Search

Objectives: The present study aims to investigate the effects of age, gender, and level of education on P300 in a healthy population, aged 50 years and over; and determine the reliability metrics for different conditions and measurement methods.Method: Auditory and visual oddball recordings of 171 healthy adults were investigated. A fully automated preprocessing was applied to elicit ERP P300. Maximum peak amplitude, latency and mean amplitudes were measured. Data were stratified by age, gender, and education to determine group-level differences by using repeat measures of ANOVA. The internal consistency of P300 was calculated by a split-half method using odd-even segments. Test-retest reliability was assessed by calculating the intraclass correlation coefficient (ICC).Results: Maximum peak P300 amplitudes were higher in the 50-64 years age group compared to the >65 years age group; and females showed increased P300 amplitudes compared to males. P300 measures showed fair to good internal consistency and poor to good test-retest reliability.Conclusion: Age and gender should be taken into account when designing ERP studies with elderly individuals. P300 showed good internal consistency in general, between gender groups and age groups. Long-term test-retest reliability was lower but acceptable. These findings can be interpreted as the strength of P300 by being an objective and reliable method independent of cultural differences. Here we underline several factors that may affect P300 measures and discuss other possible factors that should be standardized for P300 to be used in clinical settings.

In many animals, vocal-acoustic communication is fundamental for facilitating social behaviors. For the vocal plainfin midshipman fish, the detection and localization of social acoustic signals are critical to the species’ reproductive success. Here, we show that the utricle, an inner ear end organ often thought to primarily serve a vestibular function, serves an auditory function that is seasonally plastic and modulated by the animal’s reproductive state effectively enhancing auditory sensitivity to courting male advertisement calls.

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.

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.

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).

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.

Auditory selective attention is a crucial top-down cognitive mechanism for understanding speech in noise. Cochlear implant (CI) users display great variability in speech-in-noise performance that is not easily explained by peripheral auditory profile or demographic factors. Thus, it is imperative to understand if auditory cognitive processes such as selective attention explain such variability. The presented study directly addressed this question by quantifying attentional modulation of cortical auditory responses during an attention task and comparing its individual differences with speech-in-noise performance. In our attention experiment, participants with CI were given a pre-stimulus visual cue that directed their attention to either of two speech streams and were asked to select a deviant syllable in the target stream. The two speech streams consisted of the female voice saying “Up” five times every 800 ms and the male voice saying “Down” four times every 1 s. The onset of each syllable elicited distinct event-related potentials (ERPs). At each syllable onset, the difference in the amplitudes of ERPs between the two attentional conditions (attended - ignored) was computed. This ERP amplitude difference served as a proxy for attentional modulation strength. Our group-level analysis showed that the amplitude of ERPs was greater when the syllable was attended than ignored, exhibiting that attention modulated cortical auditory responses. Moreover, the strength of attentional modulation showed a significant correlation with speech-in-noise performance. These results suggest that the attentional modulation of cortical auditory responses may provide a neural marker for predicting CI users’ success in clinical tests of speech-in-noise listening.

Neural activations during auditory oddball tasks may be endophenotypes for psychosis and bipolar disorder. The authors investigated oddball neural deviations that discriminate multiple diagnostic groups across the schizophrenia-bipolar spectrum (schizophrenia, schizoaffective disorder, psychotic bipolar disorder, and nonpsychotic bipolar disorder) and clarified their relationship to clinical and cognitive features.Auditory oddball responses to standard and target tones from 64 sensor EEG recordings were compared across patients with psychosis (total N=597; schizophrenia, N=225; schizoaffective disorder, N=201; bipolar disorder with psychosis, N=171), patients with bipolar disorder without psychosis (N=66), and healthy comparison subjects (N=415) from the second iteration of the Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP2) study. EEG activity was analyzed in voltage and in the time-frequency domain (low, beta, and gamma bands). Event-related potentials (ERPs) were compared with those from an independent sample collected during the first iteration of B-SNIP (B-SNIP1; healthy subjects, N=211; psychosis group, N=526) to establish the repeatability of complex oddball ERPs across multiple psychosis syndromes (r values0.94 between B-SNIP1 and B-SNIP2).Twenty-six EEG features differentiated the groups; they were used in discriminant and correlational analyses. EEG variables from the N100, P300, and low-frequency ranges separated the groups along a diagnostic continuum from healthy to bipolar disorder with psychosis/bipolar disorder without psychosis to schizoaffective disorder/schizophrenia and were strongly related to general cognitive function (r=0.91). P50 responses to standard trials and early beta/gamma frequency responses separated the bipolar disorder without psychosis group from the bipolar disorder with psychosis group. P200, N200, and late beta/gamma frequency responses separated the two bipolar disorder groups from the other groups.Neural deviations during auditory processing are related to psychosis history and bipolar disorder. There is a powerful transdiagnostic relationship between severity of these neural deviations and general cognitive performance. These results have implications for understanding the neurobiology of clinical syndromes across the schizophrenia-bipolar spectrum that may have an impact on future biomarker research.

Objective Cochlear implants (CIs) provide access to the auditory world for deaf individuals. We investigated whether CIs enforce attentional alterations of auditory cortical processing in post-lingually deafened CI users compared to normal-hearing (NH) controls. Methods Event-related potentials (ERPs) were recorded in 40 post-lingually deafened CI users and in a group of 40 NH controls using an auditory three-stimulus oddball task, which included frequent standard tones (Standards) and infrequent deviant tones (Targets), as well as infrequently occurring unique sounds (Novels). Participants were exposed twice to the three-stimulus oddball task, once under the instruction to ignore the stimuli (ignore condition), and once under the instruction to respond to infrequently occurring deviant tones (attend condition). Results The allocation of attention to auditory oddball stimuli exerted stronger effects on N1 amplitudes at posterior electrodes in response to Standards and to Targets in CI users than in NH controls. Other ERP amplitudes showed similar attentional modulations in both groups (P2 in response to Standards, N2 in response to Targets and Novels, P3 in response to Targets). We also observed a statistical trend for an attenuated attentional modulation of Novelty P3 amplitudes in CI users compared to NH controls. Conclusions ERP correlates of enhanced CI-mediated auditory attention are confined to the latency range of the auditory N1, suggesting that enhanced attentional modulation during auditory stimulus discrimination occurs primarily in associative auditory cortices of CI users. Significance The present ERP data support the hypothesis of attentional alterations of auditory cortical processing in CI users. These findings may be of clinical relevance for the CI rehabilitation.

The auditory mismatch negativity (MMN) is significantly reduced in schizophrenia. Notably, a similar MMN reduction can be achieved with NMDA receptor (NMDAR) antagonists. Both phenomena have been interpreted as reflecting an impairment of predictive coding or, more generally, the “Bayesian brain” notion that the brain continuously updates a hierarchical model to infer the causes of its sensory inputs. Specifically, predictive coding views perceptual inference as an NMDAR-dependent process of minimizing hierarchical precision-weighted prediction errors (PEs). Disturbances of this putative process play a key role in hierarchical Bayesian theories of schizophrenia.Here, we provide empirical evidence for this clinical theory, demonstrating the existence of multiple, hierarchically related PEs in a “roving MMN” paradigm. We applied a computational model, the Hierarchical Gaussian Filter (HGF), to single-trial EEG data from healthy volunteers that received the NMDAR antagonist S-ketamine in a placebo-controlled, double-blind, within-subject fashion. Using an unrestricted analysis of the entire time-sensor space, our computational trial-by-trial analysis indicated that low-level PEs (about stimulus transitions) are expressed early (102-207ms post-stimulus), while high-level PEs (about transition probability) are reflected by later components (152-199ms, 215-277ms) of single-trial responses. Furthermore, we find that ketamine significantly diminished the expression of high-level PE responses, implying that NMDAR antagonism disrupts inference on abstract statistical regularities.Our findings are consistent with long-standing notions that NMDAR dysfunction may cause positive symptoms in schizophrenia by impairing hierarchical Bayesian inference about the world’s statistical structure. Beyond their relevance for schizophrenia, our results illustrate the potential of computational single-trial analyses for assessing potential disease mechanisms.

OBJECTIVES: The objectives were to measure the effect of stimulus rate and vowel-change direction on the acoustic change complex (ACC) latencies and amplitudes and compare ACC metrics to behavioral measures of vowel-contrast detection for infants tested under the age of 1 year. We tested the hypothesis that the direction of spectral energy shift from a vowel change would result in differences in the ACC, owing to the sensitivity of cortical neurons to the direction of frequency change. We evaluated the effect of the stimulus rate (1/s vs. 2/s) on the infants’ ACC. We evaluated the ACC amplitude ratio’s sensitivity (proportion of ACCs present for each change trial) and compared it to perceptual responses obtained using a visually-reinforced infant speech discrimination paradigm (VRISD). This report provides normative data from infants for the ACC towards the ultimate goal of developing a clinically useful index of neural capacity for vowel discrimination. DESIGN: Twenty-nine infants, nine females, aged 4.0–11.8 months, participated. All participants were born at full-term and passed their newborn hearing screens. None had risk factors for hearing or neurologic impairment. Cortical auditory evoked potentials were obtained in response to synthesized vowel tokens /a/, /i/, /o/ and /u/ presented at a rate of 1- or 2/s in an oddball stimulus paradigm with a 25% probability of the deviant stimulus. All combinations of vowel tokens were tested at the two rates. The ACC was obtained in response to the deviant stimulus. The infants were also tested for vowel-contrast detection using a VRISD paradigm with the same combinations of vowel tokens used for the ACC. The mean age at the time of the ACC test was 5.4 months, while the mean age at the behavioral test was 6.8 months. RESULTS: Variations in ACC amplitude and latency occurred as a function of the initial vowel token and the contrast token. However, the hypothesis that the direction of vowel (spectral) change would result in significantly larger change responses for high-to-low spectral changes was not supported. The contrasts with /a/ as the leading vowel of the contrast pair resulted in the largest ACC amplitudes than other conditions. Significant differences in the ACC presence and amplitude were observed as a function of rate, with 2/s resulting in ACCs with the largest amplitude ratios. Latency effects of vowel contrast and rate were present, but not systematic. The ACC amplitude ratio’s sensitivity for detecting a vowel contrast was greater for the 2/s rate than the 1/s rate. For an amplitude ratio criterion of ≥ 1.5, the sensitivity was 93% for ACC component P2-N2 at 2/s, whereas at 1/s sensitivity was 70%. VRISD tests of vowel-contrast detection had a 71% hit and a 21% false-positive rate. Many infants who could not reach performance criteria for VRISD had ACC amplitude ratios ≥ 2.0. DISCUSSION: The ACC for vowel contrasts presented at a rate of 2/s is a robust index of vowel-contrast detection when obtained in typically developing infants under the age of 1 year. The ACC is present in over 90% of infants tested at this rate when an amplitude ratio criterion of ≥1.5 is used to define a response. The amplitude ratio appears to be a sensitive metric for the difference between a control and contrast condition. The ACC can be obtained in infants who do not yet exhibit valid behavioral responses for vowel change contrasts and may be useful for estimating neural capacity for discriminating these sounds.

This study aimed to validate the existence and investigate the characteristics of the transient responses from conventional auditory steady-state responses (ASSRs) using deconvolution methods capable of dealing with amplitude modulated (AM) stimulation. Conventional ASSRs to seven stimulus rates were recorded from 17 participants. A deconvolution method was selected and modified to accommodate the AM stimulation. The calculated responses were examined in terms of temporal features with respect to different combinations of stimulus rates. Stable transient responses consisting of early stage brainstem responses and middle latency responses were reconstructed consistently for all rate combinations, which indicates that the superposition hypothesis is applicable to the generation of approximately 80 Hz ASSRs evoked by AM tones (AM-ASSRs). The new transient responses are characterized by three pairs of peak-troughs named as n(0)p(0), n(1)p(1), and n(2)p(2) within 40 ms. Compared with conventional ABR-MLRs, the n(0)p(0) indicates the first neural activity where p(0) might represent the main ABR components; the n(1) is the counterpart of N10; the p(2) is corresponding to the robust Pa at about 30 ms; the p(1) and n(2) are absent of real counterparts. The peak–peak amplitudes show a slight decrease with increasing stimulation rate from 75 to 95 Hz whereas the peak latencies change differently, which is consistent with the known rate-effect on AEPs. This is direct evidence for a transient response derived from AM-ASSRs for the first time. The characteristic components offer insight into the constitution of AM-ASSRs and may be promising in clinical applications and fundamental studies.

Objective Altered sensory processing is common in intellectual disability (ID). Here, we study electroencephalographic responses to auditory stimulation in human subjects presenting a rare condition (mutations in SYNGAP1) which causes ID, epilepsy and autism. Methods Auditory evoked potentials, time-frequency and inter-trial coherence analyses were used to compare subjects with SYNGAP1 mutations with Down syndrome (DS) and neurotypical (NT) participants (N = 61 ranging from three to 19 years of age). Results Altered synchronization in the brain responses to sound were found in both ID groups. The SYNGAP1 mutations group showed less phase-locking in early time windows and lower frequency bands compared to NT, and in later time windows compared to NT and DS. Time-frequency analysis showed more power in beta-gamma in the SYNGAP1 group compared to NT participants. Conclusions This study indicated reduced synchronization as well as more high frequencies power in SYNGAP1 mutations, while maintained synchronization was found in the DS group. These results might reflect dysfunctional sensory information processing caused by excitation/inhibition imbalance, or an imperfect compensatory mechanism in SYNGAP1 mutations individuals. Significance Our study is the first to reveal brain response abnormalities in auditory sensory processing in SYNGAP1 mutations individuals, that are distinct from DS, another ID condition.

Objective We measured the neurophysiological responses of both active and sham transcranial magnetic stimulation (TMS) for both single pulse (SP) and paired pulse (PP; long interval cortical inhibition (LICI)) paradigms using TMS-EEG (electroencephalography). Methods Nineteen healthy subjects received active and sham (coil 90° tilted and touching the scalp) SP and PP TMS over the left dorsolateral prefrontal cortex (DLPFC). We measured excitability through SP TMS and inhibition (i.e., cortical inhibition (CI)) through PP TMS. Results Cortical excitability indexed by area under the curve (AUC(25-275ms)) was significantly higher in the active compared to sham stimulation (F(1,18) = 43.737, p Conclusion The significant differences between active and sham stimulation in both excitatory and inhibitory neurophysiological responses showed that active stimulation elicits responses from the cortex that are different from the non-specific effects of sham stimulation. Significance Our study reaffirms that TMS-EEG represents an effective tool to evaluate cortical neurophysiology with high fidelity.

Current clinical phenomenological diagnosis in psychiatry neither captures biologically homologous disease entities nor allows for individualized treatment prescriptions based on neurobiology. In this report, we studied two large samples of cases with schizophrenia, schizoaffective, and bipolar I disorder with psychosis, presentations with clinical features of hallucinations, delusions, thought disorder, affective, or negative symptoms. A biomarker approach to subtyping psychosis cases (called psychosis Biotypes) captured neurobiological homology that was missed by conventional clinical diagnoses. Two samples (called “B-SNIP1” with 711 psychosis and 274 healthy persons, and the “replication sample” with 717 psychosis and 198 healthy persons) showed that 44 individual biomarkers, drawn from general cognition (BACS), motor inhibitory (stop signal), saccadic system (pro- and anti-saccades), and auditory EEG/ERP (paired-stimuli and oddball) tasks of psychosis-relevant brain functions were replicable (r’s from .96–.99) and temporally stable (r’s from .76–.95). Using numerical taxonomy (k-means clustering) with nine groups of integrated biomarker characteristics (called bio-factors) yielded three Biotypes that were virtually identical between the two samples and showed highly similar case assignments to subgroups based on cross-validations (88.5%–89%). Biotypes-1 and -2 shared poor cognition. Biotype-1 was further characterized by low neural response magnitudes, while Biotype-2 was further characterized by overactive neural responses and poor sensory motor inhibition. Biotype-3 was nearly normal on all bio-factors. Construct validation of Biotype EEG/ERP neurophysiology using measures of intrinsic neural activity and auditory steady state stimulation highlighted the robustness of these outcomes. Psychosis Biotypes may yield meaningful neurobiological targets for treatments and etiological investigations.

The human auditory system often relies on relative pitch information to extract and identify auditory objects; such as when the same melody is played in different keys. The current study investigated the mental chronometry underlying the active discrimination of unfamiliar melodic six-tone patterns by measuring behavioural performance and event-related potentials (ERPs). In a roving standard paradigm, such patterns were either repeated identically within a stimulus train, carrying absolute frequency information about the pattern, or shifted in pitch (transposed) between repetitions, so only relative pitch information was available to extract the pattern identity. Results showed that participants were able to use relative pitch to detect when a new melodic pattern occurred. Though in the absence of absolute pitch sensitivity significantly decreased and behavioural reaction time to pattern changes increased. Mismatch-Negativity (MMN), an ERP indicator of auditory deviance detection, was elicited at approximately 206 ms after stimulus onset at frontocentral electrodes, even when only relative pitch was available to inform pattern discrimination. A P3a was elicited in both conditions, comparable in amplitude and latency. Increased latencies but no differences in amplitudes of N2b, and P3b suggest that processing at higher levels is affected when, in the absence of absolute pitch cues, relative pitch has to be extracted to inform pattern discrimination. Interestingly, the response delay of approximately 70 ms on the behavioural level, already fully manifests at the level of N2b. This is in accordance with recent findings on implicit auditory learning processes and suggests that in the absence of absolute pitch cues a slowing of target selection rather than a slowing of the auditory pattern change detection process causes the deterioration in behavioural performance.

Prenatal exposure to ZIKV can cause neurologic and auditory damage. The electrophysiological responses obtained by Cortical Auditory Evoked Potentials (CAEP) may provide an objective method to investigate the function of cortical auditory pathways in children exposed to ZIKV. This case series analyzed the findings of CAEP in prenatal-period ZIKV-exposed children with and without microcephaly. The CAEP was performed in a total of 24 children. Five magnetic resonance imaging (MRI) images of the inner ear and brain of microcephalic children were analyzed and compared with CAEP measurements. Ventriculomegaly (80%), cortical/subcortical calcification (80%), and brain reduction (60%) were the most common alterations in the MRI. The P1-N1-P2 complex of the CAEP was observed in all children evaluated. The peak N2 was absent in two children. In the comparison of the CAEP measurements between the groups, children with microcephaly presented a higher amplitude of P2 (p = 0.017), which may reflect immaturity of the auditory pathways. Microcephalic and normocephalic children with prenatal exposure to ZIKV presented with the mandatory components of the CAEPs, regardless of changes in the CNS, suggesting that this population has, to some extent, the cortical ability to process sound stimuli preserved.

The classical auditory oddball paradigm is a commonly used experimental paradigm for evoking event related potentials (ERPs). The present study was aimed to explore the auditory cognitive processing mechanism of space perception of human brain. We employed an auditory oddball paradigm of binaural unbiased and biased sound intensity to compare and analyze the response characteristics of ERP. By focusing on the spatial lateralization characteristics of P300 and mismatch negativity (MMN) components, we analyzed their lateralization trends according to the laterality index. We found that both P300 and MMN components showed right-hemisphere lateralization phenomenon under the stimulation of asymmetric intensity of auditory acoustic. The results suggested that the right hemisphere of human brain played a key role in spatial information processing. The results also indicated that the hemispherical characteristics of the brain were not related to the actual spatial direction of the auditory stimulus, but were determined by the hemispherical functions of the brain. Furthermore, the results suggested that the MMN components induced by spatial differences were stronger in females than those in males.

IMPORTANCE: Although clinical criteria for identifying youth at risk for psychosis have been validated, they are not sufficiently accurate for predicting outcomes to inform major treatment decisions. The identification of biomarkers may improve outcome prediction among individuals at clinical high risk for psychosis (CHR-P). OBJECTIVE: To examine whether mismatch negativity (MMN) event–related potential amplitude, which is deficient in schizophrenia, is reduced in young people with the CHR-P syndrome and associated with outcomes, accounting for effects of antipsychotic medication use. DESIGN, SETTING, AND PARTICIPANTS: MMN data were collected as part of the multisite case-control North American Prodrome Longitudinal Study (NAPLS-2) from 8 university-based outpatient research programs. Baseline MMN data were collected from June 2009 through April 2013. Clinical outcomes were assessed throughout 24 months. Participants were individuals with the CHR-P syndrome and healthy controls with MMN data. Participants with the CHR-P syndrome who developed psychosis (ie, converters) were compared with those who did not develop psychosis (ie, nonconverters) who were followed up for 24 months. Analysis took place between December 2019 and December 2021. MAIN OUTCOMES AND MEASURES: Electroencephalography was recorded during a passive auditory oddball paradigm. MMN elicited by duration-, pitch-, and duration + pitch double-deviant tones was measured. RESULTS: The CHR-P group (n = 580; mean [SD] age, 19.24 [4.39] years) included 247 female individuals (42.6%) and the healthy control group (n = 241; mean age, 20.33 [4.74] years) included 114 female individuals (47.3%). In the CHR-P group, 450 (77.6%) were not taking antipsychotic medication at baseline. Baseline MMN amplitudes, irrespective of deviant type, were deficient in future CHR-P converters to psychosis (n = 77, unmedicated n = 54) compared with nonconverters (n = 238, unmedicated n = 190) in both the full sample (d = 0.27) and the unmedicated subsample (d = 0.33). In the full sample, baseline medication status interacted with group and deviant type indicating that double-deviant MMN, compared with single deviants, was reduced in unmedicated converters compared with nonconverters (d = 0.43). Further, within the unmedicated subsample, deficits in double-deviant MMN were most strongly associated with earlier conversion to psychosis (hazard ratio, 1.40 [95% CI, 1.03-1.90]; P = .03], which persisted over and above positive symptom severity. CONCLUSIONS AND RELEVANCE: This study found that MMN amplitude deficits were sensitive to future psychosis conversion among individuals at risk of CHR-P, particularly those not taking antipsychotic medication at baseline, although associations were modest. While MMN shows limited promise as a biomarker of psychosis onset on its own, it may contribute novel risk information to multivariate prediction algorithms and serve as a translational neurophysiological target for novel treatment development in a subgroup of at-risk individuals.

Speech is transient. To comprehend entire sentences, segments consisting of multiple words need to be memorized for at least a while. However, it has been noted previously that we struggle to memorize segments longer than approximately 2.7 s. We hypothesized that electrophysiological processing cycles within the delta band (

Objective To describe EEG patterns of critical Coronavirus Disease 2019 (COVID-19) patients with suspicion of encephalopathy and test their association with clinical outcome. Methods EEG after discontinuation of sedation in all patients, and somesthesic evoked potentials and brainstem auditive evoked potentials when EEG did not show reactivity, were performed. Clinical outcome was assessed at day 7 and 14 after neurophysiological explorations. Results 33 patients were included for analysis. We found slowed background activity in 85% of cases, unreactive activity in 42% of cases, low-voltage activity in 21% of cases and rhythmic or periodic delta waves in 61% of cases. EEG epileptic events were never recorded. Clinical outcome at day 14 was associated with unreactive background activity and tended to be associated with rhythmic or periodic delta waves and with low-voltage activity. Results of multimodal evoked potentials were in favor of a preservation of central nervous system somatosensory and auditory functions. Conclusions Among critical COVID-19 patients with abnormal arousal at discontinuation of sedation, EEG patterns consistent with encephalopathy are found and are predictive for short term clinical outcome. Significance The abnormal EEG with presence of periodic discharges and lack of reactivity could be related to encephalopathy linked to COVID-19.

Neurobiological models of emotion focus traditionally on limbic/paralimbic regions as neural substrates of emotion generation, and insular cortex (in conjunction with isocortical anterior cingulate cortex, ACC) as the neural substrate of feelings. An emerging view, however, highlights the importance of isocortical regions beyond insula and ACC for the subjective feeling of emotions. We used music to evoke feelings of joy and fear, and multivariate pattern analysis (MVPA) to decode representations of feeling states in functional magnetic resonance (fMRI) data of n = 24 participants. Most of the brain regions providing information about feeling representations were neocortical regions. These included, in addition to granular insula and cingulate cortex, primary and secondary somatosensory cortex, premotor cortex, frontal operculum, and auditory cortex. The multivoxel activity patterns corresponding to feeling representations emerged within a few seconds, gained in strength with increasing stimulus duration, and replicated results of a hypothesis-generating decoding analysis from an independent experiment. Our results indicate that several neocortical regions (including insula, cingulate, somatosensory and premotor cortices) are important for the generation and modulation of feeling states. We propose that secondary somatosensory cortex, which covers the parietal operculum and encroaches on the posterior insula, is of particular importance for the encoding of emotion percepts, i.e., preverbal representations of subjective feeling.

The progressive degeneration of the excitable cells of the ear depends on the sustained excitation of the voltage-sensitive sodium channels, so the negative pharmacological modulation could be a rational therapeutic strategy against the damage of these cells. The objective was to demonstrate the effectiveness of Vinpocetine (VPC), a potent sodium channel blocker, as a treatment for acquired sensorineural hearing loss. A phase II, longitudinal and prospective open clinical study, was conducted over a period of 12 months with patients older than 18 years, to demonstrate the effectiveness of Vinpocetine (VPC) as a treatment for acquired sensorineural hearing loss, using evoked potentials, otoacoustic emissions, audiometry and logoaudiometry, analyzing the results at 6 and 12 months of treatment with Vinpocetine (30 mg/day in 3 doses). It was observed that from 0 to 6 months there was hearing impairment (which was already expected due to the age of the patients). From 6 to 12 months and from 0 to 12 months there were significant differences with a tendency towards improvement, indicating that the aforementioned deterioration not only stopped, but that with the use of vinpocetine, the hearing capacity improved. It is concluded that Vinpocetine helps to stop hearing impairment and even improve hearing.

Objective In the present study, we investigated the role of intraoperative neuromonitoring (IONM) in internal carotid artery (ICA) injury during endoscopic endonasal skull base surgery (EESBS). Methods The study group included all 13 patients who had experienced an ICA injury during EESBS with IONM from 2004 to 2017. The medical records were reviewed for the perioperative data. The IONM reports were reviewed to evaluate the baseline somatosensory evoked potentials (SSEP), electroencephalography (EEG), and brainstem auditory evoked potentials (BAEP) and their significant changes related to ICA injury and/or the subsequent surgical/endovascular interventions. Results All 13 patients had undergone SSEP and 7 patients had BAEP monitoring during surgery. EEG was added during emergent angiography following the surgery for 5 patients. Two patients showed significant SSEP changes, and one showed significant SSEP and EEG changes, indicating cerebral hypoperfusion. Of these 3 patients, patient 1 had experienced irreversible SSEP loss with postoperative stroke. Patients 2 and 3 had SSEP and/or EEG changes that had recovered to baseline after interventions without postoperative deficits. Despite ICA injury, 10 patients showed no significant SSEP and/or EEG changes, and all 7 patients with BAEP monitoring showed no significant BAEP changes, indicating adequate cerebral and brainstem perfusion, respectively. The injured ICA was sacrificed in 4 patients, of whom 3 showed stable SSEP and 1 had experienced irreversible SSEP loss. IONM correlated with the postoperative neurologic examination findings in all cases, adequately predicting the neurologic outcomes after ICA injury. Conclusion SSEP and EEG monitoring can accurately detect cerebral hypoperfusion and provide real-time feedback during surgery. SSEP and EEG changes predicted for neurologic outcomes and guide surgical decisions regarding the preservation or sacrifice of the ICA. Comprehensive multimodality monitoring according to the surgical risks can serve to detect and guide the management of ICA injury in EESBS.

Receptive fields of primary auditory cortex (A1) neurons show excitatory neuronal frequency preference and diverse inhibitory sidebands. While the frequency preferences of excitatory neurons in local A1 areas can be heterogeneous, those of inhibitory neurons are more homogeneous. To date, the diversity and the origin of inhibitory sidebands in local neuronal populations and the relation between local cellular frequency preference and inhibitory sidebands are unknown. To reveal both excitatory and inhibitory subfields, we presented two-tone and pure tone stimuli while imaging excitatory neurons (Thy1) and two types of inhibitory neurons (parvalbumin and somatostatin) in L2/3 of mice A1. We classified neurons into six classes based on frequency response area (FRA) shapes and sideband inhibition depended both on FRA shapes and cell types. Sideband inhibition showed higher local heterogeneity than frequency tuning, suggesting that sideband inhibition originates from diverse sources of local and distant neurons. Two-tone interactions depended on neuron subclasses with excitatory neurons showing the most nonlinearity. Onset and offset neurons showed dissimilar spectral integration, suggesting differing circuits processing sound onset and offset. These results suggest that excitatory neurons integrate complex and nonuniform inhibitory input. Thalamocortical terminals also exhibited sideband inhibition, but with different properties from those of cortical neurons. Thus, some components of sideband inhibition are inherited from thalamocortical inputs and are further modified by converging intracortical circuits. The combined heterogeneity of frequency tuning and diverse sideband inhibition facilitates complex spectral shape encoding and allows for rapid and extensive plasticity.SIGNIFICANCE STATEMENTSensory systems recognize and differentiate between different stimuli through selectivity for different features. Sideband inhibition serves as an important mechanism to sharpen stimulus selectivity, but its cortical mechanisms are not entirely resolved. We imaged pyramidal neurons and two common classes of interneurons suggested to mediate sideband inhibition (parvalbumin and somatostatin positive) in the auditory cortex and inferred their inhibitory sidebands. We observed a higher degree of variability in the inhibitory sideband than in the local frequency tuning, which cannot be predicted from the relative high homogeneity of responses by inhibitory interneurons. This suggests that cortical sideband inhibition is nonuniform and likely results from a complex interplay between existing functional inhibition in the feedforward input and cortical refinement.

Aim Gamma-band auditory steady-state response (ASSR) is a neurophysiologic index that is increasingly used as a translational biomarker in the development of treatments of neuropsychiatric disorders. While gamma-band ASSR is generated by distributed networks of highly interactive temporal and frontal cortical sources, the majority of human gamma-band ASSR studies using electroencephalography (EEG) highlight activity from only a single frontocentral scalp site, Fz, where responses tend to be largest and reductions in schizophrenia patients are most evident. However, no previous study has characterized the relative source contributions to Fz, which is a necessary step to improve the concordance of preclinical and clinical EEG studies. Methods A novel method to back-project the contributions of independent cortical source components was applied to assess the independent sources and their proportional contributions to Fz as well as source-resolved responses in 432 schizophrenia patients and 294 healthy subjects. Results Independent contributions of gamma-band ASSR to Fz were detected from orbitofrontal, bilateral superior/middle/inferior temporal, bilateral middle frontal, and posterior cingulate gyri in both groups. In contrast to expectations, the groups showed comparable source contribution weight to gamma-band ASSR at Fz. While gamma-band ASSR reductions at Fz were present in the schizophrenia patients consistent with previous studies, no group differences in individual source-level responses to Fz were detected. Conclusions Small differences in multiple independent sources summate to produce scalp-level differences at Fz. The identification of independent source contributions to a single scalp sensor represents a promising methodology for measuring dissociable and homologous biomarker targets in future translational studies. This article is protected by copyright. All rights reserved.

International audience; A fundamental task for the auditory system is to process communication sounds according to their behavioral significance. In many mammalian species, pup calls became more significant for mothers than other conspecific and heterospecific communication sounds. To study the cortical consequences of motherhood on the processing of communication sounds, we recorded neuronal responses in the primary auditory cortex of virgin and mother C57BL/6 mice which had similar ABR thresholds. In mothers, the evoked firing rate in response to pure tones was decreased and the frequency receptive fields were narrower. The responses to pup and adult calls were also reduced but the amount of mutual information (MI) per spike about the pup call's identity was increased in mother mice. The response latency to pup and adult calls was significantly shorter in mothers. Despite similarly decreased responses to guinea pig whistles, the response latency, and the MI per spike did not differ between virgins and mothers for these heterospecific vocalizations. Noise correlations between cortical recordings were decreased in mothers, suggesting that the firing rate of distant neurons was more independent from each other. Together, these results indicate that in the most commonly used mouse strain for behavioral studies, the discrimination of pup calls by auditory cortex neurons is more efficient during motherhood.

Background An electrical potential not previously reported—electrical cochlear response (ECR)—observed only in implanted patients is described. Its amplitude and growth slope are a measurement of the stimulation achieved by a tone pip on the auditory nerve. The stimulation and recording system constructed for this purpose, the features of this potential obtained in a group of 43 children, and its possible clinical use are described. The ECR is obtained by averaging the EEG epochs acquired each time the cochlear implant (CI) processes a tone pip of known frequency and intensity when the patient is sleeping and using the CI in everyday mode. The ECR is sensitive to tone pip intensity level, microphone sensitivity, sound processor gain, dynamic range of electrical current, and responsiveness to electrical current of the auditory nerve portion involved with the electrode under test. It allows individual evaluation of intracochlear electrodes by choosing, one at the time, the central frequency of the electrode as the test tone pip frequency, so the ECR measurement due to a variable intensity tone pip allows to establish the suitability of the dynamic range of the electrode current. Results There is a difference in ECR measurements when patients are grouped based on their auditory behavior. The ECR slope and amplitude for the Sensitive group is 0.2 μV/dBHL and 10 μV at 50 dBHL compared with 0.04 μV/dBHL and 3 μV at 50dBHL for the Inconsistent group. The clinical cases show that adjusting the dynamic range of current based on the ECR improved the patient’s auditory behavior. Conclusions ECR can be recorded regardless of the artifact due to the electromyographic activity of the patient and the functioning of the CI. Its amplitude and growth slope versus the intensity of the stimulus differs between electrodes. The relationship between minimum ECR detection intensity level and auditory threshold suggests the possibility of estimating patient auditory thresholds this way. ECR does not depend on the subject’s age, cooperation, or health status. It can be obtained at any time after implant surgery and the test procedure is the same regardless of device manufacturer.

Phase-locking to the temporal envelope of speech is associated with envelope processing and speech perception. The phase-locked activity of the auditory pathway, across modulation frequencies, is generally assessed at group level and shows a decrease in response magnitude with increasing modulation frequency. With the exception of increased activity around 40 and 80 to 100 Hz. Furthermore, little is known about the phase-locked response patterns to modulation frequencies ≤ 20 Hz, which are modulations predominately present in the speech envelope. In the present study we assess the temporal modulation transfer function (TMTFASSR) of the phase-locked activity of the auditory pathway, from 0.5 to 100 Hz at a high-resolution and by means of auditory steady-state responses. Although the group-averaged TMTFASSR corresponds well with those reported in the literature, the individual TMTFASSR shows a remarkable intersubject variability. This intersubject variability is especially present for ASSRs that originate from the cortex and are evoked with modulation frequencies ≤ 20 Hz. Moreover, we found that these cortical phase-locked activity patterns are robust over time. These results show the importance of the individual TMTFASSR when assessing phase-locked activity to envelope fluctuations, which can potentially be used as a marker for auditory processing.

Neurophysiological measures of cognitive functioning that are abnormal in patients with schizophrenia are promising candidate biomarkers for predicting development of psychosis in individuals at clinical high risk (CHR). We examined the relationships among event-related brain potential (ERP) measures of early sensory, pre-attentional, and attention-dependent cognition, in antipsychotic-naïve help-seeking CHR patients (n = 36) and healthy control participants (n = 22). These measures included the gamma auditory steady-state response (ASSR; early sensory); mismatch negativity (MMN) and P3a (pre-attentional); and N400 semantic priming effects - a measure of using meaningful context to predict related items - over a shorter and a longer time interval (attention-dependent). Compared to controls, CHR patients had significantly smaller P3a amplitudes (d = 0.62, p = 0.03) and N400 priming effects over the long interval (d = 0.64, p = 0.02). In CHR patients, gamma ASSR evoked power and phase-locking factor were correlated (r = 0.41, p = 0.03). Reductions in mismatch negativity (MMN) and P3a amplitudes were also correlated (r = -0.36, p = 0.04). Moreover, lower gamma ASSR evoked power correlated with smaller MMN amplitudes (r = -0.45, p = 0.02). MMN amplitude reduction was also associated with reduced N400 semantic priming over the shorter but not the longer interval (r = 0.52, p 0.002). This pattern of results suggests that, in a subset of CHR patients, impairment in pre-attentional measures of early information processing may contribute to deficits in attention-dependent cognition involving rapid, more automatic processing, but may be independent from pathological processes affecting more controlled or strategic processing. Thus, combining neurophysiological indices of cognitive deficits in different domains offers promise for improving their predictive power as prognostic biomarkers of clinical outcome.

The dominant approach in investigating the individual reliability for event-related potentials (ERPs) is to extract peak-related features at electrodes showing the strongest group effects. Such a peak-based approach implicitly assumes ERP components showing a stronger group effect are also more reliable, but this assumption has not been substantially validated and few studies have investigated the reliability of ERPs beyond peaks. In this study, we performed a rigorous evaluation of the test-retest reliability of ERPs collected in a multisensory and cognitive experiment from 82 healthy adolescents, each having two sessions. By comparing group effects and individual reliability, we found that a stronger group-level response in ERPs did not guarantee higher reliability. A perspective of neural oscillation should be adopted for the analysis of reliability. Further, by simulating ERPs with an oscillation-based computational model, we found that the consistency between group-level ERP responses and individual reliability was modulated by inter-subject latency jitter and inter-trial variability. The current findings suggest that the conventional peak-based approach may underestimate the individual reliability in ERPs and a neural oscillation perspective on ERP reliability should be considered. Hence, a comprehensive evaluation of the reliability of ERP measurements should be considered in individual-level neurophysiological trait evaluation and psychiatric disorder diagnosis.

We recorded neural responses in human participants to three types of pitch-evoking regular stimuli at rates below and above the lower limit of pitch using magnetoencephalography (MEG). These bandpass filtered (1–4 kHz) stimuli were harmonic complex tones (HC), click trains (CT), and regular interval noise (RIN). Trials consisted of noise-regular-noise (NRN) or regular-noise-regular (RNR) segments in which the repetition rate (or fundamental frequency F0) was either above (250 Hz) or below (20 Hz) the lower limit of pitch. Neural activation was estimated and compared at the senor and source levels. The pitch-relevant regular stimuli (F0 = 250 Hz) were all associated with marked evoked responses at around 140 ms after noise-to-regular transitions at both sensor and source levels. In particular, greater evoked responses to pitch-relevant stimuli than pitch-irrelevant stimuli (F0 = 20 Hz) were localized along the Heschl's sulcus around 140 ms. The regularity-onset responses for RIN were much weaker than for the other types of regular stimuli (HC, CT). This effect was localized over planum temporale, planum polare, and lateral Heschl's gyrus. Importantly, the effect of pitch did not interact with the stimulus type. That is, we did not find evidence to support different responses for different types of regular stimuli from the spatiotemporal cluster of the pitch effect (∼140 ms). The current data demonstrate cortical sensitivity to temporal regularity relevant to pitch that is consistently present across different pitch-relevant stimuli in the Heschl's sulcus between Heschl's gyrus and planum temporale, both of which have been identified as a “pitch center” based on different modalities.

Psychophysical studies characterize hyperacusis as increased loudness growth over a wide-frequency range, decreased tolerance to loud sounds and reduced behavioral reaction time latencies to high-intensity sounds. While commonly associated with hearing loss, hyperacusis can also occur without hearing loss, implicating the central nervous system in the generation of hyperacusis. Previous studies suggest that ventral cochlear nucleus bushy cells may be putative neural contributors to hyperacusis. Compared to other ventral cochlear nucleus output neurons, bushy cells show high firing rates as well as lower and less variable first-spike latencies at suprathreshold intensities. Following cochlear damage, bushy cells show increased spontaneous firing rates across a wide-frequency range, suggesting that they might also show increased sound-evoked responses and reduced latencies to higher-intensity sounds. However, no studies have examined bushy cells in relationship to hyperacusis. Herein, we test the hypothesis that bushy cells may contribute to the neural basis of hyperacusis by employing noise-overexposure and single-unit electrophysiology. We find that bushy cells exhibit hyperacusis-like neural firing patterns, which are comprised of enhanced sound-driven firing rates, reduced first-spike latencies and wideband increases in excitability.

Auditory processing abnormalities in fragile X syndrome (FXS) may contribute to difficulties with language development, pattern identification, and contextual updating. METHOD: Participants with FXS (N=41) and controls (N=27) underwent auditory ERP with a 32 lead EEG cap during presentation of an oddball paradigm. Analyses included log age as a covariate. RESULTS: Data was adequate for analysis for 33 participants with FXS and 27 controls (age 4-51y, 13 females (FXS); 4-54y,11 females (control)). Participants with FXS showed larger N1 and P2 amplitudes (p’s0.05). CONCLUSION: Individuals with FXS show previously demonstrated increased in response amplitude and high frequency neural activity. Additionally, despite an overall normal developmental trajectory for most measures, individuals with FXS show age-independent but gender-dependent decreases in complex processing of novel stimuli. Many markers show strong retest reliability even in children and thus are potential biomarkers for clinical trials in FXS.

Usher syndrome has been historically categorized into one of three classical types based on the patient phenotype. However, the vestibular phenotype does not infallibly predict which Usher genes are mutated. Conversely, the Usher syndrome genotype is not sufficient to reliably predict vestibular function. Here we present a characterization of the vestibular phenotype of 90 patients with clinical presentation of Usher syndrome (59 females), aged 10.9 to 75.5 years, with genetic variants in eight Usher syndromic genes and expand the description of atypical Usher syndrome. We identified unexpected horizontal semicircular canal reactivity in response to caloric and rotational stimuli in 12.5% (3 of 24) and 41.7% (10 of 24), respectively, of our USH1 cohort. These findings are not consistent with the classical phenotypic definition of vestibular areflexia in USH1. Similarly, 17% (6 of 35) of our cohort with USH2A mutations had saccular dysfunction as evidenced by absent cervical vestibular evoked myogenic potentials in contradiction to the classical assumption of normal vestibular function. The surprising lack of consistent genotypic to vestibular phenotypic findings as well as no clear vestibular phenotypic patterns among atypical USH cases, indicate that even rigorous vestibular phenotyping data will not reliably differentiate the three USH types.

Natural conversation is multisensory: when we can see the speaker's face, visual speech cues improve our comprehension. The neuronal mechanisms underlying this phenomenon remain unclear. The two main alternatives are visually mediated phase modulation of neuronal oscillations (excitability fluctuations) in auditory neurons and visual input-evoked responses in auditory neurons. Investigating this question using naturalistic audiovisual speech with intracranial recordings in humans of both sexes, we find evidence for both mechanisms. Remarkably, auditory cortical neurons track the temporal dynamics of purely visual speech using the phase of their slow oscillations and phase-related modulations in broadband high-frequency activity. Consistent with known perceptual enhancement effects, the visual phase reset amplifies the cortical representation of concomitant auditory speech. In contrast to this, and in line with earlier reports, visual input reduces the amplitude of evoked responses to concomitant auditory input. We interpret the combination of improved phase tracking and reduced response amplitude as evidence for more efficient and reliable stimulus processing in the presence of congruent auditory and visual speech inputs.SIGNIFICANCE STATEMENTWatching the speaker can facilitate our understanding of what is being said. The mechanisms responsible for this influence of visual cues on the processing of speech remain incompletely understood. We studied these mechanisms by recording the electrical activity of the human brain through electrodes implanted surgically inside the brain. We found that visual inputs can operate by directly activating auditory cortical areas, and also indirectly by modulating the strength of cortical responses to auditory input. Our results help to understand the mechanisms by which the brain merges auditory and visual speech into a unitary perception.

Objective Aside from the cognitive impairment, patients with dementia with Lewy bodies (DLB) have a high frequency of visual hallucinations and a number of other vision-related symptoms, whereas auditory hallucinations are less frequent. To better understand the differential dysfunction of the visual network in DLB, we compared auditory and visual event-related potentials and oscillations in patients with DLB. Methods Event-related potentials elicited by visual and auditory oddball tasks were recorded in 23 patients with DLB and 22 healthy controls and analyzed in time and time-frequency domain. Results DLB patients had decreased theta band activity related to both early sensory and later cognitive processing in the visual, but not in the auditory task. Patients had lower delta and higher alpha and beta bands power related to later cognitive processing in both auditory and visual tasks. Conclusions In DLB visual event-related oscillations are characterized by a decrease in theta and lack of inhibition in alpha bands. Significance Decreased theta and a lack of inhibition in alpha band power might be an oscillatory underpinning of some classical DLB symptoms such as fluctuations in attention and high-level visual disturbances and a potential marker of dysfunction of the visual system in DLB.

Sensorineural hearing loss (SNHL) causes an overall deficit in binaural hearing, including the abilities to localize sound sources, discriminate interaural time and level differences (ITDs and ILDs, respectively), and utilize binaural cues to aid signal detection and comprehension in noisy environments. Few studies have examined the effect of SNHL on binaural coding in the central auditory system, and those that have focused on age-related hearing loss. We induced hearing loss in male and female Dutch-belted rabbits via noise overexposure and compared unanesthetized single-unit responses of their inferior colliculi [hearing loss (HL) neurons] with those of unexposed rabbits. Sound-level thresholds of HL neurons to diotic noise were elevated by 75 dB, on average. Sensitivity of firing rates of HL neurons to the azimuth of a broadband noise stimulus was reduced, on average, but was confounded by differences in sound level with respect to detection threshold between groups. We independently manipulated ITD and ILD in virtual acoustic space and found directional sensitivity in binaurally sensitive HL neurons was entirely due to ILD sensitivity and no different than that for unexposed rabbits. However, ITD sensitivity was completely absent in binaurally sensitive HL neurons for noise stimuli both in virtual acoustic space and with ITDs extending to ±3 ms. HL neurons also had weaker spike-timing precision and slightly increased spontaneous rates. Overall, ILD sensitivity was uncompromised, whereas ITD sensitivity was completely lost, implying a specific inability to use information in the timing or correlation of acoustic noise waveforms between the two ears following severe SNHL. NEW & NOTEWORTHY Sensorineural hearing loss compromises perceptual abilities that arise from hearing with two ears, yet its effects on binaural aspects of neural responses are largely unknown. We found that, following severe hearing loss because of acoustic trauma, auditory midbrain neurons specifically lost the ability to encode time differences between the arrival of a broadband noise stimulus to the two ears, whereas the encoding of sound level differences between the two ears remained uncompromised.

The way the visual system processes different scales of spatial information has been widely studied, highlighting the dominant role of global over local processing. Recent studies addressing how the auditory system deals with local–global temporal information suggest a comparable processing scheme, but little is known about how this organization is modulated by long-term musical training, in particular regarding musical sequences. Here, we investigate how non-musicians and expert musicians detect local and global pitch changes in short hierarchical tone sequences structured across temporally-segregated triplets made of musical intervals (local scale) forming a melodic contour (global scale) varying either in one direction (monotonic) or both (non-monotonic). Our data reveal a clearly distinct organization between both groups. Non-musicians show global advantage (enhanced performance to detect global over local modifications) and global-to-local interference effects (interference of global over local processing) only for monotonic sequences, while musicians exhibit the reversed pattern for non-monotonic sequences. These results suggest that the local–global processing scheme depends on the complexity of the melodic contour, and that long-term musical training induces a prominent perceptual reorganization that reshapes its initial global dominance to favour local information processing. This latter result supports the theory of “analytic” processing acquisition in musicians.

The purpose of this study was to measure the auditory evoked potentials for speech and non-speech sounds with similar spectral distributions.We developed two types of sounds, comprising naturally spoken vowels (natural speech sounds) and complex synthesized sounds (synthesized sounds). Natural speech sounds consisted of 5 Japanese vowels. Synthesized sounds consisted of a fundamental frequency and its second to fifteenth harmonics equivalent to those of natural speech sounds. The synthesized sound was filtered to have a similar spectral distribution to that of each natural speech sound. These sounds were low-pass filtered at 2000 Hz. The auditory evoked potential elicited by the natural speech sound /o/ and synthesized counterpart for /o/ were measured in 10 right-handed healthy adults with normal hearing.The natural speech sounds were significantly highly recognized as speech compared to the synthesized sounds (74.4% v.s. 13.8%, p 0.01). The natural speech and synthesized sounds for the vowel /o/ contrasted strongly for speech perception (96.9% vs. 9.4%, p0.01). However, the vowel /i/ and its counterpart were barely recognized as speech (4.7 v.s. 3.1%, p = 1.00). The N1 peak amplitudes and latencies evoked by the natural speech sound /o/ were not different from those evoked by the synthesized sound (p = 0.58 and p = 0.28, respectively). The P2 amplitudes evoked by the natural speech sound /o/ were not different from those evoked by the synthesized sound (p = 0.51). The P2 latencies evoked by the natural speech sound /o/ were significantly shorter than those evoked by the synthesized sound (p0.01). This modulation was not observed in a control study using the vowel /i/ and its counterpart (p = 0.29).The early P2 observed may reflect central auditory processing of the 'speechness' of complex sounds.

Available literature shows sex-related differences in both anatomy and functions of the auditory cortex. However, only few data are available on passive listening. By means of event-related potentials (ERPs), we analyzed the proactive and reactive stages of processing related to passive listening in 36 healthy young participants, equally balanced between genders. The anterior positivity (aP), a newly discovered pre-stimulus component originating in auditory cortices and indexing auditory readiness, was not different between genders; the post-stimulus components (the N1 and the N2, originating in primary and secondary auditory cortices) were larger in females than males. These results not only provide significant insights on sex-related differences during listening, but also encourage the potential use of passive tasks, which allow for better understanding of basic neural processing, without interferences from cognitive requirements of active tasks.

PurposeThis study aimed to investigate usefulness of acoustic change complex (ACC) as an objective measure of difference limen for intensity (DLI) in auditory neuropathy spectrum disorders (ANSD) and cochlear hearing loss (CHL).MethodThe study used a multiple static group comparison research design. Twenty normal-hearing individuals (NH), 19 individuals with ANSD, and 23 individuals with CHL underwent DLI measurement using behavioral (psychoacoustic) techniques and ACC. For eliciting ACC, a 500-ms, 1,000-Hz pure tone was presented at 80 dB SPL. Additionally, six variants of this stimulus with intensity increments of 1, 3, 4, 5, 10, and 20 dB starting 250 ms after stimulus onset were used to elicit the ACC.ResultsThe lowest intensity change that produced replicable and clearly identifiable ACC was referred as objective DLI. In comparison to NH and CHL, the behavioral as well as the objective DLI were significantly larger (poorer) in ANSD (p< .05). Significantly strong positive correlation existed between DLI obtained using behavioral and objective measures (p< .05).ConclusionsACC could be a useful objective tool to measure DLI in the clinical population, provided the individuals of the clinical population fulfill the prerequisite of the presence of Auditory Long Latency Responses.Supplemental Materialhttps://doi.org/10.23641/asha.12560132

OBJECTIVES: A cochleovestibular nerve deficiency (CVND) could compromise stimulation of nerve by electrical pulses delivered from a cochlear implant, thereby hindering activity along auditory pathway. The evaluation of children with congenital hearing loss with a high-resolution magnetic resonance imaging is presently the investigative modality of choice to diagnose CVND. The aim of this study was to determine the outcomes in pediatric cochlear implant recipients with a diagnosis of CVND. The objectives included (1) to study the prevalence of CVND among children with prelingual congenital severe to profound hearing loss; (2) to assess post cochlear implantation (CI) outcomes in children with CVND using categories of auditory performance (CAP), speech intelligibility rating (SIR), and cortical auditory evoked potentials (CAEPs); and (3) to propose a management protocol for these children. MATERIALS AND METHODS: All CI procedures performed during the study period in children 5 years or younger were included in study. All patients who were older than 5 years or had syndromic associations, multiple disabilities, second side or revision CI were excluded from the study. Children with unilateral cochleovestibular nerve aplasia and all other cases of CVND (type IIa and IIb) were advised to undergo CI on side with more radiologically robust nerve and/or cochlea anatomy. Children with bilateral CVND were included in group A, and age-matched cochlear implant candidates with normal cochleovestibular nerve anatomy were included in group B for statistical comparison of outcomes. RESULTS: In group A, post CI CAP and SIR, CAEP amplitude and latency at 12 months showed statistically significant difference (p

Mismatch negativity (MMN) amplitude has been widely shown to be diminished in schizophrenia and, more recently, in other psychotic disorders. Although there is considerable evidence linking MMN reduction to cognitive and functional deficits in schizophrenia, there is little evidence of associations with specific psychotic symptoms. Further, it is unclear if MMN reductions relate to specific symptoms, cognitive, and functional deficits transdiagnostically across different psychotic disorders. The present study examines MMN amplitude in a large cohort of cases diagnosed with psychotic disorders including schizophrenia and schizoaffective disorder (N = 116); bipolar disorder and major depressive disorder (N = 75); and other psychotic disorders (N = 25), as well as individuals with no psychotic disorder diagnoses (N = 248). Furthermore, we examined the association of MMN with symptoms, cognitive functioning, and real-world functioning to determine whether these relationships differ by diagnosis. Results showed that MMN amplitude was reduced in cases overall compared to never-psychotic individuals, with no differences between psychotic disorders. Furthermore, there were transdiagnostic associations of reduced duration MMN (MMN-D) with worse auditory hallucinations (r = .14) and disorganization (r = .14), frequency MMN (MMN-F) with real-word functioning (r = .20) and episodic memory (r = -.22), and both components with executive functioning (MMN-D: r = -.17; MMN-F: r = -.15). Our findings relating MMN reductions with cognitive and real-world functioning replicate earlier research in schizophrenia and extend these relationships to other psychotic disorders. Furthermore, our correlations with MMN-D are consistent with computational modeling research and theoretical proposals that view MMN reduction, cognitive dysfunction, and psychotic symptoms as reflecting underlying predictive coding deficits. However, differences in relationships with MMN-F suggest that additional work is warranted on this topic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Objective To test the hypothesis that human immunodeficiency virus (HIV) affects auditory-neurophysiological functions. Methods A convenience sample of 68 HIV+ and 59 HIV- normal-hearing adults was selected from a study set in Dar es Salaam, Tanzania. The speech-evoked frequency-following response (FFR), an objective measure of auditory function, was collected. Outcome measures were FFRs to the fundamental frequency (F0) and to harmonics corresponding to the first formant (F1), two behaviorally relevant cues for understanding speech. Results The HIV+ group had weaker responses to the F1 than the HIV- group; this effect generalized across multiple stimuli (d = 0.59). Responses to the F0 were similar between groups. Conclusions Auditory-neurophysiological responses differ between HIV+ and HIV- adults despite normal hearing thresholds. Significance The FFR may reflect HIV-associated central nervous system dysfunction that manifests as disrupted auditory processing of speech harmonics corresponding to the first formant.

Studies of the relationship of language and music have suggested these two systems may share processing resources involved in the computation/maintenance of abstract hierarchical structure (syntax). One type of evidence comes from ERP interference studies involving concurrent language/music processing showing interaction effects when both processing streams are simultaneously perturbed by violations (e.g., syntactically incorrect words paired with incongruent completion of a chord progression). Here, we employ this interference methodology to target the mechanisms supporting long term memory (LTM) access/retrieval in language and music. We used melody stimuli from previous work showing out-of-key or unexpected notes may elicit a musical analogue of language N400 effects, but only for familiar melodies, and not for unfamiliar ones. Target notes in these melodies were time-locked to visually presented target words in sentence contexts manipulating lexical/conceptual semantic congruity. Our study succeeded in eliciting expected N400 responses from each cognitive domain independently. Among several new findings we argue to be of interest, these data demonstrate that: (i) language N400 effects are delayed in onset by concurrent music processing only when melodies are familiar, and (ii) double violations with familiar melodies (but not with unfamiliar ones) yield a sub-additive N400 response. In addition: (iii) early negativities (RAN effects), which previous work has connected to musical syntax, along with the music N400, were together delayed in onset for familiar melodies relative to the timing of these effects reported in the previous music-only study using these same stimuli, and (iv) double violation cases involving unfamiliar/novel melodies also delayed the RAN effect onset. These patterns constitute the first demonstration of N400 interference effects across these domains and together contribute previously undocumented types of interactions to the available pool of findings relevant to understanding whether language and music may rely on shared underlying mechanisms.

Patients with schizophrenia (ScZ) often show impairments in auditory information processing. These impairments have been related to clinical symptoms, such as auditory hallucinations. Some researchers have hypothesized that aberrant low-frequency oscillations contribute to auditory information processing deficits in ScZ. A paradigm for which modulations in low-frequency oscillations are consistently found in healthy individuals is the auditory continuity illusion (ACI), in which restoration processes lead to a perceptual grouping of tone fragments and a mask, so that a physically interrupted sound is perceived as continuous. We used the ACI paradigm to test the hypothesis that low-frequency oscillations play a role in aberrant auditory information processing in patients with ScZ (N = 23). Compared with healthy control participants we found that patients with ScZ show elevated continuity illusions of interrupted, partially-masked tones. Electroencephalography data demonstrate that this elevated continuity perception is reflected by diminished 3 Hz power. This suggests that reduced low-frequency oscillations relate to elevated restoration processes in ScZ. Our findings support the hypothesis that aberrant low-frequency oscillations contribute to altered perception-related auditory information processing in ScZ.

Sound predictability resulting from repetitive patterns can be implicitly learned and often neither requires nor captures our conscious attention. Recently, predictive coding theory has been used as a framework to explain how predictable or expected stimuli evoke and gradually attenuate obligatory neural responses over time compared to those elicited by unpredictable events. However, these results were obtained using the repetition of simple auditory objects such as pairs of tones or phonemes. Here we examined whether the same principle would hold for more abstract temporal structures of sounds. If this is the case, we hypothesized that a regular repetition schedule of a set of musical patterns would reduce neural processing over the course of listening compared to stimuli with an irregular repetition schedule (and the same set of musical patterns). Electroencephalography (EEG) was recorded while participants passively listened to 6–8 min stimulus sequences in which five different four-tone patterns with temporally regular or irregular repetition were presented successively in a randomized order. N1 amplitudes in response to the first tone of each musical pattern were significantly less negative at the end of the regular sequence compared to the beginning, while such reduction was absent in the irregular sequence. These results extend previous findings by showing that N1 reflects automatic learning of the predictable higher-order structure of sound sequences, while continuous engagement of preattentive auditory processing is necessary for the unpredictable structure.

Significance Nonhuman primates have a rich repertoire of species-specific calls, but they do not show vocal learning. The usefulness of nonhuman primate models for studies of speech and language has, therefore, been questioned. This study shows that macaques can learn to produce novel sound sequences with their hands by pressing levers on a keyboard. Using awake functional MRI, we find activation of motor cortex and putamen, when the monkeys are listening to the same sound sequences they had learned to produce. The results indicate that auditory–motor training in monkeys can lead to the coupling of auditory and motor structures of the brain. This paradigm may be able to serve as a model system for the evolution of speech in primates., Human speech production requires the ability to couple motor actions with their auditory consequences. Nonhuman primates might not have speech because they lack this ability. To address this question, we trained macaques to perform an auditory–motor task producing sound sequences via hand presses on a newly designed device (“monkey piano”). Catch trials were interspersed to ascertain the monkeys were listening to the sounds they produced. Functional MRI was then used to map brain activity while the animals listened attentively to the sound sequences they had learned to produce and to two control sequences, which were either completely unfamiliar or familiar through passive exposure only. All sounds activated auditory midbrain and cortex, but listening to the sequences that were learned by self-production additionally activated the putamen and the hand and arm regions of motor cortex. These results indicate that, in principle, monkeys are capable of forming internal models linking sound perception and production in motor regions of the brain, so this ability is not special to speech in humans. However, the coupling of sounds and actions in nonhuman primates (and the availability of an internal model supporting it) seems not to extend to the upper vocal tract, that is, the supralaryngeal articulators, which are key for the production of speech sounds in humans. The origin of speech may have required the evolution of a “command apparatus” similar to the control of the hand, which was crucial for the evolution of tool use.

Purpose Complaints of auditory perceptual deficits, such as tinnitus and difficulty understanding speech in background noise, among individuals with clinically normal audiograms present a perplexing problem for audiologists. One potential explanation for these “hidden” auditory deficits is loss of the synaptic connections between the inner hair cells and their afferent auditory nerve fiber targets, a condition that has been termed cochlear synaptopathy . In animal models, cochlear synaptopathy can occur due to aging or exposure to noise or ototoxic drugs and is associated with reduced auditory brainstem response (ABR) wave I amplitudes. Decreased ABR wave I amplitudes have been demonstrated among young military Veterans and non-Veterans with a history of firearm use, suggesting that humans may also experience noise-induced synaptopathy. However, the downstream consequences of synaptopathy are unclear. Method To investigate how noise-induced reductions in wave I amplitude impact the central auditory system, the ABR, the middle latency response (MLR), and the late latency response (LLR) were measured in 65 young Veterans and non-Veterans with normal audiograms. Results In response to a click stimulus, the MLR was weaker for Veterans compared to non-Veterans, but the LLR was not reduced. In addition, low ABR wave I amplitudes were associated with a reduced MLR, but with an increased LLR. Notably, Veterans reporting tinnitus showed the largest mean LLRs. Conclusions These findings indicate that decreased peripheral auditory input leads to compensatory gain in the central auditory system, even among individuals with normal audiograms, and may impact auditory perception. This pattern of reduced MLR, but not LLR, was observed among Veterans even after statistical adjustment for sex and distortion product otoacoustic emission differences, suggesting that synaptic loss plays a role in the observed central gain. Supplemental Material https://doi.org/10.23641/asha.11977854