40-Hz Auditory Steady-state Response Research Articles

40 Hz Steady-State Response in Human Auditory Cortex Is Shaped by GABAergic Neuronal Inhibition.

The 40 Hz auditory steady-state response (ASSR), an oscillatory brain response to periodically modulated auditory stimuli, is a promising, non-invasive physiological biomarker for schizophrenia and related neuropsychiatric disorders. The 40 Hz ASSR might be amplified by synaptic interactions in cortical circuits, which are, in turn, disturbed in neuropsychiatric disorders. Here, we tested whether the 40 Hz ASSR in human auditory cortex depends on two key synaptic components of neuronal interactions within cortical circuits: excitation via N-methyl-aspartate glutamate (NMDA) receptors and inhibition via gamma-amino-butyric acid (GABA) receptors. We combined magnetoencephalography (MEG) recordings with placebo-controlled, low-dose pharmacological interventions in the same healthy human participants (13 males, 7 females). All participants exhibited a robust 40 Hz ASSR in auditory cortices, especially in the right hemisphere, under placebo. The GABAA receptor-agonist lorazepam increased the amplitude of the 40 Hz ASSR, while no effect was detectable under the NMDA-blocker memantine. Our findings indicate that the 40 Hz ASSR in auditory cortex involves synaptic (and likely intracortical) inhibition via the GABA-A receptor, thus highlighting its utility as a mechanistic signature of cortical circuit dysfunctions involving GABAergic inhibition.Significance statement The 40 Hz auditory steady-state response is a candidate non-invasive biomarker for schizophrenia and related neuropsychiatric disorders. Yet, the understanding of the synaptic basis of this neurophysiological signature in humans has remained incomplete. We combined magnetoencephalography (MEG) recordings with placebo-controlled pharmacological interventions in healthy human subjects to test the modulation of the 40 Hz ASSR in auditory cortex by two synaptic components that have been implicated in the generation of neuronal oscillations in cortical microcircuits: glutamate N-methyl-aspartate glutamate (NMDA) receptors and gamma-amino-butyric acid (GABA) -A receptors. Boosting GABAergic transmission, but not blocking NMDA-receptors, increased the amplitude of this ASSR. Thus, GABAergic inhibition modulates 40 Hz steady-state responses in auditory cortex.

Rate dependent neural responses of interaural-time-difference cues in fine-structure and envelope.

Advancements in cochlear implants (CIs) have led to a significant increase in bilateral CI users, especially among children. Yet, most bilateral CI users do not fully achieve the intended binaural benefit due to potential limitations in signal processing and/or surgical implant positioning. One crucial auditory cue that normal hearing (NH) listeners can benefit from is the interaural time difference (ITD), i.e., the time difference between the arrival of a sound at two ears. The ITD sensitivity is thought to be heavily relying on the effective utilization of temporal fine structure (very rapid oscillations in sound). Unfortunately, most current CIs do not transmit such true fine structure. Nevertheless, bilateral CI users have demonstrated sensitivity to ITD cues delivered through envelope or interaural pulse time differences, i.e., the time gap between the pulses delivered to the two implants. However, their ITD sensitivity is significantly poorer compared to NH individuals, and it further degrades at higher CI stimulation rates, especially when the rate exceeds 300 pulse per second. The overall purpose of this research thread is to improve spatial hearing abilities in bilateral CI users. This study aims to develop electroencephalography (EEG) paradigms that can be used with clinical settings to assess and optimize the delivery of ITD cues, which are crucial for spatial hearing in everyday life. The research objective of this article was to determine the effect of CI stimulation pulse rate on the ITD sensitivity, and to characterize the rate-dependent degradation in ITD perception using EEG measures. To develop protocols for bilateral CI studies, EEG responses were obtained from NH listeners using sinusoidal-amplitude-modulated (SAM) tones and filtered clicks with changes in either fine structure ITD (ITDFS) or envelope ITD (ITDENV). Multiple EEG responses were analyzed, which included the subcortical auditory steady-state responses (ASSRs) and cortical auditory evoked potentials (CAEPs) elicited by stimuli onset, offset, and changes. Results indicated that acoustic change complex (ACC) responses elicited by ITDENV changes were significantly smaller or absent compared to those elicited by ITDFS changes. The ACC morphologies evoked by ITDFS changes were similar to onset and offset CAEPs, although the peak latencies were longest for ACC responses and shortest for offset CAEPs. The high-frequency stimuli clearly elicited subcortical ASSRs, but smaller than those evoked by lower carrier frequency SAM tones. The 40-Hz ASSRs decreased with increasing carrier frequencies. Filtered clicks elicited larger ASSRs compared to high-frequency SAM tones, with the order being 40 > 160 > 80> 320 Hz ASSR for both stimulus types. Wavelet analysis revealed a clear interaction between detectable transient CAEPs and 40-Hz ASSRs in the time-frequency domain for SAM tones with a low carrier frequency.

Phenotypic analysis of multielectrode array EEG biomarkers in developing and adult male Fmr1 KO mice

Fragile X Syndrome (FXS) is a leading known genetic cause of intellectual disability with symptoms that include increased anxiety and social and sensory processing deficits. Recent electroencephalographic (EEG) studies in humans with FXS have identified neural oscillation deficits that include increased resting state gamma power, increased amplitude of auditory evoked potentials, and reduced phase locking of sound-evoked gamma oscillations. Similar EEG phenotypes are present in mouse models of FXS, but very little is known about the development of such abnormal responses. In the current study, we employed a 30-channel mouse multielectrode array (MEA) system to record and analyze resting and stimulus-evoked EEG signals in male P21 and P91 WT and Fmr1 KO mice. This led to several novel findings. First, P91, but not P21, Fmr1 KO mice have significantly increased resting EEG power in the low- and high-gamma frequency bands. Second, both P21 and P91 Fmr1 KO mice have markedly attenuated inter-trial phase coherence (ITPC) to spectrotemporally dynamic auditory stimuli as well as to 40 Hz and 80 Hz auditory steady-state response (ASSR) stimuli. This suggests abnormal temporal processing from early development that may lead to abnormal speech and language function in FXS. Third, we found hemispheric asymmetry of fast temporal processing in the mouse auditory cortex in WT but not Fmr1 KO mice. Together, these findings define a set of EEG phenotypes in young and adult mice that can serve as translational targets for genetic and pharmacological manipulation in phenotypic rescue studies.

Cortical white matter microstructural alterations underlying the impaired gamma-band auditory steady-state response in schizophrenia

The gamma-band auditory steady-state response (ASSR), primarily generated from the auditory cortex, has received substantial attention as a potential brain marker indicating the pathophysiology of schizophrenia. Previous studies have shown reduced gamma-band ASSR in patients with schizophrenia and demonstrated correlations with impaired neurocognition and psychosocial functioning. Recent studies in clinical and healthy populations have suggested that the neural substrates of reduced gamma-band ASSR may be distributed throughout the cortices surrounding the auditory cortex, especially in the right hemisphere. This study aimed to investigate associations between the gamma-band ASSR and white matter alterations in the bundles broadly connecting the right frontal, parietal and occipital cortices to clarify the networks underlying reduced gamma-band ASSR in patients with schizophrenia. We measured the 40 Hz ASSR using electroencephalography and diffusion tensor imaging in 42 patients with schizophrenia and 22 healthy comparison subjects. The results showed that the gamma-band ASSR was positively correlated with fractional anisotropy (an index of white matter integrity) in the regions connecting the right frontal, parietal and occipital cortices in healthy subjects (β = 0.41, corrected p = 0.075, uncorrected p = 0.038) but not in patients with schizophrenia (β = 0.17, corrected p = 0.46, uncorrected p = 0.23). These findings support our hypothesis that the generation of gamma-band ASSR is supported by white matter bundles that broadly connect the cortices and that these relationships may be disrupted in schizophrenia. Our study may help characterize and interpret reduced gamma-band ASSR as a useful brain marker of schizophrenia.

Aberrant thalamocortical connectivity and shifts between the resting state and task state in patients with schizophrenia.

Prominent pathological hypotheses for schizophrenia include auditory processing deficits and dysconnectivity within cerebral networks. However, most neuroimaging studies have focused on impairments in either resting-state or task-related functional connectivity in patients with schizophrenia. The aims of our study were to examine (1) blood oxygen level-dependent (BOLD) signals during auditory steady-state response (ASSR) tasks, (2) functional connectivity during the resting-state and ASSR tasks and (3) state shifts between the resting-state and ASSR tasks in patients with schizophrenia. To reduce the functional consequences of scanner noise, we employed resting-state and sparse sampling auditory fMRI paradigms in 25 schizophrenia patients and 25 healthy controls. Auditory stimuli were binaural click trains at frequencies of 20, 30, 40 and 80 Hz. Based on the detected ASSR-evoked BOLD signals, we examined the functional connectivity between the thalamus and bilateral auditory cortex during both the resting state and ASSR task state, as well as their alterations. The schizophrenia group exhibited significantly diminished BOLD signals in the bilateral auditory cortex and thalamus during the 80 Hz ASSR task (corrected p < 0.05). We observed a significant inverse relationship between the resting state and ASSR task state in altered functional connectivity within the thalamo-auditory network in schizophrenia patients. Specifically, our findings demonstrated stronger functional connectivity in the resting state (p < 0.004) and reduced functional connectivity during the ASSR task (p = 0.048), which was mediated by abnormal state shifts, within the schizophrenia group. These results highlight the presence of abnormal thalamocortical connectivity associated with deficits in the shift between resting and task states in patients with schizophrenia.

Amplitude Modulation Perception and Cortical Evoked Potentials in Children With Listening Difficulties and Their Typically Developing Peers.

Amplitude modulations (AMs) are important for speech intelligibility, and deficits in speech intelligibility are a leading source of impairment in childhood listening difficulties (LiD). The present study aimed to explore the relationships between AM perception and speech-in-noise (SiN) comprehension in children and to determine whether deficits in AM processing contribute to childhood LiD. Evoked responses were used to parse the neural origins of AM processing. Forty-one children with LiD and 44 typically developing children, ages 8-16 years, participated in the study. Behavioral AM depth thresholds were measured at 4 and 40 Hz. SiN tasks included the Listening in Spatialized Noise-Sentences Test (LiSN-S) and a coordinate response measure (CRM)-based task. Evoked responses were obtained during an AM change detection task using alternations between 4 and 40 Hz, including the N1 of the acoustic change complex, auditory steady-state response (ASSR), P300, and a late positive response (late potential [LP]). Maturational effects were explored via age correlations. Age correlated with 4-Hz AM thresholds, CRM separated talker scores, and N1 amplitude. Age-normed LiSN-S scores obtained without spatial or talker cues correlated with age-corrected 4-Hz AM thresholds and area under the LP curve. CRM separated talker scores correlated with AM thresholds and area under the LP curve. Most behavioral measures of AM perception correlated with the signal-to-noise ratio and phase coherence of the 40-Hz ASSR. AM change response time also correlated with area under the LP curve. Children with LiD exhibited deficits with respect to 4-Hz thresholds, AM change accuracy, and area under the LP curve. The observed relationships between AM perception and SiN performance extend the evidence that modulation perception is important for understanding SiN in childhood. In line with this finding, children with LiD demonstrated poorer performance on some measures of AM perception, but their evoked responses implicated a primarily cognitive deficit. https://doi.org/10.23641/asha.25009103.

Auditory Steady-State Responses in Schizophrenia: An Updated Meta-Analysis.

This meta-analysis investigates auditory steady-state responses (ASSRs) as potential biomarkers of schizophrenia, focusing on previously unexplored clinical populations, frequencies, and variables. We examined 37 studies, encompassing a diverse cohort of 1788 patients with schizophrenia, including 208 patients with first-episode psychosis, 281 at-risk individuals, and 1603 healthy controls. The results indicate moderate reductions in 40 Hz ASSRs in schizophrenia patients, with significantly greater reductions in first-episode psychosis patients and minimal changes in at-risk individuals. These results call into question the expected progression of ASSR alterations across all stages of schizophrenia. The analysis also revealed the sensitivity of ASSR alterations at 40 Hz to various factors, including stimulus type, level of analysis, and attentional focus. In conclusion, our research highlights ASSRs, particularly at 40 Hz, as potential biomarkers of schizophrenia, revealing varied implications across different stages of the disorder. This study enriches our understanding of ASSRs in schizophrenia, highlighting their potential diagnostic and therapeutic relevance, particularly in the early stages of the disease.

Neurophysiological markers that link genes and behavior in humans: examples from rare genetic syndromes associated with autism spectrum disorders

Rare genetic syndromes associated with autism spectrum disorders have several noninvasive neurophysiological markers that can be linked with molecular genetic characteristics and behavioral characteristics in these diseases. For the recently discovered Potocki–Lupski syndrome associated with disturbances on the 17p11.2 segment, a previously undescribed epileptiform activity was detected, characterized by a saw-like hypersynchronization at a frequency of 13 Hz, which may indicate a certain type of disturbance in the excitation/inhibition balance in neural networks. For a rare case of microduplication in SH3 and ankyrin repeat domains 3 (SHANK3), also associated with the Phelan–McDermid syndrome, we described a pathway from a violation in the functioning of the SHANK3 protein, through a distorted interaction of excitatory and inhibitory neurons, primarily associated with hypofunction of N-methyl-D-aspartate receptors on inhibitory neurons, to reduced temporal resolution in the auditory cortex, reflected in the absence of response following 40 Hz auditory stimulation (40 Hz auditory steady-state response) and underlying problems in speech development. For the Rett syndrome, which is caused by a mutation in methyl CpG binding protein 2 (MECP2), which has a very wide influence on many other genes, the neurophysiological findings were also diverse. Among the most promising are changes in sensorimotor rhythm, potentially associated with a key symptom of the disease, namely, stereotyped hand movements, as well as more delayed latency of the main components of the event-related potentials, which can have a cascading effect on information processing and affect the perception of basic information, including speech. This review focuses on the presentation of the concept of a neurophysiological profile, the construction of which can help not only to objectify the diagnosis of developmental disorders, but also in the construction of a mechanistic chain from gene to behavior.

Synchrony in auditory 40-Hz gamma oscillations increases in older age and correlates with hearing abilities and cortical GABA levels

Abstract Synchronized 40-Hz gamma oscillations in specific sensory and higher-order thalamocortical networks provide a neural mechanism for feature binding. Aging-related changes in gamma oscillations may cause deficits in auditory feature binding, contributing to impaired speech-in-noise perception. Gamma synchrony is controlled through inhibitory mechanisms mediated by the neurotransmitter γ-aminobutyric acid (GABA), which has been shown to decline in aging. This study investigated aging-related changes in gamma oscillations and how they relate to auditory function and cortical GABA levels. Magnetoencephalograms of 40-Hz auditory steady-state responses (ASSRs) were recorded in young and older adults by presenting amplitude-modulated tones in quiet and mixed with concurrent multi-talker babble noise. Responses in the quiet condition had longer latencies and more prominent amplitudes, indicating the 40-Hz ASSRs in noise were dominated by a sensory component and in quiet by a component involved in higher-order processing. The ASSR amplitudes increased in older adults under both stimulus conditions. However, larger ASSR amplitudes were associated with more severe hearing and speech-in-noise loss only in the noise condition. This suggests the aging-related increase in synchrony of sensory gamma oscillations has a detrimental effect on auditory processing. It may cause increased interference between competing sounds in the central auditory system, making it difficult for the aging auditory system to separate speech features from noise and bind them into a distinct perceptual object. Also in older adults, larger amplitudes of the 40-Hz ASSRs in the quiet condition were associated with higher left auditory cortex GABA concentrations measured with magnetic resonance spectroscopy, supporting GABA’s role in internally generated gamma synchrony in aging.

Gamma-band harmonic responses for beta-band auditory steady-state response are intact in patients with early stage schizophrenia.

Gamma oscillations, thought to arise from the activity of ɣ-aminobutyric acid (GABA)ergic interneurons, have potential as a biomarker for schizophrenia. Gamma-band auditory steady-state responses (ASSRs) are notably reduced in both chronic and early-stage schizophrenia patients. Furthermore, alterations in gamma-band ASSRs have been demonstrated in animal models through translational research. However, the 40-Hz harmonic responses of the 20-Hz ASSR are not as well-characterized, despite the possibility that these harmonic oscillatory responses may reflect resonant activity in neural circuits. In this study, we investigated the 40-Hz harmonic response to the 20-Hz ASSR in the early stages of schizophrenia. The study recruited 49 participants, including 15 individuals at ultra-high-risk (UHR) for psychosis, 13 patients with first-episode schizophrenia (FES), and 21 healthy controls (HCs). The 40-Hz harmonic responses of the 20-Hz ASSR were evident in all groups. Interestingly, while previous report observed reduced 40-Hz ASSRs, the 40-Hz harmonic responses of the 20-Hz ASSR were not reduced in the UHR or FES groups. These findings suggest that the gamma-band ASSR and its harmonic responses may represent distinct aspects of pathophysiology in the early stages of schizophrenia.

The Thalamocortical Mechanism Underlying the Generation and Regulation of the Auditory Steady-State Responses in Awake Mice.

The auditory steady-state response (ASSR) is a cortical oscillation induced by trains of 40 Hz acoustic stimuli. While the ASSR has been widely used in clinic measurement, the underlying neural mechanism remains poorly understood. In this study, we investigated the contribution of different stages of auditory thalamocortical pathway-medial geniculate body (MGB), thalamic reticular nucleus (TRN), and auditory cortex (AC)-to the generation and regulation of 40 Hz ASSR in C57BL/6 mice of both sexes. We found that the neural response synchronizing to 40 Hz sound stimuli was most prominent in the GABAergic neurons in the granular layer of AC and the ventral division of MGB (MGBv), which were regulated by optogenetic manipulation of TRN neurons. Behavioral experiments confirmed that disrupting TRN activity has a detrimental effect on the ability of mice to discriminate 40 Hz sounds. These findings revealed a thalamocortical mechanism helpful to interpret the results of clinical ASSR examinations.Significance Statement Our study contributes to clarifying the thalamocortical mechanisms underlying the generation and regulation of the auditory steady-state response (ASSR), which is commonly used in both clinical and neuroscience research to assess the integrity of auditory function. Combining a series of electrophysiological and optogenetic experiments, we demonstrate that the generation of cortical ASSR is dependent on the lemniscal thalamocortical projections originating from the ventral division of medial geniculate body to the GABAergic interneurons in the granule layer of the auditory cortex. Furthermore, the thalamocortical process for ASSR is strictly regulated by the activity of thalamic reticular nucleus (TRN) neurons. Behavioral experiments confirmed that dysfunction of TRN would cause a disruption of mice's behavioral performance in the auditory discrimination task.

40-Hz auditory steady-state response deficits are correlated with the severity of persistent auditory verbal hallucination in patients with schizophrenia

BackgroundAbnormal 40 Hz auditory steady-state response (ASSR) has been observed in some psychiatric disorders. Nevertheless, the role of 40 Hz ASSR in persistent auditory verbal hallucinations (pAVHs) schizophrenia (SCZ) is still unknown. This study aims to investigate whether the 40 Hz ASSR impairment is related to pAVHs and can detect pAVHs severity. MethodsWe analyzed high-density electroencephalography data that from 43 pAVHs patients (pAVH group), 20 moderate auditory verbal hallucinations patients (mid-AVH group), and 24 without auditory verbal hallucinations patients (non-AVH group). Event-related spectral perturbation and inter-trial phase coherence (ITPC) were calculated to quantify dynamic changes of the 40 Hz ASSR power and ITPC, respectively. ResultsFrontal-central, the 40 Hz ASSR power, and ITPC were significantly lower in the pAVH group than in the non-AVH group; There was no significant difference between the pAVH and mid-AVH group. The 40 Hz ASSR was significantly negatively correlated with the severity of pAVHs. The 40 Hz ASSR power, and ITPC could be used as a combinational marker to detect SCZ patients with and without pAVHs. ConclusionOur findings have shed light on the pathological mechanism of pAVHs in SCZ patients. These results can provide potential avenues for therapeutic intervention of pAVHs.

Abnormal phase entrainment of low- and high-gamma-band auditory steady-state responses in schizophrenia

IntroductionGamma-band oscillatory deficits have attracted considerable attention as promising biomarkers of schizophrenia (SZ). Notably, a reduced auditory steady-state response (ASSR) in the low gamma band (40 Hz) is widely recognized as a robust finding among SZ patients. However, a comprehensive investigation into the potential utility of the high-gamma-band ASSR in detecting altered neural oscillations in SZ has not yet been conducted.MethodsThe present study aimed to assess the ASSR using magnetoencephalography (MEG) data obtained during steady-state stimuli at frequencies of 20, 30, 40, and 80 Hz from 23 SZ patients and 21 healthy controls (HCs). To evaluate the ASSR, we examined the evoked power and phase-locking factor (PLF) in the time-frequency domain for both the primary and secondary auditory cortices. Furthermore, we calculated the phase-locking angle (PLA) to examine oscillatory phase lead or delay in SZ patients. Taking advantage of the high spatial resolution of MEG, we also focused on the hemispheric laterality of low- and high-gamma-band ASSR deficits in SZ.ResultsWe found abnormal phase delay in the 40 Hz ASSR within the bilateral auditory cortex of SZ patients. Regarding the 80 Hz ASSR, our investigation identified an aberrant phase lead in the left secondary auditory cortex in SZ, accompanied by reduced evoked power in both auditory cortices.DiscussionGiven that abnormal phase lead on 80 Hz ASSR exhibited the highest discriminative power between HC and SZ, we propose that the examination of PLA in the 80 Hz ASSR holds significant promise as a robust candidate for identifying neurophysiological endophenotypes associated with SZ. Furthermore, the left-hemisphere phase lead observed in the deficits of 80 Hz PLA aligns with numerous prior studies, which have consistently proposed that SZ is characterized by left-lateralized brain dysfunctions.

Click-train evoked steady state harmonic response as a novel pharmacodynamic biomarker of cortical oscillatory synchrony

Sensory networks naturally entrain to rhythmic stimuli like a click train delivered at a particular frequency. Such synchronization is integral to information processing, can be measured by electroencephalography (EEG) and is an accessible index of neural network function. Click trains evoke neural entrainment not only at the driving frequency (F), referred to as the auditory steady state response (ASSR), but also at its higher multiples called the steady state harmonic response (SSHR). Since harmonics play an important and non-redundant role in acoustic information processing, we hypothesized that SSHR may differ from ASSR in presentation and pharmacological sensitivity. In female SD rats, a 2 s-long train stimulus was used to evoke ASSR at 20 Hz and its SSHR at 40, 60 and 80 Hz, recorded from a prefrontal epidural electrode. Narrow band evoked responses were evident at all frequencies; signal power was strongest at 20 Hz while phase synchrony was strongest at 80 Hz. SSHR at 40 Hz took the longest time (∼180 ms from stimulus onset) to establish synchrony. The NMDA antagonist MK801 (0.025–0.1 mg/kg) did not consistently affect 20 Hz ASSR phase synchrony but robustly and dose-dependently attenuated synchrony of all SSHR. Evoked power was attenuated by MK801 at 20 Hz ASSR and 40 Hz SSHR only. Thus, presentation as well as pharmacological sensitivity distinguished SSHR from ASSR, making them non-redundant markers of cortical network function. SSHR is a novel and promising translational biomarker of cortical oscillatory dynamics that may have important applications in CNS drug development and personalized medicine.

Effects of Memantine on the Auditory Steady-State and Harmonic Responses to 40 Hz Stimulation Across Species

BackgroundClick trains elicit an auditory steady-state response (ASSR) at the driving frequency (1F) and its integer multiple frequencies (2F, 3F, etc.) called harmonics; we call this harmonic response the steady-state harmonic response (SSHR). We describe the 40 Hz ASSR (1F) and 80 Hz SSHR (2F) in humans and rats and their sensitivity to the uncompetitive NMDA antagonist memantine. MethodsIn humans (healthy control participants, n = 25; patients with schizophrenia, n = 28), electroencephalography was recorded after placebo or 20 mg memantine in a within-participant crossover design. ASSR used 1 ms, 85-dB clicks presented in 250 40/s 500-ms trains. In freely moving rats (n = 9), electroencephalography was acquired after memantine (0, 0.3, 1, 3 mg/kg) in a within-participant crossover design; 65-dB click trains used 5-mV monophasic, 1-ms square waves (40/s). ResultsAcross species, ASSR at 1F generated greater evoked power (EP) than the 2F SSHR. 1F > 2F intertrial coherence (ITC) was also detected in humans, but the opposite relationship (ITC: 2F > 1F) was seen in rats. EP and ITC at 1F were deficient in patients and were enhanced by memantine across species. EP and ITC at 2F were deficient in patients. Measures at 2F were generally insensitive to memantine across species, although in humans the ITC harmonic ratio (1F:2F) was modestly enhanced by memantine, and in rats, both the EP and ITC harmonic ratios were significantly enhanced by memantine. ConclusionsASSR and SSHR are robust, nonredundant electroencephalography signals that are suitable for cross-species analyses that reveal potentially meaningful differences across species, diagnoses, and drugs.

Effects of analysis window on 40-Hz auditory steady-state responses in cochlear implant users

Auditory steady-state responses (ASSRs) are phase-locked responses of the auditory system to the envelope of a stimulus. These responses can be used as an objective proxy to assess temporal envelope processing and its related functional outcomes such as hearing thresholds and speech perception, in normal-hearing listeners, in persons with hearing impairment, as well as in cochlear-implant (CI) users. While ASSRs are traditionally measured using a continuous stimulation paradigm, an alternative is the intermittent stimulation paradigm, whereby stimuli are presented with silence intervals in between. This paradigm could be more useful in a clinical setting as it allows for other neural responses to be analysed concurrently. One clinical use case of the intermittent paradigm is to objectively program CIs during an automatic fitting session whereby electrically evoked ASSRs (eASSRs) as well as other evoked potentials are used to predict behavioural thresholds. However, there is no consensus yet about the optimal analysis parameters for an intermittent paradigm in order to detect and measure eASSRs reliably. In this study, we used the intermittent paradigm to evoke eASSRs in adult CI users and investigated whether the early response buildup affects the response measurement outcomes. To this end, we varied the starting timepoint and length of the analysis window within which the responses were analysed. We used the amplitude, signal-to-noise ratio (SNR), phase, and pairwise phase consistency (PPC) to characterize the responses. Moreover, we set out to find the optimal stimulus duration for efficient and reliable eASSR measurements. These analyses were performed at two stimulation levels, i.e., 100% and 50% of the dynamic range of each participant. Results revealed that inclusion of the first 300 ms in the analysis window leads to overestimation of response amplitude and underestimation of response phase. Additionally, the response SNR and PPC were not affected by the inclusion of the first 300 ms in the analysis window. However, the latter two metrics were highly dependent on the stimulus duration which complicates comparisons across studies. Finally, the optimal stimulus duration for quick and reliable characterization of eASSRs was found to be around 800 ms for the stimulation level of 100% DR. These findings suggest that inclusion of the early onset period of eASSR recordings negatively influences the response measurement outcomes and that efficient and reliable eASSR measurements are possible using stimuli of around 800 ms long. This will pave the path for the development of a clinically feasible eASSR measurement in CI users.

Influence of inter-stimulus interval on 40-Hz auditory steady-state response in patients with schizophrenia

Decreased 40-Hz auditory steady-state response (ASSR) is believed to reflect abnormal gamma oscillation in patients with schizophrenia (SZ). However, previous studies have reported conflicting results due to variations in inter-stimulus interval (ISI) used. In this study, we aimed to investigate the influence of varying ISI on the 40-Hz ASSR, particularly for patients with SZ and healthy controls (HCs). Twenty-four SZ patients (aged 40.8 ± 13.9 years, male: n = 11) and 21 HCs (aged 33.3 ± 11.3 years, male: n = 8) were recruited. For every participant, 40-Hz ASSRs were acquired for three different stimulus types: 500, 2000, and 3500 ms of ISIs. Two conventional ASSR measures (total power and inter-trial coherence, ITC) were calculated. Several additional ASSR measures were also analyzed: (i) ISI-dependent power; (ii) power onset slope; (iii) power centroid latency; (iv) ISI-dependent ITC; (v) ITC onset slope (500, 2000, 3500 ms); (vi) ITC centroid latency (500, 2000, 3500 ms). As ISI increased, total power and ITC increased in patients with SZ but decreased in HCs. In addition, patients with SZ showed higher ISI-dependent ITC, which was positively correlated with the psychotic symptom severity. The abnormal ITC onset slope and centroid latency for the ISI-500 ms condition were associated with cognitive speed decline in patients with SZ. Our study confirmed that the 40-Hz ASSR could be severely influenced by ISI. Furthermore, our results showed that the additional ASSR measures (ISI-dependent ITC, ITC onset slope, ITC centroid latency) could represent psychotic symptom severity or impairment in cognitive function in patients with SZ.

80 Hz auditory steady state responses (ASSR) elicited by silent gaps embedded within a broadband noise.

Although auditory temporal processing plays an important role in speech comprehension, it cannot be measured by pure tone audiometry. Auditory temporal resolution is often assessed by behavioral gaps-in-noise test. To evaluate whether auditory temporal resolution could be objectively assessed, we measured the auditory steady state response (ASSR) elicited by silent gaps embedded within broadband noises at 80 Hz. We prepared six sound types as test stimuli. One was a continuous broadband noise without a silent interval as a control stimulus and the others were broadband noises with 80 Hz silent intervals of 0.4, 0.8, 1.6, 3.1, and 6.3 ms. Significant ASSRs were recorded only when the gap length was longer than the behavioral thresholds and the ASSR amplitude increased as the gap length increased. Eighty Hertz gap-evoked ASSR appears to reflect the neural activity related to the auditory gap processing and may be used as an objective measure of auditory temporal resolution in humans.

Next-Generation Auditory Steady-State Responses in Normal-Hearing Adults: A Pilot Test–Retest Reliability Study

The Auditory Steady-State Response (ASSR) provides objective and ear-specific information essential for early and appropriate intervention. Test–retest reliability is essential for audiological monitoring. The test–retest reliability of the ASSR has received limited attention. Only a handful of studies found in the literature investigated the test–retest reliability of old-generation ASSR using amplitude or mixed modulated stimuli. However, to our knowledge, no published reports have specifically examined the test–retest reliability of the next-generation ASSR using Chirp family stimuli as implemented in the Interacoustics Eclipse system. This pilot study investigated (a) the test–retest reliability of air conduction (AC) ASSR thresholds across two test sessions and (b) the relationship between differences in ASSR thresholds across two sessions to the residual noise levels in normal-hearing adults. Methods: Fifteen normal-hearing adults (12 females) (30 ears) with an average age of 28 years were recruited for the study. The ASSRs were recorded using a two-channel recording montage. The automatic default stimuli and recording protocol using 90 Hz ASSR, and the accuracy method (p &lt; 0.01) as implemented in the Eclipse system is used to measure ASSR. Results: The study demonstrated strong test–retest reliability for ASSR across frequencies (500 Hz, 1000 Hz, 2000 Hz, and 4000 Hz). Notably, the highest reliability was observed at 500 Hz. The mean test–retest reliability of ASSR was found to be comparable to pure-tone thresholds, but the intra-subject variability is higher for ASSR compared to pure-tone thresholds. Additionally, no significant correlation was found between the difference in ASSR residual noise levels at the threshold and the difference in ASSR thresholds at all tested frequencies. Conclusion: The next-generation system demonstrated strong test–retest reliability across the frequencies examined in this pilot study. Particularly, an improvement in reliability was observed at 500 Hz compared to the old-generation ASSR. This enhancement can be attributed to the utilization of narrow-band CE-chirp stimuli, which generate large amplitude responses, and the implementation of an improved detection paradigm involving multiple harmonics spectral and phase analysis. This pilot study only enrolled adults with normal hearing, and future investigations should include a larger sample size comprising both normal-hearing and hearing-impaired individuals, as well as the pediatric population.

Transcranial Alternating Current Stimulation Alters Auditory Steady-State Oscillatory Rhythms and Their Cross-Frequency Couplings.

Auditory cortical plasticity deficits in schizophrenia are evidenced with electroencephalographic (EEG)-derived biomarkers, including the 40-Hz auditory steady-state response (ASSR). Aiming to understand the underlying oscillatory mechanisms contributing to the 40-Hz ASSR, we examined its response to transcranial alternating current stimulation (tACS) applied bilaterally to the temporal lobe of 23 healthy participants. Although not responding to gamma tACS, the 40-Hz ASSR was modulated by theta tACS (vs sham tACS), with reductions in gamma power and phase locking being accompanied by increases in theta-gamma phase-amplitude cross-frequency coupling. Results reveal that oscillatory changes induced by frequency-tuned tACS may be one approach for targeting and modulating auditory plasticity in normal and diseased brains.