The cerebral cortex of the human brain contains approximately 20 billion neurons spread over an area of 2.5 m². The primary sensory and motor areas constitute 10% of the cerebral cortex. The rest is subsumed by modality-selective, heteromodal, paralimbic, and limbic areas collectively known as the association cortex (Fig. 22-1). The association cortex mediates the integrative processes that subserve cognition, emotion, and comportment. A systematic testing of these mental functions is necessary for the effective clinical assessment of the association cortex and its diseases. According to current thinking, there are no centers for “hearing words,” “perceiving space,” or “storing memories.” Cognitive and behavioral functions (domains) are coordinated by intersecting large-scale neural networks that contain interconnected cortical and subcortical components. Five anatomically defined large-scale networks are most relevant to clinical practice: (1) a perisylvian network for language, (2) a parietofrontal network for spatial orientation, (3) an occipitotemporal network for face and object recognition, (4) a limbic network for retentive memory, and (5) a prefrontal network for the executive control of cognition and comportment.

The areas that are critical for language make up a distributed network located along the perisylvian region of the left hemisphere. One hub, located in the inferior frontal gyrus, is known as Broca’s area. Damage to this region impairs phonology, fluency, and the grammatical structure of sentences. The location of a second hub, known as Wernicke’s area, is less clearly settled but is traditionally thought to include the posterior parts of the temporal lobe. Cerebrovascular accidents that damage this area interfere with the ability to understand spoken or written sentences as well as the ability to express thoughts through meaningful words and statements. These two hubs are interconnected with each other and with surrounding parts of the frontal, parietal, and temporal lobes. Damage to this network gives rise to language impairments known as aphasia. Aphasia should be diagnosed only when there are deficits in the formal aspects of language, such as word finding, word choice, comprehension, spelling, or grammar. Dysarthria and mutism do not by themselves lead to a diagnosis of aphasia. In approximately 90% of right-handers and 60% of left-handers, aphasia occurs only after lesions of the left hemisphere.

CLINICAL EXAMINATION

The clinical examination of language should include the assessment of naming, spontaneous speech, comprehension, repetition, reading, and writing. A deficit of naming (anomia) is the single most common finding in aphasic patients. When asked to name a common object, the patient may fail to come up with the appropriate word, may provide a circumlocutious description of the object (“the thing for writing”), or may come up with the wrong word (paraphasia). If the patient offers an incorrect but related word (“pen” for “pencil”), the naming error is known as a semantic paraphasia; if the word approximates the correct answer but is phonetically inaccurate (“plentil” for “pencil”), it is known as a phonemic paraphasia. In most anomias, the patient cannot retrieve the appropriate name when shown an object but can point to the appropriate object when the name is provided by the examiner. This is known as a one-way (or retrieval-based) naming deficit. A two-way (comprehension-based) naming deficit exists if the patient can neither provide nor recognize the correct name. Spontaneous speech is described as “fluent” if it maintains appropriate output volume, phrase length, and melody or as “nonfluent” if it is sparse and halting and average utterance length is below four words. The examiner also should note the integrity of grammar as manifested by word order (syntax), tenses, suffixes, prefixes, plurals, and possessives. Comprehension can be tested by assessing the patient’s ability to follow conversation, asking yes-no questions (“Can a dog fly?” “Does it snow in summer?”), asking the patient to point to appropriate objects (“Where is the source of illumination in this room?”), or asking for verbal definitions of single words. Repetition is assessed by asking the patient to repeat single words, short sentences, or strings of words such as “No ifs, ands, or buts.” The testing of repetition with tongue twisters such as “hippopotamus” and “Irish constabulary” provides a better assessment of dysarthria and palilalia than of aphasia. It is important to make sure that the number of words does not exceed the patient’s attention span. Otherwise, the failure of repetition becomes a reflection of the narrowed attention span (working memory) rather than an indication of an aphasic deficit. Reading should be assessed for deficits in reading aloud as well as comprehension. Alexia describes an inability to either read aloud or comprehend single words and simple sentences; agraphia (or dysgraphia) is used to describe an acquired deficit in spelling.

Aphasias can arise acutely in cerebrovascular accidents (CVAs) or gradually in neurodegenerative diseases. The syndromes listed in Table 22-1 are most applicable to the former group, where gray matter and white matter at the lesion site are abruptly and jointly destroyed. Progressive neurodegenerative diseases can have cellular, laminar, and regional specificity, giving rise to a different set of aphasias that will be described separately. The syndromes outlined below are idealizations and rarely occur in pure form.

Wernicke’s aphasia

Comprehension is impaired for spoken and written words and sentences. Language output is fluent but is highly paraphasic and circumlocutious. Paraphasic errors may lead to strings of neologisms, which lead to “jargon aphasia.” Speech contains few substantive nouns. The output is therefore voluminous but uninformative. For example, a patient attempts to describe how his wife accidentally threw away something important, perhaps his dentures: “We don’t need it anymore, she says. And with it when that was downstairs was my teeth-tick … a … den … dentith … my dentist. And they happened to be in that bag … see? …Where my two … two little pieces of dentist that I use … that I … all gone. If she throws the whole thing away … visit some friends of hers and she can’t throw them away.”

Gestures and pantomime do not improve communication. The patient may not realize that his or her language is incomprehensible and may appear angry and impatient when the examiner fails to decipher the meaning of a severely paraphasic statement. In some patients this type of aphasia can be associated with severe agitation and paranoia. The ability to follow commands aimed at axial musculature may be preserved. The dissociation between the failure to understand simple questions (“What is your name?”) in a patient who rapidly closes his or her eyes, sits up, or rolls over when asked to do so is characteristic of Wernicke’s aphasia and helps differentiate it from deafness, psychiatric disease, or malingering. Patients with Wernicke’s aphasia cannot express their thoughts in meaning-appropriate words and cannot decode the meaning of words in any modality of input. This aphasia therefore has expressive as well as receptive components. Repetition, naming, reading, and writing also are impaired.

The lesion site most commonly associated with Wernicke’s aphasia is the posterior portion of the language network. An embolus to the inferior division of the middle cerebral artery, to the posterior temporal or angular branches in particular, is the most common etiology (Chap. 32). Intracerebral hemorrhage, head trauma, and neoplasm are other causes of Wernicke’s aphasia. A coexisting right hemianopia or superior quadrantanopia is common, and mild right nasolabial flattening may be found, but otherwise, the examination is often unrevealing. The paraphasic, neologistic speech in an agitated patient with an otherwise unremarkable neurologic examination may lead to the suspicion of a primary psychiatric disorder such as schizophrenia or mania, but the other components characteristic of acquired aphasia and the absence of prior psychiatric disease usually settle the issue. Prognosis for recovery of language function is guarded.

Broca’s aphasia

Speech is nonfluent, labored, interrupted by many word-finding pauses, and usually dysarthric. It is impoverished in function words but enriched in meaning-appropriate nouns. Abnormal word order and the inappropriate deployment of bound morphemes (word endings used to denote tenses, possessives, or plurals) lead to a characteristic agrammatism. Speech is telegraphic and pithy but quite informative. In the following passage, a patient with Broca’s aphasia describes his medical history: “I see … the dotor, dotor sent me … Bosson. Go to hospital. Dotor … kept me beside. Two, tee days, doctor send me home.”

Output may be reduced to a grunt or single word (“yes” or “no”), which is emitted with different intonations in an attempt to express approval or disapproval. In addition to fluency, naming and repetition are impaired. Comprehension of spoken language is intact except for syntactically difficult sentences with a passive voice structure or embedded clauses, indicating that Broca’s aphasia is not just an “expressive” or “motor” disorder and that it also may involve a comprehension deficit in decoding syntax. Patients with Broca’s aphasia can be tearful, easily frustrated, and profoundly depressed. Insight into their condition is preserved, in contrast to Wernicke’s aphasia. Even when spontaneous speech is severely dysarthric, the patient may be able to display a relatively normal articulation of words when singing. This dissociation has been used to develop specific therapeutic approaches (melodic intonation therapy) for Broca’s aphasia. Additional neurologic deficits include right facial weakness, hemiparesis or hemiplegia, and a buccofacial apraxia characterized by an inability to carry out motor commands involving oropharyngeal and facial musculature (e.g., patients are unable to demonstrate how to blow out a match or suck through a straw). The cause is most often infarction of Broca’s area (the inferior frontal convolution; “B” in Fig. 22-1) and surrounding anterior perisylvian and insular cortex due to occlusion of the superior division of the middle cerebral artery (Chap. 32). Mass lesions, including tumor, intracerebral hemorrhage, and abscess, also may be responsible. When the cause of Broca’s aphasia is stroke, recovery of language function generally peaks within 2 to 6 months, after which time further progress is limited. Speech therapy is more successful than in Wernicke’s aphasia.

Conduction aphasia

Speech output is fluent but contains many phonemic paraphasias, comprehension of spoken language is intact, and repetition is severely impaired. Naming elicits phonemic paraphasias, and spelling is impaired. Reading aloud is impaired, but reading comprehension is preserved. The lesion sites spare the functionality of Broca’s and Wernicke’s areas but may induce a disconnection between the two. Occasionally, a transient Wernicke’s aphasia may rapidly resolve into a conduction aphasia. The paraphasic output in conduction aphasia interferes with the ability to express meaning, but this deficit is not nearly as severe as the one displayed by patients with Wernicke’s aphasia. Associated neurologic signs in conduction aphasia vary according to the primary lesion site.

Transcortical aphasias: fluent and nonfluent

Clinical features of fluent (posterior) transcortical aphasia are similar to those of Wernicke’s aphasia, but repetition is intact. The lesion site disconnects the intact core of the language network from other temporoparietal association areas. Associated neurologic findings may include hemianopia. Cerebrovascular lesions (e.g., infarctions in the posterior watershed zone) and neoplasms that involve the temporoparietal cortex posterior to Wernicke’s area are common causes. The features of nonfluent (anterior) transcortical aphasia are similar to those of Broca’s aphasia, but repetition is intact and agrammatism is less pronounced. The neurologic examination may be otherwise intact, but a right hemiparesis also can exist. The lesion site disconnects the intact language network from prefrontal areas of the brain and usually involves the anterior watershed zone between anterior and middle cerebral artery territories or the supplementary motor cortex in the territory of the anterior cerebral artery.

Global and isolation aphasias

Global aphasia represents the combined dysfunction of Broca’s and Wernicke’s areas and usually results from strokes that involve the entire middle cerebral artery distribution in the left hemisphere. Speech output is nonfluent, and comprehension of language is severely impaired. Related signs include right hemiplegia, hemisensory loss, and homonymous hemianopia. Isolation aphasia represents a combination of the two transcortical aphasias. Comprehension is severely impaired, and there is no purposeful speech output. The patient may parrot fragments of heard conversations (echolalia), indicating that the neural mechanisms for repetition are at least partially intact. This condition represents the pathologic function of the language network when it is isolated from other regions of the brain. Broca’s and Wernicke’s areas tend to be spared, but there is damage to the surrounding frontal, parietal, and temporal cortex. Lesions are patchy and can be associated with anoxia, carbon monoxide poisoning, or complete watershed zone infarctions.

Anomic aphasia

This form of aphasia may be considered the “minimal dysfunction” syndrome of the language network. Articulation, comprehension, and repetition are intact, but confrontation naming, word finding, and spelling are impaired. Word-finding pauses are uncommon, so language output is fluent but paraphasic, circumlocutious, and uninformative. The lesion sites can be anywhere within the left hemisphere language network, including the middle and inferior temporal gyri. Anomic aphasia is the single most common language disturbance seen in head trauma, metabolic encephalopathy, and Alzheimer’s disease.

Pure word deafness

The most common causes are either bilateral or left-sided middle cerebral artery (MCA) strokes affecting the superior temporal gyrus. The net effect of the underlying lesion is to interrupt the flow of information from the auditory association cortex to the language network. Patients have no difficulty understanding written language and can express themselves well in spoken or written language. They have no difficulty interpreting and reacting to environmental sounds since primary auditory cortex and auditory association areas of the right hemisphere are spared. Because auditory information cannot be conveyed to the language network, however, it cannot be decoded into neural word representations, and the patient reacts to speech as if it were in an alien tongue that cannot be deciphered. Patients cannot repeat spoken language but have no difficulty naming objects. In time, patients with pure word deafness teach themselves lipreading and may appear to have improved. There may be no additional neurologic findings, but agitated paranoid reactions are common in the acute stages. Cerebrovascular lesions are the most common cause.

Pure alexia without agraphia

This is the visual equivalent of pure word deafness. The lesions (usually a combination of damage to the left occipital cortex and to a posterior sector of the corpus callosum—the splenium) interrupt the flow of visual input into the language network. There is usually a right hemianopia, but the core language network remains unaffected. The patient can understand and produce spoken language, name objects in the left visual hemifield, repeat, and write. However, the patient acts as if illiterate when asked to read even the simplest sentence because the visual information from the written words (presented to the intact left visual hemifield) cannot reach the language network. Objects in the left hemifield may be named accurately because they activate nonvisual associations in the right hemisphere, which in turn can access the language network through transcallosal pathways anterior to the splenium. Patients with this syndrome also may lose the ability to name colors, although they can match colors. This is known as a color anomia. The most common etiology of pure alexia is a vascular lesion in the territory of the posterior cerebral artery or an infiltrating neoplasm in the left occipital cortex that involves the optic radiations as well as the crossing fibers of the splenium. Because the posterior cerebral artery also supplies medial temporal components of the limbic system, a patient with pure alexia also may experience an amnesia, but this is usually transient because the limbic lesion is unilateral.

Apraxia and aphemia