Clinical manifestations

Presentation and course

Word deafness. “Word deafness,” an auditory agnosia that affects only verbal material, presents as a profound deficit in the comprehension and repetition of spoken language. Despite this, they retain other language-processing abilities, such as reading, writing, and speaking. Several studies have used psycholinguistic measures to characterize a phonemic-processing deficit in word deafness (70; 04; 59; 10; 36; 68). However, the observed deficits may also be due to an inability to process acoustic stimuli with rapid temporal resolution. Patients with word deafness often exhibit impaired processing of consonants, which are characterized by fast formant frequency transitions between 20 to 50 ms, whereas the processing of vowels, which are characterized by slow formant frequency transitions between 100 to 150 ms, is relatively spared (70; 04; 98; 67; 63; 82). The deficits exhibited in word deafness are not specific to speech sounds. For example, although healthy persons require around 1 to 3 ms between 2 clicks to perceive them as distinct, patients with word deafness require between 15 to 300 ms (01; 04; 87; 09; 30). This suggests a general auditory temporal processing deficit, although the relationship between the verbal and nonverbal temporal processing deficits associated with word deafness remains unclear. Slevc and colleagues found that training on rapid auditory events improved their patients’ ability to perceive rapid temporal differences for non-speech, but not for speech, sounds (79). Furthermore, patients with word deafness may also have difficulty recognizing auditory objects (29). There may be distinct subtypes of word deafness, each resulting from different patterns of lesions (04; 64). Patients with word deafness may have modality-specific dissociations with preservation of number-word processing, despite profound deficits in non-number-word processing (19); this may indicate that the distinction between number word and non-number word processing arises at a sublexical level of representations in speech perception.

Nonverbal auditory agnosia. Nonverbal auditory agnosia refers to the inability to recognize environmental sounds. Two subtypes of nonverbal auditory agnosia have been proposed: patients with the perceptual-discriminative subtype are unable to analyze the frequency and/or time structure of sounds and so are unable to identify whether 2 consecutive sounds are identical, whereas patients with the associative-semantic subtype have an abnormal linkage of sound percepts with meaning and are impaired at audio-visual matching or naming. For instance, patients with the associative-semantic subtype are unable to match an environmental sound (eg, “moo”) with an associated visual picture (eg, a cow). Apperceptive forms of auditory agnosia often affect several domains (eg, music and environmental sounds) because of defects in the analysis of acoustic features that are relevant to multiple domains (12; 44). Amusia and phonagnosia can also be similarly divided into apperceptive and associative subtypes (28). Amusia (often called “tone deafness”) and phonagnosia are disorders affecting a patient’s ability to perceive or understand specific aspects of music and voices, respectively.

Generalized auditory agnosia. Generalized auditory agnosia refers to a generalized decrease in ability to recognize both verbal and nonverbal sounds. Generalized auditory agnosia may also occur with selected preserved auditory abilities. For example, after a right temporoparietal stroke, a left-handed man lost the ability to understand both speech and environmental sounds, although he could match, describe, and sing melodies (54). He had normal hearing acuity and preserved reading and writing, but poor verbal comprehension (although slower speech, single-syllable words, and minimal written cues facilitated his verbal comprehension). He also had difficulty distinguishing tone sequences and discriminating two clicks and short-versus-long tones, particularly in the left ear.

Patients with cortical deafness typically deny hearing any sounds, although they still respond to them (55).

Patients with auditory agnosia may have anosognosia for the deficit (44).

Deficits in higher-level segregation processes have been reported following a right hemisphere lesion affecting non-primary auditory cortex (31). A 33-year-old woman developed an unusual pattern of acquired central auditory deficits after an infarct in the right middle cerebral artery territory, causing damage to the part of the auditory cortex including the planum temporale, as well as involving the posterior insula and inferior parietal lobule, but sparing the medial portion of Heschl gyrus. She reported difficulty segregating speech from noise and segregating elements of music. The deficits were most pronounced for sounds presented to the left ear and affected the segregation of words, music, and more basic abstract stimuli. Clinical tests showed no evidence of abnormal cochlear function. Additional testing demonstrated difficulties with auditory segregation in her left ear that spanned multiple domains, including words-in-noise and music streaming. These symptoms were considered analogous to the visual symptom of simultaneous agnosia.

Central auditory dysfunction in Alzheimer disease. Central auditory dysfunction occurs as part of the dementing process in Alzheimer disease; detectable central auditory dysfunction may precede clinical dementia and might possibly be an early marker of incident dementia (27; 25; 24; 23; 72; 11; 89). Indeed, reduced executive functioning is associated with impairments in central auditory processing (26). Slight and moderate peripheral hearing loss markedly increases the risk of environmental sound recognition deficits, suggesting an interaction between peripheral hearing loss and Alzheimer disease pathology (11). Other studies have found an association between hearing loss in Alzheimer disease and loss of brainstem and cerebellar volume (50).

Prognosis and complications

Cortical auditory disorders are generally enduring syndromes, although reversible or partly reversible cases have been reported, for example, in association with seizures, treatment of pineal tumors, and cerebral vasospasm associated with subarachnoid hemorrhage (66; 69; 92; 15; 37).

Therapeutic outcomes have been inconsistent for reasons that are not yet clear. Although some studies find that intensive therapy leads to little or no recovery (97), the outcome may depend on how soon after onset that therapy is initiated, with therapy provided soon after syndrome onset leading to the greatest benefit (32). There do not appear to be any negative consequences of therapy.

Clinical vignette

Case 1. Nonverbal auditory agnosia (74). A right-handed 62-year-old man (patient “M”) developed the sudden onset of right-sided numbness and difficulty speaking. MRI showed an extensive lesion involving the left temporal and parietal cortex. Language function largely recovered since the infarct, with fluent speech and no measurable speech comprehension impairments, although he did have occasional word-finding difficulties (usually with long or infrequent words). However, even 12 years later, the patient exhibited a severe persistent impairment in nonverbal auditory comprehension. At age 74, extensive audiological and behavioral testing was conducted to characterize M’s unusual neuropsychological profile. The patient exhibited persistent and severe auditory agnosia for nonverbal sounds in the absence of verbal comprehension deficits or peripheral hearing problems. Acoustical analyses suggested that his residual processing of a minority of environmental sounds might rely on his speech-processing abilities. The patient’s and healthy controls’ neural responses to verbal and nonverbal auditory stimuli using functional magnetic resonance imaging (fMRI) were also examined. In the patient’s brain, contralateral (right) temporal cortex, as well as perilesional (left) anterior temporal cortex, were strongly responsive to verbal, but not to nonverbal, sounds, a pattern that stands in marked contrast to the controls’ data. This substantial reorganization of auditory processing likely supported the recovery of M’s speech processing.

Case 2. Apperceptive generalized auditory agnosia (12). A 48-year-old right-handed man became confused after a minor motor vehicle accident. He complained of nausea and a headache. On examination his blood pressure was 230/120 mm Hg. He had a left central facial paresis with preserved limb power, left-sided visual and sensory neglect, left-sided hyperreflexia, and a left Babinski sign. An unenhanced head CT scan showed an extensive lobar hemorrhage involving the right temporal lobe with extension to the parietal lobe.

Four years later he awoke with a loud noise (“like a spaceship landing”), vomited, and complained of headache and right arm numbness. On examination, his blood pressure was 156/95 mm Hg. His examination was otherwise significant for disorientation, diplopia on left gaze, and complete deafness. He became progressively more obtunded. An unenhanced head CT scan showed an isolated hemorrhage of the left inferior colliculus with obstruction of the cerebral aqueduct and secondary hydrocephalus.

He improved with insertion of an intraventricular drain and by discharge 2 weeks later he still had no speech comprehension and instead experienced loud and disturbing bilateral subjective tonal tinnitus. His auditory acuity as measured by pure-tone audiometry gradually improved into the normal range over several months. Auditory brainstem-evoked responses, which did not change in the 4 years after the second event, showed a normal response to left-sided clicks, but absent waves IV and V to right-sided clicks, indicating damage to the corresponding generators of these waveforms in the superior olivary complex and inferior colliculus.

By 4 years after the second hemorrhage he had regained some understanding of speech by reading printed books while listening to the corresponding audiobooks. Although he had excellent performance distinguishing words from nonwords (eg, bus vs. mus), he had a persistent and significantly impaired ability to distinguish minimal pairs of real words (eg, bear vs. pear) and he still could not recognize music and had impaired ability to recognize environmental sounds. Psychophysical studies demonstrated that his most striking impairment was in the analysis of sounds with a time structure that evolved over time periods of from several to tens of milliseconds.

Biological basis

Etiology and pathogenesis

Central auditory pathways extend from the brainstem to the cerebral cortex.

After sound transduction by the inner hair cells in the cochlea, electrical information is transmitted to the brainstem by the auditory nerve. After initial ipsilateral processing in the dorsal and ventral cochlear nuclei and the nucleus of the trapezoid body, impulses project bilaterally (with a contralateral dominance) to the superior olivary complex and then through the lateral lemniscus to the inferior colliculi in the midbrain. From the inferior colliculi, there is a further partial decussation as the pathway projects to the medial geniculate nucleus before cortical processing in the primary auditory cortex in Heschl gyrus of the medial temporal lobe. Analysis of complex acoustic features progresses over longer time windows at successive stages of the central auditory pathway from brainstem to cortex and involves recruitment of increasingly distributed networks along the way (12). These central auditory pathways with multilevel decussations provide some degree of redundancy for processing speech: indeed, speech can be recognized even when the auditory input is markedly degraded, especially after a period of training, when facilitated by expectations, context, and cross-modal cues (eg, lip-reading) (12).

Central auditory disorders generally result from developmental abnormalities or acquired damage involving the temporoparietal regions, especially the superior temporal and auditory cortices (80; 60) but can result from brainstem and subcortical lesions (45). Bilateral lesions appear to be implicated in severe discrimination deficits (02; 55; 09; 88; 80). Unilateral right hemisphere lesions can lead to deficient discrimination with normal association (93; 18), deficient association with normal discrimination (81), or deficient association and deficient discrimination (21). Unilateral left hemisphere lesions have been implicated in deficient association (73), with normal discrimination (93), although most studies did not test discrimination due to a focus on language deficits.

In children, cortical auditory disorders are primarily developmental, but may also be acquired secondary to head injury or tumor (52). Other causes of central auditory disorders in adults include Landau-Kleffner syndrome, adrenoleukodystrophy, and mitochondrial disorders (eg, MELAS) (90; 15; 22; 47). Central auditory processing disorder is presumed to result from the dysfunction of processes and neural mechanisms dedicated to audition, although it may stem from a more generalized dysfunction, such as an attention deficit or a neural timing deficit, which affects performance across modalities (03). Because auditory processing disorders are enduring syndromes, such problems are likely to persist into adulthood.

In adults, central auditory disorders are usually acquired, most often from a unilateral or bilateral stroke involving the auditory cortices of the temporal lobes (85; 07; 61; 06; 86; 29; 38; 51; 80; 31; 44). Bilateral lesions may be staged/sequential or simultaneous. Central auditory disorders may also occur with head trauma, infectious encephalitis (particularly herpes simplex encephalitis), and with neurodegenerative diseases, such as Alzheimer disease (35; 20; 52; 65; 40; 43; 11; 95; 71).

One case of auditory agnosia was reported with sequential bilateral putamenal hemorrhages (84). Other causes of central auditory disorders in adults include paraneoplastic encephalitis, multiple sclerosis, and Moyamoya disease (53; 62). Cases in which adults display symptoms of central auditory disorders in the absence of brain abnormalities are most likely due to developmental causes.

Several studies have found a strong link between deficits in processing verbal and nonverbal stimuli. In a study investigating verbal and nonverbal comprehension deficits in the same aphasic patients, Varney found that impairments in environmental sound recognition were only seen in subjects with impaired verbal comprehension (91). Aphasic patients with intact verbal comprehension also had intact nonverbal comprehension. In an analysis of a large group of patients with unilateral brain damage, Schnider and colleagues found that the semantic deficits exhibited by the patients with left hemisphere damage were highly correlated with their scores on the Western Aphasia Battery (42; 75). Saygin and colleagues performed a large-scale neuropsychological and lesion-mapping study to compare the abilities of aphasic patients to match environmental sounds and complex linguistic phrases to associated pictures (73); they found that the aphasic patients were equally impaired in the verbal and nonverbal domains, showing extremely high correlations between accuracy (r = 0.74) and reaction times (r = 0.95). Using both lesion overlays and a novel lesion-symptom mapping technique called voxel-based lesion-symptom mapping (05), Saygin and colleagues found that damage to the posterior regions in the left middle and superior temporal gyri and to the inferior parietal predicted deficits in both speech and environmental sound processing. In fact, Wernicke area was more strongly associated with performance in the nonverbal than the verbal domain. The large overlap between regions for processing sounds in the verbal and nonverbal domain suggests that their processing shares neural resources. fMRI studies with normal controls have been consistent with this hypothesis (46).

Dissociations between the processing of verbal and nonverbal sounds, although rare, have been reported (74). For example, a right-handed man (patient “M”) suffered a left hemisphere stroke and had persistent difficulty with environmental sound comprehension, despite having largely recovered language function (74). fMRI revealed the contralateral (right) temporal cortex, as well as the perilesional (left) anterior temporal cortex, were strongly responsive to verbal, but not to environmental, sounds. Thus, reorganization of auditory processing may explain the recovery of M’s language comprehension abilities.

The neuroanatomical locus of lesions causing word deafness is debated. Word deafness has been reported following bilateral lesions to the temporal lobes (59; 87; 98; 09; 67; 96; 69; 29), unilateral left temporal lobe lesions (70; 10; 58; 94; 82; 79), or lesions to subcortical areas (30). Most reported cases of word deafness had lesions to the bilateral superior temporal cortex (71% of 59 reviewed cases) (64). A case study reported the presence of word deafness following lesions to the superior temporal gyrus bilaterally (69); resolution of the lesions following medical treatment also resolved the patient’s word deafness. Cases of unilateral damage to the left temporal cortex (16 out of 59 reviewed cases) tend to extend deep into subcortical transcallosal projections, suggesting that word deafness is a “disconnection syndrome.” However, this claim has been directly tested in a word deafness patient with unilateral left temporal lobe damage (79): diffusion tensor imaging revealed that transcallosal white matter connections from the right auditory cortex to the left temporal lobe remained intact, undermining the claim that word deafness following unilateral left damage is necessarily due to a disconnection between auditory processing in the 2 hemispheres. In another case associated with a small stroke in the left temporal gyrus, selective impairment in auditory language processing was accompanied by intact processing of nonspeech sounds and normal speech, reading, and writing (51). Behavioral and neuroimaging results in this case could not be easily integrated into either a pure cortical or disconnection framework because damage to the primary auditory cortex in the left superior temporal gyrus was only partial and Wernicke area was not completely isolated from left- or right-hemisphere input (51). The discrepancy between speech and nonspeech sounds raised the possibility of selective damage to a language-specific left-lateralized network involved in phoneme processing (51).

Several studies have investigated the neuroanatomical locus of both acquired and developmental amusia. A meta-analysis of case and group studies indicated a network of superior temporal, temporoparietal, insular, and frontal areas as the neural substrate for the deficits associated with amusia (83). Most of these regions were in the right hemisphere. Developmental amusia has been linked with abnormalities in cortical thickness (33) and functional connectivity (34). Developmental amusics exhibited decreased frontotemporal connectivity and increased connectivity between the auditory cortex and the default mode network during the resting state (48).

Examples of generalized auditory agnosia from unilateral lesions are rare, but in one case a 73-year-old right-handed man developed generalized auditory agnosia following a subcortical ischemic stroke involving the left acoustic radiation (85).

Epidemiology

The prevalence of central auditory processing disorders in children is 2% to 3%, with a 2:1 ratio of boys to girls (17). Developmental amusia affects approximately 4% of the general population (39).

Differential diagnosis

Cortical auditory disorders must be differentiated from disorders of hearing acuity, memory, attention, and language. Difficulty arises because these disorders are not mutually exclusive and may coexist to some extent in the same person. In adults, sensory aphasia, other language disorders, and dementia must be ruled out (56). For example, a person with a syntactical language disorder will have a comprehension deficit that is proportional to the complexity of the syntax of the spoken message. Thus, shorter, less complex sentences (eg, “The cat meowed”) will be more easily comprehended than longer, more complex sentences (eg, “The cat with the brown stripes sitting on a fence meowed”). Patients with disease or acquired injury of the frontal lobes from stroke, tumor, infection, hydrocephalus, etc. may also have an intrinsic inability to initiate behavior (ie, abulia). The inability to respond to the environment in any fashion should not be misconstrued either as a sensory aphasia or a form of cortical auditory disorder. One should also consider language barriers for nonnative speakers. Because many children with central auditory processing disorder also have attention disorders, it is important to include attentional tests in their evaluation. Children with delayed or disordered overall language skills may present similarly to those with auditory processing disorders, although their comprehension difficulty may not originate from impaired auditory processing. The challenge for the clinician arises from the possible co-occurrence of language disorders and auditory processing disorders in the same patient.

The symptoms of dyslexia and other reading disorders also significantly overlap those of auditory processing disorders. Due to the phonological processing deficits seen across these disorders, differentiating between dyslexia and auditory processing disorders can be difficult (16; 78). Children with dyslexia and reading disorders perform significantly more poorly than controls on tasks of auditory encoding and processing. Both children and adults with these types of developmental learning difficulties can demonstrate auditory processing difficulties (16; 78).

Diagnostic workup

The diagnostic workup for central auditory disorders should include the following and may include testing by an audiologist, speech-language pathologist, and neuropsychologist. The spheres of assessment and tests are representative of those that could be used.

Management

Following a diagnostic workup, therapy should focus on the specific auditory processing deficit. Management should target compensation and restoration for the disorder. Speech-language pathologists most often treat patients with cortical auditory disorders, although audiologists and neuropsychologists may also treat such patients. The optimal length and intensity for therapy vary with syndrome severity and the patient’s response to treatment. Most clinicians will review and revise therapy goals and objectives, as well as session length and frequency, on a continual basis.

For children with cortical auditory processing disorders, special accommodations within the school environment are frequently suggested and may result in improved academic performance.