Results of clinicopathological studies and animal experiments conducted over more than a century have provided information concerning functional specialization in different regions of the cerebral cortex. For example, large primary sensory areas are recognized for general somatic sensation, smell, vision, and hearing. Smaller areas exist for taste and vestibular sensation (i.e., awareness of position and movement of the head). Motor areas are also present from which contraction of skeletal muscles can be elicited by electrical stimulation. The remainder of the neocortex, accounting for most of its area, is usually referred to as association cortex, which may be closely related functionally to the sensory areas or to more complex levels of behavior, communication, and the intellect.
In certain surgical procedures, it is essential to identify the motor area, a sensory area, or even a particular region within these areas. Identification of sensory areas requires operating on a conscious patient under local anesthesia. This is possible because the brain does not perceive pain
when injured in ways that would be painful elsewhere in the body. Electrical stimulation of the human cerebral cortex has provided information more detailed than that obtainable by observing the effects of destructive wounds and diseases.
Since 1980, the classical studies of functional localization have been largely confirmed and extended by means of modern noninvasive techniques (see Chapter 4). The cortex can be electrically stimulated by an externally applied magnetic field, for example, or electrodes on the scalp can record potentials evoked by transcutaneous stimulation of peripheral nerves. Magnetoencephalography (see Chapter 4), although available in only a few centers, can also provide accurate localization of cortical function, expecially in the walls of sulci. Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are used to map regional cerebral blood flow or oxygen or glucose uptake, to provide information about cortical activity in the normal brain, and to detect abnormal function. Functional nuclear magnetic resonance imaging (fMRI) provides similar information with superior anatomical resolution.
FIGURE 15-1 Motor and primary sensory areas on the lateral surface of the left cerebral hemisphere. Some of Brodmann's numbered areas, based on cytoarchitecture, are also shown.
Parietal, Occipital, and Temporal Cortex
The parietal, occipital, and temporal lobes contain primary sensory areas, which are the destinations of pathways that begin in the various sensory organs. Adjacent to each primary sensory area is a larger region of association cortex, which interprets and uses the incoming data. Much of the frontal lobe is also considered to be association cortex; it receives input from the sensory lobes, instructs the motor areas, and is also involved in subjective feelings, thought, judgment, and the planning of activities.
GENERAL SOMATIC SENSATION
The first somesthetic area (primary somatic sensory area) occupies the postcentral gyrus on the lateral surface of the hemisphere and the posterior part of the paracentral lobule on the medial surface (Figs. 15-1 and 15-2). It consists of areas 3, 1, and 2 of the Brodmann cytoarchitectural
map. Electrical stimulation of the first somesthetic area elicits modified forms of the tactile sense such as a tingling sensation. It is possible to elicit motor responses by stimulating the first somesthetic area, as well as eliciting sensory responses from the motor area in the precentral gyrus. The functions of the two areas overlap to some extent, and they are often considered as a sensorimotor strip that surrounds the central sulcus. The overlap is greater in laboratory animals than in humans. The postcentral gyrus and its extension in the paracentral lobule are designated as the first somatic sensory area because they have the highest density of points that produce localized sensations on electrical stimulation.
FIGURE 15-2 Motor and primary sensory areas on the medial surface of the left cerebral hemisphere. Some of Brodmann's numbered areas, based on cytoarchitecture, are also shown.
The ventral posterior nucleus of the thalamus is the main source of afferent fibers for the first somatic sensory area. This thalamic nucleus is the site of termination of all the fibers of the medial lemniscus and of most of the fibers of the spinothalamic and trigeminothalamic tracts. The thalamocortical projection traverses the internal capsule and cerebral white matter, conveying data for the various modalities of somatic sensation. Thalamocortical fibers for cutaneous sensibility end preferentially in the anterior part of the first somatosensory area, and those for deep sensibility, including proprioception, end in the posterior part.
The contralateral half of the body is represented as inverted. The pharyngeal region, tongue, and jaws are represented in the most ventral part of the somesthetic area, followed by the face, hands, arms, trunk, and thighs. The area for the remainder of the legs and the perineum is in the extension of the somesthetic cortex on the medial surface of the hemisphere. The size of the cortical area for a particular part of the body is determined by the functional importance of the part and its need for sensitivity. The area for the face, especially the lips, is disproportionately large, and a large area is assigned to the hand, particularly the thumb and index finger. A picture of the body with the proportions of its cortical map is known as a homunculus (Fig. 15-3).
A crude form of awareness persists for pain, heat, and cold sensations on the affected opposite side of the body if the first somesthetic
area has been destroyed. There is poor localization of the stimulus, for which qualitative and quantitative interpretations are diminished or absent. The somesthetic cortex must be intact for any appreciation of the more discriminative sensations of fine touch, position, and movement of the parts of the body.
FIGURE 15-3 Homunculi of the primary somatosensory area (left) and primary motor area (right).
An additional or second somesthetic area has been demonstrated in primates, including humans. This small area is located in the dorsal wall of the lateral sulcus in line with the postcentral gyrus and may extend onto the insula. The parts of the body are represented bilaterally, although contralateral representation predominates. The second sensory area receives input from the intralaminar nuclei and from the posterior group of nuclei of the thalamus. The afferent fibers to these nuclei come,
respectively, from the reticular formation and from the spinothalamic and trigeminothalamic tracts. Consequently, the area is mainly involved in the less discriminative aspects of sensation. An intact second somesthetic area may explain such residual sensibility as exists after destruction of the first somatic sensory area. No clinical disorder has been ascribed to a lesion in the second somesthetic area.
Parietal Lobe Lesions
A destructive lesion in the somesthetic association cortex may leave the somesthetic area itself intact. Then, a defect in understanding the significance of sensory information, called agnosia, is present. In this disorder, awareness of the general senses persists, but the significance of the information received on the basis of previous experience is elusive. There are several types ofagnosia, depending on the sense that is most affected. A lesion that destroys a large portion of the somesthetic association cortex causes tactile agnosia and astereognosis, which are closely related. They combine when a person is unable to identify a common object, such as a pair of scissors, held in the hand while the eyes are closed. It is impossible to correlate the surface texture, shape, size, and weight of the object or to compare the sensations with previous experiences. Astereognosis includes a loss of awareness of the spatial relations of parts of the contralateral side of the body. The most extreme form of the condition is cortical neglect, in which the patient ignores and even denies the existence of one side of the body and of the corresponding visual field. The condition most often is caused by large lesions in the superior part of the right parietal lobe.
Association fibers connect the somesthetic association cortex with the motor areas of the frontal lobe, providing interpreted proprioceptive and other sensory input needed for the accurate execution of movements. Consequently, damage to the parietal lobe can cause apraxia, which is discussed also in connection with the premotor cortex.
The somesthetic association cortex is located mainly in the superior parietal lobule on the lateral surface of the hemisphere and in the precuneus on the medial surface. Much of it coincides with Brodmann's areas 5 and 7. This association cortex receives fibers from the first somesthetic area, and its thalamic connections are with the lateral posterior nucleus and the pulvinar. Data pertaining to the general senses are integrated in this association area, permitting, for example, assessment of the characteristics of an object held in the hand and its identification without visual aid.
The primary visual area surrounds the calcarine sulcus on the medial surface of the occipital lobe, extending over the occipital pole in some brains (see Fig. 15-2). The area is more extensive than Figure 15-2 suggests because most of it is located in the walls of the deep calcarine sulcus, in which secondary folds are also present. The primary visual cortex, which corresponds to area 17 of Brodmann's map, is called the striate area because it contains the line of Gennari (see Chapter 14), which is just visible to the unaided eye. The chief source of afferent fibers to area 17 is the lateral geniculate body of the thalamus by way of the geniculocalcarine tract.
Visual Cortex Lesions
A destructive lesion that involves the striate cortex of a hemisphere causes an area of blindness in the opposite visual field. The size and location of the defect are determined by the extent and location of the lesion. With a large unilateral lesion in the occipital lobe (e.g., an infarction caused by a thrombus in the posterior cerebral artery), central vision may be spared. This clinical observation is known as macular sparing. (The macula lutea is the central part of the retina that is opposite the pupil.) The relatively large area of cortex devoted to central vision may be partly spared by the lesion. It has also been suggested that anastomoses between branches of the middle and posterior cerebral arteries partly maintain the posterior part of area 17 after occlusion of the posterior cerebral artery. The occipital cortex and adjacent posterior parietal cortex are necessary for certain types of eye movement (see Chapter 8), and it has been suggested that in some cases, macular sparing is an artifact of testing caused by uncontrollable slight movements of the patient's eyes during examination of the visual fields.
The primary visual cortex, through a synaptic relay in the lateral geniculate body, receives data from the lateral (temporal) half of the ipsilateral retina and the medial (nasal) half of the contralateral retina. The left half of the field of vision is, therefore, represented in the visual area of the right hemisphere and vice versa (see also Chapter 20). Spatial patterns are also present within the striate area. The lower retinal quadrants (upper field of vision) project onto the lower wall of the calcarine sulcus, and the upper retinal quadrants (lower field of vision) project onto the upper wall of the sulcus. Another pattern is related to central and peripheral vision. The center of the retina, which is responsible for central vision of maximal discrimination, is represented at the occipital pole in the posterior part of area 17; the peripheral retina is represented more anteriorly. Thus, the part of area 17 that receives signals for central vision accounts for a disproportionately large amount (i.e., one third) of the primary visual cortex.
The extensive visual association cortex surrounds the primary visual area on the medial, lateral, and inferior surfaces of the hemisphere (see Figs. 15-1 and 15-2), extending from areas 18 and 19 (occipital lobe) to the posterior part of the parietal lobe and the lateral and inferior parts of the temporal lobe. These areas receive fibers from area 17 and have reciprocal connections with other cortical areas and with the
pulvinar of the thalamus. The role of this association cortex includes, among other complex aspects of vision, the relating of present to past visual experiences, recognition of what is seen, and appreciation of its significance. Different parts of the visual association cortex have different functions. These have been determined experimentally in monkeys and have been inferred from the deficits that follow destructive lesions in the human brain. The cortex of the superior part of the occipital lobe and posterior part of the parietal lobe is functionally distinct from that of the inferior parts of the occipital and temporal lobes. These two large regions of visual association cortex are known, respectively, as the “where?”and the “what?” streams of visual processing. Whereas the dorsal “where?” stream analyzes motion and spatial relations, the ventral “what?” stream identifies colors and familiar shapes such as faces and letters. Lesions that involve the visual association cortex result in various types of visual agnosia.
Destructive lesions in visual association cortex cause disorders attributable to malfunction of the “where?” and “what?” streams of visual data processing. Bilateral lesions that involve the superior parts of area 19 cause visual disorientation, with an inability to recognize the extent of the visual field and to perceive moving objects. A lesion in the superior part of the occipital lobe commonly extends onto the adjacent visual association cortex of the parietal lobe, causing ocular apraxia, which is the inability to direct the gaze at a consciously selected target in the visual field because rapid eye movements (i.e., saccades; see Chapter 8) are inaccurate. Ocular apraxia is associated with optic ataxia, which is a loss of the ability to carry out visually guided movements of the hands. The combination of visual disorientation, ocular apraxia, and optic ataxia is known as Balint's syndrome.
A lesion in the inferior surface of the occipital cortex anterior to the primary visual area causes acquired achromatopsia, which is loss of color vision in the contralateral halves of the visual fields of both eyes, indicating the normal involvement of this cortex in color vision.
The inferolateral surface of the temporal lobe (inferior temporal and the lateral and medial occipitotemporal gyri) is also visual association cortex. Electrical stimulation of this region evokes vivid hallucinations of scenes from the past, indicating a role of this cortex in the storage or recall of visual memories. Destruction ofthe inferior surfaces of the occipital and temporal lobes associated with damage to the superior part of the visual association cortex causes apperceptive visual agnosia, which can take various forms. The lesions are usually bilateral but are sometimes present only on the right side. The condition is called prosopagnosia when the patient has an impaired recognition of previously known familiar faces. This is part of a more general failure to appreciate shapes, and patients are also unable to make simple pictures by putting together a few pieces. Other types of apperceptive agnosia include an inability to recognize buildings or familiar objects viewed from unusual angles. The posterior part of the medial occipitotemporal gyrus (fusiform gyrus) is particularly associated with recognition of faces and is known as the fusiform face area.
Corticotectal fibers connect the visual cortex, the visual association cortex, and the posterior part of the parietal lobe with the superior colliculus of the midbrain. Through indirect connections, the superior colliculus controls the oculomotor, trochlear, and abducens nuclei (see Chapter 8). This is part of a pathway for fixation of gaze and for tracking of a moving object in the field of vision. It also participates in the accommodation-convergence reaction when looking at a near object. These motor aspects of the occipital and parietal cortex are related to those of the frontal eye field, which are described later in this chapter.
The primary auditory area (acoustic area) is concealed because it is located in the ventral wall of the lateral sulcus (Fig. 15-4; see also Fig. 15-1). The superior surface of the superior temporal gyrus, forming the floor of the sulcus, is marked by transverse temporal gyri. The two most anterior
of these, called Heschl's convolutions, are the classical landmarks for the auditory area, which corresponds to Brodmann's areas 41 and 42. Recordings made from neurosurgical patients indicate that only the posteromedial part of this region is primary auditory cortex.
FIGURE 15-4 Primary auditory cortex on the superior surface of the left temporal lobe, exposed by removing the frontal and parietal opercula.
The medial geniculate body of the thalamus is the principal source of axons that end in the primary auditory cortex, with these fibers constituting the auditory radiation in the cerebral white matter. A spatial representation is present in the auditory area with respect to the pitch of sounds. Impulses for low frequencies impinge on the anterolateral part of the area, and impulses for high frequencies impinge on the posteromedial part. The medial geniculate body receives signals that originate in both ears, ensuring bilateral cortical representation (see Chapter 21).
Auditory Cortex Lesions
An epileptic seizure that originates in the primary auditory area typically begins with perception of a roaring sound, apparently originating from somewhere contralateral to the affected temporal lobe. With other types of temporal lobe epilepsy, auditory hallucinations are usually not localized by the patient to either of the ears.
Sometimes a unilateral destructive lesion involving the auditory area results in difficulty with the interpretation of complex combinations of sounds, but it causes almost no impairment of hearing in the contralateral ear. Large bilateral lesions in the temporal lobes are rare, but they can cause bilateral deafness, among other symptoms.
The taste area (gustatory area) is adjacent to the general sensory area for the tongue at the inferior end of the postcentral gyrus (area 43,
Fig. 15-1) and extends onto the insula and then anteriorly to the frontal operculum. Nerve impulses from taste buds reach the gustatory nucleus in the brain stem (i.e., the rostral part of the solitary nucleus; see Chapters 7 and 8). Fibers from the gustatory nucleus travel in the ipsilateral central tegmental tract to the most medial part of the medial division of the ventral posterior nucleus of the thalamus. The pathway is completed by thalamocortical fibers.
The auditory association cortex for more elaborate perception of acoustic information occupies the floor of the lateral sulcus behind the auditory area (the region labeled planum temporale in Fig. 15-4) and the posterior part of Brodmann's area 22 on the lateral surface of the superior temporal gyrus. In the left cerebral hemisphere of most people, the region of cortex thus defined is also known as Wernicke's areaand is of major importance in language functions. Bilateral destruction of the auditory association cortices causes auditory agnosia, in which patients fail to identify and respond appropriately to complex sounds. In severe cases, speech cannot be distinguished from other auditory stimuli. If the lesion is located in the hemisphere (usually the left) that is dominant for linguistic functions, the patient has receptive aphasia, a condition discussed later in this chapter. A lesion on the right side can cause amusia, which is loss of the ability to recognize previously familiar voices and music.
Most of the fibers of the olfactory tract (see Chapter 17) end in the region of the limen insulae and the uncus (area 34) and the underlying amygdaloid body. Some end in the entorhinal cortex (area 28), which is also a major component of the limbic system (see Chapter 18) used for acquiring and recalling memories. The proximity of olfactory and gustatory areas in the region of the insula suggests that this may be a site of integration of the two special senses that are functionally related to feeding. Insular cortex is also involved in the control of visceral functions. The lateral part of the orbital surface of the frontal lobe receives projections from the primary olfactory areas and is presumed to be involved in behavioral reactions to recognized odors.
Neuroanatomical tracing studies in animals reveal ascending fibers from the vestibular nuclei that are almost entirely crossed, travel near the medial lemniscus, and end in and near the medial division of the ventral posterior nucleus (VPm) of the thalamus. The VPm also receives fibers for somatic sensation from the head. In studies of monkeys, electrical stimulation of the vestibular nerve evokes potentials in the anterior end of the intraparietal sulcus, in the nearby somatosensory cortex, and in the posterior part of the insula. These areas are strategically placed for the integration of vestibular input with proprioceptive signals from muscles that act on the head. Similar areas have been identified by PET and fMRI scans after stimulation of the human vestibular nerve. No cortical area is known that is activated exclusively by the vestibular system. The cortical projection of the vestibular system presumably contributes to motor regulation, awareness of spatial orientation, and sensations of vertigo and nausea associated with excessive vestibular stimulation.
OTHER ASSOCIATION CORTEX
Areas of association cortex adjacent to the main sensory areas and closely related functionally to them have already been described. Additional association cortex is located in the parietal lobe and in the posterior part of the temporal lobe. Data reaching the sensory areas and analyzed in the adjacent association cortex are correlated in this intervening region to yield a comprehensive assessment of the immediate environment. The association cortex of the three “sensory” lobes has abundant connections with cortex of the frontal lobe through long fasciculi in the white matter of the cerebral hemisphere (see Chapter 16). Complex and flexible behavioral patterns are formulated on the basis of experience, emotional
tones are added, and overt expression may follow through the motor system.
The anterior part of the temporal lobe, similar to the area for visual memory on its inferolateral surface, appears to have special properties related to thought and memory. Electrical stimulation of this region in conscious subjects may elicit recall of objects seen, music heard, or other experiences in the recent or distant past. Patients with a temporal lobe tumor may have auditory or visual hallucinations that reproduce earlier events. The connections and functions of the medial parts of the temporal lobe, along with those of the cingulate gyrus, are discussed in more detail in Chapter 18.
The total expanse of parieto-occipitotemporal and frontal association cortex is responsible for many of the unique qualities of the human brain. Engrams, or long-term memory traces, are laid down over the years, possibly as macromolecular changes in neurons and structural changes in synapses throughout the cerebral cortex. These form the basis of learning at an intellectual level and of skills acquired through practice. The complex neuronal circuitry of the cortex permits the coalescence of memory traces in the form of ideas and conceptual, abstract thinking. Recently acquired information is not consolidated into long-term memory if bilateral lesions are present in the limbic system (see Chapter 18). There is no localized disease that causes loss of established memories, indicating that the engram is contained in many parts of the brain. Rare instances of permanent amnesia that occur after head injury are probably caused by failure of the recalling mechanisms because most amnesic patients eventually recover their memories. The eventual failure of all intellectual function in advanced cases of Alzheimer's disease and other types of dementia is attributed to the loss of enormous numbers of neurons throughout the cerebral cortex and in various subcortical nuclei. For more information about memory, see Chapter 18.
The neocortex of the frontal lobe has a special role in motor activities, in the attributes of judgment and foresight, and in determining mood or affect.
PRIMARY MOTOR AREA
The primary motor area has been identified on the basis of elicitation of motor responses at a low threshold of electrical stimulation. The area is located in the precentral gyrus, including the anterior wall of the central sulcus, and in the anterior part of the paracentral lobule on the medial surface of the hemisphere (see Figs. 15-1 and 15-2). Neurons other than pyramidal cells are not easily recognized in this cortex, and the six layers are difficult to define. Giant pyramidal cells (Betz cells), present in small numbers in layer 5, occur only in the primary motor area.
The main sources of input to area 4 are the other motor areas of the cortex, the somesthetic cortex, and the posterior division of the ventral lateral thalamic nucleus (VLp), which, in turn, receives input from the cerebellum. Although area 4 contributes fibers to several motor pathways, the efferents that give it a special significance are those included in thepyramidal system, which comprises the corticospinal and corticobulbar tracts. In monkeys, 30% of these fibers arise in area 4; another 30% come from area 6; and about 40% arise in the parietal lobe, notably the first somatic sensory area. The Betz cells contribute some 30,000 large, thickly myelinated axons to the corticospinal tract of each side, accounting for about 3% of the tract's axons. The rapidly conducting axons of Betz cells probably have some terminal branches that synapse directly with motor neurons. Other neurons in the primary motor cortex have axons that end in the motor regions of the reticular formation (see also Chapter 23).
Electrical or magnetic stimulation of the primary motor area elicits contraction of muscles that are mainly on the opposite side of the body. Although cortical control of the skeletal musculature is predominantly contralateral, there is some ipsilateral control of most of the muscles of the head and of the axial muscles of the body. The body is represented in the motor area as inverted, with the pattern or homunculus (see Fig. 15-3) being similar to that of the somesthetic cortex. The sequence, from below upward, begins with the pharynx, larynx, tongue, and face; the region for muscles of the head comprises about one third of area 4. Continuing dorsally, there is a small region
for muscles of the neck, followed by a large area for muscles of the hand; this is consistent with the functional importance of manual dexterity. Next in order are small areas for the arm, shoulder, trunk, and thigh, continuing with an area on the medial surface of the hemisphere for the remainder of the leg and the foot.
The primary motor area has a lower threshold of excitability than other areas from which contraction of skeletal muscles can be elicited by electrical stimulation. Contractions are usually of contralateral muscles, as has been noted, and the muscles responding depend on the part of area 4 that is stimulated. The response typically involves muscles that make up a functional group, although contraction of a single muscle occasionally occurs. Studies with microelectrodes in laboratory animals indicate that small clusters of columns of cortical neurons control individual muscles.
SUPPLEMENTARY AND CINGULATE MOTOR AREAS
A supplementary motor area and a cingulate motor area have been identified by cortical stimulation in primates, including humans. The supplementary motor area is located in the part of area 6 that lies on the medial surface of the hemisphere (see Fig. 15-2), and the cingulate motor area is located in the adjoining cortex of the anterior half of the cingulate sulcus. Both of these cortical areas receive input from many other cortical areas and from the ventral anterior (VA) and the anterior division of the ventral lateral (VLa) nucleus of the thalamus. Efferent axons go into the corticospinal and corticobulbar tracts, to motor regions of the reticular formation, and to the primary motor area (Fig. 15-5).
Motor Cortex Lesions
The primary motor area may be abnormally irritated by, for example, a small tumor or a splinter of bone from a fracture of the skull. The resulting scarring of cortical tissue causes episodes of abnormal excitation of the neurons, with involuntary twitching movements of the corresponding part of the body. Most frequently, this is the mouth, tongue, or thumb, regions that account for much of the area of the precentral gyrus. Typically, these movements are the beginning of a jacksonian seizure. As the abnormal cortical activity spreads across the precentral gyrus, a progression of jerking movements to other muscles takes place, leading eventually to generalized convulsions. The study of this type of epilepsy by John Hughlings Jackson (1835-1911, English clinical neurologist) provided early evidence for the representation of the opposite side of the body in the precentral and postcentral gyri. For more about epilepsy, see Chapters 9 and 18.
Damage in the primary motor area, without involvement of adjacent cortex or underlying white matter, is seldom encountered clinically. Deficits resulting from such damage are inferred from results of experiments on nonhuman primates and from isolated human cases in which part of area 4 was removed as a therapeutic procedure, as in the treatment of jacksonian epilepsy.
A destructive lesion in area 4 results in paresis (weakness) of the affected part of the opposite side of the body. The muscles involved are flaccid if the damage is restricted to the precentral gyrus. The much more common condition of spastic paralysis is characteristically caused by lesions that spread beyond area 4 or that interrupt fibers in the subcortical white matter or internal capsule. Considerable recovery occurs with time, with the residual deficit being most evident as weakness in the distal parts of the limbs.
Electrical stimulation in humans indicates a somatotopic organization of the supplementary motor area, with the face represented rostrally and the lower limbs in the caudal part of the region. The effects of stimulation are predominantly contralateral and are preceded by a conscious urge to make the movements. Increased regional blood flow in the supplementary motor area can be demonstrated during the mental processes that precede the execution of a movement. The anterior cingulate area exhibits increased activity during anticipation of motor and purely cognitive tasks.
Results of experiments in monkeys indicate that loss of function of the supplementary motor
area may cause the spasticity of muscles paralyzed as the result of an “upper motor neuron” lesion. Infarctions involving the human supplementary and cingulate motor areas of either side cause loss of most volitional movements and loss of the power of speech. Evidently, patients with this condition, known as akinetic mutism, have no motivation or will to move or speak. These patients often recover completely after a few weeks. Akinetic mutism is more severe and longer lasting if bilateral lesions are present. A clinically similar condition, also called akinetic mutism, can follow infarction of the medial part of the reticular formation in the rostral pons or midbrain (see Chapter 23).
FIGURE 15-5 Connections of the motor areas of the cerebral cortex. The primary motor area is influenced by many other cortical areas, but descending motor projections from all cortical motor areas are also present. The interactions of the cerebellum and basal ganglia with the cerebral cortex are discussed in Chapters 10, 12, and 23. VA, ventral anterior; VLa, ventral lateral anterior; VLp, ventral lateral posterior.
The premotor area is situated in Brodmann's area 6 anterior to the primary motor area on the lateral surface of the hemisphere (see Fig. 15-1). In addition to connections with other cortical areas, the premotor cortex receives fibers from the VA and the anterior division of the VLa nucleus of the thalamus, which, in turn, receive input from the pallidum of the corpus striatum (Chapter 12).
The premotor area contributes to motor function as one of the sources of the pyramidal and other descending motor pathways and by its influence on the primary motor cortex (seeFig. 15-5 and Chapter 23). The premotor and supplementary motor areas generate programs for motor routines necessary for skilled voluntary action, both when a new program is established and when a previously learned program is altered. In general, the primary motor area is the cortex through which commands are channeled for the execution of movements. In contrast, the premotor and supplementary motor areas program skilled motor activity and thus direct the primary motor area in its execution. Connections of the premotor area with the posterior part of the parietal lobe provide an integrated system for the use of visual, proprioceptive, and other sensory information in the preparation of movements.
The term apraxia refers to the result of a cerebral lesion characterized by impairment in the performance of learned movements in the absence of paralysis. One form of apraxia follows a lesion that involves the premotor area. The disability includes functional impairment of muscles that work on the proximal joints of the limbs, especially the shoulder. The ability to carry out tasks at arm's length is then severely impaired. Other forms of apraxia are caused by lesions that involve the somesthetic association cortex of the parietal lobe because proprioception is a necessary background for motor proficiency. When the disability affects writing, it is called agraphia. Agraphia without impairment of speech typically results from damage to the left angular gyrus, which is located in the inferior part of the parietal lobe, a site strategically placed between the visual association cortex and the cortical language areas, which are discussed later.
Frontal Eye Field
The frontal eye field is located in the lower part of area 8 on the lateral surface of the hemisphere. It controls voluntary conjugate saccadic movements of the eyes. Electrical stimulation of the frontal eye field causes deviation of the eyes to the opposite side. The cortex of the frontal eye field is also active during pursuit movements, but this and convergence of the eyes are principally directed by the cortex of the occipital lobe and adjacent parts of the parietal lobe. Convergence is another ocular movement that is not controlled by the frontal eye fields. The connections of the cortical eye fields are explained in connection with eye movements in Chapter 8.
Destruction of the frontal eye field causes conjugate deviation of the eyes toward the side of the lesion. This condition is frequently seen as part of a larger syndrome dominated by hemiplegia and is attributable to a large vascular lesion that puts the motor areas of the cortex out of action. The deviated eyes are directed (as if in horror) away from the paralyzed side of the body. The patient, if conscious, cannot voluntarily move his or her eyes in the opposite direction, but this movement does occur when the eyes follow an object moving across the field of vision.
The large expanse of cortex in the frontal lobe from which motor responses are not elicited on stimulation falls under the heading of association cortex. This region envelops the frontal pole and is called the prefrontal cortex. Corresponding to Brodmann's areas 9, 10, 11, and 12, it is well developed only in primates, especially in humans. The prefrontal cortex has extensive connections through association fasciculi (see Chapter 16) with the cortex of the parietal, temporal, and occipital lobes, thus gaining access to contemporary sensory experience and to the repository of data derived from past experiences. Reciprocal connections are also present with the amygdaloid body in the temporal lobe and with the mediodorsal thalamic nucleus, forming a system that determines affective reactions to present situations on the basis of past experiences. The prefrontal cortex also monitors behavior and exercises control based on such higher mental faculties as judgment and foresight. The lateral part of the orbital surface of the frontal lobe has already been mentioned as association cortex for olfaction. This is a sense that can evoke a wide range of mental and visceral feelings, such as pleasurable anticipation, nostalgia, disgust, nausea, and so on.
FUNCTIONAL AREAS WITHIN THE PREFRONTAL CORTEX
The use of language is a peculiarly human accomplishment, requiring special neural mechanisms in association areas of the cerebral cortex. Areas of the cortex that have particular roles with respect to language have been known for more than a century from the study of patients with cortical damage caused by occlusion of blood vessels. The infarcted regions of the brain were first identified postmortem.
More accurate information was obtained with the availability of computed tomography and nuclear magnetic resonance imaging (MRI) to scan the brains of living patients. With PET and, more recently, fMRI, it is possible to localize parts of the normal brain that are selectively activated in such activities as listening, reading, speaking, and writing. (These imaging techniques are reviewed in Chapter 4.)
Prefrontal Lobe Disorders
Knowledge of the functions of the prefrontal cortex is derived largely from the effects of diseases and injuries. Some diseases affect the frontal lobes more than other parts of the brain. Examples include general paralysis of the insane (one of many effects of syphilis, a bacterial infection) and Pick's disease (in which neurons degenerate for no known reason, leading to dementia). The prefrontal cortex can also be damaged by appropriately placed tumors and by penetrating injuries.
The classical case of prefrontal lobe damage was that of Phineas Gage, an American railroad construction worker injured in 1848 by the premature explosion of a blasting charge. This drove an iron-tamping rod (105 cm long and 3 cm in diameter) through his head. The missile entered through Gage's left cheek and emerged from his right frontal bone, anterior to the coronal suture, having passed through the left orbit and the anterior parts of both frontal lobes of the brain. Gage's motor and speech areas were spared by the injury, and the most conspicuous abnormalities were in his changed personality, with loss of his former industriousness, self-restraint, patience, and consideration for others. These changes persisted until his death nearly 20 years later.
The operation of prefrontal leukotomy (or lobotomy) was introduced by de Egas Moniz in 1935. This simple surgical procedure, which interrupts the connections between the thalami and the cortices of the orbital surfaces of the frontal lobes, was formerly performed as treatment for various mental disorders.
A person with bilateral loss of function of the prefrontal cortex typically becomes rude, inconsiderate to others, incapable of accepting advice, and unable to anticipate the consequences of rash or reckless words or actions. The patient no longer suffers from anxiety or depression or even from severe pain, although there is no loss of awareness of pain. Despite the profoundly changed personality, memory and intellect are spared. The awarding of a share of the Nobel Prize for medicine and physiology to de Egas Moniz in 1949 recognized prefrontal leukotomy as a major advance in the relief of suffering but perhaps without due concern for the importance of the accompanying personality changes. By the 1960s, the operation was reserved for patients with severe affective disorders who did not respond to drugs and psychotherapy. Since the 1970s, the operation has seldom been deemed justifiable. Stereotactic lesions beneath the heads of the caudate nuclei may relieve affective disorders with fewer adverse effects than complete prefrontal leukotomy, but the consequences of the operation are still permanent.
Behavioral and Affective Disorders
The ventral and medial parts of the prefrontal cortex are those most associated with acceptable social interactions. Acquired sociopathy is a name given to the abnormal behavioral state that follows bilateral damage to this region. Lesions in the right ventral prefrontal cortex can cause anosognosia, in which the patient does not acknowledge that there is anything wrong with a paralyzed limb or other severe disability or loss of cognitive powers. Causative lesions include tumors, surgical damage, and hemorrhage from an aneurysm of the anterior communicating artery. Slowly developing bilateral degeneration of extensive areas of prefrontal cortex occurs in general paralysis of the insane, which is a manifestation of syphilis of the central nervous system, and in Pick's disease, the cause of which is unknown. The same areas degenerate in some cases of Alzheimer's disease (see also Chapter 12). These are diseases in which dementia or generalized deterioration of the memory and intellect are present, but the involvement of the prefrontal cortex causes additional behavioral abnormalities similar to those that occur after prefrontal leukotomy.
Depression can occur with many diseases that affect the cerebral cortex, although detectable lesions are absent from the majority of people with this disabling symptom. A single cortical lesion in a depressed patient is more likely to be located in the inferior part of the prefrontal cortex than elsewhere, but the causal relationship, if any, is not understood.
Two cortical areas have specialized language functions (Fig. 15-6). The receptive language area (also called the sensory language area or posterior speech area) consists of the auditory association cortex (Wernicke's area) in the posterior part of the superior temporal gyrus. Reading involves visual association cortex in the inferior parts of the occipital and temporal lobes, which is connected with Wernicke's area (for interpretation of words) and with the cortex of the angular gyrus (for formulation of commands that can be sent to the motor cortex for writing). The expressive speech area (Broca's area, motor speech area, or anterior speech area) occupies the opercular and triangular parts of the inferior frontal gyrus, corresponding to Brodmann's areas 44 and 45, together with the adjacent anterior part of the insula. The integrity of the supplementary motor area on the medial surface of the hemisphere is also necessary for normal speech. The language areas are situated in the left hemisphere with few exceptions, and this is, therefore, the dominant hemisphere as a rule with respect to language. The receptive and expressive language areas are in communication with each other through the superior longitudinal (arcuate) fasciculus in the white matter of the hemisphere (Chapter 16).
FIGURE 15-6 The cortical language areas.
fMRI investigations reveal activation in the posterior part of the right superior temporal gyrus associated with speaking. This area may send instructions to the primary motor cortical areas for the muscles of articulation and respiration, which are bilateral.
Memory traces established in one hemisphere (e.g., in the cortex of the left hemisphere as a result of some particular activity involving the right hand) are transferred to the cortex of the other hemisphere through the corpus callosum. Therefore, bilateral cortical memory patterns exist for previous experiences.
LEFT HEMISPHERE FUNCTIONS
In right-handed people and in most left-handed people, language is a function of the left hemisphere. The “talking” hemisphere is said to be
dominant relative to the “nontalking” hemisphere. A left-sided cerebral lesion is therefore more serious than one in the right hemisphere because aphasia may be added to other neurological deficits. The reverse is true for the few whose right hemisphere is dominant for linguistic functions.
Damage to the language areas or their connections results in aphasia; there are several types, depending on the location of the lesion (seeTable 15-1). Receptive aphasia (Wernicke's aphasia), in which auditory and visual comprehension of language, naming of objects, and repetition of a sentence spoken by the examiner are all defective, is caused by a lesion in the receptive language area, notably in Wernicke's area. Infarcts that isolate the sensory language area from surrounding parietal and temporal cortex may cause anomic aphasia (isolation syndrome), characterized by fluent but circumlocutory speech caused by word-finding difficulties. Some authorities doubt the existence of anomic aphasia as a distinct clinical entity because most patients with lesions in the left parietal lobe have difficulty with naming. Some patients cannot understand words and sentences or produce intelligible speech, but they can correctly repeat what the examiner says. This disorder is called transcortical aphasia of the receptive (or sensory) type, and it is associated with destruction of cortex in the middle temporal gyrus, inferior and posterior to Wernicke's receptive language area.
Alexia refers to loss of the ability to read and is a common accompaniment of aphasia caused by temporal or parietal lobe lesions. In most cases, alexia is accompanied by agraphia, the inability to write. Pure alexia (without agraphia and with normal comprehension of spoken words) may result either from a single lesion lateral to the occipital horn of the left lateral ventricle or from a combination of two lesions, one in the left occipital lobe and the other in the splenium of the corpus callosum. Such lesions sever connections between both visual cortices and the unilaterally located language areas. Dyslexia is incomplete alexia and is characterized by an inability to read more than a few lines with understanding. Developmental dyslexia is a common condition in children of normal intelligence who have difficulty learning to read. MRI examination reveals that some such children lack the usual anatomical asymmetry in the size of the planum temporale on the left and right sides.
Expressive aphasia (Broca's aphasia), which is caused by a lesion in Broca's area of the frontal lobe, is characterized by hesitant and distorted speech with relatively good comprehension. Whereas a patient with Broca's aphasia can hear that he or she is talking nonsense, one with receptive aphasia talks fluently without being aware of the failure to produce meaningful words. A cortical lesion anterior to Broca's expressive speech area causes transcortical aphasia of the expressive (or motor) type. The impairment of spontaneous speech is similar to Broca's aphasia, but the patient can accurately repeat words or phrases spoken by someone else. The term global aphasia refers to a virtually complete loss of the ability to communicate after destruction of the cortex on both sides of the lateral sulcus. This is one of the consequences of occlusion of the left middle cerebral artery (see Chapter 25).
Interruption of the arcuate fasciculus connecting Wernicke's and Broca's areas causes conduction aphasia, in which the patient has poor repetition of a sentence spoken by the examiner but relatively good comprehension and spontaneous speech. Aphasia can also result from lesions in the subcortical gray matter of the hemisphere that is dominant for speech. In subcortical aphasia, the patient has impairment of language production and comprehension associated with dysarthria (attributable to faulty control of the muscles of the larynx and mouth) and contralateral hemiparesis. The lesion is most commonly either laterally located in the left thalamus or involves the head of the left caudate nucleus.
Patients usually have some recovery of function, even in severe cases of aphasia. This is attributed to assumption of linguistic functions by the intact contralateral cerebral hemisphere.
Although factors that determine hemispheral dominance for speech are not well known, heredity is almost certainly involved to some extent. The planum temporale posterior to the auditory area on the dorsal (superior) surface of the superior temporal gyrus (see Fig. 15-4) is larger in the left than in the right hemisphere in 65% of human brains and larger on the right side in only 11% of brains. This indicates that the dominance with respect to language may be
reflected in structural asymmetry because the left planum temporale constitutes a large part of Wernicke's receptive language area. Functional MRI shows that the left planum temporale is less active than the adjacent cortical areas (i.e., superior temporal sulcus, middle temporal gyrus, angular gyrus) in subjects listening to words. This observation indicates that the planum temporale may be involved in stages of auditory processing that precede the paying of attention to formed elements of language.
TABLE 15-1 Agnosias, Aphasias, and Other Disorders of the Association Cortex
About 75% of the population is right-handed, preferring the right hand for skilled tasks. In these people, the right hand is controlled by the left cerebral hemisphere, which is also the dominant hemisphere for language. Handedness is not always correlated with linguistic dominance because 70% of those who are left-handed have their language areas in the left hemisphere rather than in the one that controls the left hand.
RIGHT HEMISPHERE FUNCTIONS
For some activities, the right hemisphere is the dominant one in most people. The most notable faculty residing in the right hemisphere is three-dimensional, or spatial, perception. The evidence is derived partly from studies of patients with right-sided lesions and partly from investigation of those in whom the corpus callosum has been transected as a therapeutic measure in severe epilepsy. After commissurotomy, these patients were able to copy drawings and arrange blocks in a desired position more efficiently with the left hand than with the right hand. The right hemisphere is therefore better equipped to direct such acts.
Spatial awareness extends to the whole body and its surroundings, and this awareness is lost contralaterally in the condition of cortical neglect discussed in connection with the somesthetic association cortex. Severe cortical neglect most often occurs after development of a right-sided lesion. The condition of anosognosia, discussed in connection with the prefrontal cortex, is also caused by right-sided damage. Anosognosia can also develop after injury to the right parietal lobe.
Although it is not essential for verbal communication, the right cerebral cortex, on both sides of the lateral sulcus (sylvian fissure), is necessary for prosody, which is the combination of tones, cadences, and emphasis on particular words and syllables that normally contribute to the thoughts being conveyed. Loss of function of the right perisylvian cortex leads toaprosodia, in which the voice is monotonous and the speech apparently has no emotional content. Related abilities for which the right hemisphere dominates are singing, the playing of musical instruments, and the recognition and appreciation of music. Musical skills and comprehension are commonly lost (amusia) after the development of vascular occlusions that cause infarction of the posterior part of the right superior temporal gyrus. Patients severely aphasic from lesions in the left hemisphere sometimes retain the ability to sing.
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