Increased cortical reactivity to repeated tones at 8 months in infants with later ASD.

Dysregulation of cortical excitation/inhibition (E/I) has been proposed as a neuropathological mechanism underlying core symptoms of autism spectrum disorder (ASD). Determining whether dysregulated E/I could contribute to the emergence of behavioural symptoms of ASD requires evidence from human infants prior to diagnosis. In this prospective longitudinal study, we examine differences in neural responses to auditory repetition in infants later diagnosed with ASD. Eight-month-old infants with (high-risk: n = 116) and without (low-risk: n = 27) an older sibling with ASD were tested in a non-linguistic auditory oddball paradigm. Relative to high-risk infants with typical development (n = 44), infants with later ASD (n = 14) showed reduced repetition suppression of 40-60 Hz evoked gamma and significantly greater 10-20 Hz inter-trial coherence (ITC) for repeated tones. Reduced repetition suppression of cortical gamma and increased phase-locking to repeated tones are consistent with cortical hyper-reactivity, which could in turn reflect disturbed E/I balance. Across the whole high-risk sample, a combined index of cortical reactivity (cortical gamma amplitude and ITC) was dimensionally associated with reduced growth in language skills between 8 months and 3 years, as well as elevated levels of parent-rated social communication symptoms at 3 years. Our data show that cortical 'hyper-reactivity' may precede the onset of behavioural traits of ASD in development, potentially affecting experience-dependent specialisation of the developing brain.

Auditory Discrimination Learning: Role of Working Memory.

Perceptual training is generally assumed to improve perception by modifying the encoding or decoding of sensory information. However, this assumption is incompatible with recent demonstrations that transfer of learning can be enhanced by across-trial variation of training stimuli or task. Here we present three lines of evidence from healthy adults in support of the idea that the enhanced transfer of auditory discrimination learning is mediated by working memory (WM). First, the ability to discriminate small differences in tone frequency or duration was correlated with WM measured with a tone n-back task. Second, training frequency discrimination around a variable frequency transferred to and from WM learning, but training around a fixed frequency did not. The transfer of learning in both directions was correlated with a reduction of the influence of stimulus variation in the discrimination task, linking WM and its improvement to across-trial stimulus interaction in auditory discrimination. Third, while WM training transferred broadly to other WM and auditory discrimination tasks, variable-frequency training on duration discrimination did not improve WM, indicating that stimulus variation challenges and trains WM only if the task demands stimulus updating in the varied dimension. The results provide empirical evidence as well as a theoretic framework for interactions between cognitive and sensory plasticity during perceptual experience.

Human decision making based on variations in internal noise: an EEG study.

Perceptual decision making is prone to errors, especially near threshold. Physiological, behavioural and modeling studies suggest this is due to the intrinsic or 'internal' noise in neural systems, which derives from a mixture of bottom-up and top-down sources. We show here that internal noise can form the basis of perceptual decision making when the external signal lacks the required information for the decision. We recorded electroencephalographic (EEG) activity in listeners attempting to discriminate between identical tones. Since the acoustic signal was constant, bottom-up and top-down influences were under experimental control. We found that early cortical responses to the identical stimuli varied in global field power and topography according to the perceptual decision made, and activity preceding stimulus presentation could predict both later activity and behavioural decision. Our results suggest that activity variations induced by internal noise of both sensory and cognitive origin are sufficient to drive discrimination judgments.

Intervention for infants at risk of developing autism: a case series.

Theory and evidence suggest the potential value of prodromal intervention for infants at risk of developing autism. We report an initial case series (n = 8) of a parent-mediated, video-aided and interaction-focused intervention with infant siblings of autistic probands, beginning at 8-10 months of age. We outline the theory and evidence base behind this model and present data on feasibility, acceptability and measures ranging from parent-infant social interaction, to infant atypical behaviors, attention and cognition. The intervention proves to be both feasible and acceptable to families. Measurement across domains was successful and on larger samples promise to be an effective test of whether such an intervention in infancy will modify emergent atypical developmental trajectories in infants at risk for autism.

Atypical audiovisual speech integration in infants at risk for autism.

The language difficulties often seen in individuals with autism might stem from an inability to integrate audiovisual information, a skill important for language development. We investigated whether 9-month-old siblings of older children with autism, who are at an increased risk of developing autism, are able to integrate audiovisual speech cues. We used an eye-tracker to record where infants looked when shown a screen displaying two faces of the same model, where one face is articulating/ba/and the other/ga/, with one face congruent with the syllable sound being presented simultaneously, the other face incongruent. This method was successful in showing that infants at low risk can integrate audiovisual speech: they looked for the same amount of time at the mouths in both the fusible visual/ga/- audio/ba/and the congruent visual/ba/- audio/ba/displays, indicating that the auditory and visual streams fuse into a McGurk-type of syllabic percept in the incongruent condition. It also showed that low-risk infants could perceive a mismatch between auditory and visual cues: they looked longer at the mouth in the mismatched, non-fusible visual/ba/- audio/ga/display compared with the congruent visual/ga/- audio/ga/display, demonstrating that they perceive an uncommon, and therefore interesting, speech-like percept when looking at the incongruent mouth (repeated ANOVA: displays x fusion/mismatch conditions interaction: F(1,16) = 17.153, p = 0.001). The looking behaviour of high-risk infants did not differ according to the type of display, suggesting difficulties in matching auditory and visual information (repeated ANOVA, displays x conditions interaction: F(1,25) = 0.09, p = 0.767), in contrast to low-risk infants (repeated ANOVA: displays x conditions x low/high-risk groups interaction: F(1,41) = 4.466, p = 0.041). In some cases this reduced ability might lead to the poor communication skills characteristic of autism.

Multicentre investigation on electrically evoked compound action potential and stapedius reflex: how do these objective measures relate to implant programming parameters?

OBJECTIVES: The aims of this study were to collect data on electrically evoked compound action potential (eCAP) and electrically evoked stapedius reflex thresholds (eSRT) in HiResolution(TM) cochlear implant (CI) users, and to explore the relationships between these objective measures and behavioural measures of comfort levels (M-levels). METHODS: A prospective study on newly implanted subjects was designed. The eCAP was measured intra-operatively and at first fitting through neural response imaging (NRI), using the SoundWave(TM) fitting software. The eSRT was measured intra-operatively by visual monitoring of the stapes, using both single-electrode stimulation and speech bursts (four electrodes stimulated at the same time). Measures of M-levels were performed according to standard clinical practice and collected at first fitting, 3 and 6 months of CI use. RESULTS: One hundred seventeen subjects from 14 centres, all implanted unilaterally with a HiResolution CII Bionic Ear(®) or HiRes 90K(®), were included in the study. Speech burst stimulation elicited a significantly higher eSRT success rate than single-electrode stimulation, 84 vs. 64% respectively. The NRI success rate was 81% intra-operatively, significantly increasing to 96% after 6 months. Fitting guidelines were defined on the basis of a single NRI measurement. Correlations, analysis of variance, and multiple regression analysis were applied to generate a predictive model for the M-levels. DISCUSSION: Useful insights were produced into the behaviour of objective measures according to time, electrode location, and fitting parameters. They may usefully assist in programming the CI when no reliable feedback is obtained through standard behavioural procedures.

Differential habituation to repeated sounds in infants at high risk for autism.

It has been suggested that poor habituation to stimuli might explain atypical sensory behaviours in autism. We investigated habituation to repeated sounds using an oddball paradigm in 9-month-old infants with an older sibling with autism and hence at high risk for developing autism. Auditory-evoked responses to repeated sounds in control infants (at low risk of developing autism) decreased over time, demonstrating habituation, and their responses to deviant sounds were larger than responses to standard sounds, indicating discrimination. In contrast, neural responses in infants at high risk showed less habituation and a reduced sensitivity to changes in frequency. Reduced sensory habituation may be present at a younger age than the emergence of autistic behaviour in some individuals, and we propose that this could play a role in the over responsiveness to some stimuli and undersensitivity to others observed in autism.

Plasticity of tonotopic maps in humans: influence of hearing loss, hearing aids and cochlear implants.

CONCLUSION: This paper reviews psychoacoustical and electrophysiological evidence for reorganization of the human central auditory system in case of auditory deprivation and rehabilitation. OBJECTIVE: To investigate the plasticity of cortical tonotopic maps in cochlear-damaged subjects. METHODS: Frequency discrimination scores were analysed in subjects with high frequency hearing loss to test for potential perceptual correlates of auditory deprivation- and rehabilitation-induced plasticity. In cochlear implant patients, electrically evoked auditory cortical responses were obtained using EEG to study scalp potential maps. RESULTS: Perceptual changes in frequency discrimination were observed at the lesion-edge frequency of steeply sloping hearing loss. Although these results are not direct proof of cortical plasticity, no peripheral phenomenon has been found to explain them. The reversal of such auditory deprivation-induced plasticity, a phenomenon that may be termed rehabilitation plasticity, can be studied in hearing-impaired subjects fitted with a hearing aid. Cochlear implant subjects provide another interesting model for studying rehabilitation plasticity in that even profound to total deafness is made partially reversible by cochlear implantation. We found that the auditory cortex of deaf subjects with at least 3 months of cochlear implant experience is organized in a way similar to the tonotopy described in normal-hearing subjects.

Evidence of a tonotopic organization of the auditory cortex in cochlear implant users.

Deprivation from normal sensory input has been shown to alter tonotopic organization of the human auditory cortex. In this context, cochlear implant subjects provide an interesting model in that profound deafness is made partially reversible by the cochlear implant. In restoring afferent activity, cochlear implantation may also reverse some of the central changes related to deafness. The purpose of the present study was to address whether the auditory cortex of cochlear implant subjects is tonotopically organized. The subjects were thirteen adults with at least 3 months of cochlear implant experience. Auditory event-related potentials were recorded in response to electrical stimulation delivered at different intracochlear electrodes. Topographic analysis of the auditory N1 component (approximately 85 ms latency) showed that the locations on the scalp and the relative amplitudes of the positive/negative extrema differ according to the stimulated electrode, suggesting that distinct sets of neural sources are activated. Dipole modeling confirmed electrode-dependent orientations of these sources in temporal areas, which can be explained by nearby, but distinct sites of activation in the auditory cortex. Although the cortical organization in cochlear implant users is similar to the tonotopy found in normal-hearing subjects, some differences exist. Nevertheless, a correlation was found between the N1 peak amplitude indexing cortical tonotopy and the values given by the subjects for a pitch scaling task. Hence, the pattern of N1 variation likely reflects how frequencies are coded in the brain.

Effects of auditory pathway anatomy and deafness characteristics? Part 2: On electrically evoked late auditory responses.

The purpose of this study was to distinguish the effects of different parameters on latencies of wave N1, wave P2, and inter-peak interval N1-P2 of electrical late auditory responses (ELARs). ELARs were recorded from four intra-cochlear electrodes in fourteen adult HiRes90K cochlear implant users who had at least three months of experience. The relationship between latencies and stimulation sites in the cochlea was characterized to assess the influence of the auditory pathway anatomy on ELARs, i.e., whether the speed of neural propagation varies according to the place that is activated in the cochlea. Audiograms before implantation, duration of deafness, and psychophysics at first fitting were used to describe the influence of deafness characteristics on latencies. The stimulation sites were found to have no effect on ELAR latency and, while there was no influence of psychophysics on latency, a strong relationship was shown with duration of deafness and the pre-implantation audiogram. Thus, ELAR latency was longer for poorer audiograms and longer durations of deafness and this relationship appeared to be independent of stimulation parameters such as stimulation site. Comparison between these findings and those from the equivalent study on EABR waves IIIe and Ve latency [Guiraud, J., Gallego, S., Arnold, L., Boyle, P., Truy, E., Collet, L., 2007. Effects of auditory pathway anatomy and deafness characteristics? (1): On electrically evoked auditory brainstem responses. Hear. Res. 223 (1-2), 48-60] shows that, while ELAR and EABR latencies are related with parameters that reflect the integrity of the auditory pathway, ELAR latency is less dependent on stimulation parameters than EABR latency.

Effects of auditory pathway anatomy and deafness characteristics? (1): On electrically evoked auditory brainstem responses.

The purpose of this study was to distinguish the effects of different parameters on latencies of wave IIIe, wave Ve, and interpeak interval IIIe-Ve of electrical auditory brainstem responses (EABRs). EABRs were recorded from all the intra-cochlear electrodes in eight adult HiRes90K((R)) cochlear implant users. The relationship between latencies and stimulation sites in the cochlea was characterized to assess activity along the auditory pathway. Audiograms before implantation, psychophysics at first fitting and duration of deafness were used to describe the influence of deafness on latencies. A decreasing baso-apical latency gradient was found for waves IIIe and Ve, while the interpeak interval IIIe-Ve remained the same along the electrode array. Electrical stimulation enabling to stimulate various parts of the cochlea at the same time, this could indicate an anatomical way of compensating for the delay the acoustic wave takes to reach the cochlea apex in a non-implanted ear. However, psychophysical levels were also found to increase at the cochlear base showing that the latency gradient could result from an increasing gradient of neural degeneration toward the base. Correlations of EABR latencies with psychophysics, audiometric data and duration of deafness show that factors linked to deafness have indeed an influence on EABR latencies. The possible explanations for the latency shift observed, whether they are anatomical and/or pathological, are exposed.