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

Newborns discriminate novel from harmonic sounds: a study using magnetoencephalography

Objective: We investigated whether newborns respond differently to novel and deviant sounds during quiet sleep. Methods: Twelve healthy neonates were presented with a three-stimulus oddball paradigm, consisting of frequent standard (76%), infrequent deviant (12%), and infrequent novel stimuli (12%). The standards and deviants were counterbalanced between the newborns and consisted of 500 and 750 Hz tones with two upper harmonics. The novel stimuli contained animal, human, and mechanical sounds. All stimuli had a duration of 300 ms and the stimulus onset asynchrony was 1 s. Evoked magnetic responses during quiet sleep were recorded and averaged offline. Results: Two deflections peaking at 345 and 615 ms after stimulus onset were observed in the evoked responses of most of the newborns. The first deflection was larger to novel and deviant stimuli than to the standard and, furthermore, larger to novel than to deviant stimuli. The second deflection was larger to novel and deviant stimuli than to standards, but did not differ between the novels and deviants. Conclusions: The two deflections found in the present study reflect different mechanisms of auditory change detection and discriminative processes. Significance: The early brain indicators of novelty detection may be crucial in assessing the normal and abnormal cortical function in newborns. Further, studying evoked magnetic fields to complex auditory stimulation in healthy newborns is needed for studying the newborns at-risk for cognitive or language problems

Music training alters the course of adolescent auditory development

Fundamental changes in brain structure and function during adolescence are well characterized, but the extent to which experience modulates adolescent neurodevelopment are not. Musical experience provides an ideal case for examining this question because the influence of music training begun early in life is well known. We investigated the effects of in-school music training, previously shown to enhance auditory skills, versus another in-school training program that did not focus on development of auditory skills (active control). We tested adolescents on neural responses to sound and language skills before they entered high school (pre-training) and again three years later. Here we show that in-school music training begun in high school prolongs the stability of subcortical sound processing and accelerates maturation of cortical auditory responses. Although phonological processing improved in both the music training and active control groups, the enhancement was greater in adolescents who underwent music training. Thus, music training initiated as late as adolescence can enhance neural processing of sound and confer benefits for language skills. These results establish the potential for experience-driven brain plasticity during adolescence, and demonstrate that in-school programs can engender these changes

Impact of Introducing Cortical Auditory Evoked Potentials (CAEP) into the Newborn Hearing Assessment Pathway

Cortical Auditory Evoked Potentials (CAEPs) are electrophysiological responses in the cortex in response to sounds. In recent years it has become possible to measure CAEPs and the technology is clinically available. The aim of this research was to demonstrate if CAEPs are feasible to use in a clinical setting and to see if the CAEPs were helpful in optimising hearing aid use for infants under 6 months by showing if a child could detect speech tokens when aided. Recording of CAEPs with speech tokens presented in the free field was introduced into the audiology pathway for infants with a PCHI in 2011-2015 at a UK clinical service. Thirty-four children had followed an audiology pathway prior to CAEP introduction and forty-four children followed a pathway after the introduction of CAEP (using unaided and aided responses). Results showed that the median age at hearing aid fitting prior to CAEP introduction was 9.2 months and after the inclusion of CAEPs reduced to 3.9 months. The current study demonstrates that the inclusion of CAEP recording in the pathway facilitated earlier hearing aid fitting for milder-impairments. Two studies were conducted to better understand these findings. The first was a focus group to determine the factors that influenced parents’ acceptance of early aiding or early referral for cochlear implants. Eight sets of parents participated and they discussed all factors that affected their decision making process. The findings showed that hearing the speech tokens and seeing the clear pass/fail response was helpful for parents. The second study evaluated clinicians’ viewpoints. A questionnaire was developed and completed by 49 clinicians around the world (including the UK). Clinicians used the CAEPs to verify or modify hearing aid fittings and to counsel parents, reinforcing the need for hearing aids. The impact of the research has resulted in earlier hearing aid fitting, cochlear implant referrals and improved hearing aid use for children under the age of 6 months and allowed for honest, informative discussions with families

Doctor of Philosophy

dissertationAbnormalities in language and communication, auditory sensitivity, and complex information processing are associated with autism, yet the neural underpinnings are unknown. The studies in this dissertation examine neurodevelopment of several brain regions implicated in these abnormalities. We first examine age-related changes in midsagittal corpus callosum area in a large cross-sectional cohort from early childhood to adulthood. Increased variability in total corpus callosum area and atypical regional development in the rostrum and isthmus are found in autism compared with typical controls. In autism, larger areas are associated with reduced severity of autism behaviors, higher intelligence, and faster speed of processing, providing support to theories of underconnectivity in the autism brain. Longitudinal maturation of Heschl's gyrus gray matter and white matter and planum temporale during childhood and adolescence in autism and a typically developing sample are then described. Despite previous crosssectional studies reporting typical Heschl's gyrus structure in autism, reduced developmental trajectories in the right gray matter and atypical white matter maturation are identified. Our longitudinal findings also expand on previous reports of reduced planum temporale asymmetry in autism by showing that the reduced asymmetry develops during later childhood and adolescence. In addition to the case-control comparisons, different developmental trajectories in those individuals with autism with delayed versus early language onset in Heschl's gyrus white matter and planum temporale asymmetry iv are apparent. Finally, individuals with autism exhibit associations between smaller Heschl's gyrus volumes and reduced auditory sensitivity and higher language function, and smaller planum temporale volumes associated with increased vocabulary aptitude. Our findings highlight the importance of longitudinal studies of brain development and examining behavioral profiles of individuals to identify functional and maladaptive pathological neurodevelopment

Processing acoustic change and novelty in newborn infants

Research on event-related potential (ERP) correlates of auditory deviance-detection in newborns provided inconsistent results; temporal and topographic ERP characteristics differed widely across studies and individual infants. Robust and reliable ERP responses were, however, obtained to sounds (termed ‘novel’ sounds), which cover a wide range of frequencies and widely differ from the context provided by a repeating sound [Kushnerenko et al., (2002) NeuroReport, 13, 1843–1848]. The question we investigated here is whether this effect can be attributed to novelty per se or to acoustic characteristics of the ‘novel’ sounds, such as their wide frequency spectrum and high signal energy compared with the repeated tones. We also asked how sensitivity to these stimulus aspects changes with development. Twelve newborns and 11 adults were tested in four different oddball conditions, each including a ‘standard’ sound presented with the probability of 0.8 and two types of infrequent ‘deviant’ sounds (0.1 probability, each). Deviants were (i) ‘novel’ sounds (diverse environmental noises); (ii) white-noise segments, or harmonic tones of (iii) a higher pitch, or (iv) higher intensity. In newborns, white-noise deviants elicited the largest response in all latency ranges, whereas in adults, this phenomenon was not found. Thus, newborns appear to be especially sensitive to sounds having a wide frequency spectrum. On the other hand, the pattern of results found for the late discriminative ERP response indicates that newborns may also be able to detect novelty in acoustic stimulation, although with a longer latency than adults, as shown by the ERP response. Results are discussed in terms of developmental refinement of the initially broadly tuned neonate auditory system

EVALUATION OF AUDITORY CORTICAL PLASTICITY FROM FIRST AMPLIFICATION TO ONE YEAR OF HEARING AID USE: THE RELATIONSHIP BETWEEN AIDED CORTICAL AUDITORY EVOKED POTENTIALS (ACAEPs) AND SPEECH PERCEPTION OUTCOMES AMONG HEARING-IMPAIRED ADULT PATIENTS

Over the last decade, aided cortical auditory evoked potentials (ACAEPs) have continued to be a focus of interest due to the lack of adequate tools to objectively assess cortical auditory activity in response to amplified stimuli. The majority of authors have investigated the direct relationship between behavioral thresholds and ACAEPs and the evolution of ACAEP waves among children with sensorineural hearing loss (SNHL) undergoing rehabilitation. In contrast, scarce data are available regarding changes in ACAEPs over time in adult hearing aid users, particularly in relation to speech perception outcomes. The main goal of this project was to investigate the relationship between ACAEPs and speech perception capability over time in post-lingual SNHL adult patients who were first-time hearing aid users. We hypothesized that, in patients with better speech understanding, a modification of the P1-N1-P2 complex could be expected as a result of neuroplastic changes due to hearing aid amplification. A longitudinal prospective clinical study was conducted on 72 new hearing aid users suffering from symmetrical, sloping SNHL. Patients were assessed at three different time points: baseline (T0), 6 months after the initial assessment (T6), and 12 months after the initial assessment (T12). All the participants went through the same evaluation protocol, which included pure-tone audiometry, speech audiometry tests, ACAEPs recorded with two different stimuli (1000 Hz and 2000 Hz) and questionnaires assessing hearing aid benefit. Analysis of amplitude values at the three different time points demonstrated an increasing tendency for all waves in both experimental conditions (p<0.01). Latencies seemed to become shorter from T0 to T12 for each wave and in the case of 1 kHz and 2 kHz stimuli. (p<0.05). Linear regression analysis found that only P2 amplitude showed a statistically significant increase in its variation while matrix sentence test (MST) and speech intellection threshold (SIT) decreased in both experimental conditions, even when the analysis was adjusted for age and daily hearing aid use (p<0.05). The data collected in this study provide new evidence regarding the relationship between ACAEPs and the speech recognition capability of adults who are new hearing aid users. In both experimental conditions, we observed larger P2 amplitude in patients with better speech perception outcomes. It should be underlined that, even though P2 may reflect auditory processing beyond sensation, its increase could be an expression of neural activity associated with the acquisition process driven by exposure to sounds and speech. The observation that P2 amplitude tended to improve as SIT and MST scores decreased might be, in the future, a further object of investigation to assess its reliability as a marker of speech perception improvement; it may assist hearing aid dispensers and audiologists as a source of feedback in the evaluation of listening benefits in hard-to-test patients

Children with congenital unilateral sensorineural hearing loss : etiology, newborn diagnostics, and hearing aid amplification

Congenital unilateral sensorineural hearing loss (uSNHL) comprises about 25% of the sensorineural hearing losses (SNHLs) found through newborn hearing screening (NHS) programs. Even if children with congenital uSNHL struggle in school and everyday listening situations, studies on etiology, hearing aid (HA) outcomes and intervention are few, so it is still unknown when and how intervention is optimally provided. The overall aim of the PhD project was to study the causes and mechanisms underlying congenital uSNHL and the effects of intervention. The four studies describe effects of HA amplification on pediatric congenital uSNHL (Study I), a basic research study of the transient-evoked otoacoustic emission (TEOAE, Study II), and causes for congenital uSNHL and affected auditory mechanisms (Studies III and IV). In Study I six school-aged children with congenital uNSHL were studied. They all had HA experience and were fitted with HAs late in development. Outcomes showed both HA benefit and dis-benefit. HA benefit was found in one-to-one communication, whereas dis-benefit was found for sound localization accuracy. A close relationship was found between aided sound localization and neural maturation. In Study II neonatal TEOAE heredity was studied in 454 twins, showing that TEOAE levels are largely inherited. Neonatal female twins with male co-twins did not show masculinized (i.e., reduced) TEOAE levels, contrary to the twin testosterone transfer hypothesis proposed previously based on young adult twin’s OAEs. Studies III and IV investigated etiology in 20 infants with congenital uSNHL, consecutively recruited from the newborn hearing screening (NHS) program in Region Stockholm. Malformations were found in 64% of the 14 infants tested with imaging, 50% showed no cochlear nerve on the impaired side, and 29% showed inner ear malformations. All 20 infants tested negative for congenital cytomegalovirus (cCMV) infection. The interaural acoustic reflex threshold and auditory brainstem response (ABR) results indicated a lack of loudness recruitment. Of the 18 infants that were genetically tested, 28% received a genetic diagnosis. All three infants with comorbidities observed at birth received a genetic diagnosis, whereas 13% (n = 2/15) of the infants without comorbidities observed at birth received a genetic diagnosis. The overall results indicate that congenital uSNHL is different from bilateral SNHL, with many malformations, different auditory mechanisms, and a less explored genetic workup. Based on the results we recommend imaging for all congenital uSNHL, and genetic testing for alleged syndromic congenital uSNHL, due to high diagnostic yields. Late-fitted HAs can give both benefits and dis-benefits to school-aged children depending on the listening situation. Finally, HAs may be more efficient if loudness recruitment differences may be taken into account in the HA fitting to children with congenital uSNHL, and if HAs were fitted earlier in development, although this needs to be specifically evaluated in future research

Left hemisphere enhancement of auditory activation in language impaired children

Specific language impairment (SLI) is a developmental disorder linked to deficient auditory processing. In this magnetoencephalography (MEG) study we investigated a specific prolonged auditory response (N250m) that has been reported predominantly in children and is associated with level of language skills. We recorded auditory responses evoked by sine-wave tones presented alternately to the right and left ear of 9–10-year-old children with SLI (n = 10) and children with typical language development (n = 10). Source analysis was used to isolate the N250m response in the left and right hemisphere. In children with language impairment left-hemisphere N250m responses were enhanced compared to those of controls, while no group difference was found in the right hemisphere. Consequently, language impaired children lacked the typical right-ward asymmetry that was found in control children. Furthermore, left but not right hemisphere N250m responses correlated positively with performance on a phonological processing task in the SLI group exclusively, possibly signifying a compensatory mechanism for delayed maturation of language processing. These results suggest that enhanced left-hemisphere auditory activation reflects a core neurophysiological manifestation of developmental language disorders, and emphasize the relevance of this developmentally specific activation pattern for competent language development. © 2019, The Author(s).Peer reviewe