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Electrically evoked frequency-following responses (eFFRs) provide insight in the phase-locking ability of brainstem of cochlear-implant (CI) users. eFFRs can potentially be used to gain insight in the individual differences in the biological limitation on temporal encoding of the electrically stimulated auditory pathway, which can be inherent to the electrical stimulation itself and/or the degenerative processes associated with hearing loss. One of the major challenge of measuring eFFRs in CI users is the process of isolating the stimulation artifact from the neural response, as both the response and the artifact overlap in time and have similar frequency characteristics. Here we introduce a new artifact removal method based on template subtraction that successfully removes the stimulation artifacts from the recordings when CI users are stimulated with pulse trains from 128 to 300 pulses per second in a monopolar configuration. Our results show that, although artifact removal was successful in all CI users, the phase-locking ability of the brainstem to the different pulse rates, as assessed with the eFFR differed substantially across participants. These results show that the eFFR can be measured, free from artifacts, in CI users and that they can be used to gain insight in individual differences in temporal processing of the electrically stimulated auditory pathway.

PurposeAttempts to use current-focussing strategies with cochlear implants (CI) to reduce neural spread-of-excitation have met with only mixed success in human studies, in contrast to promising results in animal studies. Although this discrepancy could stem from between-species anatomical and aetiological differences, the masking experiments used in human studies may be insufficiently sensitive to differences in excitation-pattern width.MethodsWe used an interleaved-masking method to measure psychophysical excitation patterns in seven participants with four masker stimulation configurations: monopolar (MP), partial tripolar (pTP), a wider partial tripolar (pTP + 2), and, importantly, a condition (RP + 2) designed to produce a broader excitation pattern than MP. The probe was always in partial-tripolar configuration.ResultsWe found a significant effect of stimulation configuration on both the amount of on-site masking (mask and probe on same electrode; an indirect indicator of sharpness) and the difference between off-site and on-site masking. Differences were driven solely by RP + 2 producing a broader excitation pattern than the other configurations, whereas monopolar and the two current-focussing configurations did not statistically differ from each other.ConclusionA method that is sensitive enough to reveal a modest broadening in RP + 2 showed no evidence for sharpening with focussed stimulation. We also showed that although voltage recordings from the implant accurately predicted a broadening of the psychophysical excitation patterns with RP + 2, they wrongly predicted a strong sharpening with pTP + 2. We additionally argue, based on our recent research, that the interleaved-masking method can usefully be applied to non-human species and objective measures of CI excitation patterns.

Literacy acquisition is a complex process with genetic and environmental factors influencing cognitive and neural processes associated with reading. Previous research identified factors that predict word reading fluency (WRF), including phonological awareness (PA), rapid automatized naming (RAN), and speech-in-noise perception (SPIN). Recent theoretical accounts suggest dynamic interactions between these factors and reading, but direct investigations of such dynamics are lacking. Here, we investigated the dynamic effect of phonological processing and speech perception on WRF. More specifically, we evaluated the dynamic influence of PA, RAN, and SPIN measured in kindergarten (the year prior to formal reading instruction), first grade (the first year of formal reading instruction) and second grade on WRF in second and third grade. We also assessed the effect of an indirect proxy of family risk for reading difficulties using a parental questionnaire (Adult Reading History Questionnaire, ARHQ). We applied path modeling in a longitudinal sample of 162 Dutch-speaking children of whom the majority was selected to have an increased family and/or cognitive risk for dyslexia. We showed that parental ARHQ had a significant effect on WRF, RAN and SPIN, but unexpectedly not on PA. We also found effects of RAN and PA directly on WRF that were limited to first and second grade respectively, in contrast to previous research reporting pre-reading PA effects and prolonged RAN effects throughout reading acquisition. Our study provides important new insights into early prediction of later word reading abilities and into the optimal time window to target a specific reading-related subskill during intervention.

To obtain combined behavioural and electrophysiological measures of pitch perception, we presented harmonic complexes, bandpass filtered to contain only high-numbered harmonics, to normal-hearing listeners. These stimuli resemble bandlimited pulse trains and convey pitch using a purely temporal code. A core set of conditions consisted of six stimuli with baseline pulse rates of 94, 188 and 280 pps, filtered into a HIGH (3365-4755 Hz) or VHIGH (7800-10,800 Hz) region, alternating with a 36% higher pulse rate. Brainstem and cortical processing were measured using the frequency following response (FFR) and auditory change complex (ACC), respectively. Behavioural rate change difference limens (DLs) were measured by requiring participants to discriminate between a stimulus that changed rate twice (up-down or down-up) during its 750-ms presentation from a constant-rate pulse train. FFRs revealed robust brainstem phase locking whose amplitude decreased with increasing rate. Moderate-sized but reliable ACCs were obtained in response to changes in purely temporal pitch and, like the psychophysical DLs, did not depend consistently on the direction of rate change or on the pulse rate for baseline rates between 94 and 280 pps. ACCs were larger and DLs lower for stimuli in the HIGH than in the VHGH region. We argue that the ACC may be a useful surrogate for behavioural measures of rate discrimination, both for normal-hearing listeners and for cochlear-implant users. We also showed that rate DLs increased markedly when the baseline rate was reduced to 48 pps, and compared the behavioural and electrophysiological findings to recent cat data obtained with similar stimuli and methods.

We describe a scalp-recorded measure of tonotopic selectivity, the "cortical onset response" (COR) and compare the results between humans and cats. The COR results, in turn, were compared with psychophysical masked-detection thresholds obtained using similar stimuli and obtained from both species. The COR consisted of averaged responses elicited by 50-ms tone-burst probes presented at 1-s intervals against a continuous noise masker. The noise masker had a bandwidth of 1 or 1/8th octave, geometrically centred on 4000 Hz for humans and on 8000 Hz for cats. The probe frequency was either - 0.5, - 0.25, 0, 0.25 or 0.5 octaves re the masker centre frequency. The COR was larger for probe frequencies more distant from the centre frequency of the masker, and this effect was greater for the 1/8th-octave than for the 1-octave masker. This pattern broadly reflected the masked excitation patterns obtained psychophysically with similar stimuli in both species. However, the positive signal-to-noise ratio used to obtain reliable COR measures meant that some aspects of the data differed from those obtained psychophysically, in a way that could be partly explained by the upward spread of the probe's excitation pattern. Our psychophysical measurements also showed that the auditory filter width obtained at 8000 Hz using notched-noise maskers was slightly wider in cat than previous measures from humans. We argue that although conclusions from COR measures differ in some ways from conclusions based on psychophysics, the COR measures provide an objective, noninvasive, valid measure of tonotopic selectivity that does not require training and that may be applied to acoustic and cochlear-implant experiments in humans and laboratory animals.

Cochlear implant (CI) users show limited sensitivity to the temporal pitch conveyed by electric stimulation, contributing to impaired perception of music and of speech in noise. Neurophysiological studies in cats suggest that this limitation is due, in part, to poor transmission of the temporal fine structure (TFS) by the brainstem pathways that are activated by electrical cochlear stimulation. It remains unknown, however, how that neural limit might influence perception in the same animal model. For that reason, we developed non-invasive psychophysical and electrophysiological measures of temporal (i.e., non-spectral) pitch processing in the cat. Normal-hearing (NH) cats were presented with acoustic pulse trains consisting of band-limited harmonic complexes that simulated CI stimulation of the basal cochlea while removing cochlear place-of-excitation cues. In the psychophysical procedure, trained cats detected changes from a base pulse rate to a higher pulse rate. In the scalp-recording procedure, the cortical-evoked acoustic change complex (ACC) and brainstem-generated frequency following response (FFR) were recorded simultaneously in sedated cats for pulse trains that alternated between the base and higher rates. The range of perceptual sensitivity to temporal pitch broadly resembled that of humans but was shifted to somewhat higher rates. The ACC largely paralleled these perceptual patterns, validating its use as an objective measure of temporal pitch sensitivity. The phase-locked FFR, in contrast, showed strong brainstem encoding for all tested pulse rates. These measures demonstrate the cat's perceptual sensitivity to pitch in the absence of cochlear-place cues and may be valuable for evaluating neural mechanisms of temporal pitch perception in the feline animal model of stimulation by a CI or novel auditory prostheses.

Dyslexia has frequently been related to atypical auditory temporal processing and speech perception. Results of studies emphasizing speech onset cues and reinforcing the temporal structure of the speech envelope, that is, envelope enhancement (EE), demonstrated reduced speech perception deficits in individuals with dyslexia. The use of this strategy as auditory intervention might thus reduce some of the deficits related to dyslexia. Importantly, reading-skill interventions are most effective when they are provided during kindergarten and first grade. Hence, we provided a tablet-based 12-week auditory and phonics-based intervention to pre-readers at cognitive risk for dyslexia and investigated the effect on auditory temporal processing with a rise time discrimination (RTD) task. Ninety-one pre-readers at cognitive risk for dyslexia (aged 5-6) were assigned to two groups receiving a phonics-based intervention and playing a story listening game either with (n = 31) or without (n = 31) EE or a third group playing control games and listening to non-enhanced stories (n = 29). RTD was measured directly before, directly after and 1 year after the intervention. While the groups listening to non-enhanced stories mainly improved after the intervention during first grade, the group listening to enhanced stories improved during the intervention in kindergarten and subsequently remained stable during first grade. Hence, an EE intervention improves auditory processing skills important for the development of phonological skills. This occurred before the onset of reading instruction, preceding the maturational improvement of these skills, hence potentially giving at risk children a head start when learning to read. A video abstract of this article can be viewed at https://www.youtube.com/watch?v=e0BfT4dGXNA

Auditory processing of temporal information in speech is sustained by synchronized firing of neurons along the entire auditory pathway. In school-aged children and adults with dyslexia, neural synchronization deficits have been found at cortical levels of the auditory system, however, these deficits do not appear to be present in pre-reading children. An alternative role for subcortical synchronization in reading development and dyslexia has been suggested, but remains debated. By means of a longitudinal study, we assessed cognitive reading-related skills and subcortical auditory steady-state responses (80 Hz ASSRs) in a group of children before formal reading instruction (pre-reading), after 1 year of formal reading instruction (beginning reading), and after 3 years of formal reading instruction (more advanced reading). Children were retrospectively classified into three groups based on family risk and literacy achievement: typically developing children without a family risk for dyslexia, typically developing children with a family risk for dyslexia, and children who developed dyslexia. Our results reveal that children who developed dyslexia demonstrate decreased 80 Hz ASSRs at the pre-reading stage. This effect is no longer present after the onset of reading instruction, due to an atypical developmental increase in 80 Hz ASSRs between the pre-reading and the beginning reading stage. A forward stepwise logistic regression analysis showed that literacy achievement was predictable with an accuracy of 90.4% based on a model including three significant predictors, that is, family risk for dyslexia (R = 0.31), phonological awareness (R = 0.23), and 80 Hz ASSRs (R = 0.26). Given that: (1) abnormalities in subcortical ASSRs preceded reading acquisition in children who developed dyslexia; and (2) subcortical ASSRs contributed to the prediction of literacy achievement, subcortical auditory synchronization deficits may constitute a pre-reading risk factor in the emergence of dyslexia.

Research demonstrated that a dyslexia diagnosis is mainly given after the most effective time for intervention has passed, referred to as the dyslexia paradox. Although some pre-reading cognitive measures have been found to be strong predictors of early literacy acquisition, i.e., phonological awareness (PA), letter knowledge (LK), and rapid automatized naming (RAN), more insight in the variability of pre-reading profiles might be of great importance for early identification of children who have an elevated risk for developing dyslexia and to provide tailor-made interventions. To address this issue, this study used a latent profile analysis (LPA) to disentangle different pre-reading profiles in a sample of 1091 Dutch-speaking kindergartners. Four profiles emerged: high performers (16.50%), average performers (40.24%), below-average performers with average IQ (25.57%), and below-average performers with below-average IQ (17.69%). These results suggested two at-risk profiles diverging in IQ, which are presumably more likely to develop dyslexia later on. Although below-average profiles differed significantly in rapid naming and IQ, no clear evidence for the double-deficit theory was found in Dutch-speaking kindergartners. Educational level and reading history of the parents appeared to be predictive for children's classification membership. Our results point towards the heterogeneity that is already present in kindergartners and the possibility to identify at-risk profiles prior to reading instruction, which may be the foundation for earlier targeted interventions. However, more extended research is needed to determine the stability of these profiles across time and across different languages.

There is an ongoing debate whether phonological deficits in dyslexics should be attributed to (a) less specified representations of speech sounds, like suggested by studies in young children with a familial risk for dyslexia, or (b) to an impaired access to these phonemic representations, as suggested by studies in adults with dyslexia. These conflicting findings are rooted in between study differences in sample characteristics and/or testing techniques. The current study uses the same multivariate functional MRI (fMRI) approach as previously used in adults with dyslexia to investigate phonemic representations in 30 beginning readers with a familial risk and 24 beginning readers without a familial risk of dyslexia, of whom 20 were later retrospectively classified as dyslexic. Based on fMRI response patterns evoked by listening to different utterances of /bA/ and /dA/ sounds, multivoxel analyses indicate that the underlying activation patterns of the two phonemes were distinct in children with a low family risk but not in children with high family risk. However, no group differences were observed between children that were later classified as typical versus dyslexic readers, regardless of their family risk status, indicating that poor phonemic representations constitute a risk for dyslexia but are not sufficient to result in reading problems. We hypothesize that poor phonemic representations are trait (family risk) and not state (dyslexia) dependent, and that representational deficits only lead to reading difficulties when they are present in conjunction with other neuroanatomical or--functional deficits.