Chapter 21: Higher Cortical Functions

The human cerebral cortex represents, in some ways, the pinnacle of evolution. In addition to containing networks of neurons related to the initiation of movement and to sensation from the body and the special sensory organs, the cortex is the substrate for functions that include comprehension, cognition, communication, reasoning, problem-solving, abstraction, imagining, and planning.

The frontal lobes contain phylogenetically "new" parts of the cortex, and serve as an "executive" part of the cortex. They participate in higher order functions that include reasoning and abstraction; planning and initiating of activity; monitoring and shaping of behavior to ensure adaptive actions; inhibiting maladaptive behavior; prioritizing and sequencing actions; problem solving; and coordinating elementary motor and sensory functions into a coherent and goal-directed stream of behavior.

Damage to the frontal lobes (as can occur, eg, with brain tumors or head trauma) can produce profound behavioral changes. Several syndromes are especially common: Following damage to the dorsolateral part of the frontal lobes (the convexity), patients tend to become indifferent, abulic, or apathetic (mute and motionless in some cases). Following damage to the orbitofrontal area of the cortex, there is a syndrome of disinhibition, in which the patient appears labile and irritable. These patients are inattentive and distractible, with impaired judgment and loss of the usual inhibitions and social graces. Damage to the medial part of the frontal lobes can produce a syndrome of akinesia (lack of spontaneous movements) and apathy. Injury to the basal part of the frontal lobes can also result in impairment of memory. These frontal lobe syndromes are more frequently seen in patients with bilateral lesions.

Language is the comprehension and communication of abstract ideas. This cortical function is separate from the neural mechanisms related to primary visual, auditory, and motor function.

The ability to think of the right words, to program and coordinate the sequence of muscle contractions necessary to produce intelligible sounds, and to assemble words into meaningful sentences depends on Broca's area (areas 44 and 45) within the inferior frontal gyrus, located just anterior to the motor cortex controlling the lips and tongue.

The ability to comprehend language, including speech, is dependent on Wernicke's area. This area is located in the posterior part of the superior temporal gyrus within the auditory association cortex (area 22).

The arcuate fasciculus provides a crucial arc-shaped pathway within the hemisphere white matter, connecting Wernicke's and Broca's areas (Fig 21–1). Because the arcuate fasciculus connects the speech comprehension area (Wernicke's area) with the area responsible for production of speech (Broca's area), damage to this white matter tract produces impairment of repetition.

Dysarthria

Dysarthria is a speech disorder in which the mechanism for speech is damaged by lesions in the corticobulbar pathways; in one or more cranial nerve nuclei or nerves V, VII, IX, X, and XII; in the cerebellum; or in the muscles that produce speech sounds. Dysarthria is characterized by dysfunction of the phonation, articulation, resonance, or respiration aspects of speech.

Aphasia

Aphasia refers to loss or impairment of language function as a result of brain damage. Several distinct types of aphasia result from lesions in specific regions of the cerebral hemispheres (Table 21–1). In testing for aphasia, the clinician first listens to the patient's spontaneous speech and then explores the patient's speech during conversation. Speech may be categorized as fluent (more than 50 words per minute, effortless, absence of dysarthria, normal phrase length, and normal intonation). In contrast, nonfluent aphasia is effortful, with decreased verbal output (less than 50 words per minute), poor articulation, degradation of inflection and melodic aspects of speech, and agrammatism (ie, the tendency to omit small, grammatical words, verb tenses, and plurals and to use only nouns and verbs). Naming (usually examined by asking patients to name objects presented to them), repetition of phrases such as "dog," "automobile," "President Kennedy," "no ifs, ands, or buts," and comprehension of spoken language are also tested. Comprehsion can be assessed in patients with impaired speech output by observing the response to yes-no questions of graded difficulty ("Is your name John?" "Are we in a hospital room?" "Are we in a church?" "Do helicopters eat their young?").

Aphasia with Impaired Repetition

In most common forms of aphasia, the ability to repeat spoken language is impaired. Broca's, Wernicke's, and global aphasia are frequently seen in clinical practice.

A. Broca's Aphasia

Broca's aphasia is common, and is usually caused by a lesion in the inferior frontal gyrus in the dominant hemisphere (Broca's area; Fig 21–1). The patient has difficulty naming even simple objects. Repetition is impaired, but comprehension of spoken language is normal. The patient is usually aware of the deficit and appropriately concerned about it.

Most lesions that involve Broca's area also involve the neighboring motor cortex. Patients are often hemiplegic, with the arm more affected than the leg. Broca's aphasia often occurs as a result of strokes, most commonly affecting the middle cerebral artery territory.

B. Wernicke's Aphasia

This common form of aphasia is caused by a lesion in or near the superior temporal gyrus, in Wernicke's area (see Figs 21–1 and 21–2). Because this part of the cortex is not located adjacent to the motor cortex, there is usually no hemiplegia.

Patients with Wernicke's aphasia have fluent speech, but repetition and comprehension are impaired. The patient usually has difficulty naming objects and produces both literal paraphasias (eg, "wellow" instead of "yellow") and verbal paraphasias (eg, "mother" instead of "wife"). Neologisms (meaningless, nonsensical words, eg, "baffer") are used commonly and speech may be circumlocutory (ie, wordy but meaningless). Patients with Wernicke's aphasia usually do not appear concerned about, or even aware of, their speech disorder. Wernicke's aphasia commonly occurs as a result of embolic strokes.

C. Global Aphasia

Large lesions in the dominant hemisphere, which involve Broca's area in the frontal lobe, Wernicke's area in the temporal lobe, and the interconnecting arcuate fasciculus, can produce global aphasia (see Fig 21–2). In this nonfluent aphasia, both repetition and comprehension are severely impaired. Global aphasia most commonly occurs as a result of large infarctions in the dominant hemisphere, often because of occlusion of the carotid or middle cerebral artery.

D. Conduction Aphasia

In this unusual aphasia, verbal output is fluent and paraphasic. Comprehension of spoken language is intact, but repetition is severely impaired. Naming is impaired, although the patient often is able to select the correct name from a list. Conduction aphasia is a result of a lesion involving the arcuate fasciculus, in the white matter underlying the temporal–parietal junction; this lesion disconnects Wernicke's area from Broca's area.

Aphasias with Intact Repetition

A. Isolation Aphasias

In these unusual aphasias, repetition is spared, but comprehension is impaired. These aphasias are also referred to as transcortical aphasias because the lesion is usually in the cortex surrounding Wernicke's or Broca's area, or both. Depending on the location of the lesion, these aphasias may be fluent or nonfluent and comprehension may be impaired or preserved.

B. Anomic Aphasia

Anomia (difficulty finding the correct word) can occur in a variety of conditions, including toxic and metabolic encephalopathies. When anomia occurs as an aphasic disorder, speech may be fluent but devoid of meaning as a result of word-finding difficulty. The patient has difficulty naming objects. Comprehension and repetition are relatively normal. The presence of anomic aphasia is of little value in localizing the area of dysfunction. Focal lesions throughout the dominant hemisphere or, in some cases, in the nondominant hemisphere, can produce anomic aphasia, and anomia is also commonly present in toxic and metabolic encephalopathies.

Alexia

Alexia (the inability to read) can occur as part of aphasic syndromes or as an isolated abnormality. Aphasic alexia refers to impaired reading in Broca's, Wernicke's, global, and isolation aphasias.

A. Alexia with Agraphia

This disorder, in which there is impairment of reading and writing, is seen with pathologic lesions at the temporal– parietal junction area, particularly the angular gyrus. Because lesions of the angular gyrus also produce Gerstmann's syndrome (see later section in this chapter) and anomia, the constellation of agraphia, Gerstmann's syndrome, and anomia may occur together.

B. Alexia without Agraphia

Alexia without agraphia is a striking disorder in which the patient is unable to read, although writing is not impaired. Patients with this disorder are capable of writing a paragraph but, when asked to read it, cannot do so.

This syndrome occurs when there is damage to the left (dominant) visual cortex and to the splenium of the corpus callosum (Fig 21–3). As a result of damage to the left visual cortex, there is a right-sided homonymous hemianopsia and written material in the right half of the visual world is not processed. Written material presented to the left visual field is processed in the visual cortex on the right side. However, neurons in the visual cortex on the two sides are normally interconnected via axons that project through the splenium. As a result of damage to the splenium, visual information in the right visual cortex cannot be transmitted to the visual cortex in the left (dominant) hemisphere and, thus, is disconnected from the speech comprehension (Wernicke's) area.

Most commonly, this disorder occurs as a result of infarctions in the territory of the posterior cerebral artery on the left, which damage both the left-sided visual cortex and the posterior part of the corpus callosum. An example is shown in Figure 21–4.

Agnosia

Agnosia—difficulty in identification or recognition—is usually considered to be caused by disturbances in the association functions of the cerebral cortex. Astereognosis is a failure of tactile recognition of objects and is usually associated with parietal lesions of the contralateral hemisphere. Visual agnosia, the inability to recognize things by sight (eg, objects, pictures, persons, spatial relationships) can occur with or without hemianopsia on the dominant side. It is a result of parieto-occipital lesions or the interruption of fibers in the splenium of the corpus callosum.

Prosopagnosia is a striking syndrome in which the patient loses the ability to recognize familiar faces. The patient may be able to describe identifying features such as eye color, length and color of hair, and presence or absence of a mustache. However, even spouses, friends, or relatives may not be recognized. Although the anatomic basis for this syndrome remains controversial, lesions in the temporal and occipital lobes, in some cases bilateral, have been suggested to be causative.

Unilateral neglect is a syndrome in which the patient fails to respond to stimuli in one half of space, contralateral to a hemispheric lesion. The patient may fail to respond to visual, tactile, and auditory stimuli. In its full-blown form, the syndrome is very striking: The patient may bump into things in the neglected visual field, will fail to dress or shave the neglected half of the body, and will be unaware of motor or sensory deficits on the neglected side. The unilateral neglect may be especially apparent when the patient is asked to draw a flower or fill in the numbers on a clock (Fig 21–5).

Unilateral neglect is commonly seen as a result of parietal lobe damage but is also found after injury to other parts of the cerebral hemispheres (frontal lobe, cortical white matter, deep structures such as basal ganglia, etc). Unilateral neglect is most easily demonstrated following injury to the right cerebral hemisphere (left-sided unilateral neglect), as illustrated by the case shown in Figure 21–6.

Anosognosia

Anosognosia, the lack of awareness of disease or denial of illness, may occur together with the unilateral neglect syndrome. For example, patients with left hemiparesis often neglect the paralyzed limbs and may even deny that they are part of their body, attributing them to a doll or another patient. Even when the patient is aware of the deficit, he may not be appropriately concerned about it.

Apraxia

Apraxia, the inability to carry out motor acts correctly despite intact motor and sensory pathways, intact comprehension, and full cooperation, can occur following injury to a variety of cortical and subcortical sites. Ideomotor apraxia is the inability to perform motor responses upon verbal command, when these responses were previously carried out spontaneously. For example, the patient may fail to show his teeth on command, although he can do this spontaneously. Providing patients with objects to be used (eg, giving them a hairbrush and asking them to demonstrate how to brush their hair) leads to improvement of their performance. Damage to a variety of sites, including Broca's area, the corpus callosum, and the arcuate fasciculus, can cause ideomotor apraxia. Ideational apraxia is characterized by an abnormality in the conception of movements, so the patient may have difficulty doing anything at all, or may have problems sequencing the different components of a complex act although each separate component can be performed correctly. In ideational apraxia, introduction of objects to be used does not improve performance. Ideational apraxia may be seen after lesions of the left temporal–parietal–occipital area.

Gerstmann's Syndrome

This tetrad of clinical findings includes right–left disorientation, finger agnosia (difficulty identifying or recognizing the fingers), impaired calculation, and impaired writing. The presence of this tetrad suggests dysfunction in the angular gyrus of the left hemisphere.

Although the projection systems of motor and sensory pathways are relatively similar on the left and right, each hemisphere is specialized and dominates the other in some specific functions. The left hemisphere controls language and speech in most people; the right hemisphere leads in interpreting three-dimensional images and spaces. Other distinctions have been postulated, such as music understanding in the left hemisphere, arithmetic and design in the right.

Cerebral dominance is related to handedness. Most right-handed people are left-hemisphere dominant; so are 70% of left-handed people, while the remaining 30% are right-hemisphere dominant. This dominance is reflected in anatomic differences between the hemispheres. The slope of the left lateral fissure is less steep, and the upper aspect of the left superior temporal gyrus (the planum temporale) is broader in people with left-hemisphere dominance.

When neurosurgery is contemplated for a patient, it can be useful for one to establish which cerebral hemisphere is dominant for speech. Typically, amobarbital or thiopental sodium is injected into a carotid artery while the patient is counting aloud and making rapidly alternating movements of the fingers of both hands. When the carotid artery of the dominant side is injected, a much greater and longer interference with speech function occurs than with injection of the other side.

The three types of memory are immediate recall, short-term memory, and long-term (or remote) memory.

Immediate recall is the phenomenon that allows people to remember and repeat a small amount of information shortly after reading or hearing it. In tests, most people can repeat, parrot-like, a short series of words or numbers for up to 10 minutes. The anatomic substrate is thought to be the auditory association cortex.

Short-term memory can last up to an hour. Tests usually involve short lists of more complicated numbers (eg, telephone numbers) or sentences for a period of an hour or less. This type of memory is associated with intactness of the deep temporal lobe. If a patient's temporal lobe is stimulated during surgery or irritated by the presence of a lesion, he or she may experience déjà vu, characterized by sudden flashes of former events or by the feeling that new sensations are old and familiar ones. (Occasionally, the feeling of déjà vu occurs spontaneously in normal, healthy persons.)

Long-term memory allows people to remember words, numbers, other persons, events, and so forth for many years. The formation of memories appears to involve the strengthening of certain synapses. Long-term potentiation (LTP), a process triggered by the accumulation of calcium in postsynaptic neurons following high-frequency activity, appears to play an important role in the processes underlying memory. Experimental and clinical observations suggest that the encoding of long-term memory involves the hippocampus and adjacent cortex in the medial temporal lobes. The medial thalamus and its target areas in the frontal lobes are also involved, together with the basal forebrain nucleus of Meynert (Fig 21–7).

Dysfunction of the cerebral cortex, alone or together with dysfunction of deeper structures, can lead to some forms of epilepsy. Epilepsy is characterized by sudden, transient alterations of brain function, usually with motor, sensory, autonomic, or psychic symptoms; it is often accompanied by alterations in consciousness. Coincidental pronounced alterations in the electroencephalogram (EEG) may be detected during these episodes (see Chapter 23).

The epilepsies are a heterogeneous group of disorders. In the broadest sense, they can be categorized into disorders characterized by generalized or partial (focal, local) seizures. Some types of seizures are due to lesions in specific parts of the brain and thus have localizing value.

Focal (Jacksonian) Epilepsy

Seizures resulting from focal irritation of a portion of the motor cortex may be manifested within the corresponding peripheral area. These are termed focal motor seizures, and they suggest damage to a discrete, specific part of the brain. For example, if the motor cortex for the hand is involved, the seizure may be confined to the hand. Consciousness may be retained, and the seizure may spread over the rest of the adjacent motor cortex to involve adjacent peripheral parts. The spread of seizure activity, as it extends over the homunculus on the motor cortex, may take the form of an orderly "march" over the body (see Fig 10–14). Focal motor seizures can occur with or without a march. This type of seizure is most commonly associated with structural lesions such as brain tumor or glial scar. Electrical stimulation of the exposed cortex during neurosurgery has aided in mapping the cortex and in understanding localized, partial seizures. For example, electrical stimulation of various regions within the primary motor cortex results in movement of specific body parts (see Fig 21–8), in accordance with the organization of the motor homunculus as shown in Figure 10–14.

Complex Partial Epilepsy

There are several types of complex partial epilepsy. In temporal lobe epilepsy, the seizure may begin with psychic or complex sensory symptoms (eg, a feeling of excitement or fear, an abnormal feeling of familiarity—déjà vu; complex visual or auditory hallucinations) or autonomic symptoms (eg, unusual epigastric sensations). Olfactory or gustatory sensations are often reported. These may be followed by automatisms, simple or complex patterned movements, incoherent speech, turning of the head and eyes, smacking of the lips or chewing, twisting, and writhing movements of the extremities, clouding of consciousness, and amnesia. Complex acts and movements such as walking or fastening or unfastening buttons may occur for several seconds or as long as 10 minutes. Temporal lobe foci (spikes, sharp waves, or combinations of these) are frequently associated with this type of epilepsy. These complex partial seizures may, in some patients, generalize so that the patient has tonic–clonic seizures. Pathology in the temporal lobe (eg, glial scarring or a tumor) is often present.