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Recent empirical findings suggest that altered neural synchronization, which is hypothesized to be associated with an imbalance of excitatory (E) and inhibitory (I) neuronal activities, may underlie a core pathophysiological mechanism in patients with schizophrenia. The auditory steady-state response (ASSR) examined by electroencephalography (EEG) and magnetoencephalography (MEG) has been proposed as a potential biomarker for evaluating altered neural synchronization in schizophrenia. For this review, we performed a comprehensive literature search for papers published between 1999 and 2021 examining ASSRs in patients with schizophrenia. Almost all EEG-ASSR studies reported gamma-band ASSR reductions, especially to 40-Hz stimuli both in power and/or phase synchronization in chronic and first-episode schizophrenia. In addition, similar to EEG-ASSR findings, MEG-ASSR deficits to 80-Hz stimuli (high gamma) have been reported in patients with schizophrenia. Moreover, the 40-Hz ASSR is likely to be a predictor of the onset of schizophrenia. Notably, increased spontaneous (or ongoing) broadband (30-100 Hz) gamma power has been reported during ASSR tasks, which resembles the increased spontaneous gamma activity reported in animal models of E/I imbalance. Further research on ASSRs and evoked and spontaneous gamma oscillations is expected to elucidate the pathophysiology of schizophrenia with translational implications.

Auditory development after bilateral cochlear implantation in children has been measured using source localization of multi-channel late latency responses. It is not clear, however, whether this development can be tracked using a more clinically feasible method of recording from one active recording electrode placed at mid-line center of the head (Cz).In this prospective cohort study, cortical auditory-evoked potential responses (CAEPs) were recorded from Cz referenced to each earlobe (Cz-CAEP) from 222 children with bilateral cochlear implant (CI); 128 (mean ± SD age: 2.78 ± 3.30 years) received both CIs in the same surgery (simultaneous group) and 94 (aged 7.72 ± 4.45 years) received a second CI after 4.21 ± 2.98 years of unilateral CI use. We sought to (1) identify cortical development over the first couple of years of bilateral CI use; (2) measure known asymmetries in auditory development between the CIs; and (3) detect the effects of bilateral rather than unilateral CI use. 4556 Cz-CAEPs were recorded across the cohort over 33.50 ± 7.67 months duration of bilateral CI use. Given concerns related to peak picking, amplitude areas were measured across two response time windows (50 to 199 ms and 200 to 400 ms).Results indicated that small response amplitudes occur at initial CI use and amplitudes increase in the negative or positive direction rapidly over the first months of CI use in both time windows. Asymmetries between Cz-CAEPs evoked by each CI were found in the sequential group and reduced with bilateral CI use, particularly in the first time window; these differences increased with longer inter-implant delay. Bilaterally evoked Cz-CAEPs were larger in amplitude than unilateral responses from either CI in the simultaneous group. In the sequential group, bilateral responses were similar to responses from the first implanted side but increased in relative amplitude with bilateral CI use. The Cz-CAEP measures were not able to predict asymmetries or bilateral benefits in speech perception measures.The Cz-CAEP was able to indicate cortical detection of CI input and showed gross morphological changes with bilateral CI use. Findings indicate Cz-CAEPs can be used to identify gross changes in auditory development in children with bilateral CIs, but they are less sensitive to tracking the remaining abnormalities that are measured by multi-channel CAEPs and speech perception testing.

This narrative review brings together the findings regarding the differences in the auditory event-related potentials (ERPs) between patients with depressive disorder and non-depressed control subjects. These studies' results can inform us of the possible alterations in sensory-cognitive processing in depressive disorders and the potential of using these ERPs in clinical applications. Auditory P3, mismatch negativity (MMN) and loudness dependence of auditory evoked potentials (LDAEP) were the subjects of the investigation. A search in PubMed yielded 84 studies. The findings of the reviewed studies were not highly consistent, but some patterns could be identified. For auditory P3b, the common findings were attenuated amplitude and prolonged latency among depressed patients. Regarding auditory MMN, especially the amplitude of duration deviance MMN was commonly attenuated, and the amplitude of frequency deviance MMN was increased in depressed patients. In LDAEP studies, generally, no differences between depressed patients and non-depressed controls were reported, although some group differences concerning specific depression subtypes were found. This review posits that future research should investigate whether certain stimulus conditions are particularly efficient at separating depressed and non-depressed participant groups. Future studies should contrast responses in different subpopulations of depressed patients, as well as different clinical groups (e.g., depressive disorder and anxiety disorder patients), to investigate the specificity of the auditory ERP alterations for depressive disorders. peerReviewed

In this study, we examined the neuronal responses of a frontal cortical area in an echolocating bat to behaviorally relevant acoustic stimuli and compared them with those in the primary auditory cortex (A1). In contrast to the A1, neurons in the bat frontal auditory field are not frequency tuned but showed a higher selectivity for social signals such as communication calls. The results presented here indicate that the frontal auditory field may represent an additional processing center for behaviorally relevant sounds.

The electrically evoked compound action potential (eCAP) is a direct measure of the responsiveness of the auditory nerve to electrical stimulation from a cochlear implant (CI). CIs offer a unique opportunity to study the auditory nerve’s electrophysiological behavior in individual human subjects over time. In order to understand exactly how the eCAP relates to the condition of the auditory nerve, it is crucial to compare changes in the eCAP over time in a controlled model of deafness-induced auditory nerve degeneration. In the present study, 10 normal-hearing young adult guinea pigs were implanted and deafened 4 weeks later, so that the effect of deafening could be monitored within-subject over time. Following implantation, but before deafening, most examined eCAP characteristics significantly changed, suggesting increasing excitation efficacy (e.g., higher maximum amplitude, lower threshold, shorter latency). Conversely, inter-phase gap (IPG) effects on these measures – within-subject difference measures that have been shown to correlate well with auditory nerve survival – did not vary for most eCAP characteristics. After deafening, we observed an initial increase in excitability (steeper slope of the eCAP amplitude growth function (AGF), lower threshold, shorter latency and peak width) which typically returned to normal-hearing levels within a week, after which a slower process, probably reflecting spiral ganglion cell loss, took place over the remaining 6 weeks (e.g., decrease in maximum amplitude, AGF slope, peak area, and IPG effect for AGF slope; increase in IPG effect for latency). Our results suggest that gradual changes in peak width and latency reflect the rate of neural degeneration, while peak area, maximum amplitude, and AGF slope reflect neural population size, which may be valuable for clinical diagnostics.

Infrequent deviants in a rapid sequence of sounds elicit a negative cortical potential over the frontocentral midline (mismatch negativity, MMN) followed by a positive deflection (P3a). Both cortical potentials are consistently attenuated in patients with schizophrenia (SZ), and, to a lesser degree, in patients with bipolar disorder (BP).Since it is unclear when MMN and P3a deficits arise relative to the emergence of symptoms, we examined whether MMN and P3a alterations are already detectable in children with familial high risk.Using 128-channel electroencephalography, we recorded auditory MMN and P3a evoked by a deviation in sound duration, frequency, or both in 51 children with familial high-risk for SZ (FHR-SZ), 41 children with familial high-risk for BP (FHR-BP), and 39 population-based children (PBC) at a mean age of 12.10.MMN amplitude evoked by a duration deviant was larger in children with FHR-BP compared to PBC and FHR-SZ. P3a amplitude in response to a duration ∗ frequency deviant was larger in children with FHR-BP compared to children with FHR-SZ, but not compared to PBC. MMN- and P3a-peak latency did not differ between groups.At an age of around 12 years, children with FHR-BP display enhanced neural sensitivity to change detection of duration deviants, while FHR-SZ showed a normal response pattern. Longitudinal recordings in high-risk children during adolescence are required to elucidate the temporal trajectories of MMN and P3a responses and how they relate to the emergence of first clinical symptoms in SZ and BP.

Individuals at clinical high risk (CHR) for psychosis exhibit a compromised mismatch negativity (MMN) response, which indicates dysfunction of pre-attentive deviance processing. Event-related potential and time-frequency (TF) information, in combination with clinical and cognitive profiles, may provide insight into the pathophysiology and psychopathology of the CHR stage and predict the prognosis of CHR individuals. A total of 92 individuals with CHR were recruited and followed up regularly for up to 3 years. Individuals with CHR were classified into three clinical subtypes demonstrated previously, specifically 28 from Cluster 1 (characterized by extensive negative symptoms and cognitive deficits), 31 from Cluster 2 (characterized by thought and behavioral disorganization, with moderate cognitive impairment), and 33 from Cluster 3 (characterized by the mildest symptoms and cognitive deficits). Auditory MMN to frequency and duration deviants was assessed. The event-related spectral perturbation (ERSP) and inter-trial coherence (ITC) were acquired using TF analysis. Predictive indices for remission were identified using logistic regression analyses. As expected, reduced frequency MMN (fMMN) and duration MMN (dMMN) responses were noted in Cluster 1 relative to the other two clusters. In the TF analysis, Cluster 1 showed decreased theta and alpha ITC in response to deviant stimuli. The regression analyses revealed that dMMN latency and alpha ERSP to duration deviants, theta ITC to frequency deviants and alpha ERSP to frequency deviants, and fMMN latency were significant MMN predictors of remission for the three clusters. MMN variables outperformed behavioral variables in predicting remission of Clusters 1 and 2. Our findings indicate relatively disrupted automatic auditory processing in a certain CHR subtype and a close affinity between these electrophysiological indexes and clinical profiles within different clusters. Furthermore, MMN indexes may serve as predictors of subsequent remission from the CHR state. These findings suggest that the auditory MMN response is a potential neurophysiological marker for distinct clinical subtypes of CHR.

Event-related brain potentials (ERPs) elicited by auditory stimuli unrelated to a current visual-cognitive task (i.e., task-irrelevant auditory probes) can be used to evaluate the level of mental workload. Towards the evaluation of workload in the shortest possible time, the present study with a multiple-stimulus paradigm (Takeda and Kimura, 2014, Int. J. Psychophysiol.) examined whether manipulating time intervals between probes could improve the temporal resolution in evaluating workload. Probes were presented in four interval conditions as a combination of two mean interval lengths [long (600 ms) vs. short (300 ms)] and two interval variabilities [variable (five levels) vs. fixed], while participants were performing a driving game at slow and fast speeds (i.e., imposing low and high workload, respectively). For each interval condition, the minimum data length required to obtain a significant difference in the amplitude of ERPs (i.e., auditory N1 and P2) between the slow and fast driving tasks was estimated. The N1 difference was significant in all four interval conditions but the required minimum data lengths to observe this difference did not greatly differ across the interval conditions (about 60-90 s). The P2 difference was significant only in the long-variable condition and the required minimum data length was about 120 s. These results suggest that, at least with a multiple-stimulus paradigm, manipulations of time intervals between probes did not greatly improve the temporal resolution in evaluating mental workload; at present, long-variable intervals would be optimal for evaluating mental workload in detail.

International audience; During speaking or listening, endogenous motor or exogenous visual processes have been shown to fine-tune the auditory neural processing of incoming acoustic speech signal. To compare the impact of these cross-modal effects on auditory evoked responses, two sets of speech production and perception tasks were contrasted using EEG. In a first set, participants produced vowels in a self-paced manner while listening to their auditory feedback. Following the production task, they passively listened to the entire recorded speech sequence. In a second set, the procedure was identical except that participants also watched online their own articulatory movements. While both endogenous motor and exogenous visual processes fine-tuned auditory neural processing, these cross-modal effects were found to act differentially on the amplitude and latency of auditory evoked responses. A reduced amplitude was observed on auditory evoked responses during speaking compared to listening, irrespective of the auditory or audiovisual feedback. Adding orofacial visual movements to the acoustic speech signal also speeded up the latency of auditory evoked responses, irrespective of the perception or production task. Taken together, these results suggest distinct motor and visual influences on auditory neural processing, possibly through different neural gating and predictive mechanisms.

Auditory evoked potentials can be estimated by synchronous averaging when the responses to the individual stimuli are not overlapped. However, when the response duration exceeds the inter-stimulus interval, a deconvolution procedure is necessary to obtain the transient response. The iterative randomized stimulation and averaging and the equivalent randomized stimulation with least squares deconvolution have been proven to be flexible and efficient methods for deconvolving the evoked potentials, with minimum restrictions in the design of stimulation sequences. Recently, a latency-dependent filtering and down-sampling (LDFDS) methodology was proposed for optimal filtering and dimensionality reduction, which is particularly useful when the evoked potentials involve the complete auditory pathway response (i.e., from the cochlea to the auditory cortex). In this case, the number of samples required to accurately represent the evoked potentials can be reduced from several thousand (with conventional sampling) to around 120. In this article, we propose to perform the deconvolution in the reduced representation space defined by LDFDS and present the mathematical foundation of the subspace-constrained deconvolution. Under the assumption that the evoked response is appropriately represented in the reduced representation space, the proposed deconvolution provides an optimal least squares estimation of the evoked response. Additionally, the dimensionality reduction provides a substantial reduction of the computational cost associated with the deconvolution. matlab/Octave code implementing the proposed procedures is included as supplementary material.

In schizophrenia, a disorder associated with N-methyl-D-aspartate receptor (NMDAR) hypofunction, auditory cortical plasticity deficits have been indexed by the synchronized electroencephalographic (EEG) auditory steady-state gamma-band (40-Hz) response (ASSR) and the early auditory evoked gamma-band response (aeGBR), both considered to be target engagement biomarkers for NMDAR function, and potentially amenable to treatment by NMDAR modulators. As transcranial direct current stimulation (tDCS) is likely dependent on NMDAR neurotransmission, this preliminary study, conducted in 30 healthy volunteers, assessed the off-line effects of prefrontal anodal tDCS and sham (placebo) treatment on 40-Hz ASSR and aeGBR. Anodal tDCS failed to alter aeGBR but increased both 40-Hz ASSR power, as measured by event-related spectral perturbations (ERSP), and phase locking, as measured by inter-trial phase consistency (ITPC). Inter-individual differences in tDCS-induced increases in ERSP were negatively related to baseline ERSPs. These findings provide tentative support for further study of tDCS as a potential NMDAR neuromodulatory intervention for synchronized auditory gamma response deficits.

Hearing-impaired children (HIC) have difficulty understanding speech in noise, which may be due to difficulty parsing concurrent sound object based on harmonicity cues. Using long latency auditory evoked potentials (LLAEPs) and object-related negativity (ORN), a neural metric of concurrent sound segregation, this study investigated the sensitivity of HIC in processing harmonic relation. The participants were 14 normal-hearing children (NHC) with an average age of 7.82 ± 1.31 years and 17 HIC with an average age of 7.98 ± 1.25 years. They were presented with a sequence of 200 Hz harmonic complex tones that had either all harmonic in tune or the third harmonic mistuned by 2%, 4%, 8%, and 16% of its original value while neuroelectric brain activity was recorded. The analysis of scalp-recorded LLAEPs revealed lower N2 amplitudes elicited by the tuned stimuli in HIC than control. The ORN, isolated in difference wave between LLAEP elicited by tuned and mistuned stimuli, was delayed and smaller in HIC than NHC. This study showed that deficits in processing harmonic relation in HIC, which may contribute to their difficulty in understanding speech in noise. As a result, top-down and bottom-up rehabilitations aiming to improve processing of basic acoustic characteristics, including harmonics are recommended for children with hearing loss.

Two of the most used objective measures are electrically evoked action potentials (ECAPs) and electrically evoked stapedius reflex thresholds (ESRTs). Although stimuli used for these measures differ considerably, both measures are influenced by subjective loudness percept. We focus on the subjective maximum acceptable loudness (MAL) to investigate if loudness sensitivity varied along the electrode array during ECAP recordings. In addition, we explored how the MAL reached during an ECAP recording related to the postoperative ESRT.Uni- and bilaterally implanted young CI users (Loudness tolerance during ECAP recordings was lowest at the two apical-most electrode contacts (number 1 and 2). There was a moderate correlation between the MAL achieved during ECAP recordings and ESR maximum stimulation amplitudes. (r: 0.44344).ECAP recordings should commence at basal or medial contacts to increase the users' comfort and loudness tolerance, especially in young CI users. A higher maximum stimulation appears to increase the chance of the automatic determination of ECAP thresholds for all electrode contacts.

The use of objective measures in cochlear implant (CI) mapping, has greatly contributed to the refinement of the setting of audible and comfortable stimulation levels, which serve as the basis of the mapping process, especially in cases of infants and young children. In addition, objective measures can also confirm the integrity of the CI system. Current CI objective measures mainly reflect neural activity from the auditory nerve and brainstem site. An objective cortical CI measure that reflects directly central auditory activity is greatly needed, especially since it is closely related to CI outcomes in both children and adults. Recording the brain activity currently requires an external evoked potential (EP) system including scalp electrodes, rendering it impractical for widespread clinical use. This study aimed to assess the feasibility of recording cortical auditory evoked potentials (CAEPs) directly and solely through the cochlear implant in response to external acoustic stimulation in the non-implanted ear.A total of nine CI users (four females and five males) participated, including seven post-lingual adults (23 to 72 years), and two pediatric cases, one teenager (15 years), and one child (8 years)-both pre-lingual. All participants had a residual hearing in the ear contralateral to the ear with CI. CAEPs were recorded in the implanted ear in response to acoustic stimulation of the non-implanted ear, consisting of a brief tonal stimulus at comfortable listening levels. Recordings used an intracranial montage consisting of an intracochlear apical electrode (active) and one of the two ( case and ring ) extra-cochlear implanted electrodes serving as reference electrodes. The CI CAEPs were compared with a single-channel conventional CAEP recording obtained simultaneously via scalp electrodes (Fz-mastoid) using a standard EP system and an external trigger from the CI system. Statistical comparisons were made between the CI and the scalp recorded CAEPs and for differences between the CI CAEP measures acquired using the ring and the case as the reference electrode.CAEPs recorded directly and solely through the CI were equivalent to the standard scalp recorded CAEP responses. CAEP responses acquired using the case electrode as the reference were highly correlated in terms of morphology, latencies, and amplitudes of the CAEP components. The CI CAEP latencies of the two pediatric cases were consistent with their normal developed age group and delayed relative to adult CAEP latencies, as expected.This study demonstrated the feasibility of recording long latency CAEPs directly and solely through CI in adults with residual hearing, in response to acoustic stimulation of the non-implanted ear. The CI CAEPs closely resembled the CAEPs recorded simultaneously by an external EP system and via scalp electrodes. The ability to record directly from the implant, without the need of an external recording system, presents an innovative method with many clinical and research implications.

Adaptation to the sensory environment is essential in everyday life, to anticipate future events and quickly detect and respond to changes; and to distinguish vocal variations in congeners, for communication. The aim of the current study was to explore the effects of the nature (vocal/non-vocal) of the information to be encoded, on the establishment of auditory regularities. In electrophysiology, neural adaptation is measured by the 'Repetition Positivity' (RP), which refers to an increase in positive potential, with the increasing number of repetitions of a same stimulus. The RP results from the combined variation of several ERP components; the P1, the first positivity (∼100 ms) may reflect the onset of repetition effects. We recorded auditory evoked potentials during a roving paradigm in which trains of 4, 8 or 16 repetitions of the same stimulus were presented. Sequences of vocal and non-vocal complex stimuli were delivered, to study the influence of the type of stimulation on the characteristics of the brain responses. The P1 to each train length, and the RP responses were recorded between 90 and 200 ms, reflecting adaptation for both vocal and non-vocal stimuli. RP was not different between vocal and non-vocal sequences (in latency, amplitude and spatial organization) and was found to be similar to that found in previous studies using pure tones, suggesting that the repetition suppression phenomena is somehow independent of the nature of the stimulus. However, results showed faster stabilization of the P1 amplitude for non-vocal stimuli than for vocal stimuli, which require more repetitions. This revealed different dynamics for the establishment of regularity encoding for non-vocal and vocal stimuli, indicating that the richness of vocal sounds may require further processing before full neural adaptation occurs.

The ability to generalize across specific experiences is vital for the recognition of new patterns, especially in speech perception considering acoustic–phonetic pattern variability. Indeed, behavioral research has demonstrated that listeners are able via a process of generalized learning to leverage their experiences of past words said by difficult-to-understand talker to improve their understanding for new words said by that talker. Here, we examine differences in neural responses to generalized versus rote learning in auditory cortical processing by training listeners to understand a novel synthetic talker. Using a pretest–posttest design with EEG, participants were trained using either (1) a large inventory of words where no words were repeated across the experiment (generalized learning) or (2) a small inventory of words where words were repeated (rote learning). Analysis of long-latency auditory evoked potentials at pretest and posttest revealed that rote and generalized learning both produced rapid changes in auditory processing, yet the nature of these changes differed. Generalized learning was marked by an amplitude reduction in the N1–P2 complex and by the presence of a late negativity wave in the auditory evoked potential following training; rote learning was marked only by temporally later scalp topography differences. The early N1–P2 change, found only for generalized learning, is consistent with an active processing account of speech perception, which proposes that the ability to rapidly adjust to the specific vocal characteristics of a new talker (for which rote learning is rare) relies on attentional mechanisms to selectively modify early auditory processing sensitivity.

OBJECTIVE: This study aimed to 1) characterize the amount and the speed of recovery from neural adaptation at the auditory nerve (AN), and 2) assess their associations with advanced age in postlingually deafened adult cochlear implant (CI) users. DESIGN: Study participants included 25 postlingually deafened adult, Cochlear™ Nucleus® device users, ranging in age between 24.83 and 83.21 years at the time of testing. The stimulus was a 100-ms pulse train presented at four pulse rates: 500, 900, 1800 and 2400 pulses per second (pps). The pulse trains were presented at the maximum comfortable level measured for the 2400-pps pulse train. The electrically evoked compound action potential (eCAP) evoked by the last pulse of the pulse train (i.e., the probe pulse) was recorded. The remaining pulses of the pulse train served as the pulse-train masker. The time interval between the probe pulse and the last pulse of the pulse-train masker (i.e., masker-probe-interval, MPI) systematically increased from 0.359 ms up to 256 ms. The adaptation recovery function (ARF) was obtained by plotting normalized eCAP amplitudes (re: the eCAP amplitude measured at the MPI of 256 ms) as a function of MPIs. The adaptation recovery ratio (ARR) was defined as the ratio between the eCAP amplitude measured at the MPI of 256 ms and that measured for the single-pulse stimulus presented at the same stimulation level. The time constants of the ARF were estimated using a mathematical model with an exponential function with up to three components. Generalized Linear Mixed effects Models were used to compare ARRs and time constants measured at different electrode locations and pulse rates, as well as to assess the effect of advanced age on these dependent variables. RESULTS: There were three ARF types observed in this study. The ARF type observed in the same study participant could be different at different electrode locations and/or pulse rates. Substantial variations in both the amount and the speed of neural adaptation recovery among study participants were observed. The ARR was significantly affected by pulse rate but was not affected by electrode location. The effect of electrode location on the time constants of the ARF were not statistically significant. Pulse rate had a statistically significant effect on τ(1,) but not on τ(2) or τ(3). There was no statistically significant effect of age on the ARR or the time constants of the ARF. CONCLUSIONS: Neural adaptation recovery processes at the AN demonstrate substantial variations among human CI users. The recovery pattern can be nonmonotonic with up to three phases. While the amount of neural adaptation recovery decreases as pulse rate increases, only the speed of the first phase of neural adaptation recovery is affected by pulse rate. Electrode location or advanced age has no robust effect on neural adaptation recovery processes at the level of the AN for a 100-ms pulse-train masker with pulse rates of 500–2400 pps. The lack of sufficient participants in this study who were 40 years of age or younger at the time of testing might have precluded a thorough assessment of the effect of advanced age.

Sound-level coding in the auditory nerve is achieved through the progressive recruitment of auditory nerve fibers (ANFs) that differ in threshold of activation and in the stimulus level at which the spike rate saturates. To investigate the functional state of the ANFs, the electrophysiological tests routinely used in clinics only capture the first action potentials firing in synchrony at the onset of the acoustic stimulation. Assessment of other properties (e.g., spontaneous rate and adaptation time constants) requires single-fiber recordings directly from the nerve, which for ethical reasons is not allowed in humans. By combining neuronal activity measurements at the round window and signal-processing algorithms, we constructed a peristimulus time response (PSTR), with a waveform similar to the peristimulus time histograms (PSTHs) derived from single-fiber recordings in young adult female gerbils. Simultaneous recordings of round-window PSTR and single-fiber PSTH provided models to predict the adaptation kinetics and spontaneous rate of the ANFs tuned at the PSTR probe frequency. The predictive model derived from gerbils was then validated in female mice and finally applied to humans by recording PSTRs from the auditory nerve in normal-hearing patients who underwent cerebellopontine angle surgeries. A rapid adaptation time constant of ∼3 ms and a mean spontaneous rate of ∼22 spikes/s in the 4 kHz frequency range were found. This study offers a promising diagnostic tool to map the human auditory nerve, thus opening new avenues to better understanding auditory neuropathies, tinnitus, and hyperacusis.SIGNIFICANCE STATEMENTNeural adaptation in auditory nerve fibers corresponds to the reduction in the neuronal activity to prolonged or repeated sound stimulation. For obvious ethical reasons, single-fiber recordings from the auditory nerve are not feasible in humans, creating a critical gap in extending data obtained using animal models to humans. Using electrocochleography in rodents, we inferred adaptation kinetics and spontaneous discharge rates of the auditory nerve fibers in humans. Routinely used in basic and clinical laboratories, this tool will provide a better understanding of auditory disorders such as neuropathies, tinnitus, and hyperacusis, and will help to improve hearing-aid fittings.

The neurophysiological assessment of infants in their first developmental year can provide important information about the functional changes of the brain and supports the study of behavioral and developmental characteristics. Infants' cortical auditory evoked potentials (CAEPs) reflect cortical maturation and appear to predict subsequent language abilities. This study aimed to identify CAEP components to two auditory stimulus intensities in 1-month-old infants and to understand how these are associated with social interactive and self-regulatory behaviors. In addition, it examined whether CAEPs predicted developmental outcomes when infants were assessed at 12 months of age. At 1 month, P2 and N2 components were present for both auditory stimulus intensities, with an increased P2 amplitude being observed for the higher-intensity stimuli. We also observed that an increased P2 amplitude in the lower intensity predicted receptive and expressive language competencies at 12 months. These results are consistent with previous findings indicating an association between auditory processing and developmental outcomes in infants. This study suggests that specific auditory neurophysiological markers are associated with developmental outcomes in the first developmental year.

OBJECTIVE: This study aimed to investigate the associations between advanced age and the amount and the speed of neural adaptation of the electrically-stimulated auditory nerve (AN) in postlingually deafened adult cochlear implant (CI) users. DESIGN: Study participants included 26 postlingually deafened adult CI users, ranging in age between 28.7 and 84.0 years (mean: 63.8 years, std: 14.4 years) at the time of testing. All study participants used a Cochlear(™) Nucleus® device with a full electrode array insertion in the test ear. The stimulus was a 100-ms pulse train with a pulse rate of 500, 900, 1800 or 2400 pulses per second (pps) per channel. The stimulus was presented at the maximum comfortable level measured at 2400 pps with a presentation rate of 2 Hz. Neural adaptation of the AN was evaluated using electrophysiological measures of the electrically evoked compound action potential (eCAP). The amount of neural adaptation was quantified by the adaptation index (AI) within three time windows: around 0–8 ms (window 1), 44–50 ms (window 2) and 94–100 ms (window 3). The speed of neural adaptation was quantified using a two-parameter power law estimation. In 23 participants, four electrodes across the electrode array were tested. In three participants, three electrodes were tested. Results measured at different electrode locations were averaged for each participant at each pulse rate in order to get an overall representation of neural adaptation properties of the AN across the cochlea. Linear Mixed Models (LMMs) were used 1) to evaluate the effects of age at testing and pulse rate on the speed of neural adaptation, and 2) to assess the effects of age at testing, pulse rate, and duration of stimulation (i.e., time window) on the amount of neural adaptation in these participants. RESULTS: There was substantial variability in both the amount and the speed of neural adaptation of the AN among study participants. The amount and the speed of neural adaptation increased at higher pulse rates. In addition, larger amounts of adaptation were observed for longer durations of stimulation. There was no significant effect of age on the speed or the amount of neural adaptation. CONCLUSIONS: The amount and the speed of neural adaptation of the AN are affected by both the pulse rate and the duration of stimulation, with higher pulse rates and longer durations of stimulation leading to faster and greater neural adaptation. Advanced age does not affect neural adaptation of the AN in postlingually deafened, middle-aged and elderly adult CI users.

BACKGROUND: Diminished synaptic gain-the sensitivity of postsynaptic responses to neural inputs-may be a fundamental synaptic pathology in schizophrenia. Evidence for this is indirect, however. Furthermore, it is unclear whether pyramidal cells or interneurons (or both) are affected, or how these deficits relate to symptoms. \ud \ud METHODS: People with schizophrenia diagnoses (PScz) (n = 108), their relatives (n = 57), and control subjects (n = 107) underwent 3 electroencephalography (EEG) paradigms-resting, mismatch negativity, and 40-Hz auditory steady-state response-and resting functional magnetic resonance imaging. Dynamic causal modeling was used to quantify synaptic connectivity in cortical microcircuits. \ud \ud RESULTS: Classic group differences in EEG features between PScz and control subjects were replicated, including increased theta and other spectral changes (resting EEG), reduced mismatch negativity, and reduced 40-Hz power. Across all 4 paradigms, characteristic PScz data features were all best explained by models with greater self-inhibition (decreased synaptic gain) in pyramidal cells. Furthermore, disinhibition in auditory areas predicted abnormal auditory perception (and positive symptoms) in PScz in 3 paradigms. \ud \ud CONCLUSIONS: First, characteristic EEG changes in PScz in 3 classic paradigms are all attributable to the same underlying parameter change: greater self-inhibition in pyramidal cells. Second, psychotic symptoms in PScz relate to disinhibition in neural circuits. These findings are more commensurate with the hypothesis that in PScz, a primary loss of synaptic gain on pyramidal cells is then compensated by interneuron downregulation (rather than the converse). They further suggest that psychotic symptoms relate to this secondary downregulation.

Objective: Tinnitus can result from auditory system reorganization due to neural activity dysfunctions. Auditory stimulation can cause temporary or persistent tinnitus alleviation by altering the neural generators. The present study investigated the changes in Late-Latency Auditory Evoked Potentials (LLAEPs) after tinnitus suppression using auditory stimulation with short-term Residual Inhibition (RI) and long-term Tinnitus Masker (TM). Methods: The study included 40 participates with equal numbers in the Tinnitus Group (TG), including the chronic tinnitus subjects, and the Control Group (CG), including matched volunteers. The participants had normal hearing in conventional audiometry. All the participants underwent LLAEP recording pre-intervention and after a one-minute auditory stimulation (RI), as well as a pre-intervention Dichotic Digit Test (DDT) as a behavioral assessment of the selective attention. Moreover, TG underwent a 3-month course of TM, a third LLAEP recording post-TM, a second DDT post-TM, and the Tinnitus Handicap Inventory (THI) before and after the TM. Results: In the baseline LLAEP recording, the TG had significantly later N1, P3a, and P3b latencies, as well as significantly lower P3a and P3b amplitudes. The second LLAEP recording showed a significant intragroup increase in P3a amplitude and a significant decrease in P3a latency in the TG, while no significant intragroup difference was observed in the CG. In the third LLAEP recording performed on TG, the P3a amplitude and latency had significant changes compared to the second recording, while the N1 latency was significantly decreased. Moreover, the DDT and THI scores had significant improvement after the TM in TG. Conclusions: The present study showed the neurophysiological changes after short-term (RI) and long-term (TM) auditory stimulations in tinnitus subjects. The LLAEP changes suggest that these interventions lead to tinnitus suppression through common mechanisms. The electrophysiological observation was also confirmed using behavioral assessments. Level of evidence: This study type is a “comparative study” with the level of evidence “3”.

To analyze the effect of masking on the Cortical Auditory Evoked Potential with speech stimulus in young adults.Fourteen individuals aged between 19 and 28 years of both sexes with no hearing loss participated in the study. The Cortical Auditory Evoked Potential examination was performed with synthetic speech stimulus /ba/ simultaneous to Speech Shaped Noise presented under three conditions: steady noise with a 30 dB SPLep intensity (weak steady noise), steady noise with a 65 dB SPLep intensity o (strong steady noise) and modulated noise with 30 dB SPLep and 65 dB SPLep intensities at 25Hz and modulation period of 40 ms.Higher latencies were observed in the cortical components, except P2, in the condition of strong steady noise and more meaningful measures of amplitude of the cortical components P1, N1 and P2 in the condition of modulated noise with statistically significant difference in comparison to the strong steady noise condition. There was worse wave morphology in the condition of strong steady noise, when compared to the other records. The average electrophysiological thresholds for the conditions of strong steady noise and modulated noise were 60 dB SPLep and 49 dB SPLep, respectively, showing a 11.7 dB mean difference.We could infer that there was a lower masking effect of modulated noise when compared to the strong steady noise condition, in the amplitude measurements of the cortical components and an average difference of 11.7 dB between the electrophysiological thresholds (interpreted as the measure of the Masking Release).analisar o efeito do mascaramento estável e modulado no Potencial Evocado Auditivo Cortical com estímulo de fala em adultos-jovens.participaram 14 indivíduos com idades entre 19 e 28 anos de ambos os sexos e sem perda auditiva. O exame de Potencial Evocado Auditivo Cortical foi realizado com estímulo de fala sintética /ba/ simultâneo ao ruído Speech Shaped Noise apresentado em três condições: ruído estável com intensidade de 30 dB NPSpe (ruído estável fraco), ruído estável com intensidade de 65 dB NPSpe (ruído estável forte) e ruído modulado em intensidade de 30 dB NPSpe e 65 dB NPSpe em 25Hz e com período de modulação de 40 ms.foram observadas maiores latências nos componentes corticais, exceto P2, na condição de ruído estável forte e medidas mais robustas de amplitude dos componentes corticais P1, N1 e P2 na condição de ruído modulado com diferença estatística significativa na comparação com a condição de ruído estável forte. Houve pior morfologia na condição de ruído estável forte, quando comparado aos demais registros. Os limiares eletrofisiológicos médios para as condições de ruído estável forte e ruído modulado foram 60 dB NPSpe e 49 dB NPSpe, respectivamente, mostrando 11,7 dB de diferença média.podemos inferir que houve um menor efeito mascarante do ruído modulado, comparado à condição de ruído estável forte, nas medidas de amplitude dos componentes corticais e uma diferença média de 11,7 dB entre os limiares eletrofisiológicos (interpretado como a medida do Benefício do Mascaramento Modulado).

Attentional models of time perception assume that the perceived duration of a stimulus depends on the extent to which attentional resources are allocated to its temporal information. Here, we studied the effects of auditory distraction on time perception, using a combined attentional-distraction duration-discrimination paradigm. Participants were confronted with a random sequence of long and short tone stimuli, most of which having a uniform (standard) pitch and only a few a different (deviant) pitch. As observed in previous studies, pitch-deviant tones impaired the discrimination of tone duration and triggered a sequence of event-related potentials (ERPs) reflecting a cycle of deviance detection, involuntary attentional distraction, and reorientation (MMN, P3a, RON). Contrasting ERPs of short and long tone durations revealed that long tones elicited a more pronounced fronto-central contingent negative variation (CNV) in the time interval after the expected offset of the short tone as well as a more prominent centro-parietal late positive complex (LPC). Relative to standard-pitch tones, deviant-pitch tones especially impaired the correct discrimination of long tones, which was associated with a reduction of the CNV and LPC. These results are interpreted within the theoretical framework of resource-based models of time perception, in which involuntary distraction due to a deviant event led to a withdrawal of attentional resources from the processing of time information.

Objective The purpose of this study was to determine better- ear listening effect on spatial separation with the N1–P2 complex. Methods Twenty individuals with normal hearing participated in this study. The speech stimulus /ba/ was presented in front of the participant (0°). Continuous Speech Noise (5 dB signal-to-noise ratio) was presented either in front of the participant (0°), left-side (-90°), or right-side (+90°). N1- P2 complex has been recorded in quiet and three noisy conditions. Results There was a remarkable effect of noise direction on N1, P2 latencies. When the noise was separated from the stimulus, N1 and P2 latency increased in terms of when noise was co-located with the stimulus. There was no statistically significant difference in N1-P2 amplitudes between the stimulus-only and co-located condition. N1-P2 amplitude was increased when the noise came from the sides, according to the stimulus-only and co-located conditions. Conclusion These findings demonstrate that the latency shifts on N1-P2 complex explain cortical mechanisms of spatial separation in better-ear listening.

Decreased mismatch negativity (MMN) is a proposed biomarker for psychotic disorders. However, the magnitude of the effect appears to be attenuated in first-episode populations. Furthermore, how mismatch negativity amplitudes are related to brain connectivity in this population is unclear. In this study, we used high-density EEG to record duration-deviant MMN from 22 patients with first-episode psychosis (FEP) and 23 age-matched controls (HC). Consistent with past work, we found decreased MMN amplitude in FEP over a large area of the frontal scalp. We also found decreased latency over the occipital scalp. MMN amplitude was negatively correlated with antipsychotic dose. We used Granger causality to investigate directional connectivity between frontal, midline, left, and right scalp during MMN and found reduced connectivity in FEP compared to HC and following deviant stimuli compared to standard stimuli. FEP participants with smaller decreases in connectivity from standard to deviant stimuli had worse disorganization symptoms. On the other hand, connectivity from the front of the scalp following deviant stimuli was relatively preserved in FEP compared to controls. Our results suggest that a relative imbalance of bottom-up and top-down perceptual processing is present in the early stages of psychotic disorders.

Long-latency auditory evoked potentials (LLAEPs) may help further advances in understanding consciousness under general anesthesia and promote more objective means of assessing sedation depth than conventional clinical signs. Among the LLAEP components, the auditory N1 shows promise as a measure of sedation depth and a marker of consciousness, but findings are so far inconclusive. Research with animals can help elucidate the effects of various anesthetics on the N1 and other LLAEPs, but investigations of LLAEPs under anesthesia in animals is lacking. To address this deficit, we examined the P1, N1, P2, and N2, along with their corresponding peak-to-peak complexes, in 10 Wistar rats anesthetized with 1.5–2 % isoflurane in pure oxygen and again after recovery. While under anesthesia, subdermal needle electrodes were inserted and secured for electroencephalographic (EEG) recordings. LLAEPs were assessed during a 20-min, passive, two-tone (500 ms inter-tone interval) paradigm with randomized short (1 s) and long (5 s) inter-pair intervals (IPIs). Overall, while the LLAEP peaks under isoflurane were less defined, they were not eliminated. The peak-to-peak amplitudes, particularly the P1-N1, were significantly smaller under isoflurane than during post-recovery. Our preliminary findings indicate that isoflurane produces global suppression across LLAEP components, presumably reflecting impaired integration of top-down and bottom-up attention and sensory systems under profound sedation with isoflurane.

Objectives –Mismatch negativity (MMN) has been demonstrated as a potential biomarker for pre-attentive processing and prognosis in patients with psychosis. However, previous studies mainly evaluated the reliability of MMN across only two repeated sessions, which is inadequate to draw a convincing conclusion. The current study aimed to assess multi-session test-retest reliability in duration-related MMN (dMMN) and frequency-related MMN (fMMN). Methods –We recorded four repeated sessions of electroencephalography (EEG) from 16 healthy participants in an oddball task. MMNs were extracted and their reliability was evaluated by intra-class coefficient (ICC). We also analyzed the correlation between fMMN and dMMN. Results –Both dMMN and fMMN amplitudes exhibited good test-retest reliability, and fMMN had better reliability (average ICC = 0.7279) than dMMN (average ICC = 0.6974). Moreover, dMMN and fMMN showed more than moderate linear correlation in amplitudes (r = 0.598, CI: [0.100, 0.857]). Conclusion –Both the duration- and frequency-related MMN amplitudes were highly reliable across four-session experiments. These results provide further evidence for the potential utility of MMNs as biomarkers in research into brain function, and prognosis in psychotic illness.

Reward associations are known to shape the brain's processing of visual stimuli, but relatively less is known about how reward associations impact the processing of auditory stimuli. We leveraged the high-temporal resolution of electroencephalography (EEG) and event-related potentials (ERPs) to investigate the influence of low- and high-magnitude stimulus-reward associations in an auditory oddball task. We associated fast, correct detection of certain auditory target stimuli with larger monetary rewards, and other auditory targets with smaller rewards. We found enhanced attentional processing of the more highly rewarded target stimuli, as evidenced by faster behavioral detection of those stimuli compared with lower-rewarded stimuli. Neurally, higher-reward associations enhanced the early sensory processing of auditory targets. Targets associated with higher-magnitude rewards had higher amplitude N1 and mismatch negativity (MMN) ERP components than targets associated with lower-magnitude rewards. Reward did not impact the latency of these early components. Higher-reward magnitude also decreased the latency and increased the amplitude of the longer-latency P3 component, suggesting that reward also can enhance the final processing stages of auditory target stimuli. These results provide insight into how the sensory and attentional neural processing of auditory stimuli is modulated by stimulus-reward associations and the magnitude of those associations, with higher-magnitude reward associations yielding enhanced auditory processing at both early and late stages compared with lower-magnitude reward associations.

Paired pulse suppression is an electrophysiological method used to evaluate sensory suppression and often applied to patients with psychiatric disorders. However, it remains unclear whether the suppression comes from specific inhibitory mechanisms, refractoriness, or fatigue. In the present study, to investigate mechanisms of suppression induced by an auditory paired pulse paradigm in 19 healthy subjects, magnetoencephalography was employed. The control stimulus was a train of 25-ms pure tones of 65 dB SPL for 2500 ms. In order to evoke a test response, the sound pressure of two consecutive tones at 2200 ms in the control sound was increased to 80 dB (Test stimulus). Similar sound pressure changes were also inserted at 1000 (CS2) and 1600 (CS1) ms as conditioning stimuli. Four stimulus conditions were used; (1) Test alone, (2) Test + CS1, (3) Test + CS1 + CS2, and (4) Test + CS2, with the four sound stimuli randomly presented and cortical responses averaged at least 100 times for each condition. The baseline-to-peak and peak-to-peak amplitudes of the P50m, N100m, and P200m components of the test response were compared among the four conditions. In addition, the response to CS1 was compared between conditions (2) and (3). The results showed significant test response suppression by CS1. While the response to CS1 was significantly suppressed when CS2 was present, it did not affect suppression of the test response by CS1. It was thus suggested that the amplitude of the response to a conditioning stimulus is not a factor to determine the inhibitory effects of the test response, indicating that suppression is due to an external influence on the excitatory pathway.