Effects of adult familiarity on social behaviours in Angelman syndrome.

BACKGROUND: Individuals with Angelman syndrome appear strongly motivated by social contact, but there have been few studies that have examined the relationship between sociability and familiarity. In this study we compared social behaviour in Angelman syndrome when in contact with mothers and strangers. METHODS: We systematically manipulated adult familiarity, eye contact and speech to examine the effect on social approach behaviours in children with Angelman syndrome. Eleven children (deletion 15q11-13) participated and were observed during interactions with their mother and an unfamiliar adult, while adult eye contact and talking were manipulated. Laughing and smiling, looking and social approach were observed. RESULTS: There was no effect of familiarity on laughing and smiling or eye contact. Participants showed more social approach towards their mother than the unfamiliar adult but only when their mother was looking at them. CONCLUSIONS: In Angelman syndrome, looking at adults, laughing and smiling appear to be unaffected by the familiarity of the adult. However, approach behaviours are more common with mothers than strangers. The function of the approach behaviours might be to increase investment from the primary caregiver.

Acoustic analysis of the voice in pediatric cochlear implant recipients: a longitudinal study.

OBJECTIVE: To characterize inherent acoustic abnormalities of the deaf pediatric voice and the effect of artificially restoring auditory feedback with cochlear implantation. DESIGN: Inception cohort. SETTING: Academic referral center. PATIENTS: Twenty-one children with severe to profound hearing loss (15 prelingually deaf, 6 postlingually deaf) accepted into the cochlear implant program were followed for up to 6 months. Patients unable to perform the vocal exercises were excluded. INTERVENTIONS: Objective voice analysis was performed using the Computerized Speech Laboratory (Kay Elemetrics) prior to cochlear implantation, at the time of implant activation and at 2 and 6 months postactivation. Assessments were based on sustained phonations and dynamic ranges. MAIN OUTCOME MEASURE: Fundamental frequency, long-term control of fundamental frequency (vF0) and long-term control of amplitude (vAM) were derived from sustained phonations. The dynamic frequency range was derived from scale exercises. Formant frequencies (F1, F2, F3) were determined using linear predictive coding. RESULTS: Fundamental frequency was not altered by implant activation or experience (P = 0.342). With profoundly deaf subject, the most prevalent acoustic abnormality was a poor long-term control of frequency (vF0, 2.81%) and long-term control of amplitude (vAm, 23.58%). Implant activation and experience had no effect on the long-term control of frequency (P = 0.106) but normalized the long-term control of amplitude (P = 0.007). The mean frequency range increased from 311.9 Hz preimplantation to 483.5 Hz postimplantation (P = 0.08). The F1/F2 ratio remained stable (P = 0.476). CONCLUSION: In children, severe to profound deafness results in poor long-term control of frequency and amplitude. Cochlear implantation restores control of amplitude only and implies the need for additional rehabilitative strategies for restoration of control of frequency.

An analogue assessment of repetitive hand behaviours in girls and young women with Rett syndrome.

BACKGROUND: Rett syndrome is a neurodevelopmental disorder that almost exclusively affects females. In addition to neurodevelopmental regression and loss of hand skills, apraxia, deceleration of head growth, and increasing spasticity and scoliosis, a number of behavioural features are also seen, including stereotypic hand movements, hyperventilation and breath holding. The aim of the study was to investigate the extent to which analogue environmental conditions affected the frequency of repetitive hand behaviour in eight girls and young women with Rett syndrome. METHOD: The frequency of repetitive hand movements was observed every 10 s for four 4-min sessions under the following conditions: Continuous Adult Attention, Adult Demands, Stimulation and No Stimulation. RESULTS: The frequency of repetitive hand movements was high -- they occurred in above 60% of all intervals in all conditions for all participants and at nearly 100% for some participants in some conditions. For one participant the frequency of repetitive hand movements was somewhat reduced in the Stimulation condition; for another it was relatively increased in the No Stimulation condition. CONCLUSIONS: Overall, environmental manipulations had relatively limited effects on repetitive hand behaviours. Repetitive hand behaviour in Rett syndrome may be maintained by automatic reinforcement or neurochemical processes and may not be primarily influenced by contingent reinforcement.

Middle ear instillation of gentamicin and streptomycin in chinchillas: electrophysiological appraisal of selective ototoxicity.

The purpose of this study was to investigate selective vestibular ototoxicity of gentamicin and streptomycin in the chinchilla model. In total, 10 chinchillas underwent left middle ear instillation of one of three agents: gentamicin, streptomycin and saline. Electrophysiological data (otoacoustic emissions (OAEs), auditory brainstem evoked response (ABRs), and ice-water electronystagmography were recorded before and after instillation. Animals were sacrificed for temporal bone studies using scanning electron microscopy. Morphological changes in the cochlear and vestibular neuroepithelia were correlated with electrophysiological changes. Widespread ipsilateral cochlear and vestibular neuroepithelial injuries were observed and correlated with loss of OAEs, ABRs and ice-water caloric response. This study provides no evidence of selective vestibular ototoxicity of gentamicin or streptomycin. Morphological damage correlates with, but precedes loss of electrophysiological parameters. Chinchillas, like other small mammals, may not be an ideal model for the study of human ototoxicity.

Behaviour problems in adult women with Rett syndrome.

BACKGROUND: Despite considerable interest in the genetic, physical and neurological aspects of Rett syndrome (RS), there have been few studies of associated behavioural and emotional features. Furthermore, few case studies or surveys have included adult women with RS. The main aim of the present study was to compare behaviour problems in a sample of women with RS against data from normative samples. METHODS: The primary carers of 50 women with RS completed the community version of the Aberrant Behavior Checklist. RESULTS: Women with RS were rated as having lower levels of irritability, hyperactivity and inappropriate speech behaviours than normative samples of adults with intellectual disability. CONCLUSIONS: A number of factors may affect the presentation of behaviour problems in women with RS (e.g. cognitive impairments or physical disabilities). Therefore, more research is needed in order to generate information about the behavioural phenotype of RS. The implications of the present data for future research are also discussed.

Contralateral suppression of DPOAE measured in real time.

The aim of this study was to measure contralateral suppression of distortion product otoacoustic emissions (DPOAE) in real time. A total of 10 human subjects were studied with a novel device to record DPOAE without signal time averaging, using digital narrow band pass filtering. Real time DPOAE levels were recorded at 2f1-f2 using primary tone settings of f2/f1 = 1.22 and L1 = 70 dB SPL, L2 = 65 dB SPL, at five values of f2 between 2.2 and 7.7 kHz. An acoustic stimulus was applied intermittently to the contralateral ear to cause DPOAE suppression. Characteristic features of contralateral suppression were identified and distinguished from small spontaneous variations in the real time DPOAE signal. Magnitude of suppression increased with contralateral stimulus intensity. Onset latency of suppression was around 43 ms (31-95 ms). Potential clinical applications are discussed in the light of these findings, including a role in improving the specificity of neonatal hearing screening.

Arterial blood supply to the auditory cortex of the chinchilla.

Utilizing optical imaging we identified and named the arteries that supply the primary auditory cortex in the chinchilla (Chinchilla laniger). The primary auditory cortex is located 2-3 mm caudal to the medial cerebral artery and is supplied by it. Using corrosion casts and scanning electron microscopy we visualized the capillary networks in the auditory cortex and found regional variations in the densities of the capillary bed. We hypothesize that the uneven capillary densities observed in the auditory cortex correspond to neurologically more active areas.

The inner ear of dogs with X-linked nephritis provides clues to the pathogenesis of hearing loss in X-linked Alport syndrome.

Alport syndrome is an inherited disorder of type IV collagen with progressive nephropathy, ocular abnormalities, and high-tone sensorineural deafness. In X-linked Alport syndrome, mutations in the COL4A5 gene encoding the alpha5 chain of type IV collagen lead to loss of the alpha3/alpha4/alpha5 network and increased susceptibility of the glomerular basement membrane to long-term damage. The molecular defects that underlie the otopathology in this disease remain poorly understood. We used a canine model of X-linked Alport syndrome to determine the expression of type IV collagen alpha-chains in the inner ear. By 1 month in normal adult dogs, the alpha3, alpha4, and alpha5 chains were co-expressed in a thin continuous line extending along the basilar membrane and the internal and external sulci, with the strongest expression along the lateral aspect of the spiral ligament in the basal turn of the cochlea. Affected dogs showed complete absence of the alpha3/alpha4/alpha5 network. The lateral aspect of the spiral ligament is populated by tension fibroblasts that express alpha-smooth muscle actin and nonmuscle myosin and are postulated to generate radial tension on the basilar membrane via the extracellular matrix for reception of high frequency sound. We propose that in Alport syndrome, the loss of the alpha3/alpha4/alpha5 network eventually weakens the interaction of these cells with their extracellular matrix, resulting in reduced tension on the basilar membrane and the inability to respond to high frequency sounds.

Exploration of psychometric properties of the developmental behavior checklist.

The Developmental Behavior Checklist (DBC; Einfeld & Tonge, 1995) is one of a very small number of psychopathology assessment instruments designed specifically for use with children and adolescents with mental retardation. In the present study, a factor analysis of the DBC was performed using a sample of 531 children and adolescents. This analysis revealed a factor structure sharing a good deal of overlap with the factor analyses of the DBC's developers. Furthermore, the high levels of internal consistency of the DBC subscales were replicated. Further research and development is needed on the DBC and other instruments for children and adolescents with mental retardation.

Assessment of vocabulary development in children after cochlear implantation.

OBJECTIVES: To assess vocabulary development in children following cochlear implantation and to evaluate the effect of age at implantation on performance. DESIGN: Retrospective study (mean follow-up, 3(1/2) years). SETTING: Tertiary center. PATIENTS: Children with prelingual deafness provided with a cochlear implant between 1988 and 1999, who serially performed the Peabody Picture Vocabulary Test-Revised (60 patients) and the Expressive One-Word Picture Vocabulary Test-Revised (52 patients). The children were subgrouped into those receiving implants at younger than 5 years and at 5 years or older. OUTCOME MEASURES: Age-equivalent vocabulary test score and gap index (chronological age minus the age-equivalent score, divided by the chronological age at the time of testing) were calculated. For each test, the following were performed: calculation of rate of change for age-equivalent score; comparison of earliest and latest gap indices means (the cohort and intergroup and intragroup comparison); and multiple regression analysis demonstrating the effect of age at implantation, sex, communication mode, etiology of deafness, and residual hearing on the rate of vocabulary development. RESULTS: Expressive and receptive vocabulary development rates were 0.93 and 0.71 (age-equivalent scores per year), respectively. Subgrouped by age at implantation, the children's rates (for both vocabularies) were not statistically different (Peabody Picture Vocabulary Test-Revised, P =.90; Expressive One-Word Picture Vocabulary Test-Revised, P =.23). The global latest gap indices were significantly less than the earliest (Peabody Picture Vocabulary Test-Revised, P =.048; Expressive One-Word Picture Vocabulary Test-Revised, P<.001), indicating an improvement in age-appropriate vocabulary development over time. The age subgroups demonstrated similar results, except for the younger group's receptive gap index. On multiple regression analysis, the significant predictive variables were residual hearing (Expressive One-Word Picture Vocabulary Test-Revised) and male sex and oral communication mode (Peabody Picture Vocabulary Test-Revised). CONCLUSIONS: Children with cochlear implants developed their vocabularies at rates that were sufficient to prevent an increase in their gap indices as related to ideal scores at testing. A late age at implantation does not singularly preclude beneficial development of vocabulary.

The effects of age of cochlear implantation on speech perception outcomes in prelingually deaf children.

We have made a retrospective analysis on 70 prelingually deaf children (78% congenital; age range 2-15 years) followed for up to 5 years post-implant during which both closed set speech perception tests (TAC, WIPI) and open set tasks (PBK, GASP) were administered. We used a binary partitioning algorithm to optimally divide our dataset on the basis of age at implantation This technique achieves an optimal split when the heterogeneity of the data is most reduced (maximal drop in deviance). For the closed set speech perception tests (TAC and WIPI) partitioning best divided-out data at age 4.4 years. For the open set tests optimal division was at a higher age of implantation (GASP word, 5.6 years; PBK word, 8.4 years). Using these partitioning values, we have found statistically significant differences between rate of improvement of scores in the younger implanted children compared with those implanted later.

Vocabulary acquisition rate after pediatric cochlear implantation and the impact of age at implantation.

OBJECTIVE: studies of early vocabulary development after pediatric cochlear implantation show growth rates that approach normality. Do these growth rates continue to rise over time and, therefore, allow a 'catch up' with ideal scores for age, or do they decline after an initial peak. Could age at implantation be a decisive factor in that process? DESIGN: retrospective study (mean follow-up 4 years). PATIENTS: pre-lingually deaf children implanted between 1988 and1999, who serially performed Peabody Picture Vocabulary Test-Revised (PPVT), (37 patients) and Expressive One-word Picture Vocabulary Test-Revised (EOWPVT), (35 patients). OUTCOME MEASURES: the mean rates of age equivalent scores were determined for the whole follow-up period and analyzed further for two post-implant periods (the two halves of follow-up duration of individual patients). After sub-grouping by age at implantation (younger or older than 5 years old), the same analysis was executed for each subgroup. RESULTS: the mean EOWPVT rate of the earlier period was higher than that of the later period (1.33 vs. 0.67, P<0.01) and the mean PPVT rate of the earlier period was higher than that of the later period (0.72 vs. 0.5). The latter difference was not statistically significant (P>0.05). Within subgroups by age at implantation, the PPVT mean rates were stable for younger implanted patients (0.56 for both periods) and dropped for the older implanted sub-group (0.87-0.43, P>0.05). The EOWPVT mean rates declined significantly for the older patients group (1.72-0.55, P<0.01) but insignificantly for the younger patients (0.99-0.77, P>0.05). CONCLUSIONS: vocabulary acquisition rates decline in the post-implantation period. This is more pronounced with older implanted children and the EOWPVT rates. This information on the time course development of vocabulary after implantation would be valuable in counseling and planning habilitation in addition to candidate selection.

Behavioural and emotional features in Rett syndrome.

PURPOSE/METHOD: There is increasing agreement that many genetic disorders have characteristic behavioural phenotypes; that is genetic anomalies have specific effects on behaviour. In this paper the existing literature is reviewed with an aim to identify behavioural and emotional features that are candidates for Rett syndrome (RS) specific behaviours. RESULT/CONCLUSION: A number of behavioural and emotional features have been reported to be common in individuals with RS. These behaviours may constitute an RS-specific profile of behaviour or behavioural phenotype. Alternatively, these behaviours may simply reflect the multiple disabilities found in individuals with severe or profound cognitive impairment. The diagnostic criteria for Rett syndrome include a number of the behavioural features, such as hand stereotypies and breathing difficulties, although other behavioural features are not included.

Differential vulnerability of inner and outer hair cell systems to chronic mild hypoxia and glutamate ototoxicity: insights into the cause of auditory neuropathy.

OBJECTIVE: To describe the effects of long-term mild hypoxia and of glutamate poisoning on the functional properties of the cochlea. METHODS: Outer hair cell activity was monitored using otoacoustic emissions and cochlear microphonics, and inner hair cell/cochlear afferent function was measured using neural responses (cochlear action potentials or auditory brainstem responses [ABRs]). RESULTS: In contrast to the effects of acute anoxia, in which all aspects of cochlear function are simultaneously lost, mild, long-term hypoxia results in a clear differential effect on outer versus inner hair cell systems. During a 2-hour period of mild hypoxia, ABR amplitude and threshold deteriorate significantly, whereas outer hair cell function, as reflected by otoacoustic emissions, shows little or no change. A similar dissociation between inner and outer hair cell function is observed during instillation of glutamate (1-10 mM), where the cochlear microphonic and the otoacoustic emissions are unchanged, whereas cochlear action potential amplitudes are reduced. CONCLUSION: These studies demonstrate a difference in vulnerability of inner and outer hair cell systems. The inner hair cell/cochlear afferent system is vulnerable to long-term, mild hypoxia; this may be an etiologic factor in hearing loss of cochlear origin, particularly in high-risk birth infants with auditory neuropathy.

Tonotopic mapping in auditory cortex of the adult chinchilla with amikacin-induced cochlear lesions.

We have found a reorganization of tonotopic maps (based on neuron response thresholds) in primary auditory cortex of the adult chinchilla after amikacin-induced basal cochlear lesions. We find an over-representation of a frequency that corresponds to the border area of the cochlear lesion. The reorganization observed is similar in extent to that previously seen in a developmental model. The properties of neurons within the over-represented area were investigated in order to determine whether their responses originated from a common input (an indication of true plasticity) or represented only the result of truncating the activity of the sensory epithelium ("pseudo-plasticity"). Some aspects of our data fit with a true plasticity model and indicate the potential for the deafferented cortex of the mature cortex to regain connections with the surviving sensory epithelium.

Three distinct auditory areas of cortex (AI, AII, and AAF) defined by optical imaging of intrinsic signals.

Using pure-tone sound stimulation, three separate auditory areas are revealed by optical imaging of intrinsic signals in the temporal cortex of the chinchilla (Chinchilla laniger). These areas correlate with primary auditory cortex (AI) and two secondary areas, AII and the anterior auditory field (AAF). We have distinguished AI on the basis of concurrent single-unit electrophysiological recording; neurons within the AI intrinsic signal region have short (<15 ms) onset-response latencies compared with neurons recorded in AII and the AAF. Within AI, AII, and AAF we have been able to define cochleotopic or tonotopic organization from the differences in intrinsic signal areas evoked by pure tones at octave-spaced frequencies from 500 Hz to 16 kHz. The maps in AI and AII are arranged orthogonal to each other.

Local haemodynamic changes associated with neural activity in auditory cortex.

We used an optical technique to study haemodynamic changes associated with acoustically driven activity in auditory cortex of the chinchilla. Such changes are first detectable c. 0.5 s after stimulation, peak at 2-3 s, and decay within a further 3-6 s. This intrinsic signal imaging reveals activity in separate cortical areas, including primary auditory cortex (AI), secondary auditory cortex (AII) and an anterior auditory field (AAF). We have measured the timing of haemodynamics associated with each area, and find that AI has a different time course from AII and AAF; its haemodynamic change recovers more rapidly. We also show that within AI and AII, place specific activity related to acoustic stimulus frequency can be resolved by this optical imaging method. Our results show the close association between blood flow change and the local metabolic demands of neural activity. The data provide information about the potential of other functional imaging methods (e.g. PET, fMRI) which rely on activity related haemodynamic events.

Middle ear instillation of gentamicin and streptomycin in chinchillas: morphologic appraisal of selective ototoxicity.

OBJECTIVE: To determine selective cochlear and vestibular ototoxicity of two aminoglycoside antibiotics (gentamicin and streptomycin) in the chinchilla model. Middle ear application of these agents mirrors the clinical practice of chemical vestibular ablation used in Meniere's disease. BACKGROUND: Middle ear instillation of gentamicin or streptomycin has become a popular form of vestibular ablative treatment for disabling Meniere's disease. The vestibular selectivity of these two drugs applied in this fashion has clinical support but is not fully established in humans. Our understanding in this regard has largely been limited to animal models exposed to systemic infusion of aminoglycosides. METHOD: Ten chinchillas underwent left middle ear instillation of one of three agents using variable dosing schedules: gentamicin (n = 6), streptomycin (n = 2), and saline (n = 2) as control. Animals were sacrificed for temporal bone studies using scanning electron microscopy. Morphologic changes in the cochlear and vestibular neuroepithelia were identified. RESULTS: Widespread cochlear and vestibular neuroepithelial injuries were observed with both gentamicin and streptomycin. Contralateral ototoxicity was variable and not related to the total dose of drug delivered. The effect of these two aminoglycosides on the dark cells of the vestibular system appeared negligible. CONCLUSION: We were unable to confirm the selective damage of vestibular end-organ in the chinchilla by either gentamicin or streptomycin, a phenomenon that is generally perceived to occur in humans. Chinchillas, like other small mammals, may not be an ideal model for the study of human ototoxicity.

Increased otoacoustic-emission amplitude secondary to cochlear lesions.

OBJECTIVE: The measurements of transient evoked otoacoustic emissions and distortion-product otoacoustic emissions are being used increasingly, both as an objective hearing test clinically, and as a research tool to investigate the micromechanical aspects of cochlear function. We hypothesized that localized damage in the apical or middle cochlear turns may have an influence on the micromechanics and the function of adjacent, apparently normal cochlea. For that purpose, we used an animal model of localized apical and middle-turn cochlear lesions. METHOD: Extent of damage was assessed by scanning electron microscopy and the function of the damaged cochlea by change in the otoacoustic emission (OAE) levels. RESULTS: We found that localized damage to the apical or middle turn may be accompanied by an increase in OAE measured from adjacent apparently normal cochlea. CONCLUSION: Explanations to this phenomenon are suggested, and possible clinical associations such as to Meniere's disease and to sudden hearing loss are reviewed.

Plasticity of tonotopic maps in auditory midbrain following partial cochlear damage in the developing chinchilla.

There is substantial reorganization of the midbrain (inferior colliculus) tonotopic map following neonatally induced partial cochlear lesions in the chinchilla. The most obvious feature of this remapping is a large "iso-frequency" region in the ventral sector of the central nucleus of inferior colliculus (ICC). Neurons in this region exhibit similar threshold and tuning properties, with a common characteristic frequency which corresponds to the high-frequency audiometric cutoff. This overrepresented frequency range also corresponds to the high-frequency border of the cochlear lesion. Alterations to the tonotopic map corresponding to lower frequencies, in more dorsal regions of ICC, depend on the extent and degree of the cochlear lesion. When there is minimal damage to apical (low-frequency) cochlear areas, the dorsal ICC has relatively normal frequency representations. With more extensive apical cochlear lesions there is a corresponding disruption of ICC tonotopic representation of the low frequencies. We conclude that the tonotopic map within the ICC can become (re)organized postnatally according to the abnormal pattern of neural activity from the auditory periphery. Similar reorganization can be expected to occur in human infants with a partial cochlear hearing loss from birth.