Auditory function in Pelizaeus-Merzbacher disease.

Pelizaeus-Merzbacher disease (PMD; MIM 312080), an inherited defect of central nervous system myelin formation, affects individuals in many ways, including their hearing and language abilities. The aim of this study was to assess the auditory abilities in 18 patients with PMD by examining the functional processes along the central auditory pathways using auditory brainstem responses (ABR) and cortical auditory evoked potentials (CAEP) in response to speech sounds. The significant ABR anomalies confirm the existence of dyssynchrony previously described at the level of the brainstem in patients with PMD. Despite the significant auditory dyssynchrony observed at the level of the brainstem, CAEPs were present in most patients, albeit somehow abnormal in terms of morphology and latency, resembling a type of auditory neuropathy spectrum disorder.

Central auditory processing disorders in children and adults.

Central auditory processing disorders (CAPD) can affect children and adults of all ages due to a wide variety of causes. CAPD is a neurobiologic deficit in the central auditory nervous system (CANS) that affects those mechanisms that underlie fundamental auditory perception, including localization and lateralization; discrimination of speech and non-speech sounds; auditory pattern recognition; temporal aspects of audition, including integration, resolution, ordering, and masking; and auditory performance with competing and/or degraded acoustic signals (American Speech-Language-Hearing Association, 2005a, b). Although it is recognized that central auditory dysfunction may coexist with other disorders, CAPD is conceptualized as a sensory-based auditory disorder. Administration of behavioral and/or electrophysiologic audiologic tests that have been shown to be sensitive and specific to dysfunction of the CANS is critical for a proper diagnosis of CAPD, in addition to assessments and collaboration with a multidisciplinary team. Intervention recommendations for CAPD diagnosis are based on the demonstrated auditory processing deficits and related listening and related complaints. This chapter provides an overview of current definitions and conceptualizations, methods of diagnosis of, and intervention for, CAPD. The chapter culminates with a case study illustrating pre- and posttreatment behavioral and electrophysiologic diagnostic findings.

Age-related deterioration of the representation of space in human auditory cortex.

One of the principal auditory disabilities associated with older age is difficulty in locating and tracking sources of sound. This study investigated whether these difficulties are associated with deterioration in the representation of space in the auditory cortex. In psychophysical tests, half of a group of older (>60 years) adults displayed spatial acuity similar to that of young adults throughout the frontal horizontal plane. The remaining half had considerably poorer spatial acuity at the more peripheral regions of frontal space. Computational modeling of electroencephalographic responses to abrupt location shifts demonstrated marked differences in the spatial tuning of populations of cortical neurons between the older adults with poor spatial acuity on the one hand, and those with good spatial acuity, as well as young adults, on the other hand. In those with poor spatial acuity, cortical responses contained little information with which to distinguish peripheral locations. We demonstrate a clear link between neural responses and spatial acuity measured behaviorally, and provide evidence for age-related changes in the coding of horizontal space.

Waist circumference is associated with pitch pattern sequence score in older male adults.

OBJECTIVE: While obesity may increase the risk for neurodegenerative diseases such as Alzheimer's disease, the relationship between waist circumference (WC) and central auditory dysfunction is unknown. We aimed to investigate the relationship of WC and pitch pattern sequence (PPS) score in adults. DESIGN: The association of WC with PPS score was analysed. STUDY SAMPLE: Volunteer helpers at a community hospital, 391 adults ≥40 years, with normal or symmetrical sensorineural hearing loss were randomly selected. RESULTS: After adjusting for age, gender, pure-tone average, systemic diseases, and habits, WC was significantly negatively associated with PPS. In a subgroup analysis by gender and age, the PPS score was negatively associated with WC only for males who were older than 55 years old, but not for males who were younger than 55 years old or females in either age group. Meanwhile, central obesity showed positive association with abnormal PPS recognition ability (PPS score < 90%) of borderline significance only for males who were older than 55 years old, but not for males who were younger than 55 years old or females in both age groups. CONCLUSIONS: WC or central obesity is an independent risk factor for poor central auditory function, especially in older male subjects.

Auditory function in children with Charcot-Marie-Tooth disease.

The peripheral manifestations of the inherited neuropathies are increasingly well characterized, but their effects upon cranial nerve function are not well understood. Hearing loss is recognized in a minority of children with this condition, but has not previously been systemically studied. A clear understanding of the prevalence and degree of auditory difficulties in this population is important as hearing impairment can impact upon speech/language development, social interaction ability and educational progress. The aim of this study was to investigate auditory pathway function, speech perception ability and everyday listening and communication in a group of school-aged children with inherited neuropathies. Twenty-six children with Charcot-Marie-Tooth disease confirmed by genetic testing and physical examination participated. Eighteen had demyelinating neuropathies (Charcot-Marie-Tooth type 1) and eight had the axonal form (Charcot-Marie-Tooth type 2). While each subject had normal or near-normal sound detection, individuals in both disease groups showed electrophysiological evidence of auditory neuropathy with delayed or low amplitude auditory brainstem responses. Auditory perception was also affected, with >60% of subjects with Charcot-Marie-Tooth type 1 and >85% of Charcot-Marie-Tooth type 2 suffering impaired processing of auditory temporal (timing) cues and/or abnormal speech understanding in everyday listening conditions.

Central auditory function in early Alzheimer's disease and in mild cognitive impairment.

OBJECTIVE: to investigate auditory function in subjects with early Alzheimer's disease, mild cognitive impairment and with subjective memory complaints, in search of signs of central auditory processing dysfunction even in early stages of cognitive impairment. DESIGN AND SUBJECTS: a consecutive group of men and women, referred to the Memory Clinic at the Karolinska University Hospital, was approached for inclusion in this prospective study. One hundred and thirty-six subjects, mean age 64 years (range 50-78 years), diagnosed with Alzheimer's disease (n = 43), mild cognitive impairment (n = 59) or with subjective memory complaints (n = 34), were included. METHODS: auditory function was assessed with pure tone audiometry, speech perception in quiet and in background noise and dichotic digits tests with two or three digits. RESULTS: pure tone audiometry and speech perception scores in quiet and in background noise were normal for age and without between-group differences. Dichotic digits tests showed strongly significant differences between the three groups, where the Alzheimer's disease group performed significantly poorer than the other two groups, with the mild cognitive impairment group in an intermediate position. CONCLUSIONS: our results demonstrate that central auditory processing dysfunction is highly evident in subjects with Alzheimer's disease, and to a considerable extent even in subjects with mild cognitive impairment.

Electrophysiological manifestations in adults with HIV/AIDS submitted and not submitted to antiretroviral therapy.

BACKGROUND: auditory evoked potentials (AEP) assess the neuroelectric activity on the auditory pathway -from the auditory nerve to the cerebral cortex - in response to an acoustic stimulus or event. Studies have demonstrated electrophysiological abnormalities in individuals with HIV/AIDS. AIM: to characterize the hearing electrophysiological manifestations in adults with HIV/AIDS by comparing the results obtained in the group exposed to antiretroviral therapy with those obtained in the group not exposed to such treatment. METHOD: electrophysiological evaluation of hearing (Auditory Brainstem Response - ABR, Auditory Middle Latency Response - AMLR and P300) was conducted in 56 individuals with HIV/AIDS: 24 participants composed group I (not exposed to antiretroviral treatment) and 32 participants composed group II (exposed to treatment). RESULTS: alterations in every AEP were observed in individuals with HIV/ AIDS, especially in the ABR. Indeed, the group exposed to antiretroviral treatment presented more alterations. CONCLUSION: individuals with HIV/AIDS may present alterations on the central and peripheral auditory nervous system. The group exposed to antiretroviral therapy presents more alterations on the brainstem auditory pathway.

Manifestações eletrofisiológicas em adultos com HIV/AIDS submetidos e não-submetidos à terapia anti-retroviral / Electrophysiological manifestations in adults with HIV/AIDS submitted and not submitted to antiretroviral therapy

BACKGROUND: auditory evoked potentials (AEP) assess the neuroelectric activity on the auditory pathway -from the auditory nerve to the cerebral cortex - in response to an acoustic stimulus or event. Studies have demonstrated electrophysiological abnormalities in individuals with HIV/AIDS. AIM: to characterize the hearing electrophysiological manifestations in adults with HIV/AIDS by comparing the results obtained in the group exposed to antiretroviral therapy with those obtained in the group not exposed to such treatment. METHOD: electrophysiological evaluation of hearing (Auditory Brainstem Response - ABR, Auditory Middle Latency Reponse - AMLR and P300) was conducted in 56 individuals with HIV/AIDS: 24 participants composed group I (not exposed to antiretroviral treatment) and 32 participants composed group II (exposed to treatment). RESULTS: alterations in every AEP were observed in individuals with HIV/ AIDS, especially in the ABR. Indeed, the group exposed to antiretroviral treatment presented more alterations. CONCLUSION: individuals with HIV/AIDS may present alterations on the central and peripheral auditory nervous system. The group exposed to antiretroviral therapy presents more alterations on the brainstem auditory pathway.

TEMA: os potenciais evocados auditivos (PEA) avaliam a atividade neuroelétrica na via auditiva, desde o nervo auditivo até o córtex cerebral, em resposta a um estímulo ou evento acústico. Estudos demonstram anormalidades eletrofisiológicas em indivíduos com HIV/AIDS. OBJETIVO: caracterizar as manifestações eletrofisiológicas da audição em adultos com HIV/AIDS, comparando os resultados obtidos no grupo exposto a tratamento anti-retroviral com os obtidos no grupo não exposto a tratamento. MÉTODO: realizada avaliação eletrofisiológica da audição (PEATE, PEAML e P300) em 56 indivíduos portadores do HIV/AIDS, sendo 24 do Grupo I (não expostos ao tratamento anti-retroviral) e 32 do Grupo II (expostos ao tratamento). RESULTADOS: foram encontradas alterações em todos os PEA nos indivíduos com HIV/AIDS, principalmente no PEATE; sendo que neste, o grupo exposto ao tratamento antiretroviral apresentou mais alterações. CONCLUSÃO: indivíduos com HIV/AIDS podem apresentar alterações no sistema nervoso auditivo periférico e central, sendo que o grupo exposto a tratamento anti-retroviral apresenta mais alterações na via auditiva em tronco encefálico.

Pitch discrimination in cerebellar patients: evidence for a sensory deficit.

In the last two decades, a growing body of research showing cerebellar involvement in an increasing number of nonmotor tasks and systems has prompted an expansion of speculations concerning the function of the cerebellum. Here, we tested the predictions of a hypothesis positing cerebellar involvement in sensory data acquisition. Specifically, we examined the effect of global cerebellar degeneration on primary auditory sensory function by means of a pitch discrimination task. The just noticeable difference in pitch between two tones was measured in 15 healthy controls and in 15 high functioning patients afflicted with varying degrees of global cerebellar degeneration caused by hereditary, idiopathic, paraneoplastic, or postinfectious pancerebellitis. Participants also performed an auditory detection task assessing sustained attention, a test of verbal auditory working memory, and an audiometric test. Patient pitch discrimination thresholds were on average five and a half times those of controls and were proportional to the degree of cerebellar ataxia assessed independently. Patients and controls showed normal hearing thresholds and similar performance in control tasks in sustained attention and verbal auditory working memory. These results suggest there is an effect of cerebellar degeneration on primary auditory function. The findings are consistent with other recent demonstrations of cerebellar-related sensory impairments, and with robust cerebellar auditorily evoked activity, confirmed by quantitative meta-analysis, across a range of functional neuroimaging studies dissociated from attention, motor, affective, and cognitive variables. The data are interpreted in the context of a sensory hypothesis of cerebellar function.

Cognitive deficits associated with acquired amusia after stroke: a neuropsychological follow-up study.

Recent evidence on amusia suggests that our ability to perceive music might be based on the same neural resources that underlie other higher cognitive functions, such as speech perception and spatial processing. We studied the neural correlates of acquired amusia by performing extensive neuropsychological assessments on 53 stroke patients with a left or right hemisphere middle cerebral artery (MCA) stroke 1 week, 3 months, and 6 months after the stroke. In addition, structural magnetic resonance imaging (MRI) was performed on all patients 1 week and 6 months post-stroke. Based on their performance on a shortened version of the Montreal Battery of Evaluation of Amusia (MBEA), the patients were classified as amusic (n=32) or non-amusic (n=21). MRI results showed that the incidence of auditory cortex and frontal lobe damage was significantly higher in the amusic group than in the non-amusic group, but the two groups did not differ in respect to lesion laterality. Cognitively, amusia was associated with general deficits in working memory and learning, semantic fluency, executive functioning, and visuospatial cognition, as well as hemisphere-specific deficits in verbal comprehension, mental flexibility, and visuospatial attention (unilateral spatial neglect). Moreover, the recovery of music perception ability was related to the recovery of verbal learning, visuospatial perception and attention, and focused attention, especially in amusic patients. Together, these results suggest the ability to perceive music is closely linked to other higher cognitive functions.

Brainstem response amplitudes in neonatal chronic lung disease and differences from perinatal asphyxia.

OBJECTIVE: To examine neuronal function of the auditory brainstem in neonatal chronic lung disease (CLD) and detect any differences from perinatal asphyxia. METHODS: Infants with CLD and infants after perinatal asphyxia were studied at term (37-42 weeks postconceptional age). Wave amplitudes of maximum length sequence brainstem auditory evoked response (MLS BAER) were recorded and compared between CLD and asphyxia. RESULTS: The amplitudes of waves I, III and V, and V/I and V/III amplitude ratios in CLD infants did not differ from those in normal term controls at all click rates 21-910/s. The slopes of amplitude-rate functions were all similar to those in the controls. In infants after asphyxia, however, wave III and V amplitudes were smaller than those in both the controls and CLD infants, particularly at high-rate stimulation. The intercepts of amplitude-rate functions for waves III and V were smaller than in both the controls and CLD infants, although there were no significant differences in the slopes of these functions. CONCLUSIONS: No abnormalities in MLS BAER amplitudes were found in CLD infants but the amplitudes were significantly reduced in asphyxiated infants, resulting in major differences between CLD and perinatal asphyxia. SIGNIFICANCE: There is no major neuronal impairment in the auditory brainstem in CLD but there is in perinatal asphyxia. This difference may be, at least partly, related to the difference in the nature of hypoxia associated with the two problems; the hypoxia is chronic and sublethal in CLD, but is often acute, lethal and associated with ischaemia in perinatal asphyxia.

Auditory neuropathy in streptozotocin-induced diabetic mouse.

An investigation of the mechanism of damage to the peripheral nervous system and central nervous system in diabetes mellitus (DM) is highly important in current neurological research. Auditory neuropathy is a hearing disorder in which the auditory brainstem evoked potential is absent or severely abnormal. This study investigated auditory neuropathy caused by streptozotocin in mouse model. In order to assess diabetic auditory neuropathy, we evaluated auditory brainstem response (ABR) for the evaluation of sensorineural function in peripheral auditory nerve. Auditory middle latency response (AMLR) was employed to assess the middle response in the midbrain. STZ groups significantly increased the absolute latencies IV and the interpeak latencies I-III and I-IV of ABR compared with STZ 0 group. Pa latency of AMLR also significantly increased in proportion to STZ dosage. Taken together, our results demonstrate that STZ-induced DM may impair the auditory pathway from peripheral auditory nerve to midbrain in the mouse model. We suggest that the STZ-induced diabetic mouse model may be useful for the evaluation of auditory pathway impairment by using ABR and AMLR tests.

Changes in brainstem auditory evoked response latencies in term neonates with hyperbilirubinemia.

Ninety term neonates with hyperbilirubinemia were studied with brainstem auditory evoked response to clarify the ototoxic effect of hyperbilirubinemia, and detect any differences in ototoxic effect between different levels of total serum bilirubin. The response threshold in these neonates was significantly elevated (P < 0.001). All wave latencies and I-V interval increased significantly (P < 0.05-0.0001), and correlated weakly with total serum bilirubin (r = 0.24-0.28, all P < 0.05). Twenty-five neonates (28%) had abnormal responses, including 14 (16%) with elevated thresholds or increased wave I latency, suggesting peripheral auditory impairment, and 16 (18%) with increased I-V interval, suggesting central auditory impairment. Wave V latency and I-V interval were longer in neonates with total serum bilirubin of <20 mg/dL than in those with bilirubin 11-15 mg/dL (P < 0.05). However, there were no significant differences in response variables between neonates with total serum bilirubin 11-15 mg/dL and those with bilirubin 16-20 mg/dL, and between neonates with bilirubin 16-20 mg/dL and those with bilirubin >20 mg/dL. Thus, although the acute ototoxic effect of hyperbilirubinemia tends to be more significant at a higher rather than lower level of total serum bilirubin, auditory impairment does not increase closely with the increase in bilirubin.

Evidence for a neurophysiologic auditory deficit in children with benign epilepsy with centro-temporal spikes.

Benign focal epilepsy in childhood with centro-temporal spikes (BECTS) is one of the most common forms of epilepsy. Recent studies have questioned the benign nature of BECTS, as they have revealed neuropsychological deficits in many domains including language. The aim of this study was to investigate whether the epileptic discharges during the night have long-term effects on auditory processing, as reflected on electrophysiological measures, during the day, which could underline the language deficits. In order to address these questions we recorded base line electroencephalograms (EEG), sleep EEG and auditory event related potentials in 12 children with BECTS and in age- and gender-matched controls. In the children with BECTS, 5 had unilateral and 3 had bilateral spikes. In the 5 patients with unilateral spikes present during sleep, an asymmetry of the auditory event related component (P85-120) was observed contralateral to the side of epileptiform activity compared to the normal symmetrical vertex distribution that was noted in all controls and in 3 the children with bilateral spikes. In all patients the peak to peak amplitude of this event related potential component was statistically greater compared to the controls. Analysis of subtraction waveforms (deviant - standard) revealed no evidence of a mismatch negativity component in any of the children with BECTS. We propose that the abnormality of P85-120 and the absence of mismatch negativity during wake recordings in this group may arise in response to the long-term effects of spikes occurring during sleep, resulting in disruption of the evolution and maintenance of echoic memory traces. These results may indicate that patients with BECTS have abnormal processing of auditory information at a sensory level ipsilateral to the hemisphere evoking spikes during sleep.

Delayed automatic detection of change in speech sounds in adults with autism: a magnetoencephalographic study.

OBJECTIVE: Autism is a form of pervasive developmental disorder in which dysfunction in interpersonal relationships and communication is fundamental. This study evaluated neurophysiological abnormalities at the basic level of language processing, i.e. automatic change detection of speech and non-speech sounds, using magnetoencephalographic recording of mismatch response elicited by change in vowels and tones. METHODS: The auditory magnetic mismatch field (MMF) was evaluated in 9 adults with autism and 19 control subjects using whole-head magnetoencephalography. The MMF in response to the duration change of a pure tone or vowel /a/ and that in response to across-phoneme change between vowels /a/ and /o/, were recorded. RESULTS: The groups were not significantly different in MMF power under any conditions. However, the autism group showed a left-biased latency prolongation of the MMF particularly under the across-phoneme change condition, and this latency delay was significantly associated with greater symptom severity. CONCLUSIONS: These results suggest that adults with autism are associated with delayed processing for automatic change detection of speech sounds. These electrophysiological abnormalities at the earliest level of information processing may contribute to the basis for language deficits observed in autism. SIGNIFICANCE: These results provide the first evidence for delayed latency of phonetic MMF in adults with autism.

Middle-latency auditory-evoked magnetic fields in patients with auditory cortex lesions.

OBJECTIVE: To demonstrate the influence of auditory cortex lesions on auditory middle-latency responses (AMLRs) and middle-latency auditory-evoked magnetic fields (MLAEFs) in humans. MATERIAL AND METHODS: A total of 15 normal subjects, 9 patients with left auditory cortex lesions and 1 patient with a right auditory cortex lesion were studied. MLAEFs were recorded from each hemisphere of the brain in a magnetically shielded room using a 37-channel SQUID gradiometer. Simultaneously, AMLRs were recorded from the scalp at the vertex, C3 and C4. Tone bursts were used as auditory stimuli. RESULTS: Pam responses of the MLAEF, which are typically evoked in the latency range of the Pa of the AMLR, and are localized at the auditory cortex as dipoles, were impaired or abolished over the left auditory cortex lesion in the patients with left-hemisphere lesions, but the Pa of the AMLR persisted. CONCLUSION: The main generator of the Pam in MLAEF was demonstrated to be the auditory cortex. The results also show that the Pa of the AMLR is evoked only partly from the auditory cortex.

Deficits of musical timbre perception after unilateral temporal-lobe lesion revealed with multidimensional scaling.

Thirty patients with unilateral temporal lobe excisions and 15 normal control subjects were tested in a task involving judgements of timbre dissimilarity in single tone and melodic conditions. Perceptual correlates of spectral and temporal parameters resulting from changing the number of harmonics and rise-time duration, respectively, were investigated by using a multidimensional scaling technique. The results of subjects with left temporal lobe lesion suggest that they were able to use the spectral and temporal envelopes of tones independently in making perceptual judgements of single tones. In the melodic condition, their results were significantly different from those of normal control subjects, suggesting that left temporal lesions do affect subtle aspects of timbre perception, despite these patients' preserved ability to make discrimination judgements using traditional paradigms. The major finding of this study concerns perceptual ratings obtained by subjects with right temporal lobe lesion, which revealed a disturbed perceptual space in both conditions. The most distorted results were obtained with single tones, in which the temporal parameter was less prominent. Tones were grouped according to their spectral content, but the results did not reflect a coherent underlying perceptual dimension. In general, the data from both patient groups (left lesions and right lesions) showed that the extraction of temporal cues was easier in the melodic than in the single tone condition, suggesting that the different durations and frequencies heard in a musical phrase enhance the importance of certain physical parameters. The findings of the present study replicate and extend previous results showing that timbre perception depends mainly upon the integrity of right neocortical structures, although a contribution of left temporal regions is also apparent. These data also demonstrate that multidimensional techniques are sensitive to more subtle perceptual disturbances that may not be revealed by discrimination paradigms.

Auditory brainstem responses elicited by 1000-Hz tone bursts in patients with sensorineural hearing loss.

Auditory brainstem responses were measured in response to 1000-Hz tone bursts from 115 patients with sensorineural hearing loss, presumably of cochlear origin. Mean wave V latencies and variability were comparable to those observed in normal hearing subjects for similar stimuli. The range of interaural differences in wave V latencies for 1000-Hz tone bursts were slightly greater than those observed for clicks, which may not be surprising, given the greater variability in wave V latencies for tonal stimulation, even in normal-hearing subjects. These differences, however, were not affected either by the magnitude or symmetry of hearing loss for frequencies at and above 1000 Hz. These data suggest that tone burst ABRs might be useful in otoneurologic evaluations, especially for patients with asymmetric hearing loss.