Genetic Variations and Associated Electrophysiological and Behavioral Traits in Children with Childhood Apraxia of Speech

abstract: Childhood Apraxia of Speech (CAS) is a severe motor speech disorder that is difficult to diagnose as there is currently no gold-standard measurement to differentiate between CAS and other speech disorders. In the present study, we investigate underlying biomarkers associated with CAS in addition to enhanced phenotyping through behavioral testing. Cortical electrophysiological measures were utilized to investigate differences in neural activation in response to native and non-native vowel contrasts between children with CAS and typically developing peers. Genetic analysis included full exome sequencing of a child with CAS and his unaffected parents in order to uncover underlying genetic variation that may be causal to the child’s severely impaired speech and language. Enhanced phenotyping was completed through extensive behavioral testing, including speech, language, reading, spelling, phonological awareness, gross/fine motor, and oral and hand motor tasks. Results from cortical electrophysiological measures are consistent with previous evidence of a heightened neural response to non-native sounds in CAS, potentially indicating over specified phonological representations in this population. Results of exome sequencing suggest multiple genetic variations contributing to the severely affected phenotype in the child and provide further evidence of heterogeneous genomic pathways associated with CAS. Finally, results of behavioral testing demonstrate significant impairments evident across tasks in CAS, suggesting underlying sequential processing deficits in multiple domains. Overall, these results have the potential to delineate functional pathways from genetic variations to the brain to observable behavioral phenotypes and motivate the development of preventative and targeted treatment approaches.Dissertation/ThesisDoctoral Dissertation Speech and Hearing Science 201

Determination and evaluation of clinically efficient stopping criteria for the multiple auditory steady-state response technique

Background: Although the auditory steady-state response (ASSR) technique utilizes objective statistical detection algorithms to estimate behavioural hearing thresholds, the audiologist still has to decide when to terminate ASSR recordings introducing once more a certain degree of subjectivity. Aims: The present study aimed at establishing clinically efficient stopping criteria for a multiple 80-Hz ASSR system. Methods: In Experiment 1, data of 31 normal hearing subjects were analyzed off-line to propose stopping rules. Consequently, ASSR recordings will be stopped when (1) all 8 responses reach significance and significance can be maintained for 8 consecutive sweeps; (2) the mean noise levels were ≤ 4 nV (if at this “≤ 4-nV” criterion, p-values were between 0.05 and 0.1, measurements were extended only once by 8 sweeps); and (3) a maximum amount of 48 sweeps was attained. In Experiment 2, these stopping criteria were applied on 10 normal hearing and 10 hearing-impaired adults to asses the efficiency. Results: The application of these stopping rules resulted in ASSR threshold values that were comparable to other multiple-ASSR research with normal hearing and hearing-impaired adults. Furthermore, in 80% of the cases, ASSR thresholds could be obtained within a time-frame of 1 hour. Investigating the significant response-amplitudes of the hearing-impaired adults through cumulative curves indicated that probably a higher noise-stop criterion than “≤ 4 nV” can be used. Conclusions: The proposed stopping rules can be used in adults to determine accurate ASSR thresholds within an acceptable time-frame of about 1 hour. However, additional research with infants and adults with varying degrees and configurations of hearing loss is needed to optimize these criteria

Clinical and audiological outcomes of cochlear implantation : A retrospective study of 55 cases

CI are auditory prostheses designed to link an internal device, which is interfaced with the cochlear nerve, to an external device, which uses a specific speech coding strategy to translate acoustic information into electric stimulation. This allows the transmission of acoustic information to the central auditory pathway. A sophisticated multidisciplinary team approach that addresses the varied needs of the deaf recipients is required. The essential works of the aural/oral (re)habilitation program include listening skill development, speech therapy, speech-reading training and language instruction. This study aims to evaluate the etiology and epidemiology of hearing loss in 55 CI cases. Surgical techniques and audiometric and radiological results were assessed preoperatively and postoperatively with a minimum follow up time of six months. The acquired and congenital hearing loss incidences were almost equal in our group of patients. All arrays of CI postoperatively were in the first turn of the cochlear basis, and the dominant used device was Cochlear Nucleus (Australia). CI is considered as an oto-surgical procedure with a low risk and low complication rate compared with other surgical techniques. Moreover, the audiological protocol was performed like an international classification to achieve the exact indication of CI, and there is a considerable improvement in the average of PTA threshold and the average of SDT records post-CI. Similar results of hearing improvement were published by other authors. Finally, it is important to note that the present study is retrospective. Further prospective trials are recommended to investigate the SDT two years after obtaining a phonetic rehabilitation, especially to pre-lingually deaf children and adult groups

Theories of developmental dyslexia: Insights from a multiple case study of dyslexic adults

A multiple case study was conducted in order to assess three leading theories of developmental dyslexia: the phonological, the magnocellular (auditory and visual) and the cerebellar theories. Sixteen dyslexic and 16 control university students were administered a full battery of psychometric, phonological, auditory, visual and cerebellar tests. Individual data reveal that all 16 dyslexics suffer from a phonological deficit, 10 from an auditory deficit, 4 from a motor deficit, and 2 from a visual magnocellular deficit. Results suggest that a phonological deficit can appear in the absence of any other sensory or motor disorder, and is sufficient to cause a literacy impairment, as demonstrated by 5 of the dyslexics. Auditory disorders, when present, aggravate the phonological deficit, hence the literacy impairment. However, auditory deficits cannot be characterised simply as rapid auditory processing problems, as would be predicted by the magnocellular theory. Nor are they restricted to speech. Contrary to the cerebellar theory, we find little support for the notion that motor impairments, when found, have a cerebellar origin, or reflect an automaticity deficit. Overall, the present data support the phonological theory of dyslexia, while acknowledging the presence of additional sensory and motor disorders in certain individuals

Operant measurement of auditory threshold in prelingually deaf users of cochlear implants: II

Two experiments evaluated an operant procedure for establishing stimulus control using auditory and electrical stimuli as a baseline for measuring the electrical current threshold of electrodes implanted in the cochlea. Twenty-one prelingually deaf children, users of cochlear implants, learned a Go/No Go auditory discrimination task (i.e., pressing a button in the presence of the stimulus but not in its absence). When the simple discrimination baseline became stable, the electrical current was manipulated in descending and ascending series according to an adapted staircase method. Thresholds were determined for three electrodes, one in each location in the cochlea (basal, medial, and apical). Stimulus control was maintained within a certain range of decreasing electrical current but was eventually disrupted. Increasing the current recovered stimulus control, thus allowing the determination of a range of electrical currents that could be defined as the threshold. The present study demonstrated the feasibility of the operant procedure combined with a psychophysical method for threshold assessment, thus contributing to the routine fitting and maintenance of cochlear implants within the limitations of a hospital setting.FAPESPConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CNP