Auditory steady state responses elicited by silent gaps embedded within a broadband noise.

BACKGROUND: Auditory temporal processing plays an important role in speech comprehension. Usually, behavioral tests that require subjects to detect silent gaps embedded within a continuous sound are used to assess the ability of auditory temporal processing in humans. To evaluate auditory temporal processing objectively, the present study aimed to measure the auditory steady state responses (ASSRs) elicited by silent gaps of different lengths embedded within a broadband noise. We presented a broadband noise with 40-Hz silent gaps of 3.125, 6.25, and 12.5 ms. RESULTS: The 40-Hz silent gaps of 3.125, 6.25, and 12.5 ms elicited clear ASSRs. Longer silent gaps elicited larger ASSR amplitudes and ASSR phases significantly differed between conditions. CONCLUSION: The 40 Hz gap-evoked ASSR contributes to our understanding of the neural mechanisms underlying auditory temporal processing and may lead to the development of objective measures of auditory temporal acuity in humans.

Emergence and function of cortical offset responses in sound termination detection.

Offset responses in auditory processing appear after a sound terminates. They arise in neuronal circuits within the peripheral auditory system, but their role in the central auditory system remains unknown. Here, we ask what the behavioral relevance of cortical offset responses is and what circuit mechanisms drive them. At the perceptual level, our results reveal that experimentally minimizing auditory cortical offset responses decreases the mouse performance to detect sound termination, assigning a behavioral role to offset responses. By combining in vivo electrophysiology in the auditory cortex and thalamus of awake mice, we also demonstrate that cortical offset responses are not only inherited from the periphery but also amplified and generated de novo. Finally, we show that offset responses code more than silence, including relevant changes in sound trajectories. Together, our results reveal the importance of cortical offset responses in encoding sound termination and detecting changes within temporally discontinuous sounds crucial for speech and vocalization.

Auditory thalamus dysfunction and pathophysiology in tinnitus: a predictive network hypothesis.

Tinnitus is the perception of a 'ringing' sound without an acoustic source. It is generally accepted that tinnitus develops after peripheral hearing loss and is associated with altered auditory processing. The thalamus is a crucial relay in the underlying pathways that actively shapes processing of auditory signals before the respective information reaches the cerebral cortex. Here, we review animal and human evidence to define thalamic function in tinnitus. Overall increased spontaneous firing patterns and altered coherence between the thalamic medial geniculate body (MGB) and auditory cortices is observed in animal models of tinnitus. It is likely that the functional connectivity between the MGB and primary and secondary auditory cortices is reduced in humans. Conversely, there are indications for increased connectivity between the MGB and several areas in the cingulate cortex and posterior cerebellar regions, as well as variability in connectivity between the MGB and frontal areas regarding laterality and orientation in the inferior, medial and superior frontal gyrus. We suggest that these changes affect adaptive sensory gating of temporal and spectral sound features along the auditory pathway, reflecting dysfunction in an extensive thalamo-cortical network implicated in predictive temporal adaptation to the auditory environment. Modulation of temporal characteristics of input signals might hence factor into a thalamo-cortical dysrhythmia profile of tinnitus, but could ultimately also establish new directions for treatment options for persons with tinnitus.

Effect of Kv3 channel modulators on auditory temporal resolution in aged Fischer 344 rats.

AUT00063 and AUT00202 are novel pharmaceutical modulators of the Kv3 subfamily of voltage-gated K+ channels. Kv3.1 channels, which control fast firing of many central auditory neurons, have been shown to decline with age and this may contribute to age-related deficits in central auditory processing. In the present study, the effects of the two novel compounds that specifically modulate Kv3 channels on auditory temporal processing were examined in aged (19-25-month-old) and young-adult (3-5 month-old) Fischer 344 rats (F344) using a behavioral gap-prepulse inhibition (gap-PPI) paradigm. The acoustic startle response (ASR) and its inhibition induced by a gap in noise were measured before and after drug administration. Hearing thresholds in tested rats were evaluated by the auditory brainstem response (ABR). Aged F344 rats had significantly higher ABR thresholds, lower amplitudes of ASR, and weaker gap-PPI compared with young-adult rats. No influence of AUT00063 and AUT00202 administration was observed on ABR hearing thresholds in rats of both age groups. AUT00063 and AUT00202 had suppressive effect on ASR of F344 rats that was more pronounced with AUT00063. The degree of suppression depended on the dose and age of the rats. Both compounds significantly improved the gap-PPI performance in gap detection tests in aged rats. These results indicate that AUT00063 and AUT00202 may influence intrinsic firing properties of neurons in the central auditory system of aged animals and have the potential to treat aged-related hearing disorders.

Modulation Spectra Capture EEG Responses to Speech Signals and Drive Distinct Temporal Response Functions.

Speech signals have a unique shape of long-term modulation spectrum that is distinct from environmental noise, music, and non-speech vocalizations. Does the human auditory system adapt to the speech long-term modulation spectrum and efficiently extract critical information from speech signals? To answer this question, we tested whether neural responses to speech signals can be captured by specific modulation spectra of non-speech acoustic stimuli. We generated amplitude modulated (AM) noise with the speech modulation spectrum and 1/f modulation spectra of different exponents to imitate temporal dynamics of different natural sounds. We presented these AM stimuli and a 10-min piece of natural speech to 19 human participants undergoing electroencephalography (EEG) recording. We derived temporal response functions (TRFs) to the AM stimuli of different spectrum shapes and found distinct neural dynamics for each type of TRFs. We then used the TRFs of AM stimuli to predict neural responses to the speech signals, and found that (1) the TRFs of AM modulation spectra of exponents 1, 1.5, and 2 preferably captured EEG responses to speech signals in the δ band and (2) the θ neural band of speech neural responses can be captured by the AM stimuli of an exponent of 0.75. Our results suggest that the human auditory system shows specificity to the long-term modulation spectrum and is equipped with characteristic neural algorithms tailored to extract critical acoustic information from speech signals.

The gap prepulse inhibition of the acoustic startle (GPIAS) paradigm to assess auditory temporal processing: Monaural versus binaural presentation.

The Gap Prepulse Inhibition of the Acoustic Startle Reflex (GPIAS) is a paradigm used to assess auditory temporal processing in both animals and humans. It consists of the presentation of a silent gap embedded in noise and presented a few milliseconds before a startle sound. The silent gap produces the inhibition of the startle reflex, a phenomenon called gap-prepulse inhibition (GPI). This paradigm is also used to detect tinnitus in animal models. The lack of inhibition by the silent gaps is suggested to be indicative of the presence of tinnitus "filling-in" the gaps. The current research aims at improving the GPIAS technique by comparing the GPI produced by monaural versus binaural silent gaps in 29 normal-hearing subjects. Two gap durations (5 or 50 ms), each embedded in two different frequency backgrounds (centered around 500 or 4 kHz). Both low- and high- frequency narrowband noises had a bandwidth of half an octave. Overall, the startle magnitude was greater for the binaural versus the monaural presentation, which might reflect binaural loudness summation. In addition, the GPI was similar between the monaural and the binaural presentations for the high-frequency background noise. However, the GPI was greater for the low-frequency background noise for the binaural, compared to the monaural, presentation. These findings suggest that monaural GPIAS might be more suited to detect tinnitus compared to the binaural presentation.

S-EQUOL: a neuroprotective therapeutic for chronic neurocognitive impairments in pediatric HIV.

Chronic neurocognitive impairments, commonly associated with pediatric human immunodeficiency virus type 1 (PHIV), are a detrimental consequence of early exposure to HIV-1 viral proteins. Strong evidence supports S-Equol (SE) as an efficacious adjunctive neuroprotective and/or neurorestorative therapeutic for neurocognitive impairments in adult ovariectomized female HIV-1 transgenic (Tg) rats. There remains, however, a critical need to assess the therapeutic efficacy of SE when treatment occurs at an earlier age (i.e., resembling a therapeutic for children with PHIV) and across the factor of biological sex. Utilization of a series of signal detection operant tasks revealed prominent, sex-dependent neurocognitive deficits in the HIV-1 Tg rat, characterized by alterations in stimulus-reinforcement learning, the response profile, and temporal processing. Early (i.e., postnatal day 28) initiation of SE treatment precluded the development of chronic neurocognitive impairments in all (i.e., 100%) HIV-1 Tg animals, albeit not for all neurocognitive domains. Most notably, the therapeutic effects of SE are generalized across the factor of biological sex, despite the presence of endogenous hormones. Results support, therefore, the efficacy of SE as a neuroprotective therapeutic for chronic neurocognitive impairments in the post-cART era; an adjunctive therapeutic that demonstrates high efficacy in both males and females. Optimizing treatment conditions by evaluating multiple factors (i.e., age, neurocognitive domains, and biological sex) associated with PHIV and HIV-1 associated neurocognitive disorders (HAND) affords a key opportunity to improve the therapeutic efficacy of SE.

Event-related potentials following gaps in noise: The effects of the intensity of preceding noise.

Auditory temporal resolution is critical for the perception of speech. It is often studied using gap detection methods in which a silent period (or "gap") is inserted in a long duration auditory stimulus. When the gap is inserted in a frequently occurring standard stimulus, it elicits a negative-going event-related potential, called the deviant-related negativity (DRN). A time-efficient multi-deviant paradigm was employed in which a standard 200 ms noise burst was presented on 50% of trials and a deviant stimulus, containing a gap, on the remaining 50% of trials. Seven different deviants were constructed by inserting a gap in the centre of the standard. The duration of the seven gaps ranged from 2 to 40 ms. In different conditions, the intensity of the noise burst was either 60 or 80 dB SPL. Ten adults watched a silent video while ignoring the auditory sequence. As expected, the amplitude of the DRN increased as gap duration became longer, regardless of the intensity of the noise in which the gap occurred. The intensity of the noise burst also affected the DRN measured peak-to-peak (DRN-to-following positivity). This was reduced when the gap occurred in the lower intensity noise burst. The time efficient multi-deviant paradigm can thus be employed to determine the effects of factors known to affect gap detection: the duration of the gap, and the intensity of the sound in which the gap is inserted.

Spatial-Temporal Signals and Clinical Indices in Electrocardiographic Imaging (II): Electrogram Clustering and T-wave Alternans.

During the last years, attention and controversy have been present for the first commercially available equipment being used in Electrocardiographic Imaging (ECGI), a new cardiac diagnostic tool which opens up a new field of diagnostic possibilities. Previous knowledge and criteria of cardiologists using intracardiac Electrograms (EGM) should be revisited from the newly available spatial-temporal potentials, and digital signal processing should be readapted to this new data structure. Aiming to contribute to the usefulness of ECGI recordings in the current knowledge and methods of cardiac electrophysiology, we previously presented two results: First, spatial consistency can be observed even for very basic cardiac signal processing stages (such as baseline wander and low-pass filtering); second, useful bipolar EGMs can be obtained by a digital processing operator searching for the maximum amplitude and including a time delay. In addition, this work aims to demonstrate the functionality of ECGI for cardiac electrophysiology from a twofold view, namely, through the analysis of the EGM waveforms, and by studying the ventricular repolarization properties. The former is scrutinized in terms of the clustering properties of the unipolar an bipolar EGM waveforms, in control and myocardial infarction subjects, and the latter is analyzed using the properties of T-wave alternans (TWA) in control and in Long-QT syndrome (LQTS) example subjects. Clustered regions of the EGMs were spatially consistent and congruent with the presence of infarcted tissue in unipolar EGMs, and bipolar EGMs with adequate signal processing operators hold this consistency and yielded a larger, yet moderate, number of spatial-temporal regions. TWA was not present in control compared with an LQTS subject in terms of the estimated alternans amplitude from the unipolar EGMs, however, higher spatial-temporal variation was present in LQTS torso and epicardium measurements, which was consistent through three different methods of alternans estimation. We conclude that spatial-temporal analysis of EGMs in ECGI will pave the way towards enhanced usefulness in the clinical practice, so that atomic signal processing approach should be conveniently revisited to be able to deal with the great amount of information that ECGI conveys for the clinician.

Atypical Multisensory Integration and the Temporal Binding Window in Autism Spectrum Disorder.

The present study examined the relationship between multisensory integration and the temporal binding window (TBW) for multisensory processing in adults with Autism spectrum disorder (ASD). The ASD group was less likely than the typically developing group to perceive an illusory flash induced by multisensory integration during a sound-induced flash illusion (SIFI) task. Although both groups showed comparable TBWs during the multisensory temporal order judgment task, correlation analyses and Bayes factors provided moderate evidence that the reduced SIFI susceptibility was associated with the narrow TBW in the ASD group. These results suggest that the individuals with ASD exhibited atypical multisensory integration and that individual differences in the efficacy of this process might be affected by the temporal processing of multisensory information.

A Cortico-Collicular Amplification Mechanism for Gap Detection.

Auditory cortex (AC) is necessary for the detection of brief gaps in ongoing sounds, but not for the detection of longer gaps or other stimuli such as tones or noise. It remains unclear why this is so, and what is special about brief gaps in particular. Here, we used both optogenetic suppression and conventional lesions to show that the cortical dependence of brief gap detection hinges specifically on gap termination. We then identified a cortico-collicular gap detection circuit that amplifies cortical gap termination responses before projecting to inferior colliculus (IC) to impact behavior. We found that gaps evoked off-responses and on-responses in cortical neurons, which temporally overlapped for brief gaps, but not long gaps. This overlap specifically enhanced cortical responses to brief gaps, whereas IC neurons preferred longer gaps. Optogenetic suppression of AC reduced collicular responses specifically to brief gaps, indicating that under normal conditions, the enhanced cortical representation of brief gaps amplifies collicular gap responses. Together these mechanisms explain how and why AC contributes to the behavioral detection of brief gaps, which are critical cues for speech perception, perceptual grouping, and auditory scene analysis.

Theta and Gamma Bands Encode Acoustic Dynamics over Wide-Ranging Timescales.

Natural sounds contain acoustic dynamics ranging from tens to hundreds of milliseconds. How does the human auditory system encode acoustic information over wide-ranging timescales to achieve sound recognition? Previous work (Teng et al. 2017) demonstrated a temporal coding preference for the theta and gamma ranges, but it remains unclear how acoustic dynamics between these two ranges are coded. Here, we generated artificial sounds with temporal structures over timescales from ~200 to ~30 ms and investigated temporal coding on different timescales. Participants discriminated sounds with temporal structures at different timescales while undergoing magnetoencephalography recording. Although considerable intertrial phase coherence can be induced by acoustic dynamics of all the timescales, classification analyses reveal that the acoustic information of all timescales is preferentially differentiated through the theta and gamma bands, but not through the alpha and beta bands; stimulus reconstruction shows that the acoustic dynamics in the theta and gamma ranges are preferentially coded. We demonstrate that the theta and gamma bands show the generality of temporal coding with comparable capacity. Our findings provide a novel perspective-acoustic information of all timescales is discretised into two discrete temporal chunks for further perceptual analysis.

Everything has Its Time: Narrow Temporal Windows are Associated with High Levels of Autistic Traits Via Weaknesses in Multisensory Integration.

The present study examined whether fundamental sensory functions such as temporal processing and multisensory integration are related to autistic traits in the general population. Both a narrower temporal window (TW) for simultaneous perception, as measured by a temporal order judgement task, and a reduced ability to engage in multisensory integration during the sound-induced flash illusion task were related to higher levels of autistic traits. Additionally, a narrow TW is associated with high levels of autistic traits due to a deficiency in multisensory integration. Taken together, these findings suggest that alterations in fundamental functions produce a cascading effect on higher-order social and cognitive functions, such as those experienced by people with autism spectrum disorder.

A time-efficient multi-deviant paradigm to determine the effects of gap duration on the mismatch negativity.

The insertion of a silent period (or gap) in a frequently occurring standard stimulus elicits a negative-going event-related potential (ERP), called the Deviant-Related Negativity (DRN). This is often studied using a single-deviant paradigm. To study the effects of gaps with multiple durations, a different sequence would be required for each gap. A more time-efficient multi-deviant paradigm has been developed in which stimuli of various gap widths are included in a single sequence. In the present study, 14 young adults watched a silent video while ignoring an auditory sequence. A single run of a multi-deviant sequence was presented in which 6 different rare deviants alternated with a standard stimulus. The standard was a 200-ms white noise burst. The deviants were constructed by inserting a gap in the standard. The duration of the 6 gaps ranged from 2 to 40 ms. Participants were also presented with multiple runs of single-deviant sequences. Each of the 3 deviants was run in a separate sequence. The amplitude of the DRN elicited by the deviant increased as gap duration became longer, although it did plateau for the longer duration gaps. The amplitudes of the DRNs were larger in the single-deviant paradigm than in the multi-deviant paradigm. However, the difference was only significant when the mastoid reference was used. Behavioural data showed a mean d' of 2.1 for the 5-ms gap. None of the participants were able to detect the 2-ms gap. There was no correlation between d' and the DRN amplitude. Still, the effects of gap duration on the amplitude of the DRN were similar between the single and multi-deviant sequences. This makes the multi-deviant paradigm a possible time-saving alternative to the single-deviant paradigm.

Perceptual-learning evidence for inter-onset-interval- and frequency-specific processing of fast rhythms.

Rhythm is fundamental to music and speech, yet little is known about how even simple rhythmic patterns are processed. Here we investigated the processing of isochronous rhythms in the short inter-onset-interval (IOI) range (IOIs < 250-400 ms) using a perceptual-learning paradigm. Trained listeners (n=8) practiced anisochrony detection with a 100-ms IOI marked by 1-kHz tones, 720 trials per day for 7 days. Between pre- and post-training tests, trained listeners improved significantly more than controls (no training; n=8) on the anisochrony-detection condition that the trained listeners practiced. However, the learning on anisochrony detection did not generalize to temporal-interval discrimination with the trained IOI (100 ms) and marker frequency (1 kHz) or to anisochrony detection with an untrained marker frequency (4 kHz or variable frequency vs. 1 kHz), and generalized negatively to anisochrony detection with an untrained IOI (200 ms vs. 100 ms). Further, pre-training thresholds were correlated among nearly all of the conditions with the same IOI (100-ms IOIs), but not between conditions with different IOIs (100-ms vs. 200-ms IOIs). Thus, it appears that some task-, IOI-, and frequency-specific processes are involved in fast-rhythm processing. These outcomes are most consistent with a holistic rhythm-processing model in which a holistic "image" of the stimulus is compared to a stimulus-specific template.

Subcortical pathways: Towards a better understanding of auditory disorders.

Hearing loss is a significant problem that affects at least 15% of the population. This percentage, however, is likely significantly higher because of a variety of auditory disorders that are not identifiable through traditional tests of peripheral hearing ability. In these disorders, individuals have difficulty understanding speech, particularly in noisy environments, even though the sounds are loud enough to hear. The underlying mechanisms leading to such deficits are not well understood. To enable the development of suitable treatments to alleviate or prevent such disorders, the affected processing pathways must be identified. Historically, mechanisms underlying speech processing have been thought to be a property of the auditory cortex and thus the study of auditory disorders has largely focused on cortical impairments and/or cognitive processes. As we review here, however, there is strong evidence to suggest that, in fact, deficits in subcortical pathways play a significant role in auditory disorders. In this review, we highlight the role of the auditory brainstem and midbrain in processing complex sounds and discuss how deficits in these regions may contribute to auditory dysfunction. We discuss current research with animal models of human hearing and then consider human studies that implicate impairments in subcortical processing that may contribute to auditory disorders.

Time as context: The influence of hierarchical patterning on sensory inference.

Time, or more specifically temporal structure, is a critical variable in understanding how the auditory system uses acoustic patterns to predict input, and to filter events based on their relevance. A key index of this filtering process is the auditory evoked potential component known as mismatch negativity or MMN. In this paper we review findings of smaller MMN in schizophrenia through the lens of time as an influential contextual variable. More specifically, we review studies that show how MMN to a locally rare pattern-deviation is modulated by the longer-term context in which it occurs. Empirical data is presented from a non-clinical sample confirming that the absence of a stable higher-order structure to sound sequences alters the way MMN amplitude changes over time. This result is discussed in relation to how hierarchical pattern learning might enrich our understanding of how and why MMN amplitude modulation is disrupted in schizophrenia.

Reference values of selected auditory temporal processing tests for Polish school children.

INTRODUCTION: Distorted processing of auditory information has a negative impact on the child's cognitive development. There are only a few studies conducted by Polish researchers determining normative values of psychoacoustic tests in auditory processing disorders. They are inconsistent due to different methodologies and research protocols. OBJECTIVE: The aim of this work is to determine the reference values of selected psychoacoustic tests for the population of Polish children between 7 and 12 years of age. MATERIAL AND METHOD: The study group consisted of 213 healthy children from 7 to 12 years of age. The condition for including the child in the study was an intellectual norm, proper sound sensitivity, proper development of children's voice and speech. All children underwent two auditory temporal processing tests. The diagnostic procedure used a standardized Frequency Pattern Test (FPT) and Duration Pattern Test (DPT). The tests were carried out in accordance with the authors' recommendations, using the original versions available on the CD for 60 dB SL intensity, simultaneously for the right and left ear. RESULTS: The reference values for FPT and DPT tests were determined at various age ranges in children aged 7-12. It has been shown that auditory functions change with the child's age and development. Reference values including age, language, cultural and educational differences were prepared. CONCLUSIONS: Development of reference values for individual tests for the Polish children population is a key element in reliable diagnosis of auditory processing.

Processing of Natural Echolocation Sequences in the Inferior Colliculus of Seba's Fruit Eating Bat, Carollia perspicillata.

For the purpose of orientation, echolocating bats emit highly repetitive and spatially directed sonar calls. Echoes arising from call reflections are used to create an acoustic image of the environment. The inferior colliculus (IC) represents an important auditory stage for initial processing of echolocation signals. The present study addresses the following questions: (1) how does the temporal context of an echolocation sequence mimicking an approach flight of an animal affect neuronal processing of distance information to echo delays? (2) how does the IC process complex echolocation sequences containing echo information from multiple objects (multiobject sequence)? Here, we conducted neurophysiological recordings from the IC of ketamine-anaesthetized bats of the species Carollia perspicillata and compared the results from the IC with the ones from the auditory cortex (AC). Neuronal responses to an echolocation sequence was suppressed when compared to the responses to temporally isolated and randomized segments of the sequence. The neuronal suppression was weaker in the IC than in the AC. In contrast to the cortex, the time course of the acoustic events is reflected by IC activity. In the IC, suppression sharpens the neuronal tuning to specific call-echo elements and increases the signal-to-noise ratio in the units' responses. When presenting multiple-object sequences, despite collicular suppression, the neurons responded to each object-specific echo. The latter allows parallel processing of multiple echolocation streams at the IC level. Altogether, our data suggests that temporally-precise neuronal responses in the IC could allow fast and parallel processing of multiple acoustic streams.

Midbrain adaptation may set the stage for the perception of musical beat.

The ability to spontaneously feel a beat in music is a phenomenon widely believed to be unique to humans. Though beat perception involves the coordinated engagement of sensory, motor and cognitive processes in humans, the contribution of low-level auditory processing to the activation of these networks in a beat-specific manner is poorly understood. Here, we present evidence from a rodent model that midbrain preprocessing of sounds may already be shaping where the beat is ultimately felt. For the tested set of musical rhythms, on-beat sounds on average evoked higher firing rates than off-beat sounds, and this difference was a defining feature of the set of beat interpretations most commonly perceived by human listeners over others. Basic firing rate adaptation provided a sufficient explanation for these results. Our findings suggest that midbrain adaptation, by encoding the temporal context of sounds, creates points of neural emphasis that may influence the perceptual emergence of a beat.