It is ironic that of all the parts of the brain, we know the least about the functions of the cerebral cortex, even though it is by far the largest portion of the nervous system. But we do know the effects of damage or specific stimulation in various portions of the cortex. In the first part of this chapter, the known cortical functions are discussed; then basic theories of neuronal mechanisms involved in thought processes, memory, analysis of sensory information, and so forth are presented briefly.
Physiologic Anatomy of the Cerebral Cortex
The functional part of the cerebral cortex is a thin layer of neurons covering the surface of all the convolutions of the cerebrum. This layer is only 2 to 5 millimeters thick, with a total area of about one quarter of a square meter. The total cerebral cortex contains about 100 billion neurons.
Figure 57-1 shows the typical histological structure of the neuronal surface of the cerebral cortex, with its successive layers of different types of neurons. Most of the neurons are of three types: (1) granular(also called stellate), (2) fusiform, and (3) pyramidal, the last named for their characteristic pyramidal shape.
Figure 57-1 Structure of the cerebral cortex, showing: I, molecular layer; II, external granular layer; III, layer of pyramidal cells; IV, internal granular layer; V, large pyramidal cell layer; and VI, layer of fusiform or polymorphic cells.
(Redrawn from Ranson SW, Clark SL [after Brodmann]: Anatomy of the Nervous System. Philadelphia: WB Saunders, 1959.)
The granular neurons generally have short axons and, therefore, function mainly as interneurons that transmit neural signals only short distances within the cortex itself. Some are excitatory, releasing mainly the excitatory neurotransmitter glutamate; others are inhibitory and release mainly the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). The sensory areas of the cortex, as well as the association areas between sensory and motor areas, have large concentrations of these granule cells, suggesting a high degree of intracortical processing of incoming sensory signals within the sensory areas and association areas.
The pyramidal and fusiform cells give rise to almost all the output fibers from the cortex. The pyramidal cells are larger and more numerous than the fusiform cells. They are the source of the long, large nerve fibers that go all the way to the spinal cord. They also give rise to most of the large subcortical association fiber bundles that pass from one major part of the brain to another.
To the right in Figure 57-1 is shown the typical organization of nerve fibers within the different layers of the cerebral cortex. Note particularly the large number of horizontal fibers that extend between adjacent areas of the cortex, but note also the vertical fibers that extend to and from the cortex to lower areas of the brain and some all the way to the spinal cord or to distant regions of the cerebral cortex through long association bundles.
The functions of the specific layers of the cerebral cortex are discussed in Chapters 47 and 51. By way of review, let us recall that most incoming specific sensory signals from the body terminate in cortical layer IV. Most of the output signals leave the cortex through neurons located in layers V and VI; the very large fibers to the brain stem and cord arise generally in layer V; and the tremendous numbers of fibers to the thalamus arise in layer VI. Layers I, II, and III perform most of the intracortical association functions, with especially large numbers of neurons in layers II and III making short horizontal connections with adjacent cortical areas.
Anatomical and Functional Relations of the Cerebral Cortex to the Thalamus and Other Lower Centers
All areas of the cerebral cortex have extensive to-and-fro efferent and afferent connections with deeper structures of the brain. It is important to emphasize the relation between the cerebral cortex and the thalamus. When the thalamus is damaged along with the cortex, the loss of cerebral function is far greater than when the cortex alone is damaged because thalamic excitation of the cortex is necessary for almost all cortical activity.
Figure 57-2 shows the areas of the cerebral cortex that connect with specific parts of the thalamus. These connections act in two directions, both from the thalamus to the cortex and then from the cortex back to essentially the same area of the thalamus. Furthermore, when the thalamic connections are cut, the functions of the corresponding cortical area become almost entirely lost. Therefore, the cortex operates in close association with the thalamus and can almost be considered both anatomically and functionally a unit with the thalamus: for this reason, the thalamus and the cortex together are sometimes called the thalamocortical system. Almost all pathways from the sensory receptors and sensory organs to the cortex pass through the thalamus, with the principal exception of some sensory pathways of olfaction.
Figure 57-2 Areas of the cerebral cortex that connect with specific portions of the thalamus.
Functions of Specific Cortical Areas
Studies in human beings have shown that different cerebral cortical areas have separate functions. Figure 57-3 is a map of some of these functions as determined from electrical stimulation of the cortex in awake patients or during neurological examination of patients after portions of the cortex had been removed. The electrically stimulated patients told their thoughts evoked by the stimulation, and sometimes they experienced movements. Occasionally they spontaneously emitted a sound or even a word or gave some other evidence of the stimulation.
Figure 57-3 Functional areas of the human cerebral cortex as determined by electrical stimulation of the cortex during neurosurgical operations and by neurological examinations of patients with destroyed cortical regions.
(Redrawn from Penfield W, Rasmussen T: The Cerebral Cortex of Man: A Clinical Study of Localization of Function. New York: Hafner, 1968.)
Putting large amounts of information together from many different sources gives a more general map, as shown in Figure 57-4. This figure shows the major primary and secondary premotor and supplementary motor areas of the cortex, as well as the major primary and secondary sensory areas for somatic sensation, vision, and hearing, all of which are discussed in earlier chapters. The primary motor areas have direct connections with specific muscles for causing discrete muscle movements. The primary sensory areas detect specific sensations—visual, auditory, or somatic—transmitted directly to the brain from peripheral sensory organs.
Figure 57-4 Locations of major association areas of the cerebral cortex, as well as primary and secondary motor and sensory areas.
The secondary areas make sense out of the signals in the primary areas. For instance, the supplementary and premotor areas function along with the primary motor cortex and basal ganglia to provide “patterns” of motor activity. On the sensory side, the secondary sensory areas, located within a few centimeters of the primary areas, begin to analyze the meanings of the specific sensory signals, such as (1) interpretation of the shape or texture of an object in one’s hand; (2) interpretation of color, light intensity, directions of lines and angles, and other aspects of vision; and (3) interpretations of the meanings of sound tones and sequence of tones in the auditory signals.
Figure 57-4 also shows several large areas of the cerebral cortex that do not fit into the rigid categories of primary and secondary motor and sensory areas. These areas are called association areas because they receive and analyze signals simultaneously from multiple regions of both the motor and sensory cortices, as well as from subcortical structures. Yet even the association areas have their specializations. Important association areas include (1) the parieto-occipitotemporal association area, (2) the prefrontal association area, and (3) the limbic association area. Following are explanations of the functions of these areas.
Parieto-occipitotemporal Association Area
This association area lies in the large parietal and occipital cortical space bounded by the somatosensory cortex anteriorly, the visual cortex posteriorly, and the auditory cortex laterally. As would be expected, it provides a high level of interpretative meaning for signals from all the surrounding sensory areas. However, even the parieto-occipitotemporal association area has its own functional subareas, which are shown in Figure 57-5.
Figure 57-5 Map of specific functional areas in the cerebral cortex, showing especially Wernicke’s and Broca’s areas for language comprehension and speech production, which in 95 percent of all people are located in the left hemisphere.
1 Analysis of the Spatial Coordinates of the Body
An area beginning in the posterior parietal cortex and extending into the superior occipital cortex provides continuous analysis of the spatial coordinates of all parts of the body, as well as of the surroundings of the body. This area receives visual sensory information from the posterior occipital cortex and simultaneous somatosensory information from the anterior parietal cortex. From all this information, it computes the coordinates of the visual, auditory, and body surroundings.
2 Wernicke’s Area Is Important for Language Comprehension
The major area for language comprehension, called Wernicke’s area, lies behind the primary auditory cortex in the posterior part of the superior gyrus of the temporal lobe. We discuss this area much more fully later; it is the most important region of the entire brain for higher intellectual function because almost all such intellectual functions are language based.
3 Angular Gyrus Area Is Needed for Initial Processing of Visual Language (Reading)
Posterior to the language comprehension area, lying mainly in the anterolateral region of the occipital lobe, is a visual association area that feeds visual information conveyed by words read from a book into Wernicke’s area, the language comprehension area. This so-called angular gyrus area is needed to make meaning out of the visually perceived words. In its absence, a person can still have excellent language comprehension through hearing but not through reading.
4 Area for Naming Objects
In the most lateral portions of the anterior occipital lobe and posterior temporal lobe is an area for naming objects. The names are learned mainly through auditory input, whereas the physical natures of the objects are learned mainly through visual input. In turn, the names are essential for both auditory and visual language comprehension (functions performed in Wernicke’s area located immediately superior to the auditory “names” region and anterior to the visual word processing area).
Prefrontal Association Area
As discussed in Chapter 56, the prefrontal association area functions in close association with the motor cortex to plan complex patterns and sequences of motor movements. To aid in this function, it receives strong input through a massive subcortical bundle of nerve fibers connecting the parieto-occipitotemporal association area with the prefrontal association area. Through this bundle, the prefrontal cortex receives much preanalyzed sensory information, especially information on the spatial coordinates of the body that is necessary for planning effective movements. Much of the output from the prefrontal area into the motor control system passes through the caudate portion of the basal ganglia–thalamic feedback circuit for motor planning, which provides many of the sequential and parallel components of movement stimulation.
The prefrontal association area is also essential to carrying out “thought” processes in the mind. This presumably results from some of the same capabilities of the prefrontal cortex that allow it to plan motor activities. It seems to be capable of processing nonmotor and motor information from widespread areas of the brain and therefore to achieve nonmotor types of thinking, as well as motor types. In fact, the prefrontal association area is frequently described simply as important for elaboration of thoughts, and it is said to store on a short-term basis“working memories” that are used to combine new thoughts while they are entering the brain.
Broca’s Area Provides the Neural Circuitry for Word Formation
Broca’s area, shown in Figure 57-5, is located partly in the posterior lateral prefrontal cortex and partly in the premotor area. It is here that plans and motor patterns for expressing individual words or even short phrases are initiated and executed. This area also works in close association with the Wernicke’s language comprehension center in the temporal association cortex, as we discuss more fully later in the chapter.
An especially interesting discovery is the following: When a person has already learned one language and then learns a new language, the area in the brain where the new language is stored is slightly removed from the storage area for the first language. If both languages are learned simultaneously, they are stored together in the same area of the brain.
Limbic Association Area
Figures 57-4 and 57-5 show still another association area called the limbic association area. This area is found in the anterior pole of the temporal lobe, in the ventral portion of the frontal lobe, and in the cingulate gyrus lying deep in the longitudinal fissure on the midsurface of each cerebral hemisphere. It is concerned primarily with behavior, emotions, and motivation. We discuss in Chapter 58 that the limbic cortex is part of a much more extensive system, the limbic system, that includes a complex set of neuronal structures in the midbasal regions of the brain. This limbic system provides most of the emotional drives for activating other areas of the brain and even provides motivational drive for the process of learning itself.
Area for Recognition of Faces
An interesting type of brain abnormality called prosopagnosia is inability to recognize faces. This occurs in people who have extensive damage on the medial undersides of both occipital lobes and along the medioventral surfaces of the temporal lobes, as shown in Figure 57-6. Loss of these face recognition areas, strangely enough, results in little other abnormality of brain function.
Figure 57-6 Facial recognition areas located on the underside of the brain in the medial occipital and temporal lobes.
(Redrawn from Geschwind N: Specializations of the human brain. Sci Am 241:180, 1979. ® 1979 by Scientific American, Inc. All rights reserved.)
One wonders why so much of the cerebral cortex should be reserved for the simple task of face recognition. Most of our daily tasks involve associations with other people, and one can see the importance of this intellectual function.
The occipital portion of this facial recognition area is contiguous with the visual cortex, and the temporal portion is closely associated with the limbic system that has to do with emotions, brain activation, and control of one’s behavioral response to the environment, as we see in Chapter 58.
Comprehensive Interpretative Function of the Posterior Superior Temporal Lobe—“Wernicke’s Area” (a General Interpretative Area)
The somatic, visual, and auditory association areas all meet one another in the posterior part of the superior temporal lobe, shown in Figure 57-7, where the temporal, parietal, and occipital lobes all come together. This area of confluence of the different sensory interpretative areas is especially highly developed in the dominant side of the brain—the left side in almost all right-handed people—and it plays the greatest single role of any part of the cerebral cortex for the higher comprehension levels of brain function that we call intelligence. Therefore, this region has been called by different names suggestive of an area that has almost global importance: the general interpretative area,the gnostic area, the knowing area, the tertiary association area, and so forth. It is best known as Wernicke’s area in honor of the neurologist who first described its special significance in intellectual processes.
Figure 57-7 Organization of the somatic auditory and visual association areas into a general mechanism for interpretation of sensory experience. All of these feed also into Wernicke’s area, located in the posterosuperior portion of the temporal lobe. Note also the prefrontal area and Broca’s speech area in the frontal lobe.
After severe damage in Wernicke’s area, a person might hear perfectly well and even recognize different words but still be unable to arrange these words into a coherent thought. Likewise, the person may be able to read words from the printed page but be unable to recognize the thought that is conveyed.
Electrical stimulation in Wernicke’s area of a conscious person occasionally causes a highly complex thought. This is particularly true when the stimulation electrode is passed deep enough into the brain to approach the corresponding connecting areas of the thalamus. The types of thoughts that might be experienced include complicated visual scenes that one might remember from childhood, auditory hallucinations such as a specific musical piece, or even a statement made by a specific person. For this reason, it is believed that activation of Wernicke’s area can call forth complicated memory patterns that involve more than one sensory modality even though most of the individual memories may be stored elsewhere. This belief is in accord with the importance of Wernicke’s area in interpreting the complicated meanings of different patterns of sensory experiences.
Angular Gyrus—Interpretation of Visual Information
The angular gyrus is the most inferior portion of the posterior parietal lobe, lying immediately behind Wernicke’s area and fusing posteriorly into the visual areas of the occipital lobe as well. If this region is destroyed while Wernicke’s area in the temporal lobe is still intact, the person can still interpret auditory experiences as usual, but the stream of visual experiences passing into Wernicke’s area from the visual cortex is mainly blocked. Therefore, the person may be able to see words and even know that they are words but not be able to interpret their meanings. This is the condition called dyslexia, or word blindness.
Let us again emphasize the global importance of Wernicke’s area for processing most intellectual functions of the brain. Loss of this area in an adult usually leads thereafter to a lifetime of almost demented existence.
Concept of the Dominant Hemisphere
The general interpretative functions of Wernicke’s area and the angular gyrus, as well as the functions of the speech and motor control areas, are usually much more highly developed in one cerebral hemisphere than in the other. Therefore, this hemisphere is called the dominant hemisphere. In about 95 percent of all people, the left hemisphere is the dominant one.
Even at birth, the area of the cortex that will eventually become Wernicke’s area is as much as 50 percent larger in the left hemisphere than in the right in more than one half of neonates. Therefore, it is easy to understand why the left side of the brain might become dominant over the right side. However, if for some reason this left side area is damaged or removed in very early childhood, the opposite side of the brain will usually develop dominant characteristics.
A theory that can explain the capability of one hemisphere to dominate the other hemisphere is the following. The attention of the“mind” seems to be directed to one principal thought at a time. Presumably, because the left posterior temporal lobe at birth is usually slightly larger than the right, the left side normally begins to be used to a greater extent than the right. Thereafter, because of the tendency to direct one’s attention to the better developed region, the rate of learning in the cerebral hemisphere that gains the first start increases rapidly, whereas in the opposite, less-used side, learning remains slight. Therefore, the left side normally becomes dominant over the right.
In about 95 percent of all people, the left temporal lobe and angular gyrus become dominant, and in the remaining 5 percent, either both sides develop simultaneously to have dual function or, more rarely, the right side alone becomes highly developed, with full dominance.
As discussed later in the chapter, the premotor speech area (Broca’s area), located far laterally in the intermediate frontal lobe, is also almost always dominant on the left side of the brain. This speech area is responsible for formation of words by exciting simultaneously the laryngeal muscles, respiratory muscles, and muscles of the mouth.
The motor areas for controlling hands are also dominant in the left side of the brain in about 9 of 10 persons, thus causing right-handedness in most people.
Although the interpretative areas of the temporal lobe and angular gyrus, as well as many of the motor areas, are usually highly developed in only the left hemisphere, these areas receive sensory information from both hemispheres and are capable also of controlling motor activities in both hemispheres. For this purpose, they use mainly fiber pathways in the corpus callosum for communication between the two hemispheres. This unitary, cross-feeding organization prevents interference between the two sides of the brain; such interference could create havoc with both mental thoughts and motor responses.
Role of Language in the Function of Wernicke’s Area and in Intellectual Functions
A major share of our sensory experience is converted into its language equivalent before being stored in the memory areas of the brain and before being processed for other intellectual purposes. For instance, when we read a book, we do not store the visual images of the printed words but instead store the words themselves or their conveyed thoughts often in language form.
The sensory area of the dominant hemisphere for interpretation of language is Wernicke’s area, and this is closely associated with both the primary and secondary hearing areas of the temporal lobe. This close relation probably results from the fact that the first introduction to language is by way of hearing. Later in life, when visual perception of language through the medium of reading develops, the visual information conveyed by written words is then presumably channeled through the angular gyrus, a visual association area, into the already developed Wernicke’s language interpretative area of the dominant temporal lobe.
Functions of the Parieto-occipitotemporal Cortex in the Nondominant Hemisphere
When Wernicke’s area in the dominant hemisphere of an adult person is destroyed, the person normally loses almost all intellectual functions associated with language or verbal symbolism, such as the ability to read, the ability to perform mathematical operations, and even the ability to think through logical problems. Many other types of interpretative capabilities, some of which use the temporal lobe and angular gyrus regions of the opposite hemisphere, are retained.
Psychological studies in patients with damage to the nondominant hemisphere have suggested that this hemisphere may be especially important for understanding and interpreting music, nonverbal visual experiences (especially visual patterns), spatial relations between the person and their surroundings, the significance of “body language” and intonations of people’s voices, and probably many somatic experiences related to use of the limbs and hands. Thus, even though we speak of the “dominant” hemisphere, this is primarily for language-based intellectual functions; the so-called nondominant hemisphere might actually be dominant for some other types of intelligence.
Higher Intellectual Functions of the Prefrontal Association Areas
For years, it has been taught that the prefrontal cortex is the locus of “higher intellect” in the human being, principally because the main difference between the brains of monkeys and of human beings is the great prominence of the human prefrontal areas. Yet efforts to show that the prefrontal cortex is more important in higher intellectual functions than other portions of the brain have not been successful. Indeed, destruction of the language comprehension area in the posterior superior temporal lobe (Wernicke’s area) and the adjacent angular gyrus region in the dominant hemisphere causes much more harm to the intellect than does destruction of the prefrontal areas. The prefrontal areas do, however, have less definable but nevertheless important intellectual functions of their own. These functions can best be explained by describing what happens to patients in whom the prefrontal areas have become damaged, as follows.
Several decades ago, before the advent of modern drugs for treating psychiatric conditions, it was found that some patients could receive significant relief from severe psychotic depression by severing the neuronal connections between the prefrontal areas of the brain and the remainder of the brain, that is, by a procedure called prefrontal lobotomy. This was done by inserting a blunt, thin-bladed knife through a small opening in the lateral frontal skull on each side of the head and slicing the brain at the back edge of the prefrontal lobes from top to bottom. Subsequent studies in these patients showed the following mental changes:
1. The patients lost their ability to solve complex problems.
2. They became unable to string together sequential tasks to reach complex goals.
3. They became unable to learn to do several parallel tasks at the same time.
4. Their level of aggressiveness was decreased, sometimes markedly, and, in general, they lost ambition.
5. Their social responses were often inappropriate for the occasion, often including loss of morals and little reticence in relation to sexual activity and excretion.
6. The patients could still talk and comprehend language, but they were unable to carry through any long trains of thought, and their moods changed rapidly from sweetness to rage to exhilaration to madness.
7. The patients could also still perform most of the usual patterns of motor function that they had performed throughout life, but often without purpose.
From this information, let us try to piece together a coherent understanding of the function of the prefrontal association areas.
Decreased Aggressiveness and Inappropriate Social Responses
These two characteristics probably result from loss of the ventral parts of the frontal lobes on the underside of the brain. As explained earlier and shown in Figures 57-4 and 57-5, this area is part of the limbic association cortex, rather than of the prefrontal association cortex. This limbic area helps to control behavior, which is discussed in detail in Chapter 58.
Inability to Progress Toward Goals or to Carry Through Sequential Thoughts
We learned earlier in this chapter that the prefrontal association areas have the capability of calling forth information from widespread areas of the brain and using this information to achieve deeper thought patterns for attaining goals.
Although people without prefrontal cortices can still think, they show little concerted thinking in logical sequence for longer than a few seconds or a minute or so at most. One of the results is that people without prefrontal cortices are easily distracted from their central theme of thought, whereas people with functioning prefrontal cortices can drive themselves to completion of their thought goals irrespective of distractions.
Elaboration of Thought, Prognostication, and Performance of Higher Intellectual Functions by the Prefrontal Areas—Concept of a “Working Memory.”
Another function that has been ascribed to the prefrontal areas is elaboration of thought. This means simply an increase in depth and abstractness of the different thoughts put together from multiple sources of information. Psychological tests have shown that prefrontal lobectomized lower animals presented with successive bits of sensory information fail to keep track of these bits even in temporary memory, probably because they are distracted so easily that they cannot hold thoughts long enough for memory storage to take place.
This ability of the prefrontal areas to keep track of many bits of information simultaneously and to cause recall of this information instantaneously as it is needed for subsequent thoughts is called the brain’s “working memory.” This may explain the many functions of the brain that we associate with higher intelligence. In fact, studies have shown that the prefrontal areas are divided into separate segments for storing different types of temporary memory, such as one area for storing shape and form of an object or a part of the body and another for storing movement.
By combining all these temporary bits of working memory, we have the abilities to (1) prognosticate; (2) plan for the future; (3) delay action in response to incoming sensory signals so that the sensory information can be weighed until the best course of response is decided; (4) consider the consequences of motor actions before they are performed; (5) solve complicated mathematical, legal, or philosophical problems; (6) correlate all avenues of information in diagnosing rare diseases; and (7) control our activities in accord with moral laws.
Function of the Brain in Communication—Language Input and Language Output
One of the most important differences between human beings and lower animals is the facility with which human beings can communicate with one another. Furthermore, because neurological tests can easily assess the ability of a person to communicate with others, we know more about the sensory and motor systems related to communication than about any other segment of brain cortex function. Therefore, we will review, with the help of anatomical maps of neural pathways in Figure 57-8, function of the cortex in communication. From this, one will see immediately how the principles of sensory analysis and motor control apply to this art.
Figure 57-8 Brain pathways for (top) perceiving a heard word and then speaking the same word and (bottom) perceiving a written word and then speaking the same word.
(Redrawn from Geschwind N: Specializations of the human brain. Sci Am 241:180, 1979. ® 1979 by Scientific American, Inc. All rights reserved.)
There are two aspects to communication: first, the sensory aspect (language input), involving the ears and eyes, and, second, the motor aspect (language output), involving vocalization and its control.
Sensory Aspects of Communication
We noted earlier in the chapter that destruction of portions of the auditory or visual association areas of the cortex can result in inability to understand the spoken word or the written word. These effects are called, respectively, auditory receptive aphasia and visual receptive aphasia or, more commonly, word deafness and word blindness (also called dyslexia).
Wernicke’s Aphasia and Global Aphasia
Some people are capable of understanding either the spoken word or the written word but are unable to interpret the thought that is expressed. This results most frequently when Wernicke’s area in the posterior superior temporal gyrus in the dominant hemisphere is damaged or destroyed. Therefore, this type of aphasia is called Wernicke’s aphasia.
When the lesion in Wernicke’s area is widespread and extends (1) backward into the angular gyrus region, (2) inferiorly into the lower areas of the temporal lobe, and (3) superiorly into the superior border of the sylvian fissure, the person is likely to be almost totally demented for language understanding or communication and therefore is said to have global aphasia.
Motor Aspects of Communication
The process of speech involves two principal stages of mentation: (1) formation in the mind of thoughts to be expressed, as well as choice of words to be used, and then (2) motor control of vocalization and the actual act of vocalization itself.
The formation of thoughts and even most choices of words are the function of sensory association areas of the brain. Again, it is Wernicke’s area in the posterior part of the superior temporal gyrus that is most important for this ability. Therefore, a person with either Wernicke’s aphasia or global aphasia is unable to formulate the thoughts that are to be communicated. Or, if the lesion is less severe, the person may be able to formulate the thoughts but unable to put together appropriate sequences of words to express the thought. The person sometimes is even fluent with words but the words are jumbled.
Loss of Broca’s Area Causes Motor Aphasia
Sometimes a person is capable of deciding what he or she wants to say but cannot make the vocal system emit words instead of noises. This effect, called motor aphasia, results from damage to Broca’s speech area, which lies in the prefrontal and premotor facial region of the cerebral cortex—about 95 percent of the time in the left hemisphere, as shown in Figures 57-5 and 57-8. Therefore, the skilled motor patternsfor control of the larynx, lips, mouth, respiratory system, and other accessory muscles of speech are all initiated from this area.
Finally, we have the act of articulation, which means the muscular movements of the mouth, tongue, larynx, vocal cords, and so forth that are responsible for the intonations, timing, and rapid changes in intensities of the sequential sounds. The facial and laryngeal regions of the motor cortex activate these muscles, and the cerebellum, basal ganglia, and sensory cortex all help to control the sequences and intensities of muscle contractions, making liberal use of basal ganglial and cerebellar feedback mechanisms described in Chapters 55 and 56. Destruction of any of these regions can cause either total or partial inability to speak distinctly.
Figure 57-8 shows two principal pathways for communication. The upper half of the figure shows the pathway involved in hearing and speaking. This sequence is the following: (1) reception in the primary auditory area of the sound signals that encode the words; (2) interpretation of the words in Wernicke’s area; (3) determination, also in Wernicke’s area, of the thoughts and the words to be spoken; (4) transmission of signals from Wernicke’s area to Broca’s area by way of the arcuate fasciculus; (5) activation of the skilled motor programs in Broca’s area for control of word formation; and (6) transmission of appropriate signals into the motor cortex to control the speech muscles.
The lower figure illustrates the comparable steps in reading and then speaking in response. The initial receptive area for the words is in the primary visual area rather than in the primary auditory area. Then the information passes through early stages of interpretation in the angular gyrus region and finally reaches its full level of recognition in Wernicke’s area. From here, the sequence is the same as for speaking in response to the spoken word.
Function of the Corpus Callosum and Anterior Commissure to Transfer Thoughts, Memories, Training, and Other Information Between the Two Cerebral Hemispheres
Fibers in the corpus callosum provide abundant bidirectional neural connections between most of the respective cortical areas of the two cerebral hemispheres except for the anterior portions of the temporal lobes; these temporal areas, including especially the amygdala, are interconnected by fibers that pass through the anterior commissure.
Because of the tremendous number of fibers in the corpus callosum, it was assumed from the beginning that this massive structure must have some important function to correlate activities of the two cerebral hemispheres. However, when the corpus callosum was destroyed in laboratory animals, it was at first difficult to discern deficits in brain function. Therefore, for a long time, the function of the corpus callosum was a mystery.
Properly designed experiments have now demonstrated extremely important functions for the corpus callosum and anterior commissure. These functions can best be explained by describing one of the experiments: A monkey is first prepared by cutting the corpus callosum and splitting the optic chiasm longitudinally so that signals from each eye can go only to the cerebral hemisphere on the side of the eye. Then the monkey is taught to recognize different objects with its right eye while its left eye is covered. Next, the right eye is covered and the monkey is tested to determine whether its left eye can recognize the same objects. The answer to this is that the left eye cannot recognize the objects. However, on repeating the same experiment in another monkey with the optic chiasm split but the corpus callosum intact, it is found invariably that recognition in one hemisphere of the brain creates recognition in the opposite hemisphere.
Thus, one of the functions of the corpus callosum and the anterior commissure is to make information stored in the cortex of one hemisphere available to corresponding cortical areas of the opposite hemisphere. Important examples of such cooperation between the two hemispheres are the following.
1. Cutting the corpus callosum blocks transfer of information from Wernicke’s area of the dominant hemisphere to the motor cortex on the opposite side of the brain. Therefore, the intellectual functions of Wernicke’s area, located in the left hemisphere, lose control over the right motor cortex that initiates voluntary motor functions of the left hand and arm, even though the usual subconscious movements of the left hand and arm are normal.
2. Cutting the corpus callosum prevents transfer of somatic and visual information from the right hemisphere into Wernicke’s area in the left dominant hemisphere. Therefore, somatic and visual information from the left side of the body frequently fails to reach this general interpretative area of the brain and therefore cannot be used for decision making.
3. Finally, people whose corpus callosum is completely sectioned have two entirely separate conscious portions of the brain. For example, in a teenage boy with a sectioned corpus callosum, only the left half of his brain could understand both the written word and the spoken word because the left side was the dominant hemisphere. Conversely, the right side of the brain could understand the written word but not the spoken word. Furthermore, the right cortex could elicit a motor action response to the written word without the left cortex ever knowing why the response was performed.
The effect was quite different when an emotional response was evoked in the right side of the brain: In this case, a subconscious emotional response occurred in the left side of the brain as well. This undoubtedly occurred because the areas of the two sides of the brain for emotions, the anterior temporal cortices and adjacent areas, were still communicating with each other through the anterior commissure that was not sectioned. For instance, when the command “kiss” was written for the right half of his brain to see, the boy immediately and with full emotion said, “No way!” This response required function of Wernicke’s area and the motor areas for speech in the left hemisphere because these left-side areas were necessary to speak the words “No way!” But when questioned why he said this, the boy could not explain. Thus, the two halves of the brain have independent capabilities for consciousness, memory storage, communication, and control of motor activities. The corpus callosum is required for the two sides to operate cooperatively at the superficial subconscious level, and the anterior commissure plays an important additional role in unifying the emotional responses of the two sides of the brain.
Thoughts, Consciousness, and Memory
Our most difficult problem in discussing consciousness, thoughts, memory, and learning is that we do not know the neural mechanisms of a thought and we know little about the mechanisms of memory. We know that destruction of large portions of the cerebral cortex does not prevent a person from having thoughts, but it does reduce the depth of the thoughts and also the degree of awareness of the surroundings.
Each thought certainly involves simultaneous signals in many portions of the cerebral cortex, thalamus, limbic system, and reticular formation of the brain stem. Some basic thoughts probably depend almost entirely on lower centers; the thought of pain is probably a good example because electrical stimulation of the human cortex seldom elicits anything more than mild pain, whereas stimulation of certain areas of the hypothalamus, amygdala, and mesencephalon can cause excruciating pain. Conversely, a type of thought pattern that does require large involvement of the cerebral cortex is that of vision because loss of the visual cortex causes complete inability to perceive visual form or color.
We might formulate a provisional definition of a thought in terms of neural activity as follows: A thought results from a “pattern” of stimulation of many parts of the nervous system at the same time, probably involving most importantly the cerebral cortex, thalamus, limbic system, and upper reticular formation of the brain stem. This is called the holistic theory of thoughts. The stimulated areas of the limbic system, thalamus, and reticular formation are believed to determine the general nature of the thought, giving it such qualities as pleasure, displeasure, pain, comfort, crude modalities of sensation, localization to gross areas of the body, and other general characteristics. However, specific stimulated areas of the cerebral cortex determine discrete characteristics of the thought, such as (1) specific localization of sensations on the surface of the body and of objects in the fields of vision, (2) the feeling of the texture of silk, (3) visual recognition of the rectangular pattern of a concrete block wall, and (4) other individual characteristics that enter into one’s overall awareness of a particular instant. Consciousness can perhaps be described as our continuing stream of awareness of either our surroundings or our sequential thoughts.
Memory—Roles of Synaptic Facilitation and Synaptic Inhibition
Memories are stored in the brain by changing the basic sensitivity of synaptic transmission between neurons as a result of previous neural activity. The new or facilitated pathways are called memory traces.They are important because once the traces are established, they can be selectively activated by the thinking mind to reproduce the memories.
Experiments in lower animals have demonstrated that memory traces can occur at all levels of the nervous system. Even spinal cord reflexes can change at least slightly in response to repetitive cord activation, and these reflex changes are part of the memory process. Also, long-term memories result from changed synaptic conduction in lower brain centers. However, most memory that we associate with intellectual processes is based on memory traces in the cerebral cortex.
Positive and Negative Memory—“Sensitization” or “Habituation” of Synaptic Transmission
Although we often think of memories as being positive recollections of previous thoughts or experiences, probably the greater share of our memories is negative, not positive. That is, our brain is inundated with sensory information from all our senses. If our minds attempted to remember all this information, the memory capacity of the brain would be rapidly exceeded. Fortunately, the brain has the capability to learn to ignore information that is of no consequence. This results from inhibition of the synaptic pathways for this type of information; the resulting effect is called habituation. This is a type of negativememory.
Conversely, for incoming information that causes important consequences such as pain or pleasure, the brain has a different automatic capability of enhancing and storing the memory traces. This is positivememory. It results from facilitation of the synaptic pathways, and the process is called memory sensitization. We discuss later that special areas in the basal limbic regions of the brain determine whether information is important or unimportant and make the subconscious decision whether to store the thought as a sensitized memory trace or to suppress it.
Classification of Memories
We know that some memories last for only a few seconds, whereas others last for hours, days, months, or years. For the purpose of discussing these, let us use a common classification of memories that divides memories into (1) short-term memory, which includes memories that last for seconds or at most minutes unless they are converted into longer-term memories; (2) intermediate long-term memories, which last for days to weeks but then fade away; and (3) long-term memory, which, once stored, can be recalled up to years or even a lifetime later.
In addition to this general classification of memories, we also discussed earlier (in connection with the prefrontal lobes) another type of memory, called“working memory,” which includes mainly short-term memory that is used during the course of intellectual reasoning but is terminated as each stage of the problem is resolved.
Memories are frequently classified according to the type of information that is stored. One of these classifications divides memory into declarative memory and skill memory, as follows:
1. Declarative memory basically means memory of the various details of an integrated thought, such as memory of an important experience that includes (1) memory of the surroundings, (2) memory of time relationships, (3) memory of causes of the experience, (4) memory of the meaning of the experience, and (5) memory of one’s deductions that were left in the person’s mind.
2. Skill memory is frequently associated with motor activities of the person’s body, such as all the skills developed for hitting a tennis ball, including automatic memories to (1) sight the ball, (2) calculate the relationship and speed of the ball to the racquet, and (3) deduce rapidly the motions of the body, the arms, and the racquet required to hit the ball as desired—all of these activated instantly based on previous learning of the game of tennis—then moving on to the next stroke of the game while forgetting the details of the previous stroke.
Short-term memory is typified by one’s memory of 7 to 10 numerals in a telephone number (or 7 to 10 other discrete facts) for a few seconds to a few minutes at a time but lasting only as long as the person continues to think about the numbers or facts.
Many physiologists have suggested that this short-term memory is caused by continual neural activity resulting from nerve signals that travel around and around a temporary memory trace in a circuit of reverberating neurons. It has not yet been possible to prove this theory. Another possible explanation of short-term memory is presynaptic facilitation or inhibition. This occurs at synapses that lie on terminal nerve fibrils immediately before these fibrils synapse with a subsequent neuron. The neurotransmitter chemicals secreted at such terminals frequently cause facilitation or inhibition lasting for seconds up to several minutes. Circuits of this type could lead to short-term memory.
Intermediate Long-Term Memory
Intermediate long-term memories may last for many minutes or even weeks. They will eventually be lost unless the memory traces are activated enough to become more permanent; then they are classified as long-term memories. Experiments in primitive animals have demonstrated that memories of the intermediate long-term type can result from temporary chemical or physical changes, or both, in either the synapse presynaptic terminals or the synapse postsynaptic membrane, changes that can persist for a few minutes up to several weeks. These mechanisms are so important that they deserve special description.
Memory Based on Chemical Changes in the Presynaptic Terminal or Postsynaptic Neuronal Membrane
Figure 57-9 shows a mechanism of memory studied especially by Kandel and his colleagues that can cause memories lasting from a few minutes up to 3 weeks in the large snail Aplysia. In this figure, there are two synaptic terminals. One terminal is from a sensory input neuron and terminates directly on the surface of the neuron that is to be stimulated; this is called the sensory terminal. The other terminal is a presynaptic ending that lies on the surface of the sensory terminal, and it is called the facilitator terminal. When the sensory terminal is stimulated repeatedly but without stimulation of the facilitator terminal, signal transmission at first is great, but it becomes less and less intense with repeated stimulation until transmission almost ceases. This phenomenon is habituation, as was explained previously. It is a type of negative memory that causes the neuronal circuit to lose its response to repeated events that are insignificant.
Figure 57-9 Memory system that has been discovered in the snail Aplysia.
Conversely, if a noxious stimulus excites the facilitator terminal at the same time that the sensory terminal is stimulated, then instead of the transmitted signal into the postsynaptic neuron becoming progressively weaker, the ease of transmission becomes stronger and stronger; and it will remain strong for minutes, hours, days, or, with more intense training, up to about 3 weeks even without further stimulation of the facilitator terminal. Thus, the noxious stimulus causes the memory pathway through the sensory terminal to become facilitated for days or weeks thereafter. It is especially interesting that even after habituation has occurred, this pathway can be converted back to a facilitated pathway with only a few noxious stimuli.
Molecular Mechanism of Intermediate Memory
Mechanism for Habituation
At the molecular level, the habituation effect in the sensory terminal results from progressive closure of calcium channels through the terminal membrane, though the cause of this calcium channel closure is not fully known. Nevertheless, much smaller than normal amounts of calcium ions can diffuse into the habituated terminal, and much less sensory terminal transmitter is therefore released because calcium entry is the principal stimulus for transmitter release (as was discussed in Chapter 45).
Mechanism for Facilitation
In the case of facilitation, at least part of the molecular mechanism is believed to be the following:
1. Stimulation of the facilitator presynaptic terminal at the same time that the sensory terminal is stimulated causes serotonin release at the facilitator synapse on the surface of the sensory terminal.
2. The serotonin acts on serotonin receptors in the sensory terminal membrane, and these receptors activate the enzyme adenyl cyclase inside the membrane. The adenyl cyclase then causes formation of cyclic adenosine monophosphate (cAMP) also inside the sensory presynaptic terminal.
3. The cyclic AMP activates a protein kinase that causes phosphorylation of a protein that itself is part of the potassium channels in the sensory synaptic terminal membrane; this in turn blocks the channels for potassium conductance. The blockage can last for minutes up to several weeks.
4. Lack of potassium conductance causes a greatly prolonged action potential in the synaptic terminal because flow of potassium ions out of the terminal is necessary for rapid recovery from the action potential.
5. The prolonged action potential causes prolonged activation of the calcium channels, allowing tremendous quantities of calcium ions to enter the sensory synaptic terminal. These calcium ions cause greatly increased transmitter release by the synapse, thereby markedly facilitating synaptic transmission to the subsequent neuron.
Thus, in a very indirect way, the associative effect of stimulating the facilitator terminal at the same time that the sensory terminal is stimulated causes prolonged increase in excitatory sensitivity of the sensory terminal, and this establishes the memory trace. Studies by Byrne and colleagues, also in the snail Aplysia, have suggested still another mechanism of synaptic memory. Their studies have shown that stimuli from separate sources acting on a single neuron, under appropriate conditions, can cause long-term changes in membrane properties of the postsynaptic neuron instead of in the presynaptic neuronal membrane, but leading to essentially the same memory effects.
There is no obvious demarcation between the more prolonged types of intermediate long-term memory and true long-term memory. The distinction is one of degree. However, long-term memory is generally believed to result from actual structural changes, instead of only chemical changes, at the synapses, and these enhance or suppress signal conduction. Again, let us recall experiments in primitive animals (where the nervous systems are much easier to study) that have aided immensely in understanding possible mechanisms of long-term memory.
Structural Changes Occur in Synapses During the Development of Long-Term Memory
Electron microscopic pictures taken from invertebrate animals have demonstrated multiple physical structural changes in many synapses during development of long-term memory traces. The structural changes will not occur if a drug is given that blocks DNA stimulation of protein replication in the presynaptic neuron; nor will the permanent memory trace develop. Therefore, it appears that development of true long-term memory depends on physically restructuring the synapses themselves in a way that changes their sensitivity for transmitting nervous signals.
The most important of the physical structural changes that occur are the following:
1. Increase in vesicle release sites for secretion of transmitter substance
2. Increase in number of transmitter vesicles released
3. Increase in number of presynaptic terminals
4. Changes in structures of the dendritic spines that permit transmission of stronger signals
Thus, in several different ways, the structural capability of synapses to transmit signals appears to increase during establishment of true long-term memory traces.
Number of Neurons and Their Connectivities Often Change Significantly During Learning
During the first few weeks, months, and perhaps even year or so of life, many parts of the brain produce a great excess of neurons and the neurons send out numerous axon branches to make connections with other neurons. If the new axons fail to connect with appropriate neurons, muscle cells, or gland cells, the new axons themselves will dissolute within a few weeks. Thus, the number of neuronal connections is determined by specific nerve growth factorsreleased retrogradely from the stimulated cells. Furthermore, when insufficient connectivity occurs, the entire neuron that is sending out the axon branches might eventually disappear.
Therefore, soon after birth, there is a principle of “use it or lose it” that governs the final number of neurons and their connectivities in respective parts of the human nervous system. This is a type of learning. For example, if one eye of a newborn animal is covered for many weeks after birth, neurons in alternate stripes of the cerebral visual cortex—neurons normally connected to the covered eye—will degenerate, and the covered eye will remain either partially or totally blind for the remainder of life. Until recently, it was believed that very little“learning” is achieved in adult human beings and animals by modification of numbers of neurons in the memory circuits; however, recent research suggests that even adults use this mechanism to at least some extent.
Consolidation of Memory
For short-term memory to be converted into long-term memory that can be recalled weeks or years later, it must become “consolidated.” That is, the short-term memory if activated repeatedly will initiate chemical, physical, and anatomical changes in the synapses that are responsible for the long-term type of memory. This process requires 5 to 10 minutes for minimal consolidation and 1 hour or more for strong consolidation. For instance, if a strong sensory impression is made on the brain but is then followed within a minute or so by an electrically induced brain convulsion, the sensory experience will not be remembered. Likewise, brain concussion, sudden application of deep general anesthesia, or any other effect that temporarily blocks the dynamic function of the brain can prevent consolidation.
Consolidation and the time required for it to occur can probably be explained by the phenomenon of rehearsal of the short-term memory as follows.
Rehearsal Enhances the Transference of Short-Term Memory into Long-Term Memory
Studies have shown that rehearsal of the same information again and again in the mind accelerates and potentiates the degree of transfer of short-term memory into long-term memory and therefore accelerates and enhances consolidation. The brain has a natural tendency to rehearse newfound information, especially newfound information that catches the mind’s attention. Therefore, over a period of time, the important features of sensory experiences become progressively more and more fixed in the memory stores. This explains why a person can remember small amounts of information studied in depth far better than large amounts of information studied only superficially. It also explains why a person who is wide awake can consolidate memories far better than a person who is in a state of mental fatigue.
New Memories Are Codified During Consolidation
One of the most important features of consolidation is that new memories are codified into different classes of information. During this process, similar types of information are pulled from the memory storage bins and used to help process the new information. The new and old are compared for similarities and differences, and part of the storage process is to store the information about these similarities and differences, rather than to store the new information unprocessed. Thus, during consolidation, the new memories are not stored randomly in the brain but are stored in direct association with other memories of the same type. This is necessary if one is to be able to “search” the memory store at a later date to find the required information.
Role of Specific Parts of the Brain in the Memory Process
Hippocampus Promotes Storage of Memories—Anterograde Amnesia After Hippocampal Lesions
The hippocampus is the most medial portion of the temporal lobe cortex, where it folds first medially underneath the brain and then upward into the lower, inside surface of the lateral ventricle. The two hippocampi have been removed for the treatment of epilepsy in a few patients. This procedure does not seriously affect the person’s memory for information stored in the brain before removal of the hippocampi. However, after removal, these people have virtually no capability thereafter for storing verbal and symbolic types of memories (declarative types of memory) in long-term memory, or even in intermediate memory lasting longer than a few minutes. Therefore, these people are unable to establish new long-term memories of those types of information that are the basis of intelligence. This is called anterograde amnesia.
But why are the hippocampi so important in helping the brain to store new memories? The probable answer is that the hippocampi are among the most important output pathways from the “reward” and “punishment” areas of the limbic system, as explained in Chapter 58. Sensory stimuli or thoughts that cause pain or aversion excite the limbic punishment centers, and stimuli that cause pleasure, happiness, or sense of reward excite the limbic reward centers.All these together provide the background mood and motivations of the person. Among these motivations is the drive in the brain to remember those experiences and thoughts that are either pleasant or unpleasant. The hippocampi especially and to a lesser degree the dorsal medial nuclei of the thalamus, another limbic structure, have proved especially important in making the decision about which of our thoughts are important enough on a basis of reward or punishment to be worthy of memory.
Retrograde Amnesia—Inability to Recall Memories from the Past
When retrograde amnesia occurs, the degree of amnesia for recent events is likely to be much greater than for events of the distant past. The reason for this difference is probably that the distant memories have been rehearsed so many times that the memory traces are deeply ingrained, and elements of these memories are stored in widespread areas of the brain.
In some people who have hippocampal lesions, some degree of retrograde amnesia occurs along with anterograde amnesia, which suggests that these two types of amnesia are at least partially related and that hippocampal lesions can cause both. However, damage in some thalamic areas may lead specifically to retrograde amnesia without causing significant anterograde amnesia. A possible explanation of this is that the thalamus may play a role in helping the person “search” the memory storehouses and thus “read out” the memories. That is, the memory process not only requires the storing of memories but also an ability to search and find the memory at a later date. The possible function of the thalamus in this process is discussed further in Chapter 58.
Hippocampi Are Not Important in Reflexive Learning
People with hippocampal lesions usually do not have difficulty in learning physical skills that do not involve verbalization or symbolic types of intelligence. For instance, these people can still learn the rapid hand and physical skills required in many types of sports. This type of learning is called skill learning or reflexive learning; it depends on physically repeating the required tasks over and over again, rather than on symbolical rehearsing in the mind.
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