Silencing the Inner Me We all have an inner voice: that mental narrator, sometimes annoying, whose dialogue wanders from calm abstraction ("What is love?") to urgent directives ("Pizza now!") to harsh self-criticism ("Way to go, fool!"). Some researchers, observing that the development of a child's sense of self is inextricably linked to the acquisition of language, have proposed that the inner voice is essential for the self-awareness that defines our consciousness. Nevertheless, sometimes we wish that Inner Me would just shut up for a while. But what would life be like if our inner voice actually were silenced? This is just what happened to Tinna Geula Phillips. Suddenly
one day, Tinna lost the ability to communicate in any of the six languages (yes, six) that she had mastered--a devastating neurological event. But even more profound was the immediate silencing of Tinna's inner voice. For several months, Tinna was unable to process thoughts in the way we take for granted. Tinna's internal silence had robbed her of a critical tool for organizing her activities, weighing her emotions, processing abstract concepts, and considering her memories. She would later describe the experience as a near-total loss of identity. What could have happened to cause Tinna to lose the ability to talk to anyone, even herself?
Faces, coloration, smells, sounds--many species use physical and behavioral signals to engage in communication, the transmission of information between individuals. But we humans may be alone in our use of language, the highly specialized form of communication in which arbitrary symbols or behaviors are assembled and reassembled in almost infinite variety and associated with a vast range of things, actions, and concepts. Because the speakers of a language all understand the same strict set of rules, or grammar, language allows us to assemble and share information on any topic, linking thinkers of the past with those of the future. In almost everyone, verbal abilities are especially associated with the left hemisphere of the brain, while the right hemisphere plays a prominent role in spatial cognition, our ability to navigate and to understand the spatial relationships between objects. In this chapter we survey the neuroscience of this cerebral lateralization, with a special emphasis on the acquisition, use, and brain mechanisms of speech and language. Much of what we know about human brain organization comes from studies of people who have had strokes and other forms of brain injury, so we will also look at the ways in which the damaged brain can recover and adapt.
15.1The Left and Right Hemispheres of the Brain Are Different
View Animation 15.2: Brain Explorer communication Information transfer between two individuals. language Communication in which arbitrary sounds or symbols are arranged according to a grammar in order to convey an almost limitless variety of concepts. grammar All of the rules for usage of a particular language. cerebral lateralization The division of labor between the two cerebral hemispheres such that each hemisphere is specialized for particular types of processing. corpus callosum The main band of axons that connects the two cerebral hemispheres. split-brain individual An individual whose corpus callosum has been severed, halting communication between the right and left hemispheres. contralateral In anatomy, referring to a location on the opposite side of the body.
The first section of the chapter looks at the functional differences between the two hemispheres of the brain. After you've read through this material, you should be able to: 15.1.1 Describe techniques for studying the left and right hemispheres independently of each other. 15.1.2 Summarize the apparent cognitive specializations of each hemisphere as revealed by behavioral testing. 15.1.3 Discuss the relationship of handedness to cerebral lateralization. The discovery that some brain functions are lateralized should not be especially surprising; after all, other body organs also show considerable asymmetry between the right and left sides. But when we study the behavior of people, cerebral lateralization of function is masked by the rich neural connections between the hemispheres: they communicate with each other so quickly and thoroughly that they seem to act as one. So researchers have to devise clever experimental techniques for use with healthy participants and carefully analyze symptom patterns in people with neurological conditions, in order to understand the specific behavioral functions of each hemisphere. Some rare and unfortunate people develop severe epilepsy that is very difficult to control with medication. Their frequent seizures start in one hemisphere and then spread to the other hemisphere through the corpus callosum--the huge white matter pathway consisting of hundreds of millions of axons that connect the two hemispheres. A surgical treatment of last resort--so invasive that it has been performed very infrequently (Gazzaniga, 2008)--is to cut the corpus callosum, preventing the spread of the seizure discharges from one hemisphere to the other. This operation, developed in the 1960s, significantly reduced the frequency and severity of seizures in affected people. It also changed their behavior in ways that presented a research opportunity: by analyzing the cognitive, perceptual, emotional, and motor behavior of these split-brain individuals, researchers were able to catalog the individual specializations of the newly isolated cerebral hemispheres. In Nobel Prize-winning research, Roger Sperry and his collaborators applied techniques perfected in split-brain cats to study split-brain humans. The researchers realized that by exploiting the organization of the sensory systems, stimuli could be directed exclusively to one hemisphere or the other. For example, stimuli felt with the left hand, or seen only in the left visual field, are first processed in the sensory cortex of the contralateral (opposite side) hemisphere (in this case, the right hemisphere). Normally, information about the stimuli would be shared with the other hemisphere immediately, via the corpus callosum. But in split-brain individuals, the sensory information remains trapped within the receiving hemisphere, so the person's response to the stimuli reflects the processing specializations of that hemisphere in isolation. In some studies of split-brain individuals, words were projected visually to either the left or the right hemisphere. The results were dramatic. Split-brain individuals could easily read and verbally report words projected to the left hemisphere (via the right visual field) but not words directed to the right hemisphere (FIGURE 15.1). Subsequent work (Zaidel, 1976) showed that the right hemisphere does have a limited amount of linguistic ability; for example, it can recognize simple words and the emotional content of verbal material. But in most people, vocabulary and grammar are the exclusive domain of the left hemisphere. The capabilities of the "mute" right hemisphere had to be tested by nonverbal means. For example, a picture of a key might be projected to the left visual field and so reach only the right visual cortex. The participant would then be asked to touch
At the optic chiasm, half of the bers from each eye cross over, so the left hemisphere sees the right visual eld, and vice versa.
Visual cortex (B) Split-brain participant "?"
FIGURE 15.1 Language Processing in Intact and Split-Brain Individuals
Words or pictures projected to the left visual eld activate the right visual cortex. In individuals with an intact corpus callosum, activation of the right visual cortex excites corpus callosum bers, which transmit the visual information to the left hemisphere, where its verbal content is analyzed and language is produced.
In split-brain individuals, stimuli from the left visual eld reach the right-hemisphere visual cortex (visual inputs are independent of the corpus callosum), but the split corpus callosum prevents the visual information from getting from the right hemisphere to the language areas of the left hemisphere, making verbal responses to the stimuli impossible.
Split-brain individuals can respond verbally to stimuli appearing in the right visual eld because interhemispheric transfer via the corpus callosum is not required in this case.
several different objects that they could not see and hold up the correct one. Such a task could be performed correctly by the left hand (controlled by the right hemisphere) but not by the right hand (controlled by the left hemisphere). So in this case, the left hemisphere literally does not know what the left hand is doing! In general, these and Woathtseonr /sBturedeidelsovwe ith split-brain individuals provided evidence that, in most people, the The Mind's Machine Froiugnhdtathioenms oifsBprhaienraendisBsephaevcioiar l4iezed for processing spatial information. Right-hemisphere mechanisms are also crucial for face perception, for processing emotional aspects of MlaMn4geu_a15g.e01, an0d9/fo01r/c2o0ntrolling attention (as we discussed in Chapter 14).
Left Right Although sounds presented to either ear reach both sides of the brain, the auditory information is mostly processed by the contralateral hemisphere (see Chapter 6). So, verbal information presented to the left ear is rst processed by the right auditory cortex and then transmitted to speech systems in the left hemisphere. Participant repeats the word. "pa" (B)
Verbal information presented to the right ear is processed by the left auditory cortex and then passed directly to speech systems within the same hemisphere. "pa" (C) ma pa ma ma pa
When con icting information goes to both ears, the information to the right ear reaches the left hemisphere's speech system first. Subject repeats only the right-ear information.
Almost all types of behavior, from manual skills to intellectual activities, are performed better by the two hemispheres working together than by either hemisphere working alone. For this reason, and because better medical options have also been developed, the split-brain surgery has remained a very rare procedure, and the few modern forms of the operation generally cut only about a third of the corpus callosum. The two hemispheres process information differently in most people Most research on brain asymmetry in healthy people focuses on two sensory modalities: hearing and vision. That's because researchers have devised clever procedures for directing auditory or visual stimuli mostly to one hemisphere or the other and then inferring hemispheric specializations from the participants' behavior. THE RIGHT-EAR ADVANTAGE Through earphones, we can present different sounds to the two ears at the same time--a technique called dichotic presentation. So, for example, a participant may hear a particular speech sound in one ear and, at the same time, a different vowel, consonant, or word in the other ear. The participant is asked to try to identify or recall both sounds. Although this procedure may seem designed to produce confusion, in general, right-handed people identify verbal stimuli delivered to the right ear more accurately than the stimuli simultaneously presented to the left ear. This result is described as a right-ear "advantage" for verbal information. In contrast, up to 50% of left-handed individuals may show a reduced or reversed pattern, with either no difference between the ears or a clear left-ear advantage. As a consequence of the preferential connections between the right ear and the left hemisphere, the right-ear advantage for verbal stimuli confirms the idea that the left hemisphere is specialized for language (FIGURE 15.2). Although we can normally use either ear for processing speech sounds, speech presented to the right ear in dichotic presentation tests exerts stronger control over language mechanisms in the left hemisphere than does speech simultaneously presented to the left ear (Kimura, 1973). The competition between the left- and right-ear inputs is the key; presentation of speech stimuli to one ear at a time (monaural presentation) does not produce a right-ear advantage. VISUAL PERCEPTION OF LINGUISTIC STIMULI Another way to study hemispheric specialization is to use a tachistoscope test to pit the two hemispheres against each other, using a device (called a tachistoscope, surprisingly; pronounced "ta-KISS-toe-scope") that very briefly presents visual stimuli to the left or right half of the visual field (see Figure 7.10 and Figure 15.1). If the stimulus exposure lasts less than 150 milliseconds or so, input is restricted to one hemisphere because there is not enough time for the eyes to shift their direction. In humans with intact brains, of course, further processing may involve the transmission of information through the corpus callosum to the other hemisphere.
FIGURE 15.2 The Right-Ear Advantage in Dichotic Presentation (After D. Kimura. 1973. Sci. Am. 228: 70.)
Watson/Breedlove The Mind's Machine Foundations of Brain and Behavior 4e
Most tachistoscopic studies confirm the general verbal-spatial division of labor between the hemispheres. Verbal stimuli (words and letters) presented to the right visual field (so the left hemisphere) are recognized more accurately than the same input presented to the left visual field (right hemisphere). Conversely, nonverbal visual stimuli (such as faces or geometric forms) presented to the left visual field (right hemisphere) are better recognized than the same stimuli presented to the other side. Simpler visual processing, such as the detection of light, hue, or simple patterns, is performed equivalently by the two hemispheres. The left and right hemispheres differ in their auditory specializations Anatomical studies of primary auditory cortex in the left and right hemispheres are consistent with the view that the two play different roles in auditory perception. In one early postmortem study of auditory cortex, the planum temporale--an auditory region on the superior surface of the temporal lobe--was found to be larger in the left hemisphere than in the right in most of the brains studied (Geschwind and Levitsky, 1968) (FIGURE 15.3A). In only 11% of adults was the right side larger. The planum temporale includes part of a posterior cortical region called Wernicke's area, which we'll see a little later is important for language, so it seems likely that the larger left planum temporale is related to that hemisphere's language specialization. Direct evidence of this relationship, however, remains somewhat elusive: in one MRI study, for example, asymmetry of the planum temporale did not correlate with direct measures of language lateralization (Dorsaint-Pierre et al., 2006). As in adults, regions around the Sylvian fissure, including the planum temporale, are larger on the left than the right in the brains of infants and fetuses (Wada et al., 1975; Rajagopalan et al., 2011). The presence of this difference in our brains before we begin to speak therefore bolsters the view that we are born with a predisposition to acquire language in the left hemisphere. In fact, by just 12-14 weeks of gestation, a variety of genes show asymmetrical expression in the fetal human brain (Sun et al., 2005). The planum temporale likewise tends to be larger on the left than on the right in chimpanzees, but not in monkeys, indicating that this brain asymmetry evolved in an ancestral species before the hominids (including us) split off from the great apes (Gannon et al., 1998; Lyn et al., 2011). An anterior zone implicated in speech in humans (Broca's area, which we'll discuss shortly) is also larger on the left in chimps, bonobos, and gorillas, as it is in humans (Cantalupo and Hopkins, 2001). Furthermore, just as our left hemisphere is more activated than the right when we hear speech rather than other
Sectioning the brain as shown (A) by this red line...
...reveals the structures of the upper surface of the temporal lobe identi ed here, especially the planum temporale. Anterior
dichotic presentation The simultaneous delivery of different stimuli to both the right and left ears at the same time. tachistoscope test A test in which stimuli are very briefly presented to either the left or right visual half field. planum temporale An auditory region of superior temporal cortex.
FIGURE 15.3 Structural Asymmetry of the Human Planum Temporale (After G. Schlaug et al. 1995. Science 267: 699.)
If we view the brain from above as if the overlying cortex were transparent, we see that in the musician with perfect pitch the planum temporale (red) is much larger in the left hemisphere than in the right.
In the nonmusician, the asymmetry of the planum temporale is much less distinct.
Whorls Apart Because of the relationship between handedness and features such as the whorl of hair at the crown of the scalp--the whorl is clockwise in 93% of right-handers but randomly clockwise or counterclockwise in nonright-handers--it has been suggested that a single gene has a major (but not absolute) influence on asymmetries throughout the body (Klar, 2003; Corballis, 2014). Other aspects of development presumably account for the remaining variability in hand preference. prosody The perception of emotional tone-of-voice aspects of language.
sounds, the left hemisphere of monkeys is more activated than the right when they hear monkey vocalizations rather than human speech (Poremba et al., 2004), and their perception of monkey vocalizations is far more impaired by left- than by right-hemisphere damage (Heffner and Heffner, 1984). These results and others indicate that primate brains are asymmetrically organized and contain a left-hemisphere specialization for communication (but not necessarily language) (Hopkins et al., 2015). In contrast, the auditory areas of the right hemisphere play a major role in the perception of music. Musical perception is especially impaired after damage to the right hemisphere, and many aspects of music activate the right hemisphere more than the left (Zatorre et al., 1994; Nan and Friederici, 2013). In musicians, however, advanced skills and perfect pitch (the ability to accurately name a musical note just by listening to it) appear to strongly rely on left-hemisphere mechanisms (FIGURE 15.3B) and enhanced connectivity between the left and right planum temporale (Schlaug et al., 1995; Elmer et al., 2016), perhaps owing to its verbal aspects. Despite these data, we cannot assign the perception of speech and pitch entirely to the left hemisphere and the perception of music entirely to the right hemisphere. We have seen that the right hemisphere can play a role in speech perception even in people in whom the left hemisphere is speech-dominant. In addition, the perception of emotional tone-of-voice aspects of language, termed prosody, is a right-hemisphere specialization. Furthermore, although damage to the right hemisphere can impair the perception of music, it does not abolish it. Damage to both sides of the brain can more completely impair or totally wipe out musical perception (Samson et al., 2002). Thus, even though each hemisphere plays a greater role than the other in different kinds of auditory perception and other aspects of intellect, the two hemispheres appear to collaborate in most functions. The notions that the two hemispheres are so different that they need separate instruction and that some people are especially "right-brained" (supposedly more random, intuitive, and creative) or "left-brained" (supposedly logical, sequential, and analytical) lack any scientific foundation. Handedness is associated with cerebral lateralization Classic surveys of hand preferences, such as the incidence of left-handed writing in American college populations (Spiegler and Yeni-Komshian, 1983), indicated that 10- 15% of the population is left-handed, although the estimated prevalence seems to vary somewhat through history and across geographic regions (Leask and Beaton, 2007). In a tiny minority of cases, early brain injuries may prompt a shift to left-handedness, but studies of achievement, ability, and cognitive function in school-age children find little evidence of any relationship between handedness and cognitive abilities (Faurie et al., 2006). Artifacts from prehistoric human societies suggest that a predominance of right-handedness is probably an ancient human characteristic, possibly in concert with hemispheric specializations for throwing and speech (Watson, 2001). Furthermore, a preference for one hand or the other seems to be a trait we share with our closest primate relatives: population-level hand preference is observed in gorillas, chimps, and bonobos (they're mostly right-handers) and orangutans (mostly lefties) (Hopkins et al., 2015). Some researchers even argue that hemispheric asymmetry and limb preferences reflect a left-right division of labor that, as a matter of processing efficiency, arose in the first vertebrates, hundreds of millions of years ago (MacNeilage et al., 2009). This view is bolstered by the discovery that in mice, left-hemisphere neurons differ from their right-hemisphere counterparts in both their expression of neurotransmitter receptors and their physiological functioning (Kohl et al., 2011; Shipton et al., 2014). Handedness may have a genetic component, but if so, it is not a simple single-gene effect. Genes that play a role in asymmetry throughout the body, ranging from the shape of internal organs to the pattern of hair whorls on the scalp, may be involved (Corballis, 2014). In any case, the evidence indicates that cerebral lateralization may be an ancient and ubiquitous adaptation. (For other examples of the evolution of asymmetry, see A STEP FURTHER 15.1, on the website.)
Reversibly shutting down one hemisphere reveals its specializations
Scientists estimate that 90-95% of humans have a left-hemisphere specialization for language. But how can we be certain which hemisphere is dominant for language (or other functions, such as spatial memory or music perception) in people who haven't had a stroke? In some cases, prior to brain surgery for example, it can be crucial to understand an individual's specific lateralization. By injecting a short-acting anesthetic (amobarbital) into the carotid artery--first on one side (as shown in the figure) and then later, on the other--it is possible to simulate a massive stroke, shutting down each hemisphere for a few minutes (FIGURE 15.4) (Wada and Rasmussen, 1960; Sharan et al., 2011). This is just long enough to use behavioral measures to document the specializations of each hemisphere. This Wada test confirms that most people have left-hemisphere specialization for language, regardless of handedness. The reverse pattern (right-hemisphere dominance for language) is uncommon, but when it occurs, it is more usually in left-handed people. Similar results can be obtained in healthy people by using transcranial magnetic stimulation (TMS) (Knecht et al., 2002) or fMRI.
FIGURE 15.4 A Simulated Stroke The Wada test uses anesthetic to shut down one hemisphere at a time.
2 ...temporarily shuts down the cerebral hemisphere on the same side, thereby revealing the functions performed by that hemisphere.
1 Injection of the anesthetic amobarbital into the carotid artery, via a catheter...
"I can still talk just fine, but I can't seem to hold my left arm up."
Question Which hemisphere is specialized for language in an individual? Hypothesis WThaatstolna/nBgreueadgloevies a left-hemisphere function in most people, irrespective Tohf ethMeiinr dh'sanMdaecdhnineess Foundations of Brain and Behavior 4e MMT4ees_t15.04 07/15/20 Silence one hemisphere by perfusing it with anaesthetic while the person performs cognitive tasks, including speech tests. Later, repeat with the other hemisphere. In most people, shutting down the left hemisphere, but not the right hemisphere, interrupts language function
1. Summarize the cardinal differences between the left and right hemispheres of the human brain. How were these functional differences first identified? 2. Describe the dichotic presentation test and tachistoscope test. How do these tests reveal lateralization of function? 3. Discuss the representation of music in the human brain. What is the planum temporale, and how does its structure relate to musical experience? 4. Summarize the neural underpinnings of left-handedness. Do left-handers generally show reversed asymmetry, with language vested in the right hemisphere?
Wada test A test in which a short-lasting anesthetic is delivered into one carotid artery to determine which cerebral hemisphere principally mediates language.
15.2Right-Hemisphere Damage Impairs Specific Types of Cognition
astereognosis The inability to recognize objects by touching and feeling them. prosopagnosia Also called face blindness. A condition characterized by the inability to recognize faces. fusiform gyrus A region on the inferior surface of the cortex, at the junction of the temporal and occipital lobes, that has been associated with recognition of faces. agnosia The inability to recognize objects, despite being able to describe them in terms of form and color. Agnosia may occur after localized brain damage.
Our next section looks at some specific processing deficits that can result from right-hemisphere lesions. After studying this material you should be able to: 15.2.1 Itemize the types of deficits seen after right-hemisphere lesions, relating the deficits to specific anatomical locations within the hemisphere. 15.2.2 Describe the clinical features of prosopagnosia and related disorders. 15.2.3 Discuss the anatomy and specialized functions of the fusiform system. When studied with behavioral or imaging techniques that highlight differences between the hemispheres, people reliably demonstrate a right-hemisphere advantage for processing spatial stimuli. Geometric shapes and their relations, direction sense and navigation, face processing, imagined three-dimensional rotation of objects held in the mind's eye--these are a few examples of the kinds of spatial processing that preferentially rely on the right hemisphere. It is therefore no surprise that right-hemisphere lesions--especially more-posterior lesions that involve the temporal and parietal lobes--tend to produce a variety of striking impairments of spatial cognition, such as inability to recognize faces, spatial disorientation, inability to recognize objects by touch, or the complete neglect of one side of the body that we discussed in Chapter 14. The diversity of behavioral changes following injury to the parietal lobe is related partly to the large expanse of this lobe and its critical position, abutting all three of the other cortical lobes. The anterior end of the parietal region includes the postcentral gyrus, which is the primary cortical receiving area for somatic sensation. In addition to alterations in touch sensitivity on the opposite side of the body, brain injury in this area can produce impairments in much more complex forms of sensory processing. In one example, objects placed in the hand opposite the injured somatosensory area can be felt but cannot be identified by touch and active manipulation. This deficit is called astereognosis (from the Greek a-, "not"; stereos, "solid"; and gnosis, "knowledge"). More-extensive injuries in the parietal cortex, beyond the postcentral gyrus, affect interactions between or among sensory modalities, such as visual or tactile matching tasks, which require the participant to visually identify an object that is touched or to reach for an object that is identified visually. In prosopagnosia, faces are unrecognizable Suppose that one day you look in the mirror, and someone totally unfamiliar is looking back at you. As incredible as this scenario might seem, some individuals develop exactly this problem following damage to specific brain sites. In this rare syndrome, called prosopagnosia (from the Greek prosop-, "face"; a-, "not"; and gnosis, "knowledge") or face blindness, affected individuals fail to recognize not only their own faces but also the faces of relatives and friends. No amount of remedial training restores their ability to recognize anyone's face. In contrast, the ability to visually recognize objects may be retained, and the person may have no difficulty identifying people by their voices. To people with prosopagnosia, faces simply lack meaning. No disorientation or confusion accompanies this condition, nor is there evidence of diminished intellectual abilities or significant visual impairment. Research with people whose right hemispheres have been impaired during strokes or shut down by Wada tests indicates that the right hemisphere is especially important for processing faces. For example, shutting down the right hemisphere with anesthetic during the Wada test can cause difficulty in recognizing faces, whereas anesthetizing the left hemisphere has less effect on facial recognition. This effect can be especially evident for recognizing one's own face (FIGURE 15.5).
FIGURE 15.5 Use of the Right Hemisphere
From J. P. Keenan et al. 2001. Nature 409: 305, courtesy of Julian Keenan
Anesthetizing the left hemisphere in a Wada test does not interfere with a subject's ability to recognize her own face in a picture that is a composite of her face and the face of a celebrity...
...but when the right hemisphere is anesthetized, the subject interprets the composite face as that of the celebrity.
Similarly, early work found that split-brain Watson/Breedlove ThienMdiinvdid'suMaalschdinoe a better job of recognizing faces Fotuhndaattiaonres opf rBerasiennatneddBethoavtihore4reight hemisphere than to the left (Gazzaniga and Smylie, 1983). Still, MM4e_15.05 07/15/20 data from split-brain individuals and functional-imaging studies make it clear that both hemispheres have some capacity for recognizing faces. Thus, although damage restricted to the right hemisphere can impair face processing, the most complete cases of prosopagnosia are caused by bilateral damage. The fusiform gyrus, a region of cortex on the inferior surface of the brain where the occipital and temporal cortices meet (FIGURE 15.6), is a central component of a network for face recognition (Rezlescu et al., 2014) and seems to play a special role in recognizing stimuli within specific categories (Weiner and Zilles, 2016; Grill-Spector et al., 2017). Individuals with prosopagnosia following brain damage almost always have damage here. Prosopagnosia may be accompanied by additional forms of agnosia, an inability to identify individual items--makes of cars, tools, bird species, sounds, and so on--in the absence of any specific sensory deficits or memory problems (Haque et al., 2018). Functional-MRI studies of healthy people show that, as with face recognition, the fusiform region is activated not
In this view from below the brain, the cerebellum has been removed to reveal the region of cortex that normally lies opposite to it.
Fusiform gyrus The fusiform gyrus, at the juncture of the temporal and occipital lobes, is active during discrimination of objects within large categories, such as faces or birds or cars. Bilateral destruction of this region leads to prosopagnosia, the inability to recognize individual faces.
Occipital lobe FIGURE 15.6 The Fusiform Gyrus
476CHAPTER15 See Video 15.4: Face Blindness
only when people are identifying faces, but also when identifying birds, or cars, or individual members of many other categories, especially if the participants have relevant expertise (birders, car enthusiasts, and so on) (McGugin et al., 2012; Ross et al., 2018). It remains to be seen exactly how many distinct categories are individually represented in the brain, and the extent to which brain regions other than the fusiform gyrus may participate (Connolly et al., 2012). Until recently, it was believed that prosopagnosia occurred solely as a result of brain damage (acquired prosopagnosia), but a number of cases of congenital prosopagnosia (congenital means "present at birth") have now been identified. Unexpectedly, surveys reveal that about 2.5% of the general population is sufficiently impaired in processing faces to meet the criteria for congenital prosopagnosia (Kennerknecht et al., 2006; Duchaine et al., 2007). The congenital form of prosopagnosia appears to run in families, indicating a genetic aspect to the disorder (Grüter et al., 2008; De Luca et al., 2019). Congenital prosopagnosia is associated with reduced activation of the fusiform gyrus, in keeping with the anatomical findings in acquired prosopagnosia that we've already discussed. At the other end of the spectrum, some people are exceptionally good with faces. These "super-recognizers," who are about as good with faces as people with prosopagnosia are bad, are actively recruited by some police forces (Russell et al., 2009; Robertson et al., 2016), although efforts are underway to see if devices relying on artificial intelligence can do an even better job (Hill, 2020). (You can learn more, and test your own facial recognition ability, at www.testmybrain.org.) 1. In general, what are the behavioral consequences of right-hemisphere damage in humans? 2. Define, compare, and contrast two of the most striking symptoms of right-hemisphere damage: astereognosis and prosopagnosia. Which areas of the brain appear to be involved in each? 3. Is prosopagnosia always associated with brain damage? What other behavioral abnormalities may co-occur with prosopagnosia?
phoneme A sound that is produced for language. morpheme The smallest grammatical unit of a language; a word or meaningful part of a word.
15.3 Left-Hemisphere Damage Can Cause Aphasia Brain damage restricted to the left hemisphere has predictable effects on behavior, especially language processes. After reading this section, you should be able to: 15.3.1 Distinguish among aphasia, apraxia, agraphia, and alexia. 15.3.2 Describe Broca's area and the behavioral consequences of lesions that include this area. 15.3.3 Define Wernicke's area and the behavioral consequences of lesions that include this area. 15.3.4 Describe global aphasia, its causes and prognosis, and its relationship to concepts of personal identity. 15.3.5 Contrast the motor theory of speech perception with the Wernicke-Geschwind model, and discuss research findings for and against each. 15.3.6 Summarize research using brain stimulation, functional brain imaging, and ERPs to map the brain's language network. All human languages share certain basic features. Each language has basic speech sounds, or phonemes, that are assembled into simple units of meaning called morphemes (FIGURE 15.7). Morphemes are assembled into words: the word unfathomable,
for example, consists of the morphemes un-, fathom, and -able, each of which adds meaning (termed semantics in linguistics). (Note that
a morpheme is not the same thing as a syllable; there are two sylla-
bles but only one morpheme in fathom). In turn, the words are as-
sembled into meaningful strings (which may be complete sentences or just phrases) according to the language's syntax (grammatical rules). Our speech is colored and clarified both by the context of
the utterance, which is known as pragmatics in linguistics, and by
the emotional tone and emphasis (called prosody) that we add to
the things we say. Physicians and scientists have known for centuries that brain damage can disrupt our use of the basic speech sounds and gram-
mar that make up our language abilities, a disorder known as
aphasia (Finger, 1994). Left-hemisphere damage in particular can impair language to varying degrees, depending on the location and extent of the injury. In cases of severe damage, people may lose the ability to produce any speech whatsoever. People with less severe damage may exhibit speech with paraphasia--insertion of
In English, some phonemes are depicted as a combination of letters, such as "th." Words are strung together according to the grammatical rules of a language--the syntax--to communicate meaning to others.
incorrect sounds or words--along with labored, effortful speech production. Somewhere in the range of 25-50% of people who
FIGURE 15.7 It's All in a Word
have a significant stroke (see Figure 1.17) will have aphasia as a
primary symptom; for this reason, a sudden problem with language is considered to
be one of the core warning signs of a stroke (see Figure 1.18), along wWitahtswone/aBkreneedslosve
or numbness on one side and dizziness, altered vision, or confusion. SuTchhe sMyimndp'stoMmacshine syntax The grammatical rules for
are reason to seek emergency treatment immediately. Most people withFoaupndhaatisoinas aoflsBorain andcBoehnasvtirourc4teing phrases and sentences
show some impairment in writing, known as agraphia, and disturbancMesMin4er_e15a.d07ing0,6/12/20
called alexia. Brain damage that produces aphasia also produces a distinctive motor
impairment called apraxia (see Chapter 5), characterized by great difficulty in mak-
ing precise sequences of movements, despite the absence of weakness or paralysis. In
fact, as we discuss later, some theorists view aphasia as primarily a disorder of motor is caused by brain injury.
control. Research has distinguished several major categories of aphasia, differing from paraphasia A symptom of aphasia
one another in the patterns of symptoms that occur (videos of people with aphasia can
that is distinguished by the substitution
Damage to a left anterior speech zone causes nonfluent (or Broca's) aphasia
an unintended word, or a neologism (a meaningless word). agraphia The inability to write.
In the mid-1800s, French neurologist Paul Broca (1824-1880) examined a man who had lost the ability to utter more than the single syllable "tan" (FIGURE 15.8). Following postmortem analysis, Broca reported that this man, and other people with similar severe impairments of speech production, had sustained brain damage
alexia The inability to read. apraxia An impairment in the ability to carry out complex sequential movements, even though there is no muscle paralysis.
From N. F. Dronkers et al. 2007. Brain 130: 1432
Study of this brain and similar cases led Paul Broca to identify a region in the anterior left hemisphere that is specialized for speech. 5 3 1
Damage in what is now known as Broca's area is clearly evident in these horizontal sections, corresponding to levels 2 and 3 on the orientation gure.
FIGURE 15.8 The Brain of "Tan" Photo and MRI image of the preserved brain of M. Leborgne, who could only utter the syllable "tan" after his brain injury.
FIGURE 15.9 Left-Hemisphere Speech and Language Areas in Humans
Primary somatosensory cortex Supramarginal gyrus
Lesions in the left anterior Broca's area result in non uent aphasia, with reduced speech output.
Angular gyrus Damage to the temporoparietal Wernicke's area results in uent aphasia, with impaired comprehension and garbled speech output.
that included a left inferior frontal region that now bears his name--Broca's area
(FIGURE 15.9). Damage that includes Broca's area often produces a type of aphasia
Watson/Breedlovkenown as nonfluent aphasia (or Broca's aphasia). People with nonfluent aphasia have
View Activity 15.1: The Mind's Machainleot of difficulty producing speech, talking only in a labored and hesitant manner.
Reading and writing are also impaired. The ability to utter automatic speech, how-
MM4e_15.09 0e6/v1e2r/, 2i0s often preserved. Such speech includes greetings ("Hello"); short, common
expressions ("Oh my gosh!"); and swear words.
Compared with their difficulty with speech production, comprehension of language
is relatively good in people with nonfluent aphasia. Because the primary and supple-
mentary motor cortex is close to Broca's area (see Chapter 5), brain injuries that cause
nonfluent aphasia often also cause hemiplegia--paralysis of one side of the body
Broca's area A region of the frontal lobe of the brain that is involved in the production of speech. nonfluent aphasia Also called Broca's aphasia. A language impairment characterized by difficulty with speech produc-
(usually the right side, which is controlled by the left hemisphere). Sometimes there is unilateral weakness, termed hemiparesis, rather than full paralysis. The CT scans in FIGURE 15.10A and maps of lesion sites in FIGURE 15.10B are from several people with nonfluent aphasia. Seven years after a stroke, one such person still spoke slowly, using mainly nouns and very few verbs or function words (a selective loss of action words, called averbia, sometimes occurs in nonfluent aphasia),
tion but not with language comprehension.
and spoke only with great effort. When asked to repeat the phrase "Go ahead and
do it if possible," she could say only, "Go to do it," with a pause between each word.
Her pattern is typical of people with extensive left anterior damage. People with brain
lesions as extensive as hers tend to show little recovery of speech functions with the
passing of time, but people with milder damage can show significant recovery.
Wernicke's area A region of temporoparietal cortex in the brain
Damage to a left posterior speech zone causes fluent (or Wernicke's) aphasia
that is involved in the perception and production of speech. fluent aphasia Also called Wernicke's aphasia. A language impairment characterized by fluent, meaningless speech and little language comprehension. It is related
Not long after Broca's groundbreaking discovery of the left anterior speech zone, German neurologist Carl Wernicke (pronounced "VER-nih-keh") (1848-1905) described a different form of aphasia, resulting from damage to a more posterior region of the left hemisphere, on the upper part of the temporal lobe near where it joins the parietal lobe, that is now known as Wernicke's area (see Figure 15.9). Unlike people with nonfluent
aphasia, people who have this fluent aphasia (or Wernicke's aphasia) produce plenty of
SM + 2 SM + 1 SM W BW B Broca's area Wernicke's area
Primary motor cortex Primary somatosensory cortex Supramarginal gyrus
FIGURE 15.10 Brain Lesions That Produce Aphasia (After M. Naeser and R. Hayward. 1978. Neurology 28: 545.)
To make the maps shown below, brain CT scan "slices" were labeled according to the brain language regions shown in each slice: B, Broca's area; SM, supramarginal gyrus; W, Wernicke's area.
(A) This 51-year-old patient had non uent (Broca's) aphasia as a result of a stroke that included Broca's area.
(B) Here the lesions (in blue) of four patients with nonfluent (Broca's) aphasia are drawn as overlapping maps.
(C) Lesion sites for four cases of fluent (Wernicke's) aphasia are mapped on these drawings.
(D) These drawings show lesion sites for ve cases of global aphasia. Large lesions are present in every language area.
Watson/Breedlove The Mind's Machine Foundations of Brain and Behavior 4e
Image © Guillermo F. Florez, speechlessdoc.com
verbal output, but their utterances, although speech-like, tend to contain many paraphasias, such as sound substitutions (e.g., "girl" becomes "curl") and/or word substitutions (e.g., bread becomes cake). Invented nonsense words--neologisms-- are also common. Some fluent aphasias are marked by a particular difficulty in naming persons or objects--an impairment referred to as anomia. The ability to repeat words and sentences is impaired. For this reason, people with fluent aphasia are believed to have difficulty comprehending what they read or hear. Lesions that produce fluent aphasia usually include the posterior parts of the superior left temporal lobe, extending into adjacent regions of parietal cortex. Examples of lesions causing fluent aphasia are shown in FIGURE 15.10C. Sometimes people who have had strokes experience word deafness (the inability to understand spoken words), which usually means that auditory regions of the temporal lobe are particularly affected. Other people may instead experience word blindness (the inability to understand written words), usually indicating damage that includes connections to visual regions. Because the typical lesion in fluent aphasia is posterior, involving Wernicke's area, the postcentral somatosensory cortex is more likely to be damaged than precentral motor cortex. As a result, people with fluent aphasia are somewhat more likely to have a right-sided numbness than the weakness common in nonfluent aphasia.
Speechless Tinna Geula Phillips, who sustained a stroke that robbed her of all language abilities, including her inner monologue, is profiled in a documentary entitled Speechless, by filmmaker Guillermo Florez (www.speechlessdoc.com).
Widespread left-hemisphere damage can obliterate language capabilities In some people, brain injury or disease results in total loss of the ability to understand or produce language. This syndrome, called global aphasia, was the diagnosis in the case of Tinna, the woman we met at the beginning of the chapter. People with global aphasia may retain some ability to make speech-like sounds, especially emotional exclamations. But they can utter very few words, and no semblance of syntax remains. Global aphasia generally results from very large left-hemisphere lesions that encompass both anterior and posterior language zones. Frontal, temporal, and parietal cortex--including Broca's area, Wernicke's area, and the supramarginal gyrus (see Figure 15.9)--are usually affected (FIGURE 15.10D). For nearly 2 years after Tinna had a massive left-hemisphere stroke, in her forties, it was unclear whether she would ever regain the ability to communicate in any of her six languages, and even her inner monologue was banished for several months, taking with it her personal identity. Although Tinna has regained some degree of both outward and inward language, her verbal abilities remain quite impoverished. This is in keeping with the generally poor prognosis for language recovery in global aphasia. And because of the extent of their lesions, people with global aphasia often experience additional debilitating neurological impairments.
anomia The inability to name persons or objects readily. global aphasia The total loss of ability to understand language, or to speak, read, or write. connectionist model of aphasia Also called the Wernicke-Geschwind model. A theory proposing that left-hemisphere language deficits result from disconnection between the brain regions in a language network, each of which serves a particular linguistic function. arcuate fasciculus A fiber tract classically viewed as a connection between Wernicke's speech area and Broca's speech area.
Competing models describe the left-hemisphere language network Considering how language is intertwined with so many other functions, it is not surprising that a complete description of the brain's language circuitry remains elusive. The traditional connectionist model of aphasia (FIGURE 15.11)--also known as the Wernicke-Geschwind model after its leading proponents (Geschwind, 1972)--argues that language deficits result from disconnection between the brain regions in a language network. Each of these regions is proposed to serve a particular feature of language analysis or production. So, for example, this model proposes that when a word or sentence is heard, the auditory cortex transmits information about the sounds to a speech reception mechanism in Wernicke's area, where the sounds are analyzed to decode what they mean. In order for the word to be spoken aloud, the connectionist account posits, Wernicke's area transmits this information, via a bundle of axons called the arcuate fasciculus, to the expressive mechanism in Broca's area, where a speech plan is activated. Broca's area then transmits this plan to adjacent motor cortex, which controls the muscles of the chest, throat, and mouth that are used for speech
(A) Speaking a heard word 1 Information about the sound is analyzed by primary auditory cortex and transmitted to Wernicke's area. 2 Wernicke's area analyzes the sound information to determine the word that was said. 3 Under the connectionist model this information is transmitted via the arcuate fasciculus. (Note, however, that anatomical research casts doubt on this projection.) (B) Speaking a written word 1 Visual cortex analyzes the image and transmits the information about the image to the angular gyrus. 2 The angular gyrus decodes the image information to recognize the word and associate this visual form with the spoken form in Wernicke's area. 3 Information about the word is transmitted via the arcuate fasciculus to Broca's area.
4 Broca's area forms a motor plan to repeat the word and sends that information to motor cortex.
5 Motor cortex implements the plan, manipulating the larynx and related structures to say the word.
Lesions of the arcuate fasciculus disrupt the transfer from Wernicke's area to Broca's area, so the patient has dif culty repeating spoken words (so-called conduction aphasia), but may retain comprehension of spoken language (because of intact Wernicke's area) and may still be able to speak spontaneously (because of intact Broca's area).
4 Broca's area formulates a motor plan to say the appropriate word and transmits that plan to motor cortex for implementation.
A lesion of the angular gyrus disrupts the ow of information from visual cortex, so the person has dif culty saying words he has seen but not words he has heard.
FIGURE 15.11 The Connectionist Model of Aphasia (After N. Geschwind. 1979. Sci. Am. 241: 180.)
Watson/Breedlove pThroe dMuinctdi'osnM.aTchhienemodel therefore argues that people with lesions that selectively disrFuoupntdtahtieonasrocf uBaratien faansdcBicehualvuiosrw4eill especially struggle with repetition of words and phrases that they hear, despite good speech comprehension and production--a condition MM4e_15.11 06/12/20 termed conduction aphasia. Critics of the connectionist model argue that it oversimplifies the neural mechanisms of language, and furthermore, more modern fMRI data confirms that left-hemisphere language zones are not as rigidly modular as was previously believed (Blumstein and Amso, 2013). In addition, technological advances in the visualization of white matter pathways in the living brain have raised questions about the assumptions underlying the connectionist model. In diffusion tensor imaging (DTI), MRI technology is used to specifically study white matter tracts--axon bundles--within the living brain. As we discussed in Chapter 1, MRI images are created from the radio-frequency energy that is emitted by relaxing protons within water molecules. In DTI, the unique behavior of water molecules that are constrained within axons (known as fractional anisotropy) is exploited to create images of axonal fiber pathways between areas, a procedure called DTI tractography, or fiber tracking (Assaf and Pasternak, 2008). Although the technology doesn't have the resolution to portray individual axons, the origin, orientation, course, and termination of
View Activity 15.2a and b: The Connectionist Model of Aphasia conduction aphasia An impairment in the ability to repeat words and sentences. diffusion tensor imaging (DTI) A modified form of MRI in which the diffusion of water in a confined space is exploited to produce images of axonal fiber tracts. DTI tractography Also called fiber tracking. Visualization of the orientation and terminations of white matter tracts in the living brain via diffusion tensor imaging.
From M. Vandermosten et al. 2012. Neurosci. Biobehav. Rev. 36: 1532
Here, the orientation, origin, and termination of ber tracts within the left hemisphere are visualized using DTI. The left arcuate fasciculus is shown in light green.
FIGURE 15.12 DTI Fiber Tracking and the Language Areas
motor theory of language The theory that speech is perceived using the same Watson/Breedlove TlheeftM-hienmd'isspMhaecrheinmeechanisms that are used FtoounpdraotdiouncseoftBhreaicnoamndplBeexhamvioovre4me ents that go into speech. MM4e_15.12 06/12/20
axon bundles can be effectively visualized, as shown in FIGURE 15.12. Using this technique, researchers have discovered that the arcuate fasciculus, long believed to connect Wernicke's area to Broca's area, instead appears to terminate in the precentral gyrus (motor cortex) in most people, just short of Broca's area (Bernal and Altman, 2010; E. C. Brown et al., 2014). Detailed brain-imaging research, and observations in clinical cases with purely cortical lesions, similarly suggest that socalled conduction aphasia is a consequence of a specific type of lesion of superior temporal cortex, rather than the disruption of white matter pathways as proposed under the connectionist model (B. R. Buchsbaum et al., 2011). So it remains to be seen exactly how the various mechanisms of the left hemisphere collaborate to give us the verbal abilities that seem so effortless. An alternative model of speech mechanisms--the motor theory of language (Kimura, 1993; Lieberman, 2002)--suggests that the anterior and posterior left-hemisphere language zones originally evolved as specializations for programming and executing complex movements. According to the motor theory, when we listen to speech, we are analyzing the speech sounds with reference to the underlying movements of the throat and mouth that create them, and we do this analysis using the same neural systems that we would use to make those sounds ourselves. In this schema, simple phonemic units are programmed by an anterior system, and a posterior system strings speech sounds together into long sequences of movements (Kimura and Watson, 1989). Consistent with the motor theory of speech perception, deaf people who use American Sign Language--a language based entirely on movements instead of sounds--employ the same language-related regions of the left hemisphere as hearing people who use spoken language (Newman et al., 2015), and they show comparable aphasia-like symptoms after left-hemisphere damage (Corina et al., 2013). In any event, detailed imaging studies show that the brain contains several speech-related areas well outside those of the classical model (E. Bates et al., 2003; Dronkers et al., 2004), implying greater complexity than was proposed under the Wernicke-Geschwind model. Further, recent evidence that low-level aspects of speech perception occur bilaterally (Cogan et al., 2014) and that semantic processing of natural speech relies heavily on both hemispheres (Huth et al., 2016; De Heer et al., 2017) shows that much remains to be determined about exactly what is, and what is not, the exclusive domain of the left-hemisphere language network. Whatever the details may be, it seems that the answer will involve a complex network of mechanisms that link perception to action.
1. Distinguish among aphasia, agraphia, and alexia. 2. Identify the main types of aphasia, and summarize the distinctive symptoms of each. Which type of aphasia is most often associated with paralysis? 3. Provide a brief outline of the traditional "connectionist" model of aphasia. How does it get its name, and what shortcomings of the model have been identified by critics? 4. Briefly describe the motor theory of language. Can you think of ways that this theory may relate to the evolutionary origins of language? Brain mapping helps us understand the organization of language in the brain In healthy people with intact language capabilities, researchers can study the brain's language network by using two general experimental approaches. In some studies, researchers stimulate discrete regions of the cortex and measure associated changes in language function. Conversely, participants may be asked to engage in specific verbal behaviors while researchers measure associated changes in brain activity, using functional brain imaging. Together, these techniques have extended our understanding of the neural bases of language.
(A) In cortical mapping studies of many patients, stimulation of these sites interfered with speech production.
Language and Lateralization 483 (B) Mapping the brain of this bilingual patient indicated that stimulation of different regions interfered with either one language or the other, but not both. No naming errors Naming errors in English only Naming errors in Spanish only
FIGURE 15.13 Electrical Stimulation of Some Brain Sites Can Interfere with Language (Part A after W. Penfield and L. Roberts. 1959. Speech and brain-mechanisms. Princeton University Press. Princeton, NJ; B after W. H. Calvin and G. Ojemann. 1994. ConverWsaatisoonns/BwrietehdNloeviel's brain: The neural nature of thought and language. Addison-Wesley. TRheeaMdiinndg',sMMAac.)hine Foundations of Brain and Behavior 4e
MM4Eea_1rl5y.1s3tud08ie/s26o/f2t0he organization of language areas in the brain employed electrical stimulation mapping, in which a surgeon used a handheld electrode to electrically stimulate discrete regions of cortex while the effect on behavior was observed. Most of these studies collected data from people undergoing neurosurgery to remove a tumor or epileptic tissue (as in Wilder Penfield's experiments that we described in Chapter 1). Once the brain was exposed, small stimulating electrodes were touched to the surface, disrupting the normal functioning of neurons in the immediate vicinity. Because patients were given only local anesthesia, they were conscious and able to perform various cognitive tasks (the main aim of the procedure was to identify tissue that could be removed without impairing language). Data from numerous neurosurgical cases were superimposed to create a map of language-related zones of the left hemisphere (FIGURE 15.13A) (Penfield and Roberts, 1959). Stimulation anywhere within a large anterior zone often stopped speech outright. Other forms of language interference, such as misnaming or impaired repetition of words, occurred with stimulation throughout the anterior and posterior cortical speech zones. Later cortical stimulation studies revealed anatomical compartmentalization of linguistic elements such as naming, verb generation, reading, speech production, and verbal memory (Calvin and Ojemann, 1994; Corina et al., 2005). An interesting example of the effects of cortical stimulation on naming is illustrated in FIGURE 15.13B, which shows the different places where stimulation caused naming errors in English and Spanish in a bilingual person. Note that this very fine-grained approach reveals different subregions that disrupt either English or Spanish function. People who are bilingual from an early age show completely overlapping organization of their two languages at the gross neuroanatomical level (Perani and Abutalebi, 2005), and evidence is mounting that early bilingualism has far-reaching beneficial effects on brain organization and resistance to cognitive decline in later life (Costa and Sebastián-Gallés, 2014; Perani et al., 2017).
Other studies employ a noninvasive cortical stimulation technology called transcranial magnetic stimulation to further probe the organization of language areas in healthy volunteers. As we discuss next, these studies have confirmed the general organization of the left-hemisphere language network and have revealed new details about the compartmentalization of functions within traditional speech areas.
Noninvasive stimulation mapping reveals details of the brain's language areas
Transcranial magnetic stimulation (TMS; see Figure 1.20)
likewise contributes to both word meaning and sound-related
allows researchers to stimulate small clusters of cortical neu-
aspects of language (Stoeckel et al., 2009; Sakreida et al.,
rons with good precision, from outside the scalp. By using MRI 2018). So the TMS procedure is providing new insights into the
scans to select targets, TMS provides a noninvasive method for fine details of the cortical organization of language, especially in
inducing a sort of temporary brain lesion, disrupting the activity conjunction with traditional neuroimaging techniques (Devlin and
of the selected brain region for up to an hour. Alternatively, TMS Watkins, 2007; Lorca-Puls et al., 2017).
can be used along with PET or fMRI to pre-
cisely map regions of increased activity.
Using TMS mapping, researchers have generally replicated and extended the earlier findings regarding the cortical organization of language functions. For example, TMS mapping has revealed that speech produc-
Question How is Broca's area organized? Hypothesis Broca's area is made up of discrete subareas with differing linguistic functions.
tion is associated with activation of not only face areas in motor cortex, but also hand areas, confirming the linkage and possible
Test Guided by precise structural MRI scans, apply transcranial magnetic stimulation (TMS) to activate discrete regions within Broca's area.
evolutionary relationship of hand gestures
and speech (Meister et al., 2003; Onmyoji et
al., 2015). Similarly, TMS mapping has been used to show that speech perception acti-
vates specific regions that TMS shows to be
involved with speech production (S. K. Scott
and Wise, 2004), providing support for the
motor theory of language that we discussed
Impressively, the TMS temporary-lesion approach has revealed previously unknown functional subregions within Broca's area (FIGURE 15.14). In these studies, research-
ers found that anterior parts of Broca's area
words, while a more posterior part of Broca's area is important for the patterning of speech sounds (Gough et al., 2005; Klaus
Anterior regions of Broca's area appear to be important for semantic processing (word meanings), while more posterior regions within Broca's area specialize in phonological processing (sounds of words).
FIGURE 15.14 Subregions of Broca's Area Revealed by TMS
(After P. M. Gough et al. 2005. J. Neurosci. 25: 8010.)
Watson/Breedlove FuncTthieoMniandl'snMeaucrhoiniemaging technologies let us visualize activity in Foundations of Brain and Behavior 4e the brain's language zones during speech DifferMenMt4aes_p15e.c1t4s of07la/n15g/u2a0ge processing produce noticeably different patterns of brain activation, as shown in FIGURE 15.15. Passive viewing of words activates a posterior area within the left hemisphere (FIGURE 15.15A), but passive hearing of words shifts
the focus of brain activation to the temporal lobes (FIGURE 15.15B). Repeating words orally activates the motor cortex of both sides, along with supplementary motor cortex and some of the cerebellum (FIGURE 15.15C). During word repetition or reading aloud, there is little activity in Broca's area. But when participants are required to generate an appropriate verb to go with a supplied noun, language-related regions in the left hemisphere, including Broca's area, suddenly become markedly activated (FIGURE 15.15D).
(D) Generating a verb associated with each noun shown
40 -20 Speaking words 40 -20 Generating verbs
FIGURE 15.15 PET Scans of Brain Activation in Progressively More Complex Language Tasks (After M. I. Posner and M. E. Raichle. 1994. Images of mind. Scientific American Library. New York, NY.)
Even languages that sound very, very different seem to ac-
tivate much the same brain regions in native speakers. Silbo
Gomero is a very unusual whistled surrogate language of the
Canary Islands, used by shepherds (known as silbadores) to
communicate over long distances. In Silbo, whistled notes
serve as the phonemes and morphemes of a stripped-down
form of Spanish (for an audio sample of Silbo, with translation,
see A STEP FURTHER 15.2, on the website). Functional MRI
showed that long-term silbadores process Silbo using the same
left-hemisphere mechanisms that they (and everyone else) use
to process spoken language (Carreiras et al., 2005). Non-silbador
controls, in contrast, process the whistle sounds of Silbo using
completely different regions of the brain; for these people, of
course, the whistle sounds have no linguistic content. So the
brain's left-hemisphere language systems appear to be suffi-
ciently plastic to adapt to widely varying types of communica-
tion sounds, provided that they're heard early enough. In fact,
while infants appear to be born with neural specializations for
speech already in operation--they show more metabolic activity
in the left hemisphere than in the right when they hear speech,
even though they don't yet understand it (Dehaene-Lambertz
et al., 2002)--those mechanisms don't similarly respond to the
nonspeech sounds that make up Silbo Gomero (L. May et al.,
2018). The incorporation of Silbo into the language system must
therefore come about through extensive practice--the earlier
Event-related potentials (ERPs; see Chapters 2 and 14) also
provide hints about the brain's language network, by reveal-
Whistle While You Work A silbador of the Canary Islands
ing the time base for language processing. For example, study
demonstrates Silbo Gomero, a whistled language used by shepherds to communicate over long distances.
participants can be asked to read a sentence in which there is a word that is grammatically correct but, because of its mean-
ing, doesn't fit--such as "The man started the car engine and
stepped on the pancake"--while brain electrical activity is re-
corded from scalp electrodes. About 400 milliseconds after the participant reads the
word pancake, an enhancement of a distinctive ERP component called N400 (N de-
notes "negative," and the number represents the response time in milliseconds; see
Figure 14.6) is detectable (Kutas and Hillyard, 1984; Payne et al., 2015). Such N400
responses seem to be specific to word meanings and apparently originate from
temporoparietal cortex (including Wernicke's area) (Kutas and Federmeier, 2011).
In contrast, words that are inappropriate because of grammar rather than meaning
tend to elicit a positive potential about 600 milliseconds after they are encountered
(called a P600 response), indicating that detection of this level of error requires an
extra 200 milliseconds of brain processing by other components of the language
network (Osterhout, 1997; Mehravari et al., 2015). The degree to which meaning
and grammar are processed independently in the brain, however, remains to be
fully established and is an area of active investigation (Kuperberg, 2007; Brouwer et
1. Summarize and discuss the organization of language systems in the human brain. 2. Discuss the patterns of brain activity that are observed in various verbal tasks, using functional-imaging technologies and ERPs. How well do these results align with traditional models of the organization of language areas in the brain? 3. What can we learn about general principles of language localization in the brain by studying unusual languages like Silbo Gomero?
15.4 Human Languages Share Basic Features
The next part of the chapter narrows its focus to our species' most distinctive characteristic: the everyday use of language, both in the form of speech and in the written word. After studying this material, you should be able to: 15.4.1 Provide a synopsis of the evolution and distribution of human languages. 15.4.2 Identify the principle linguistic components of speech. 15.4.3 Summarize the process of language development and the acquisition of grammar and reading skills. 15.4.4 Contrast human language with nonhuman animal communication. 15.4.5 Discuss in detail the forms of dyslexia and their possible neural underpinnings. We've seen that all human languages share certain basic elements: phonemes, morphemes, and grammar. But how does each of us end up with the right set of sounds and rules--the ones we need for our particular native language? The exact number of languages that we humans employ is unknown; our best guess is that there are 6,000-7,000 different languages, of which about 1,000 have been formally studied (Wuethrich, 2000). By applying the tools of evolutionary biology to linguistics, it is possible to track the cultural evolution of language, and this suggests a closer relation between languages than previously expected. In fact, the seven major language families found today in Europe and Asia appear to trace back to a single ancestral language in use about 15,000 years ago (FIGURE 15.16; Pagel et al., 2013). The subsequent explosion of new languages may have served cultural roles more than communicative ones; for example, the adoption of a new language would help a social group to identify its members and confound its rivals. But nowadays, in the increasingly globalized modern context, we seem to be inexorably sliding in the other direction as languages are lost or absorbed and we move toward a few common languages.
From M. Pagel et al. 2013. Proc. Natl. Acad. Sci. U.S.A 110: 8471; image courtesy of Mark Pagel
This map shows the approximate distribution of the seven major language families of Europe and Asia; analysis of highly conserved features of these languages suggests that they shared a common ancestor about 15,000 years ago--the time of the last ice age.
FIGURE 15.16 The Evolution of Languages
Language families Altaic Chukchee-Kamchatkan Dravidian Inuit-Yupik Indo-European Kartvelian Uralic
© Hulton-Deutsch/Corbis Historical/Getty Images
488CHAPTER15 sensitive period Also called critical period. The period during development in which an organism can be permanently altered by a particular experience or treatment. stuttering The tendency of otherwise healthy people to produce speech sounds only haltingly, tripping over certain syllables or being unable to start vocalizing certain words. Williams syndrome A disorder characterized by impairments of spatial cognition and IQ but superior linguistic abilities. The King's Speech England's King George VI--shown here during a wartime radio broadcast--stuttered severely. His struggle and eventual success in coping with speech difficulties, as portrayed in the film The King's Speech, shows that despite the possible genetic bases of the condition, effective therapy is possible.
Language has both unlearned and learned components A child's brain is an incredible linguistic machine, rapidly acquiring the local language without need of formal instruction. Human babies start out babbling nearly all the known phonemes of all human languages, but they soon come to use only those phonemes that they hear in use around themselves. And each baby's developing language abilities are especially shaped by "parentese," the singsong speech of caregivers that helps babies to attach emotion and meaning to speech sounds (Falk, 2004). By 7 months of age, infants already have a sense of the grammar of the language used in their homes, and they react to exceptions (Marcus et al., 1999). The human brain contains specialized mechanisms for language acquisition that show a clear-cut sensitive period (or critical period): a limited span of time during which exposure and practice with language must occur in order for language skills to develop normally. This sensitive period tapers down from the maximal sensitivity of early childhood to an eventual end of special sensitivity around puberty. Individuals who are exposed to language only late in the sensitive period or after it has ended show impaired language development; as many of us know from firsthand experience, learning a second language is much more difficult in adulthood, after the sensitive period is over (Curtiss, 1989; Norrman and Bylund, 2016). In fact, people who don't start to learn a second language until later in childhood or after puberty seem to use different brain networks for each language, compared with people who learn multiple languages simultaneously in early childhood (H. Liu and Cao, 2016; Cargnelutti et al., 2019), as we discussed earlier. An important genetic aspect of language acquisition was discovered by studying an unusual family in England. Across at least three generations, about half of the members of the KE family have expressed a severe heritable language disorder. Affected family members take a long time to learn to speak and have difficulty with particular language tasks, such as learning verb tenses (Lai et al., 2001). Brain activation during language tasks is altered in these family members too (Liégeois et al., 2003). By studying the KE family's pedigree, researchers soon identified a gene, called FOXP2, that must be important for the normal acquisition of human language, because affected members of the KE family all share a mutation in this gene (FIGURE 15.17). In fact, multiple variants of FOXP2 tend to produce different abnormalities in language-associated areas of the brain (Pinel et al., 2012), probably because FOXP2 is a transcription factor that can alter expression of a variety of other genes (Vernes et al., 2011). Stuttering--the tendency of otherwise healthy people to produce speech sounds only haltingly, tripping over certain syllables or being unable to start vocalizing certain words--is likewise at least partly heritable and associated with changes in other genes (C. Kang et al., 2010). On the flip side of the coin, children born with Williams syndrome--caused by the deletion of 28 genes from chromosome 7-- have various intellectual deficits but excellent verbal skills. No one knows exactly what developmental mechanism results in this
Generation II Generation III (B) Caudate nucleus
This family tree of the KE family illustrates the transmission of a language disorder caused by mutation of the gene FOXP2 through three generations.
Regions of reduced gray matter are evident in these MRI scans of the brains of affected members of the KE family. (Crossed reference lines indicate the affected regions.)
Courtesy of the Williams Syndrome Association
Inferior frontal gyrus from two perspectives
FIGURE 15.17 A Heritable Language Disorder (Part A after K. E. Watkins et al. 2002. Brain 125: 465; B from F. Vargha-Khadem et al. 2005. Nat. Rev. Neurosci. 6: 131, courtesy of Faraneh Vargha-Khadem.)
hyperverbal behavior (Paterson and Schultz, 2007), but possession Woaftesxotnr/aBcroeepdileosvoe f the identified genes on chromosome 7--rather than TdheelMetiinodn'ssMofacthhiensee genes--produces a syndrome of very poor expres- Foundations of Brain and Behavior 4e sive language that is, in many ways, the converse of Williams synMdMro4me_e15(S.1o7me0r6v/1il5l/e2e0t al., 2005). Taken together, the evidence confirms that basic mechanisms of language are heritable components of the human brain, and the product of a long evolutionary history. Speech mechanisms may have evolved from more-ancient systems controlling gestures of the face and hands (Corballis, 2020), in agreement with the motor theory of language that we discussed earlier. Even today there is a close relationship between speaking and gesturing with the hands (Gentilucci and Dalla Volta, 2008); in fact, most people find it difficult not to gesture when speaking. The use of language is one of the key adaptations of humans, so basic capabilities probably arose in an ancient ancestor of our species. For example, the Neandertals shared our version of FOXP2 (Krause et al., 2007), so perhaps major differences in just a few genes like FOXP2 and the stuttering genes are enough to explain why we write books and give speeches and chimps do not, despite our otherwise great genetic similarity (Fisher, 2017).
The Appearance of Williams Syndrome Children with Williams syndrome often have a characteristic facial shape, caused by the loss of a copy of the elastin gene. The loss of copies of other nearby genes is thought to cause mild mental disability paired with verbal fluency.
Good Dog! Dog lovers know that their willing friends can learn to associate certain words with specific actions. Maisie here knows to "wait" until she hears "okay," at which time she will enjoy both a delicious sausage and a delighted human. Dogs can learn a small collection of words with sufficient practice (lots of practice, for some dogs), enabling communication between human and nonhuman, but instilling language is a different matter altogether. Because most animals appear to lack a capacity for grammar-- the rule for assembling units of language into new combinations--it seems that language is a uniquely human skill.
Nonhuman primates engage in elaborate vocal behavior Every day, you utter sentences that you have never said before, yet the meaning is clear to both you and your human listener because you share an understanding of the words and grammar involved. Animals generally are incapable of similar feats, instead requiring extensive training with each specific utterance in order for communication to occur at all. Speaking to your dog ("Good dog!") reportedly activates a left-hemisphere mechanism that processes meaning, as well as a right-hemisphere mechanism that assigns value and reward to those words (Andics et al., 2016), but each new combination of words that you use with your dog will have to be laboriously learned from scratch. In short, dogs and most other animals appear to lack grammar. For this reason, scientists have focused the search for nonhuman language capabilities mostly on our nearest relatives, the other primate species. Apes and monkeys employ a wide range of vocal behaviors for communication between individuals, particularly for relaying emotional information like alarm or territoriality (Cheney and Seyfarth, 2018). The shrieking, purring, peeping, growling, and cackling sounds of squirrel monkeys, for example, can generally be related to specific social situations. Chimpanzees issue specific alarm calls to alert other members of their group to the presence of a viper (Crockford et al., 2012), and gibbons deploy a sizable repertoire of hooting calls that they recombine to communicate information about predators, social conditions, and mating opportunities (Clarke et al., 2015). But despite their apparent adaptive importance, most nonhuman primate vocalizations seem to have a somewhat "preprogrammed" quality, being repeatedly produced in much the same fashion and order. Electrical stimulation of the brain indicates that vocal behavior in monkeys and apes relies primarily on subcortical systems, especially sites in the limbic system, rather than on cortex. The vocalizations elicited by subcortical stimulation are associated with strongly emotional behaviors such as defense, attack, feeding, and sex (FIGURE 15.18). Vocalizations are more common if subcortical stimulation is provided to the left hemisphere, indicating a special role of the left hemisphere in the communicative behavior of monkeys and apes (Meguerditchian and Vauclair, 2006; Taglialatela et al., 2006), mirroring what we've seen for human speech. And some monkeys, like people, show a preference for using the right ear (which has preferential connections with the left hemisphere) to listen to vocalizations from conspecifics (Hopkins et al., 2015). Nonhuman primates are unlikely to ever produce human speech, as their vocal tracts and vocal repertoires are suited to their own communication needs. But can these animals be taught other forms of communication, with features similar to those of human language? Can they learn to represent objects with symbols and to manipulate those symbols according to grammatical rules? Our closest primate relatives, the great apes (chimpanzees, gorillas, orangutans) reportedly use a variety of hand gestures for communication in the wild (Hobaiter and Byrne, 2014) and are quite capable of learning hundreds of hand gestures from American Sign Language (ASL). Classic research suggests that given enough training--it takes years--apes may learn to use ASL signs spontaneously, sometimes in novel sequences (R. A. Gardner and Gardner, 1969, 1984). Through extensive practice, apes can also be trained to communicate by assembling abstract symbols, such as colored plastic chips or computerized symbols, into new sentences (Premack, 1971; Rumbaugh, 1977).
Chimpanzees can learn to use arbitrary signs and/or symbols to communicate, but it is questionable whether this usage is equivalent to human language.
Chimpanzee Using Symbols Some researchers argue that apes (chimpanzees, gorillas, and orangutans) are able to string arbitrary symbols together into meaningful, sentence-like statements. Others believe that while apes can learn subtle associations between symbols and meanings, their communicative behavior lacks the sense of grammar that is the hallmark of human language.
Some researchers contended that apes were thus able to acquire words (or equivalent symbols) and then string them together into novel, meaningful chains; that is, they seemed to employ a grammar to communicate ideas. Other researchers argued that these sequences were simply subtle forms of imitation (Terrace, 1979), perhaps unconsciously cued by the experimenter who provided the training. Observers who are native ASL users dispute the linguistic validity of the signs generated by apes; others, such as linguist Noam Chomsky, argue that teaching primates to emulate a quintessentially human behavior in which they do not naturally engage can tell us little about the behavior, other than the obvious conclusion that ape evolution did not favor the use of language. So although the debate remains unresolved, research on the linguistic abilities of nonhuman primates at least forced researchers to sharpen their criteria of what constitutes language. Researchers are now probing the extent to which the many components of "real" language are human adaptations that evolved independently of other cognitive capabilities, in order to solve specific problems in our evolutionary past (Pinker and Jackendoff, 2005; Corballis, 2020).
These spectrograms show a variety of typical monkey vocalizations.
Each type of vocalization can be elicited through electrical stimulation of the speci c brain sites illustrated in these coronal sections of the monkey brain.
Many different species engage in vocal communication
Many nonprimate species use vocalizations--chirps, barks,
meows, songs, and more--to communicate important information
to members of their own or other species. Although these commu-
nication sounds do not constitute language, in that they lack the
features of language that we've discussed, such sounds neverthe-
less broadcast crucial signals about readiness to mate, danger, territorial defense, emotional state, and so on. Whales sing and may
perform songs that they've learned in distant oceans or from other
species (Janik 2014); and some seal mothers and pups learn each
other's vocalizations and remember them for years after separation
(Insley, 2000; Pitcher et al., 2010). In fact, many species--from elephants to bats to birds to dolphins--are capable of vocal learning
and use their vocalizations to help form social bonds and identify
individuals (Tyack, 2003; Poole et al., 2005).
In the lab, measurement with special instruments reveals that
rats and mice produce complex ultrasonic vocalizations that they
use to communicate emotional information (Panksepp, 2005;
Burgdorf et al., 2011). These ultrasonic vocalizations are associated
with FoxP2 gene expression (Shu et al., 2005; French and Fisher,
2014), providing an intriguing parallel to the situation in humans
with FOXP2 mutations that we discussed earlier.
Birds are particularly vocal animals. While many species of birds produce only simple vocalizations, species of songbirds-- canaries, zebra finches, song sparrows, etc.--produce rich and melodious vocalizations that are crucial for their social behaviors and reproductive success. A select few, such as the grey parrot, can even learn to communicate using a significant vocabulary of human
FIGURE 15.18 Electrical Stimulation of the Monkey Brain Elicits Vocalizations (After D. W. Ploog in A. Harrington. 1992. So human a brain: Knowledge and values in the neuWatson/Breedlove rTohsecMieinncde'ssM. Bacirhkinheauser. Boston, MA. Spectrograms courtesy oFofuUndwaetioJnüsrogf eBnrasi.n) and Behavior 4e
words (Pepperberg, 2008). Although birdsong has evolved quite in- MM4e_15.18 06/15/20
dependently of human speech, there are some interesting parallels between the two:
for example, the songbird brain contains a specialized left-hemisphere system for vocal
behavior (Moorman et al., 2012; Pfenning et al., 2014). What's more, juvenile birds must
learn their songs from adult tutors during a distinct critical period in order for their own
View Activity 15.3: Song Control Nuclei of the Songbird Brain
singing behavior to develop normally (Marler, 2004)--a requirement that also parallels human language. And yes, as with human speech, the FoxP2 gene is implicated in the learning and production of birdsong (Bolhuis et al., 2010). When FoxP2 expression is blocked in parts of the song control system, young males fail to properly learn and recite their tutor's song, producing errors that in some ways resemble those in the humans with abnormal FOXP2 described earlier (Haesler et al., 2007). (For more on birdsong and its social roles, see A STEP FURTHER 15.3, on the website.)
Some people struggle throughout their lives to read
Why is it so much harder to learn to read and write than to speak? Compared with
speech, the written word is a relatively new development for our species, so we hav-
en't had enough time to evolve dedicated brain mechanisms for reading and writing
of the sort we have for speech. Therefore, learning the written form of a language is
a slow and laborious chore of childhood that is vulnerable to developmental disrup-
tions that result in dyslexia (from the Greek dys, "bad," and lexis, "word"), a mild to
Some children just seem to take forever to learn to read, and not even extended
practice can make their reading easy and accurate. Affecting about 5% of children--
especially boys and left-handers--this develop-
In these drawings of the left and right upper temporal lobe from the brain of a dyslexic person, the planum temporale is nearly symmetrical; in most people the left planum
mental dyslexia is a problem unique to written language, not a general cognitive deficit. Indeed, children with dyslexia can have high IQs (B. Mor-
temporale is considerably larger. The dots and the shaded area represent regions where cellular disorganization has been found in the brains of individuals with dyslexia.
ris, 2002), and many have gone on to illustrious careers in varying fields. Instead, the problem seems to lie in connecting reading with the more
Developmental dyslexia has been associated
(A) cortex) with several types of neurological abnormalities
(FIGURE 15.19). In both postmortem investi-
gations and anatomical studies using MRI, the
brains of dyslexic people have been found to have
Planum temporale Structural abnormalities in patients with dyslexia are much more common in the left hemisphere.
aberrant layering of the neurons of the cerebral cortex, along with excessive cortical folding and clusters of extra neurons in unexpected locations (Galaburda, 1994; Chang et al., 2005). Cortical abnormalities are especially evident in the frontal and temporal lobes, possibly because of
defective migration of newborn neurons during
fetal development (Galaburda et al., 2006). Stud-
ies using fMRI confirm that people with dyslex-
ia show impaired neural activity in left posterior
Right speech zones (Pugh et al., 2000; Shaywitz et al.,
2003) while displaying a relative overactivation of
(B) Area of micropolygyria, excessive cortical folding
(C) Ectopias, clusters of neurons in unusual locations
anterior regions. Abnormality in the nearby temporoparietal region has been linked to the phonological (phoneme-processing) aspects of dyslexia
(Hoeft et al., 2006). And it looks like some of these
abnormalities have genetic bases; for example,
disruption of genes involved in brain development
FIGURE 15.19 Neural Disorganization in Dyslexia (After A. M. Galaburda et al. 1985. Ann. Neurol. 18: 222; micrographs courtesy of Albert Galaburda.)
Watson/Breedlove The Mind's Machine Foundations of Brain and Behavior 4e
and the migration of neurons into adult positions are associated with developmental dyslexia (Harold et al., 2006; Gabel et al., 2010). Taken together, imaging and behavioral studies indicate that our brains rely on two different language systems during reading: one focused on the sounds of letters, the other on the meanings of whole words. Using fMRI, researchers found that people with dyslexia often have a disconnection between these systems, impairing the coordination of sounds with their meanings (Boets et al., 2013); it has been proposed that this disconnect is the result of hyperexcitability of reading-associated cortical networks (Hancock et al., 2017). Presumably, these systems are shaped by training: as with learning any highly skilled behavior, our brains mold themselves to accommodate our acquired expertise with written language, and lifelong avoidance of reading may be responsible for some of the sensory and word meaning problems that are evident in adults with dyslexia (Goswami, 2015). This could be why remedial training in people with dyslexia induces measurable changes in the left-hemisphere systems that are used for reading (Temple et al., 2003). And there are also positive findings: for example, evidence is accumulating that people with dyslexia actually outperform unaffected individuals in certain learning domains, such as aspects of spatial learning (Schneps et al., 2012). Findings like these may have important implications for developing new educational strategies in dyslexia. Perhaps, then, coupling education interventions with early genetic screening for dyslexia will help affected people completely overcome their trouble with words. Brain damage may cause specific impairments in reading Sometimes people who learned to read just fine as children suddenly become dyslexic in adulthood as a result of disease or injury, usually to the left hemisphere. This acquired dyslexia (sometimes called alexia) offers hints about how the brain processes written language. One type of acquired dyslexia, known as deep dyslexia, is characterized by semantic errors (i.e., errors related to the meanings of words); for example, the printed word cow is read as horse. People with deep dyslexia are also unable to read aloud words that are abstract as opposed to concrete, and they make frequent errors in which they seem to fail to see small differences in words. It's as though they grasp words whole, without noting the details of the letters, so they have a hard time sounding out nonsense words. In another form of acquired dyslexia, surface dyslexia, the person makes different types of errors when reading. These people can read nonsense words without problems, indicating that they understand which letters make which sounds. But they find it difficult to recognize words in which the letter-to-sound rules are irregular. The Tough Coughs as He Ploughs the Dough by Dr. Seuss (1987), for example, would utterly confound them. In contrast to people with deep dyslexia, those with surface dyslexia have difficulties that are restricted to the details and sounds of letters. Interestingly, surface dyslexia doesn't occur in native speakers of languages that are perfectly phonetic (such as Italian, where every letter is pronounced). This finding indicates that what's lost in speakers of nonphonetic languages, like English, is purely a learned aspect of language. In contrast, deep dyslexia probably involves language mechanisms that are important for all languages. Other kinds of brain damage can impair reading. For example, people with hemispatial neglect following right parietal lobe damage (discussed in Chapter 14) disregard the left half of the world, despite having otherwise normal vision. Such people thus also fail to notice the left halves of the words that they see, necessarily resulting in poor reading. In some severe cases of acquired dyslexia, the individuals exhibit letter-by-letter reading, a striking impairment in which they laboriously spell out each word to themselves (aloud or silently). In these cases, it seems that conscious attention to the spelling of each word is the only way by which words can be identified, so reading is dramatically slower.
deep dyslexia Acquired dyslexia in which the person reads a word as another word that is semantically related. surface dyslexia Acquired dyslexia in which the person seems to attend only to the fine details of reading. Overcoming Dyslexia Many highly intelligent, highly successful people-- like Virgin Group founder Sir Richard Branson, pictured here--have coped with dyslexia on their way to fame and fortune.
© Everett Collection Inc./Alamy Stock Photo
494CHAPTER15 recovery of function The recovery of behavioral capacity following brain damage from stroke or injury.
1. How many languages do humans use, and how have they spread over time? 2. Why do researchers think that a capacity for language is inborn in the human brain? Briefly describe some pertinent research findings that support this position, including genetic evidence. 3. What are the basic linguistic components of spoken language? 4. Discuss the process of language acquisition in infants. What is the significance of the term sensitive period in this regard? 5. Summarize some of the ways in which studies of nonhuman animals help us understand the neural mechanisms of language. 6. Why do researchers believe that it is so much harder to learn to read than to learn to speak? 7. What are the two principal types of acquired dyslexia? Summarize their respective features.
15.5Recovery of Function after Brain Damage: Stabilization and Reorganization Are Crucial Stages
Perseverance and Plasticity Having survived a severe gunshot wound to the left cerebral hemisphere during an assassination attempt, former U.S. Representative Gabrielle Giffords has made striking progress in regaining her language and cognitive functions, thanks to intensive rehabilitation therapy and strategies for compensating for the damage.
Because so much of the data on cerebral lateralization and language mechanisms has been drawn from studies of people with lateralized brain damage due to strokes and other types of brain injuries, the final section of the chapter turns to the processes by which the brain recovers at least some functions following damage. After reading this material, you should be able to: 15.5.1 Discuss the prevalence of various forms of brain damage and the reasons why so many people are living with the lasting effects of brain injury. 15.5.2 Describe the typical timeline for neurological recovery from a stroke or other brain damage, and identify factors that affect this process. 15.5.3 Discuss potential therapies that can aid the process of recovery. 15.5.4 Explore how it is that children can recover from brain injury much more completely than adults can. Compared with the other organs of the body, it's all too easy to seriously damage the brain. A number of factors combine to make the brain so vulnerable: extreme complexity, delicate structure, metabolic neediness, limited capacity for regrowth, and an exposed location perched atop a thin and whippy neck. In the United States alone, according to the 2016 National Health Interview Survey (Blackwell and Villarroel, 2018), almost 7.5 million adults are survivors of stroke, and many more are living with the consequences of other disease processes, such as tumors and degenerative diseases. Traumatic brain injury (TBI) has many causes: motor vehicle accidents, injuries at work and in the home, and mishaps during recreational activities and sports (especially contact sports, as we'll see shortly). So, while prevention is always preferable to treatment, researchers are intensively studying recovery of function, with the aim of developing treatments that improve outcomes for people with brain damage. In the months following a brain injury, people often show conspicuous improvements in neural function as the injury site stabilizes, unaffected tissue reorganizes, and compensation occurs. We now know that the nervous system has much more potential for plasticity and recovery than was previously believed. For example, damaged neurons can regrow their connections under some circumstances, through a process called collateral sprouting. (For more information on collateral sprouting,
The course of recovery from nonfluent (Broca's) aphasia differs... Three patients with non uent aphasia
(B) ...from the course of recovery from fluent (Wernicke's) aphasia. High Four patients with uent aphasia
FIGURE 15.20 Courses of Recovery for People with Aphasia (After A. Kertesz and P. McCabe. 1977. Brain 100: 1.)
see A STEP FURTHER 15.4, on the website.) And, as we've discussed in several places in this book, it has become evident that the adult brain is capable of producing Wneatwsonn/eBurreoednlso;vaelthough this neurogenesis normally plays a minimal role in recovery Tfhroe mMinbdr'asiMnadchaimneage, perhaps we will learn how to bend these new neurons to our Fwouinlldaatniodnsuosf eBrtahineamndtoBerheavpiloarc4ee damaged brain tissue. MM4Oe_n1e5.2o0f th0e6/m15o/s2t0exciting prospects for brain repair following stroke or injury or in many other neurological conditions is the use of embryonic stem cells (Casarosa et al., 2014; J. Takahashi, 2018). Derived from embryos, these cells have not yet differentiated into specific roles and therefore are able to develop, under the control of local chemical cues, into the types of cells needed. Controversy surrounds the use of human embryos as cell donors, so researchers are working to find ways of creating stem cells from other sources, such as skin, that can then be placed in the brain and helped to survive, migrate, and mature into functioning replacement neurons (Emborg et al., 2013; Morizane et al., 2017). Several factors determine how thoroughly a person will recover from a brain injury. One of these is simply the passage of time. Immediate medical treatment at the onset of a stroke can greatly limit the extent of damage, reducing cell death and inflammation. (Mechanisms of brain damage, and the mitigation of brain injuries, are discussed in A STEP FURTHER 15.5, on the website.) However, it takes months for the extent of recovery to become evident. For people with aphasia following a stroke, most recovery occurs during the first 3 months following brain damage, but steady recovery continues for 1-1.5 years (FIGURE 15.20) (Kertesz et al., 1979), limited by the extent to which the left-hemisphere speech zones have been compromised. Recovery tends to be better when the brain injury is due to trauma, such as a blow to the head, rather than a stroke; this difference may be due to the generation of cell-damaging signaling chemicals in cells that have been starved of oxygen during a stroke. Older people and those with more-severe initial loss of language recover less completely (Nakagawa et al., 2019). And left-handed people show better recovery than those who are right-handed, perhaps because of reduced lateralization of function in some lefthanders. Therapeutic approaches using alternate communication channels, such as singing, can help in some cases (Racette et al., 2006). Recovery can be downright amazing in children, thanks to their greater neural plasticity: A child may show extensive language recovery even after losing the entire left hemisphere (Boshuisen et al., 2010; Lew, 2014) (FIGURE 15.21). Such observations show that undamaged brain regions can take over the functions of damaged regions,
embryonic stem cell A cell, derived from an embryo, that has the capacity to form any type of tissue. In certain very rare cases of intractable childhood epilepsy, an entire hemisphere must be surgically removed to save the child's life (Griessenauer et al., 2015). The loss of the hemisphere produces severe symptoms such as complete paralysis of one side, speech loss, and visual impairments, but if the surgery occurs early enough the child may show almost complete recovery of function over a long period of time. Several years after a hemispherectomy--radical surgery to remove the left hemisphere--the 7-year-old pictured here had recovered normal language function (including bilingual capacity!) and near normal contralateral motor control.
FIGURE 15. 21 The Amazing Resilience of a Child's Brain
From J. Borgstein and C. Grootendorst. 2002. Lancet 359: 473
In this therapy, an unaffected limb is gently restrained (in this case in a white mitten) so that the patient must use the limb that was affected by the stroke in a series of repetitive tasks.
if the damage occurs early enough in life. Unfortunately, as we age, the brain loses much of its ability to compensate for injury. Reversing this age-related decline in neuroplasticity is an important focus of neuroscience research.
Rehabilitation and retraining can help recovery from brain and spinal cord injury
Cognitive and/or perceptual handicaps that develop
from brain impairments can be modified by train-
ing; similarly, intensive training may restore some
measure of walking ability after certain spinal cord
injuries (Barbeau et al., 1998; Morawietz and Mof-
fat, 2013). But it is important to distinguish resto-
ration of function from compensation. Practice can
significantly reduce the impact of brain injury by
fostering compensatory behavior (T. A. Jones, 2017).
For example, vigorous eye movements can make up
for the scotomas (blind spots) that commonly result
FIGURE 15.22 Constraint-Induced Movement Therapy
from strokes or other injuries that affect the visual cortex. Indeed, people can develop a wide variety of
behavioral strategies after a brain injury to enable
As with recovery of language functions after stroke, a growing body of evi-
dence shows that people can substantially regain the use of limbs that have been
The Mind's Machine Foundations of Brain and Behavior 4e
paralyzed following brain injury, especially if they are forced to use the limbs repeatedly. Constraint-induced movement therapy (CIMT) persuades people to use
a stroke-affected arm by simply tying the "good" arm to a splint for up to 90% of
waking hours (Taub et al., 2002) in conjunction with daily rehabilitation therapy,
including practice moving the affected limb repeatedly (FIGURE 15.22). People who
receive this treatment reportedly regain up to 75% of normal use of the paralyzed
arm after only 2 weeks of therapy. Although the underlying mechanisms are not
well understood--they may involve a remapping of the motor cortex--it's clear that
CIMT offers substantial benefits that persist over the long term (Liepert et al., 2000;
Another surprising use of experience for rehabilitation involves a simple mirror.
Altschuler et al. (1999) treated people who had reduced use of one arm after a stroke
by placing them before a mirror with only their "good" arm visible. To these people,
it looked as though they were seeing the entire body, but what they saw were mirror
images of the good arm. The participants were told to make symmetrical fluid motions
with both arms. In the mirror, the motions looked perfectly symmetrical (of course);
surprisingly, even though their real arm movements weren't perfect, most of the par-
ticipants soon learned to use the "weak" arm more extensively. It was as though the
visible feedback, indicating that the weak arm was moving perfectly, overcame the
brain's reluctance to use that arm. It is likely that the mirror neurons of the brain, dis-
cussed in Chapter 5, mediate some of the beneficial effects of this sort of rehearsal
Brain damage will remain a serious problem for the foreseeable future--one
constraint-induced movement therapy (CIMT) A therapy for recovery of movement after stroke or injury in which the person's unaffected limb is constrained while they are required to
that will affect most of us in some way as our friends and relatives go through their lives. Perhaps the most important and encouraging message to convey to victims of stroke and other nervous system damage is that, with effort and perseverance, they can help their remarkably plastic brains to regain a significant amount of the lost
SIGNS & SYMPTOMS Contact Sports Can Be Costly Jarring blows to the head are common in a number of sports-- football, hockey, boxing, and wrestling, for example--sometimes resulting in concussion or mild traumatic brain injury (mTBI), with a range of possible symptoms including headache, mood disturbances, confusion, memory loss, and occasionally (but not usually) a brief loss of consciousness. Even one concussion, but especially a series of concussions or minor head impacts--even seemingly mild ones--puts a person at risk of permanent brain damage. Although uncomplicated concussions generally clear up with time, up to 25% of concussions may cause persistent cognitive symptoms (Ponsford, 2005), some of which may not become evident until later in the person's life (Thornton et al., 2008; Montenigro et al., 2016). In the USA alone, mTBIs result in more than 2.2 million hospital visits per year (CDC 2015); many more go unreported. In an early large-scale CT study of 338 active boxers--athletes whose whole goal is to rain blows upon the head of an opponent-- scans were abnormal in 7% (showing brain atrophy) and borderline in 12% (B. D. Jordan et al., 1992). The marked cognitive impairment that results from too many concussions, once called dementia pugilistica (the Latin pugil means "boxer") or punchdrunk syndrome (Erlanger et al., 1999), is known today as chronic traumatic encephalopathy (CTE). Evidence is mounting that
CTE is also alarmingly frequent in other athletes, especially American football players (Mez et al., 2017). Researchers have not yet agreed on a definitive diagnostic marker for CTE in living people--typically, it can be diagnosed only in postmortem analysis (McKee et al., 2016)--but one possible approach uses a special type of PET scan to detect abnormal expression of the cytostructural protein tau in the brain (Barrio et al., 2015; see Figure 4.18). Neuropathological evidence indicates that, like Alzheimer's disease, CTE in athletes is a type of tauopathy, in which excess tau protein within neurons interferes with their functioning (McKee et al., 2009). The photos in FIGURE 15.23 show the brain of a former boxer who, by his mid-thirties, was experiencing symptoms including memory loss, confusion, and a tendency to fall. As in other cases of CTE, an excessive amount of tau (brown in the photos) is evident in the brain, and it is found forming tangles within many neurons. CTE is a real and serious risk in contact sports, particularly where numerous blows to the head are sustained on a regular basis-- which is why many researchers and physicians believe that the rules of some of these sports, especially where youths are participating, are in serious need of revision (Nature, 2017). And some sports, such as boxing, should perhaps retire from the ring altogether.
FIGURE 15.23 Tau Protein in the Brain of a Boxer with CTE
Cortical gray matter magni ed x350 From McKee et al. 2009. J. Neuropathol. Exp. Neurol. 68: 709, courtesy of Ann McKee
1. Just how prevalent is brain damage due to stroke, and to other diseases? Once the brain is damaged, is recovery more or less complete in a matter of hours, days, or months? 2. Discuss some of the factors that determine how thoroughly a person will recover Watson/frBormeedblroavien injury. The Mind's Machine Found3a.tiIosnsreocf BorvaeinryanbdeBtteehravwiohre4ne brain damage is caused by trauma or when the damage is caused by stroke? What is believed to be responsible for the difference? MM44e._1D5i.s2c3uss06s/o1m5/e20of the types of therapy that appear to help maximize recovery following brain damage.
concussion A form of closed head injury caused by a jarring blow to the head, resulting in damage to the tissue of the brain with short- or long-term consequences for cognitive function. chronic traumatic encephalopathy (CTE) A form of dementia that may develop following multiple concussions, such as in athletes engaged in contact sports.
Recommended Reading Berwick, R. C., and Chomsky, N. (2015). Why Only Us: Language and Evolution. Cambridge, MA: MIT Press. Bradbury, J. W., and Vehrencamp, S. L. (2011). Principles of Animal Communication (2nd ed.). Sunderland, MA: Oxford University Press/Sinauer. Breedlove, S. M. (2017). Foundations of Neural Development. Sunderland, MA: Oxford University Press/Sinauer. Fitch, W. T. (2010). The Evolution of Language. Cambridge, UK: Cambridge University Press. Gazzaniga, M. S. (2016). Tales from Both Sides of the Brain: A Life in Neuroscience. New York, NY: Ecco. Harrison, D. W. (2015). Brain Asymmetry and Neural Systems: Foundations in Clinical Neuroscience and Neuropsychology. New York, NY: Springer. Honing, H., and Fitch, W. T. (2018). The Origins of Musicality. Cambridge, MA: MIT Press. Koelsch, S. (2012). Brain & Music. New York, NY: Wiley-Blackwell. Kolb, B., and Whishaw, I. Q. (2015). Fundamentals of Human Neuropsychology (7th ed.). New York, NY: Worth. Meyer, J. (2015). Whistled Languages: A Worldwide Enquiry on Human Whistled Speech. New York, NY: Springer. Purves, D., Cabeza, R., Huettel, S. A., LaBar, K. S., et al. (2012). Principles of Cognitive Neuroscience (2nd ed.). Sunderland, MA: Oxford University Press/Sinauer. Tomasello, M. (2010). Origins of Human Communication. Cambridge, MA: Bradford Books/MIT Press.
15 · VISUAL SUMMARY You should be able to relate each summary to the adjacent illustration, including structures and processes. Thwe online version of this Visual Summary includes links to figures, animations, and activities that will help you consolidate the material.
1 Split-brain individuals show striking examples of cerebral lateralization. Most words projected only to the right hemisphere, for example, cannot be read, but the same stimuli directed only to the left hemisphere can be read. Spatial tasks, however, are performed better by the right hemisphere than by the left. Review Figure 15.1, Animation 15.2, Video 15.3 3 Anatomical asymmetry of the hemispheres is seen in some brain regions, such as the planum temporale (larger in the left hemisphere than in the right hemisphere of most right-handed individuals). Perfect pitch in musicians is also associated with a larger left planum temporale, but the right hemisphere is dominant for many other aspects of music processing. Review Figures 15.3 and 15.4
2 Most humans show many forms of cognitive specialization of the cerebral hemispheres. For example, most people show an advantage for verbal stimuli presented to the right ear or right visual field. Review Figure 15.2 4 In most people, parietal cortical injuries produce perceptual changes, including alterations in sensory and spatial processing. Damage affecting the fusiform gyrus can produce acquired prosopagnosia, a dramatic inability to recognize the faces of familiar people. A congenital form of prosopagnosia affects about 2.5% of the population. Review Figures 15.5 and 15.6, Video 15.4
5 Languages are made up of speech sounds, called phonemes and morphemes, that are assembled into words and sentences according to syntax. The left hemisphere of the human brain contains a network of structures specialized for processing speech and language. Damage in this network can cause the language impairment aphasia. Review Figures 15.7-15.9, Activity 15.1 7 The connectionist model of aphasia involves a loop from a posterior speech reception zone to an anterior expressive zone that, when severed, may produce a conduction aphasia. However, the motor theory of language suggests that the entire circuit serves motor control and is used for both production and perception. Review Figures 15.11 and 15.12, Activity 15.2a and b 9 Studies using PET and fMRI reveal that distinct regions of the left hemisphere are active during viewing, hearing, repeating, or assembling of verbal material. ERP studies have documented differential left-hemisphere processing of speech sounds versus speech meanings. Review Figure 15.15
11 Monkeys produce emotional vocalizations but cannot produce speech. Certain species of apes can learn American Sign Language, but it is not clear that this use constitutes language. Review Figure 15.18, Activity 15.3
13 The brain can show at least partial recovery of function after injury, especially during the first year or so, as the damaged brain stabilizes and reorganizes. Retraining is a significant part of functional recovery and may involve both compensation, by establishing new solutions to adaptive demands, and reorganization of surviving networks. Review Figure 15.20
6 Left inferior frontal lesions produce an impairment in speech production called nonfluent aphasia (or Broca's aphasia). More-posterior lesions, involving the temporoparietal cortex, cause fluent aphasia (or Wernicke's aphasia). Extensive destruction of the left hemisphere causes a more complete loss of language called global aphasia. Review Figure 15.10 8 Noninvasive stimulation has confirmed the left-hemisphere organization for language functions. Stimulation of anterior regions causes speech arrest, while stimulation in other locations causes misnaming and other speech errors. Transcranial magnetic stimulation indicates that the anterior speech zone contains further subdivisions. Review Figures 15.13 and 15.14 10 Humans acquire language during an early sensitive period involving genes like FOXP2, suggesting that the newborn brain contains mechanisms for language acquisition. Review Figure 15.17 12 Acquired dyslexia is a difficulty with reading due to brain damage; in deep dyslexia there is a disturbance in reading whole words; surface dyslexia involves a difficulty with the sounds of words. Developmental dyslexia is a congenital difficulty with reading that is associated with brain abnormalities. Review Figure 15.19 14 Although young brains have remarkable capacity for recovery after injury, cumulative damage due to repeated blows to the head can cause permanent and often progressive degeneration and cognitive impairment. Review Figures 15.21 and 15.23
The Mind's Machine digital resources include additional videos, flashcards, and other study tools.
APPENDIX A Primer on Concepts and Techniques in Molecular Biology
A.1Genes Carry Information That Encodes Proteins The most important thing about genes is that they are pieces of information, inherited from parents, that affect the development and function of our cells. Information carried by the genes is of a very specific sort: each gene carries the code for putting together a specific string of amino acids to form a particular protein molecule. This is all that genes do; they do not directly encode intelligence, or memories, or any other sort of complex behavior. The various proteins, each encoded by its own gene, make up the physical structure of the cell and most of its constituents, such as enzymes, which are proteins that enable chemical reactions in our cells. All these proteins make complex behavior possible, and in that context they are also the targets upon which the forces of evolution act. Proteins are specific. For example, only cells that have liver-typical proteins will look like liver cells and be able to perform liver functions. Neurons, on the other hand, are cells that make neuron-typical proteins so that they can look and act like neurons. The genetic information for making these various proteins is crucial for an animal to live and for a nervous system to work properly. One thing we hope this book will help you understand is that everyday experience can affect whether and when particular genetic recipes for making various proteins are used. To aid in that understanding, let's review how genetic information is stored and how proteins are made. Our discussion will be brief, but many online tutorials can provide you with more detailed information (see A STEP FURTHER A.1, on the website). Genetic information is stored in molecules of DNA The information for making all of our proteins could, in theory, be stored in any sort of format--on sheets of paper, a DVD, a smartphone--but organisms on this planet store their genetic information in a chemical called deoxyribonucleic acid, or DNA. Each molecule of DNA consists of a long strand of chemicals called nucleotides strung one after the other. DNA has only four nucleotides: guanine, cytosine, thymine, and adenine (abbreviated G, C, T, and A). The particular sequence of nucleotides (e.g., GCTTACC or TGGTCC or TGA) holds the information that will eventually make a protein. Because many millions of these nucleotides can be joined one after the other, a tremendous amount of information can be stored in very little space--on a single molecule of DNA. A set of nucleotides that has been strung together can snuggle tightly against another string of nucleotides if it has the proper sequence: T nucleotides preferentially link with A nucleotides, and G nucleotides link with C nucleotides. Thus, T and A are said to be complementary nucleotides, and C and G are complementary nucleotides.
gene A length of DNA that encodes the information for constructing a particular protein. protein A long string of amino acids. Proteins are the basic building material of organisms. enzyme A complicated protein whose action increases the probability of a specific chemical reaction. deoxyribonucleic acid (DNA) A nucleic acid that constitutes the chromosomes of cells and codes hereditary information. nucleotide A portion of a DNA or RNA molecule that is composed of a single base and the adjoining sugar-phosphate unit of the strand.
FIGURE A.1 Duplication of DNA
Before cell division, all of the chromosomes in the cell must be duplicated, as illustrated here, so that each daughter cell has the full complement of genetic information.
Helicase separates the strands of parent DNA
Template 5' 3' Two daughter strands Template 5' DNA polymerase
hybridization The process by which one string of nucleotides becomes linked to a complementary series of nucleotides. chromosome A complex of condensed strands of DNA and associated protein molecules. Chromosomes are found in the nucleus of cells. eukaryote Any organism whose cells have the genetic material contained within a nuclear envelope.
In fact, most of the time, our DNA consists not of a single strand of nucleotides, but of two complementary strands of nucleotides wrapped around one another. The two strands of nucleotides are said to hybridize with (link to) one another, coiling slightly to form the famous double helix. The double-stranded DNA twists and coils further, becoming visible in microscopes as chromosomes, which resemble twisted lengths of yarn. Humans and the many other organisms known as eukaryotes store our chromosomes in a membranous sphere called a cell nucleus (plural nuclei). The ability of DNA to exist as two complementary strands of nucleotides is crucial for the duplication of the chromosomes (FIGURE A.1), but the details of that story will not concern us. Just remember that, with very few exceptions, every cell in your body has a faithful copy of all the DNA you received from your parents. DNA is transcribed to produce messenger RNA
The information from DNA is used to assemble another molecule--ribonucleic acid,
structure of a cell that contains the chromosomes.
or RNA--that serves as a template for later steps in protein synthesis. Like DNA, RNA is made up of a long string of four types of nucleotides. For RNA, those nucleotides are
ribonucleic acid (RNA)W aAtsonnu/cBleriecedalcoivde
G and C, which you'll recall are complementary to each other, plus A and U (uracil),
that implements informatiTohnefoMuinndd'isnMDaNchAi.ne which are also complementary to each other. Note that the T nucleotide is found only
which mRNA forms bases complementary MM4e_A.01 08/17/20
When a particular gene becomes active, the double strand of DNA unwinds enough
so that one strand becomes free of the other and becomes available to special cellular
machinery (including an enzyme called transcriptase) that begins transcription--
the construction of a specific string of RNA nucleotides that are complementary to
the exposed strand of DNA (FIGURE A.2). This length of RNA goes by several names:
messenger RNA (mRNA), transcript, or sometimes message. Each DNA nucleotide
that carries the code of a section of a DNA strand to the cytoplasm.
encodes a specific RNA nucleotide (an RNA G for every DNA C, an RNA C for every DNA G, an RNA U for every DNA A, and an RNA A for every DNA T). This transcript
ribosome An organelle in the cell body where genetic information is translated to produce proteins.
is made in the nucleus where the DNA resides; then the mRNA molecule moves to the cytoplasm, where protein molecules are assembled.
translation The process by which amino acids are linked together (directed by an mRNA molecule) to form protein molecules. codon A set of three nucleotides that encodes one particular amino acid. peptide A short string of amino acids. Longer strings of amino acids are called proteins.
RNA molecules direct the formation of protein molecules In the cytoplasm, special organelles called ribosomes attach themselves to a molecule of RNA, "read" the sequence of RNA nucleotides, and using that information, begin linking together amino acids to form a protein molecule. The structure and function of a protein molecule depend on which particular amino acids are put together and in what order. The decoding of an RNA transcript to manufacture a particular protein is called translation (see Figure A.2), as distinct from transcription, the construction of the mRNA molecule.
Each trio of RNA nucleotides, or codon, encodes one of 20 or so different amino acids. Special molecules associated with the ribosome recognize the codon and bring a molecule of the appropriate amino acid so that the ribosome can fuse that amino acid to the previous one. If the resulting string of amino acids is short (say, 50 amino acids or less), it is called a peptide; if it is long, it is called a protein. Thus the ribosome assembles a very particular sequence of amino acids at the behest of a very particular sequence of RNA nucleotides, which were themselves encoded in the DNA inherited from our parents. In short, the biological secret of life is that DNA makes RNA, and RNA makes protein. There are fascinating additions to this short story. Often the information from separate stretches of DNA is spliced together to make a single transcript; this so-called alternative splicing can create different transcripts from the same gene. Sometimes a protein is modified extensively after translation ends; special chemical processes can cleave long proteins to create one or several active peptides. Keep in mind that each cell has the complete library of genetic information, collectively known as the genome, but makes only a fraction of all the proteins encoded in that DNA. In modern biology we say that each cell expresses only some genes; that is, the cell transcribes certain genes and makes the corresponding gene products (protein molecules). Thus, each cell must come to express all the genes needed to perform its function. Modern biologists refer to the expression of a particular subset of the genome as cell differentiation: the process by which different types of cells acquire their unique appearance and function. During development, individual cells appear to become more and more specialized, expressing progressively fewer genes. Many molecular biologists are striving to understand which cellular and molecular mechanisms "turn on" or "turn off" gene expression, in order to understand development and pathologies, such as cancer, or to provide crucial proteins to afflicted organs in a variety of diseases.
DNA TRANSCRIPTION mRNA Cytoplasm Ribosome mRNA Protein TRANSLATION
DNA template (gene) A U T AG C RNA molecule being assembled Nuclear membrane
A.2Molecular Biologists Have Craftily Enslaved Microorganisms and Enzymes
FIGURE A.2 DNA Makes RNA, and RNA Makes Protein
Many basic methods of molecular biology are not explicitly discussed in the text, so we will not describe them in detail here. However, you should understand what some of
genome Also called genotype. All the genetic information that one
the terms mean, even if you don't know exactly how the methods are performed.
Molecular biologists have found ways to incorporate DNA from other species into
the DNA of microorganisms such as bacteria and viruses. After the foreign DNA is
incorporated, the microorganisms are allowed to reproduce rapidly, producing more a particular gene.
and more copies of the (foreign) gene of interest. At this point the geneWisatssaonid/Btoreebdelove cell differentiation The developmental
cloned, because researchers can make as many copies as they want. ToTheenMsuinrde'sthMaatchine stage in which cells acquire distinctive
the right gene is being cloned, the researcher generally clones many, maFonuynddaitfiofensreofnBtrain andchBaehraavcitoerr4isetics, such as those of neurons,
genes--each into different bacteria--and then "screens" the bacteria raMpMid4lye_tAo.0f2ind08/17/g20enes.
the rare one that has incorporated the gene of interest.
When enough copies of the DNA have been made, the microorganisms are ground sequences of DNA or RNA, or
up and the DNA extracted. If sufficient DNA has been generated, chemical steps can
then determine the exact sequence of nucleotides found in that stretch of DNA--a process known as DNA sequencing. Once the sequence of nucleotides has been de-
DNA sequencing The process by which the order of nucleotides
termined, the sequence of complementary nucleotides in the messenger RNA for that in a gene is identified.
A - 4 polymerase chain reaction (PCR) Also called gene amplification. A method for reproducing a particular RNA or DNA sequence manyfold, allowing amplification for sequencing or manipulating the sequence. transgenic Referring to an animal in which a new or altered gene has been deliberately introduced into the genome. probe In molecular biology, a manufactured sequence of DNA or RNA that is made to include a label (a colorful or radioactive molecule) that lets us track its location. gel electrophoresis A method of separating molecules of differing size or electrical charge by forcing them to flow through a gel. blotting Transferring DNA, RNA, or protein fragments to a sheet of nitrocellulose following separation via gel electrophoresis. The blotted substance can then be labeled. View Animation A.1: Gel Electrophoresis
gene can be inferred. The sequence of mRNA nucleotides tells the investigator the sequence of amino acids that will be made from that transcript, because biologists know which amino acid is encoded by each trio of DNA nucleotides. For example, scientists discovered the amino acid sequence of neurotransmitter receptors by this process. The business of obtaining many copies of DNA has been boosted by a technique called the polymerase chain reaction, or PCR. This technique exploits a special type of polymerase enzyme that, like other such enzymes, induces the formation of a DNA molecule that is complementary to an existing single strand of DNA (see Figure A.1). Because this particular polymerase enzyme (called Taq polymerase) evolved in bacteria that inhabit geothermal hot springs, it can function in a broad range of temperatures. By heating double-stranded DNA, we can cause the two strands to separate, making each strand available to polymerase enzymes that, when the temperature has decreased enough, construct a new "mate" for each strand so that they are both double-stranded again. The first PCR yields only double the original number of DNA molecules; repeating the process results in 4 times as many molecules as at first. Repeatedly heating and cooling the DNA of interest in the presence of this heat-resistant polymerase enzyme soon yields millions of copies of the original DNA molecule, which is why this process is also referred to as gene amplification. In practice, PCR usually requires the investigator to provide primers--short nucleotide sequences synthesized to hybridize on either side of the gene of interest to amplify that particular gene more than others. With PCR, sufficient quantities of DNA are produced for chemical analysis or other manipulations, such as introducing DNA into cells. For example, we might inject some of the DNA encoding a protein of interest into a fertilized mouse egg (a zygote) and then return the zygote to a pregnant mouse to grow. Occasionally the injected DNA becomes incorporated into the zygote's genome, resulting in a transgenic mouse that carries and expresses the foreign gene. Southern blots identify particular genes Suppose we want to know whether a particular individual or a particular species carries a certain gene. Because all cells contain a complete copy of the genome, we can gather DNA from just about any kind of cell population: blood, skin, or muscle, for example. After the cells are ground up, a chemical extraction procedure isolates the DNA (discarding the RNA and protein). Finding a particular gene in that DNA boils down to finding a particular sequence of DNA nucleotides. To do that, we can exploit the tendency of nucleic acids (DNA and RNA) to hybridize with one another. If we were looking for the DNA sequence GCT, for example, we could manufacture the sequence CGA (there are machines to do that), which would then stick to (hybridize with) any DNA sequence of GCT. The manufactured sequence CGA is called a probe because it is made to include a label (a colorful or radioactive molecule) that lets us track its location. Of course, such a short length of nucleotides will be found in many genes. In order for a probe to recognize one particular gene, it has to be about 15 nucleotides long. When we extract DNA from an individual, it's convenient to let enzymes cut up the very long stretches of DNA into more manageable pieces of 1,000-20,000 nucleotides each. A process called gel electrophoresis uses electrical current to separate these millions of pieces more or less by size (FIGURE A.3). Large pieces move slowly through a tube of gelatin-like material, and small pieces move rapidly. The tube of gel is then sliced and placed on top of a sheet of paper-like material called nitrocellulose. When fluid is allowed to flow through the gel and nitrocellulose, DNA molecules are pulled out of the gel and deposited on the waiting nitrocellulose. This process of making a "sandwich" of gel and nitrocellulose and using fluid to move molecules from the former to the latter is called blotting (see Figure A.3). If the gene we're looking for is among those millions of DNA fragments sitting on the nitrocellulose, our labeled probe should recognize and hybridize with the sequence. The nitrocellulose sheet is soaked in a solution containing our labeled probe; we wait
Gel electrophoresis Wells are lled with DNA solutions. -
Buffer solution Electrical current is applied to the gel. Southern blotting Weight Absorbent paper Wick
+ Bands of DNA fragments, bearing a negative charge, move toward the positive electrode. Nitrocellulose sheet
+ Smaller fragments move more rapidly than larger ones.
+ Movement continues as long as the electrical current is maintained.
Buffer solution (to transfer DNA) Hybridization
Rinse off unattached probe and make chemical label visible. Chemical labels
for the probe to find and hybridize with the gene of interest (if it is present), and we rinse the sheet to remove probe molecules that did not find the gene. Then we visualize Wthaetsponro/bBree,eediltohveer by causing the label to show its color or, if radioactive, by letting the The Mind's Machine Fporuonbdeatieoxnps oofsBerapinhoantodgBreahapvhioirc4feilm to identify the locations where the probe has accumulated. In either case, if the probe found the gene, a labeled band will be evident, correMspMon4ed_iAn.g03to t0h8e/3s1i/ze20of DNA fragment that contained the gene (see Figure A.3).
FIGURE A.3 Gel Electrophoresis and Southern Blotting
Southern blot A method of detecting a particular DNA sequence in the genome of an organism. Northern blot A method of detecting a particular RNA transcript in a tissue or organ. in situ hybridization A method for detecting particular RNA transcripts in tissue sections. antibody Also called immunoglobulin. A large protein that recognizes and permanently binds to particular shapes, normally as part of the immune system attack on foreign particles. Western blot A method of detecting a particular protein molecule in a tissue or organ. immunocytochemistry (ICC) A method for detecting a particular protein in tissues in which an antibody recognizes and binds to the protein and then chemical methods are used to leave a visible reaction product around each antibody.
This process of looking for a particular sequence of DNA is called a Southern blot, named after the man who developed the technique, Edward Southern. Southern blots are useful for determining whether related individuals share a particular gene or for assessing the evolutionary relatedness of different species. The developed blots, with their lanes of labeled bands (see Figure A.3), are often seen in popular-media accounts of DNA fingerprinting of individuals. Northern blots identify particular mRNA transcripts A method more relevant for our discussions is the Northern blot (whimsically named as the opposite of the Southern blot). A Northern blot can identify which tissues are making a particular RNA transcript. If liver cells are making a particular protein, for example, then some transcripts for the gene that encodes that protein should be present. So we can take the liver, grind it up, and use chemical processes to isolate most of the RNA (discarding the DNA and protein). The resulting mixture consists of RNA molecules of many different sizes: long, medium, and short transcripts. Gel electrophoresis will separate the transcripts by size, and we can blot the size-sorted mRNA molecules onto nitrocellulose sheets; the process is very similar to the Southern blot procedure. To see whether the particular transcript we're looking for is among the mRNAs, we construct a labeled probe (of either DNA nucleotides or RNA nucleotides) that is complementary to the mRNA transcript of interest and long enough that it will hybridize only with that particular transcript. We incubate the nitrocellulose in the probe, allow time for the probe to hybridize with the targeted transcript (if present), rinse off any unused probe molecules, and then visualize the probe as before. If the transcript of interest is present, we should see a band on the film (see Figure A.3). The presence of several bands indicates that the probe has hybridized to more than one transcript and we may need to make a more specific probe or alter chemical conditions to make the probe less likely to bind similar transcripts. Because different gene transcripts have different lengths, the transcript of interest should have reached a particular point in the electrophoresis gel: small transcripts should have moved far; large transcripts should have moved only a little. If our probe has found the right transcript, the single band of labeling should be at the point that is appropriate for a transcript of that length. In situ hybridization localizes mRNA transcripts within specific cells Northern blots can tell us whether a particular organ has transcripts for a particular gene product. For example, Northern blot analyses have indicated that thousands of genes are transcribed only in the brain. Presumably the proteins encoded by these genes are used exclusively in the brain. But such results alone are not very informative, because the brain consists of so many different kinds of glial and neuronal cells. We can refine Northern blot analyses somewhat, by dissecting out a particular part of the brain--say, the hippocampus--to isolate mRNAs. Sometimes, though, it is important to know exactly which cells are making the transcript. In that case we use in situ hybridization. With in situ hybridization we use the same sort of labeled probe, constructed of nucleotides that are complementary to (and will therefore hybridize with) the targeted transcript, as in Northern blots. Instead of using the probe to find and hybridize with the transcript on a sheet of nitrocellulose, however, we use the probe to find the transcripts in situ (Latin for "in place")--that is, on a section of tissue. After rinsing off the probe molecules that didn't find a match, we visualize the probe in the tissue section. Any cells in the section that were transcribing the gene of interest will have transcripts in the cytoplasm that should have hybridized with our labeled probe. In situ hybridization therefore can tell us exactly which cells are expressing a particular gene (FIGURE A.4 and Box 2.1).
Western blots identify particular proteins Sometimes we wish to study a particular protein rather than its transcript. In such cases we can use antibodies. Antibodies are large, complicated molecules (proteins, in fact) that our immune system adds to the bloodstream to identify and fight invading microbes, thereby arresting and preventing disease. But if we inject a rabbit or mouse with a sample of a protein of interest, we can induce the animal to create antibodies that recognize and attach to that particular protein, just as if it were an invader. Once these antibodies have been purified and chemically labeled, we can use them to search for the target protein. We grind up an organ, isolate the proteins (discarding the DNA and RNA), and separate them by means of gel electrophoresis. Then we blot these proteins out of the gel and onto nitrocellulose. Next we use the antibodies to tell us whether the targeted protein is among those made by that organ. If the antibodies identify only the protein we care about, there should be a single band of labeling (if there are two or more, then the antibodies may recognize more than one protein). Because proteins come in different sizes, the single band of label should be at the position corresponding to the size of the protein that we're studying. Such blots are called Western blots. To review, Southern blots identify particular DNA pieces (genes), Northern blots identify particular RNA pieces (transcripts), and Western blots identify particular proteins (sometimes called products). Antibodies can also tell us which cells possess a particular protein If we need to know which particular cells within an organ such as the brain are making a particular protein, we can use the same sorts of antibodies that we use in Western blots, but in this case directed at that protein in tissue sections. We slice up the brain, expose the sections to the antibodies, allow time for them to find and attach to the protein, rinse off unattached antibodies, and use chemical treatments to visualize the antibodies. Cells that were making the protein will be labeled from the chemical treatments (see Figure 1.19C). Because antibodies from the immune system are used to identify cells with the aid of chemical treatment, this method is called immunocytochemistry, or ICC. This technique can even tell us where, within the cell, the protein is found. Such information can provide important clues about the function of the protein. For example, if the protein is found in axon terminals, it may be a neurotransmitter.
Labeled probe hybridizing to RNA RNA in cytoplasm of cell
Bead of solution covering brain section, contains labeled probe. Rinse off unattached probes and make chemical label visible. Chemical label identi es hippocampal regions that had been making targeted RNA.
FIGURE A.4 In Situ Hybridization
Watson/Breedlove The Mind's Machine Foundations of Brain and Behavior 4e MM4e_A.04 08/17/20