulation to particular sites in their own brains;

1255.8 ■ Biopsychological Paradigms of Animal Behavior

Clinical Clinical Implications Implications

IS B

N 0-

55 8-

78 57

1- 9

those structures in the brain that support self-stimulation are often called pleasure centers.

Seminatural Animal Learning Paradigms

In addition to Pavlovian and operant conditioning para- digms, biopsychologists use animal learning paradigms that have been specifically designed to mimic situations that an animal might encounter in its natural environ- ment (see Gerlai & Clayton, 1999). Development of these paradigms stemmed in part from the reasonable assump-

tion that forms of learning tending to benefit an animal’s survival in the wild are likely to be more highly developed and

more directly related to innate neural mechanisms. The following are four common seminatural learning para- digms: the conditioned taste aversion, radial arm maze, Morris water maze, and conditioned defensive burying.

Conditioned Taste Aversion A conditioned taste aversion is the avoidance response that develops to tastes of food whose consumption has been followed by illness (see Garcia & Koelling, 1966). In the standard condi- tioned taste aversion experiment, rats receive an emetic (a nausea-inducing drug) after they consume a food with an unfamiliar taste. On the basis of this single conditioning trial, the rats learn to avoid the taste.

The ability of rats to readily learn the relationship be- tween a particular taste and subsequent illness unques- tionably increases their chances of survival in their natural environment, where potentially edible substances are not routinely screened by government agencies. Rats and many other animals are neophobic (afraid of new things); thus, when they first encounter a new food, they consume it in only small quantities. If they subsequently become ill, they will not consume it again. Conditioned aversions also develop to familiar tastes, but these typi- cally require more than a single trial to be learned.

Humans also develop conditioned taste aversions. Cancer patients have been reported to develop aversions to foods consumed before nausea-inducing chemotherapy (Bern- stein & Webster, 1980). Many of you will be able to testify on the basis of personal experience about the effectiveness of conditioned taste aversions. I still have vivid memories of a long-ago batch of red laboratory punch that I overzealously consumed after eating two pieces of blueberry pie. But that is another story—albeit a particularly colorful one.

The discovery of conditioned taste aversion challenged three widely accepted principles of learning (see Revusky & Garcia, 1970) that had grown out of research on tradi- tional operant and Pavlovian conditioning paradigms. First, it challenged the view that animal conditioning is always a gradual step-by-step process; robust taste aver- sions can be established in only a single trial. Second, it showed that temporal contiguity is not essential for

conditioning; rats acquire taste aversions even when they do not become ill until several hours after eating. Third, it challenged the principle of equipotentiality—the view that conditioning proceeds in basically the same manner regardless of the particular stimuli and responses under investigation. Rats appear to have evolved to readily learn associations between tastes and illness; it is only with great difficulty that they learn relations between the color of food and nausea or between taste and footshock.

Radial Arm Maze The radial arm maze taps the well- developed spatial abilities of rodents. The survival of rats in the wild depends on their ability to navigate quickly and ac- curately through their environment and to learn which lo- cations in it are likely to contain food and water. This task is much more complex for a rodent than it is for us. Most of us obtain food from locations where the supply is continu- ally replenished; we go to the market confident that we will find enough food to satisfy our needs. In contrast, the for- aging rat must learn, and retain, a complex pattern of spa- tially coded details. It must not only learn where morsels of food are likely to be found but must also remember which of these sites it has recently stripped of their booty so as not to revisit them too soon. Designed by Olton and Samuelson (1976) to study these spatial abilities, the radial arm maze (see Figure 5.26) is an array of arms—usually eight or more—radiating from a central starting area. At the end of each arm is a food cup, which may or may not be baited, de- pending on the purpose of the experiment.

In one version of the radial arm maze paradigm, rats are placed each day in a maze that has the same arms baited each day. After a few days of experience, rats rarely visit un- baited arms at all, and they rarely visit baited arms more than once in the same day—even when control procedures make it impossible for them to recognize odors left during previous visits to an arm or to make their visits in a system- atic sequence. Because the arms are identical, rats must ori- ent themselves in the maze with reference to external room

126 Chapter 5 ■ The Research Methods of Biopsychology

FIGURE 5.26 A radial arm maze.

Evolutiona Evolutionary Perspective Perspective

Watch Stimulus Generalization and Stimulus Discrimination in Operant Conditioning www.mypsychlab.com

IS B

N 0-558-78571-9

1275.8 ■ Biopsychological Paradigms of Animal Behavior

FIGURE 5.27 These photos (viewed clockwise from top left) show a rat burying a test object from which it has just received a single mild shock. (Photographs by Jack Wong.)

cues; thus, their performance can be disrupted by rotation of the maze or by changes in the appearance of the room.

Morris Water Maze Another seminatural learning par- adigm that has been designed to study the spatial abilities of rats is the Morris water maze (Morris, 1981). The rats are placed in a circular, featureless pool of cool milky water, in which they must swim until they discover the escape platform—which is invisible just beneath the surface of the water. The rats are allowed to rest on the platform before being returned to the water for another trial. Despite the fact that the starting point is varied from trial to trial, the rats learn after only a few trials to swim directly to the plat- form, presumably by using spatial cues from the room as a reference. The Morris water maze is useful for assessing the navigational skills of brain-lesioned or drugged animals.

Conditioned Defensive Burying Yet another seminat- ural learning paradigm that is useful in biopsychological research is conditioned defensive burying (e.g., Pinel &

Mana, 1989; Pinel & Treit, 1978). In studies of conditioned defensive burying, rats receive a single aversive stimulus (e.g., a shock, air blast, or noxious odor) from an object mounted on the wall of the cham- ber just above the floor, which is littered with bedding material. After a single trial, almost every rat learns that the test object is a threat and responds by flinging bed- ding material at the test object with its head and forepaws (see Figure 5.27). Antianxiety drugs reduce the amount of conditioned defensive burying, and thus the para- digm is used to study the neurochemistry of anxiety (e.g., Treit, 1987).

Before moving on to the next chapter, you need to appre- ciate that to be effective these research methods must be used together. Seldom, if ever, is an important biopsycho- logical issue resolved by use of a single method. The reason for this is that nei- ther the methods used to manipulate the brain nor the methods used to assess the behavioral consequences of these manipulations are totally selective;

Thinking CreativelyThinking Creatively

IS B

N 0-

55 8-

78 57

1- 9

128 Chapter 5 ■ The Research Methods of Biopsychology

Themes Revisited

This chapter introduced you to the two kinds of research methods used by biopsychologists: methods of studying the brain and methods of studying behavior. In the descriptions of these methods, all four of the main themes of the book were apparent.

The chapter-opening case of Professor P. alerted you to the fact that many of the methods used by biopsychologists to study the human brain are also used clinically, in either

diagnosis or treatment. The clinical implications theme came up again during discussions of brain imaging, genetic engineering, neuropsychological testing, and use of the elevated plus maze to test anxiolytic drugs.

The neuroplasticity theme arose during the discussion of the methods of cognitive neuroscience. Experience can produce

changes in brain organization that can complicate the interpretation of functional brain images.

The evolutionary perspective theme arose in the discus- sion of green fluorescent protein, first isolated from jellyfish, and again during the discussion of the rationale for using seminatural animal learning paradigms, which assess animal be- havior in environments similar to those in which it evolved.

The thinking creatively theme came up several times. The development of new research methods often requires considerable creativity, and understanding the particular weaknesses and strengths of each research method is the foundation on which creative thinking rests.NeNeuroplasticityroplasticity

Evolutiona Evolutionary Perspective Perspective

Clinical Clinical Implications Implications

Thinking CreativelyThinking Creatively

Scan your brain to see how well you remember the behav-

ioral research methods of biopsychology. In each blank,

write the name of a behavioral test or paradigm. The

correct answers are provided at the end of the exercise.

Before proceeding, review material related to your

incorrect answers and omissions.

1. Many neuropsychological assessments begin with

the ______.

2. The most common test of short-term memory is

the ______.

3. The most common invasive test of language lateralization

is the ______.

4. The most common tests of explicit memory are the

______.

Scan Your Brainanswers: (1) WAIS, (2) digit-span test, (3) sodium amytal test,

(4) repetition priming tests, (5) Wisconsin Card Sorting Test, (6) paired-image

subtraction technique, (7) open-field test, (8) colony-intruder paradigm, (9)

elevated plus maze, (10) lordosis quotient, (11) self-stimulation paradigm,

(12) radial arm maze, (13) Morris water maze.

5. A common test of frontal-lobe damage is the ______.

6. PET and fMRI studies almost always employ the ______.

7. A commonly used test of rat fearfulness is the ______.

8. Male rats’ aggressive and defensive behavior is readily

assessed by the ______.

9. The most commonly used test of anxiolytic drug

effects is the ______.

10. The most common measure of the sexual receptivity of

a female rat is the ______.

11. Animals press a lever to deliver stimulation of their

own brains in the ______.

12. The spatial abilities of foraging rodents are often

assessed with a ______.

13. The ability of a rat to find an invisible safety platform

can be assessed in a ______.

there are no methods of manipulating the brain that change only a single aspect of brain function, and there are no measures of behavior that reflect only a single psycho- logical process. Accordingly, lines of research that use a sin- gle method can usually be interpreted in more than one

way and thus cannot provide unequivocal evidence for any one interpretation. Typically, important research questions are resolved only when several methods are brought to bear on a single problem. This general approach, as you learned in Chapter 1, is called converging operations.

IS B

N 0-558-78571-9

129Key Terms

Think about It

1. The current rate of progress in the development of new and better brain-scanning devices will soon render be- havioral tests of brain damage obsolete. Discuss.

2. You are taking a physiological psychology course, and your laboratory instructor gives you two rats: one rat with a lesion in an unknown brain structure and one normal rat. How would you test the rats to determine which one has the lesion? How would you determine the behavioral effects of the lesion? How would your approach differ from one that you might use to test a human patient sus- pected of having brain damage?

3. The search for the neural mechanisms of learning should focus on forms of learning necessary for survival in the wild. Discuss.

4. All patients should complete a battery of neuropsy- chological tests both before and after neurosurgery. Discuss.

5. The methods that biopsychologists use to study behavior are fundamentally different from the methods that they use to study the brain, and these fundamental differences lead to an under appreciation of behavioral methods by those who lack expertise in their use. Discuss.

6. Functional brain-imaging techniques are impressive and widely used, but they are far from perfect. Critically evaluate them.

PART ONE Methods of Studying the Nervous System

5.1 Methods of Visualizing and Stimulating the Living Human Brain

Contrast X-ray techniques (p. 103)

Cerebral angiography (p. 103) Computed tomography (CT)

(p. 103) Magnetic resonance imaging

(MRI) (p. 104) Spatial resolution (p. 104) Positron emission tomography

(PET) (p. 104) 2-Deoxyglucose (2-DG)

(p. 104) Functional MRI (fMRI)

(p. 105) BOLD signal (p. 105) Magnetoencephalography

(MEG) (p. 106) Temporal resolution

(p. 106) Transcranial magnetic

stimulation (TMS) (p. 107)

5.2 Recording Human Psychophysiological Activity

Electroencephalography (p. 107)

Alpha waves (p. 107) Event-related potentials (ERPs)

(p. 107) Sensory evoked potential

(p. 107) Signal averaging (p. 108) P300 wave (p. 108) Far-field potentials (p. 108) Electromyography (p. 109) Electrooculography (p. 109) Skin conductance level (SCL)

(p. 110) Skin conductance response

(SCR) (p. 110) Electrocardiogram (ECG or

EKG) (p. 110) Hypertension (p. 110) Plethysmography (p. 110)

5.3 Invasive Physiological Research Methods

Stereotaxic atlas (p. 111) Bregma (p. 111) Stereotaxic instrument

(p. 111) Aspiration (p. 111) Cryogenic blockade (p. 112)

5.4 Pharmacological Research Methods

Cannula (p. 115) Neurotoxins (p. 115) Autoradiography (p. 115) Cerebral dialysis (p. 115)

Immunocytochemistry (p. 116) In situ hybridization (p. 116)

5.5 Genetic Engineering

Gene knockout techniques (p. 116)

Gene replacement techniques (p. 117)

Transgenic mice (p. 117) Green fluorescent protein

(GFP) (p. 117) Brainbow (p. 118)

PART TWO Behavioral Research Methods of Biopsychology

Behavioral paradigm (p. 118)

5.6 Neuropsychological Testing

Wechsler Adult Intelligence Scale (WAIS) (p. 120)

Digit span (p. 120) Token test (p. 120) Sodium amytal test (p. 121) Dichotic listening test (p. 121) Repetition priming tests (p. 122) Wisconsin Card Sorting Test

(p. 122)

5.7 Behavioral Methods of Cognitive Neuroscience

Cognitive neuroscience (p. 123) Constituent cognitive processes

(p. 123)

Paired-image subtraction technique (p. 123)

Default mode (p. 123) Default mode network

(p. 123)

5.8 Biopsychological Paradigms of Animal Behavior

Species-common behaviors (p. 124)

Open-field test (p. 125) Thigmotaxic (p. 125) Colony-intruder paradigm

(p. 125) Elevated plus maze (p. 125) Lordosis (p. 125) Intromission (p. 125) Ejaculate (p. 125) Lordosis quotient (p. 125) Pavlovian conditioning

paradigm (p. 125) Operant conditioning

paradigm (p. 125) Self-stimulation paradigm

(p. 125) Conditioned taste aversion

(p. 126) Radial arm maze (p. 126) Morris water maze (p. 127) Conditioned defensive burying

(p. 127)

Key Terms

IS B

N 0-

55 8-

78 57

1- 9

130 Chapter 5 ■ The Research Methods of Biopsychology

Test your comprehension of the chapter with this brief practice test. You can find the answers to these questions as well as more practice tests, activities, and other study resources at www.mypsychlab.com.

1. A method of measuring the extracellular concentration of particular neurochemicals in the brain is

a. cerebral dialysis. b. immunocytochemistry. c. extracellular unit recording. d. intracellular unit recording. e. the 2-deoxyglucose technique.

2. Mice that have had genetic material of another species (e.g., a pathological human gene) inserted into their genome are called

a. knockout mice. b. transgenic mice. c. homozygous. d. heterozygous. e. both a and d

3. The most widely used test of short-term memory is the

a. token test. b. WAIS. c. sodium amytal test. d. digit span test. e. repetition priming test.

4. The colony-intruder paradigm is commonly used to study

a. natural environment. b. spatial perception. c. reproduction. d. epigenetics. e. aggressive and defensive behavior.

5. A seminatural animal learning paradigm that is often used to study spatial ability is

a. self-stimulation paradigm. b. conditioned defensive burying paradigm. c. radial arm maze. d. Morris water maze. e. both c and d

Quick Review

IS B

N 0-558-78571-9