Auditory Steady-state Response Measurements Research Articles

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.

Decrease in gamma-band auditory steady-state response in patients with treatment-resistant schizophrenia

BackgroundThirty percent of patients with schizophrenia do not respond to non-clozapine antipsychotics and are termed treatment-resistant schizophrenia (TRS). The 40-Hz auditory steady-state response (ASSR) is a well-known to be reduced in patients with schizophrenia compared to healthy controls (HCs), suggesting impaired gamma oscillation in schizophrenia. Given no ASSR study on TRS, we aimed to examine the neurophysiological basis of TRS employing 40-Hz ASSR paradigm. MethodWe compared ASSR measures among HCs, patients with non-TRS, and patients with TRS. TRS criteria were defined by a score of 4 or higher on two items of the Positive and Negative Syndrome Scale (PANSS) positive symptoms despite standard antipsychotic treatment. Participants were examined for ASSR with 40-Hz click-train stimulus, and then time-frequency analysis was performed to calculate evoked power and phase-locking factor (PLF) of 40-Hz ASSR. ResultsA total of 79 participants were included: 27 patients with TRS (PANSS = 92.6 ± 15.8); 27 patients with non-TRS (PANSS = 63.3 ± 14.7); and 25 HCs. Evoked power in 40-Hz ASSR was lower in the TRS group than in the HC group (F2,79 = 8.37, p = 0.015; TRS vs. HCs: p = 0.012, d = 1.1) while no differences in PLF were found between the groups. ConclusionThese results suggest that glutamatergic and GABAergic neurophysiological dysfunctions are involved in the pathophysiology of TRS. Our findings warrant more comprehensive and longitudinal studies for deep phenotyping of TRS.

Acoustic deprivation modulates central gain in human auditory brainstem and cortex

Beyond reduced audibility, there is convincing evidence that the auditory system adapts according to the principles of homeostatic plasticity in response to a hearing loss. Such compensatory changes include modulation of central auditory gain mechanisms. Earplugging is a common experimental method that has been used to introduce a temporary, reversible hearing loss that induces changes consistent with central gain modulation. In the present study, young, normal-hearing adult participants wore a unilateral earplug for two weeks, during which we measured changes in the acoustic reflex threshold (ART), loudness perception, and cortically-evoked (40 Hz) auditory steady-state response (ASSR) to assess potential modulation in central gain with reduced peripheral input. The ART decreased on average by 8 to 10 dB during the treatment period, with modest increases in loudness perception after one week but not after two weeks of earplug use. Significant changes in both the magnitude and hemispheric laterality of source-localized cortical ASSR measures revealed asymmetrical changes in stimulus-driven cortical activity over time. The ART results following unilateral earplugging are consistent with the literature and suggest that homeostatic plasticity is evident in the brainstem. The novel findings from the cortical ASSR in the present study indicates that reduced peripheral input induces adaptive homeostatic plasticity reflected as both an increase in central gain in the auditory brainstem and reduced cortical activity ipsilateral to the deprived ear. Both the ART and the novel use of the 40-Hz ASSR provide sensitive measures of central gain modulation in the brainstem and cortex of young, normal hearing listeners, and thus may be useful in future studies with other clinical populations.

Quantitative electroencephalography parameters as neurophysiological biomarkers of schizophrenia-related deficits: A Phase II substudy of patients treated with iclepertin (BI 425809)

Patients with schizophrenia experience cognitive impairment related to neural network dysfunction and deficits in sensory processing. These deficits are thought to be caused by N-methyl-D-aspartate receptor hypofunction and can be assessed in patient populations using electroencephalography (EEG). This substudy from a Phase II, randomized, double-blind, placebo-controlled, parallel-group study investigating the safety and efficacy of the novel glycine transporter-1 inhibitor, iclepertin (BI 425809), assessed the potential of EEG parameters as clinically relevant biomarkers of schizophrenia and response to iclepertin treatment. Eligible patients were randomized to once-daily add-on iclepertin (2, 5, 10, or 25 mg), or placebo (1:1:1:1:2 ratio) for 12 weeks. EEG data were recorded from a subgroup of patients (n = 79) at baseline and end of treatment (EoT). EEG parameters of interest were mismatch negativity (MMN), auditory steady-state response (ASSR), and resting state gamma power, and their correlations with clinical assessments. At baseline, MMN and ASSR exhibited consistent correlations with clinical assessments, indicating their potential value as neurophysiological biomarkers of schizophrenia-related deficits. ASSR measures were positively correlated to the MATRICS Consensus Cognitive Battery overall and neurocognitive composite scores; MMN amplitude was positively correlated with Positive and Negative Syndrome Scale scores. However, correlations between change from baseline (CfB) at EoT in clinical assessments, and baseline or CfB at EoT for EEG parameters were modest and inconsistent between dose groups, which might indicate low potential of these EEG parameters as predictive and treatment response biomarkers. Further methodological refinement is needed to establish EEG parameters as useful drug development tools for schizophrenia.

Test-retest reliability of mismatch negativity and gamma-band auditory steady-state response in patients with schizophrenia

Patients with schizophrenia show widespread impairments in clinical, cognitive and psychosocial functioning. Mismatch negativity (MMN) and gamma-band auditory steady-state response (ASSR) are two neurophysiological biomarkers widely used to inform diagnosis, guide treatments and track response to interventions in schizophrenia. However, evidence for the test–retest reliability of these indices across multiple sessions in schizophrenia patients remains scarce. In the present study, we included 34 schizophrenia patients (17 females) and obtained duration MMN (dMMN), frequency MMN (fMMN) and 40-Hz ASSR data across three sessions with intervals of 2 days. Event-related spectrum perturbation (ERSP) and inter-trial coherence (ITC) were calculated following Morlet wavelet time–frequency decomposition of ASSR data. The intra-class correlation coefficient (ICC) was used to quantify the reliability of MMN and ASSR measures among the three sessions. We found fair to good reliability for dMMN amplitudes but poor reliability for fMMN amplitudes. For the ASSR measures, ERSP showed good to excellent test–retest reliability while ITC had poor to fair test–retest reliability. In addition, the average of dMMN amplitudes was significantly correlated with that of ERSP across the three sessions. In summary, we established for the first time the short-term test–retest reliability of MMN and ASSR measures in schizophrenia patients. These findings demonstrate that dMMN amplitudes and ERSP of ASSR are reliable indices which may be used in longitudinal observational studies.

The Relationship between Psychoacoustic and Electrophysiological Assessments of Temporal Resolution.

Temporal resolution is essential to speech acoustic perception. However, it may alter in individuals with auditory disorders, impairing the development of spoken and written language. The envelope of speech signals contains amplitude modulation (AM) that has critical information. Any problem reducing the listener's sensitivity to these amplitude variations (auditory temporal acuity) is likely to cause speech comprehension problems. The modulation detection threshold (MDT) test is a measure for evaluating temporal resolution. However, this test cannot be used for patients with poor cooperation; therefore, objective evaluation of MDT is essential. The main aim of this study is to find the association between the auditory steady-state response (ASSR) and psychoacoustic measurement of MDT at different intensity levels and to assess the amplitude and phase of ASSR as a function of modulation depth. This was a correlational research. Eighteen individuals (nine males and nine females) with normal hearing sensitivity, aged between 18 and 23 years, participated in this study. ASSR was recorded at fixed AM rates and variable AM depths for carrier frequencies of 1,000 and 2,000 Hz with varying intensities. The least AM depth, efficient to evoke an ASSR response, was interpreted as the physiological detection threshold of AM. The ASSR amplitude and phase, as a function of AM depth, were also evaluated at an intensity level of 60 dB hearing level (HL) with modulation rates of 40 and 100 Hz. Moreover, the Natus instrument (Biologic Systems) was used for the electrophysiological measurements. An AC40 clinical audiometer (Intra-acoustic, Denmark) was also used for the psychoacoustic measurement of MDT in a similar setting to ASSR, using the two-alternative forced choice method. Pearson's correlation test and linear regression model and paired t-test were used for statistical analyses. A significant positive correlation was found between psychoacoustic and electrophysiological measurements at a carrier frequency of 1000 Hz, with a modulation rate of 40 Hz at intensity levels of 60 dB HL (r = 0.63, p = 0.004), 50 dB HL (r = 0.52, p = 0.02). A significant positive correlation was also found at a carrier frequency of 2000 Hz, with a modulation rate of 47 Hz at 60 dB HL (r = 0.55, p = 0.01) and 50 dB HL (r = 0.67, p = 0.002) and a modulation rate of 97 Hz at 60 dB HL (r = 0.65, p = 0.003). Moreover, a significant association was found between the modulation depth and ASSR amplitude and phase increment at carrier frequencies of 1,000 and 2000 Hz, with modulation rates of 40 and 100 Hz. There was a significant correlation between ASSR and behavioral measurement of MDT, even at low intensities with low modulation rates of 40 and 47 Hz. The ASSR amplitude and phase increment was a function of modulation depth increase. The findings of this study can be used as a basis for evaluating the relationship between two approaches in the clinical population.

Unique contributions of sensory discrimination and gamma synchronization deficits to cognitive, clinical, and psychosocial functional impairments in schizophrenia

BackgroundSchizophrenia patients show widespread deficits in neurocognitive, clinical, and psychosocial functioning. Mismatch negativity (MMN) and gamma-band auditory steady-state response (ASSR) are robust translational biomarkers associated with schizophrenia and associated with cognitive dysfunction, negative symptom severity, and psychosocial disability. Although these biomarkers are conceptually linked as measures of early auditory information processing, it is unclear whether MMN and gamma-band ASSR account for shared vs. non-shared variance in cognitive, clinical, and psychosocial functioning. MethodsMultiple regression analyses with MMN, gamma-band ASSR, and clinical measures were performed in large cohorts of schizophrenia outpatients (N = 428) and healthy comparison subjects (N = 283). ResultsReduced MMN (d = 0.67), gamma-band ASSR (d = −0.40), and lower cognitive function were confirmed in schizophrenia patients. Regression analyses revealed that reduced MMN amplitude showed unique associations with lower verbal learning and negative symptoms, reduced gamma-band ASSR showed a unique association with working memory deficits, and both reduced MMN amplitude and reduced gamma-band ASSR showed an association with daily functioning impairment in schizophrenia patients. ConclusionMMN and ASSR measures are non-redundant and complementary measures of early auditory information processing that are associated with important domains of functioning. Studies are needed to clarify the neural substrates of MMN and gamma-band ASSR to improve our understanding of the pathophysiology of schizophrenia and accelerate their use in the development of novel therapeutic interventions.

Potential Destructive Binaural Interaction Effects in Auditory Steady-State Response Measurements.

An aided sound-field auditory steady-state response (ASSR) has the potential to be used to objectively validate hearing-aid (HA) fittings in clinics. Each aided ear should ideally be tested independently, but it is suspected that binaural testing may be used by clinics to reduce test time. This study simulates dichotic ASSR sound-field conditions to examine the risk of making false judgments due to unchecked binaural effects. Unaided ASSRs were recorded with a clinical two-channel electroencephalography (EEG) system for 15 normal hearing subjects using a three-band CE-Chirp® stimulus. It was found that the noise corrected power of a response harmonic can be suppressed by up to 10 dB by introducing large interaural time differences equal to half the time period of the stimulus envelope, which may occur in unilateral HA users. These large interaural time differences also changed the expression of ASSR power across the scalp, resulting in dramatically altered topographies. This would lead to considerably lower measured response power and possibly nondetections, evidencing that even well fit HAs are fit poorly (false referral), whereas monaural ASSR tests would pass. No effect was found for simulated lateralizations of the stimulus, which is beneficial for a proposed aided ASSR approach. Full-scalp ASSR recordings match previously found 40 Hz topographies but demonstrate suppression of cortical ASSR sources when using stimuli in interaural envelope antiphase.

Test-retest reliability of time-frequency measures of auditory steady-state responses in patients with schizophrenia and healthy controls.

BackgroundAuditory steady-state response (ASSR) paradigms have consistently demonstrated gamma band abnormalities in schizophrenia at a 40-Hz driving frequency with both electroencephalography (EEG) and magnetoencephalography (MEG). Various time-frequency measures have been used to assess the 40-Hz ASSR, including evoked power, single trial total power, phase-locking factor (PLF), and phase-locking angle (PLA). While both EEG and MEG studies have shown power and PLF ASSR measures to exhibit excellent test-retest reliability in healthy adults, the reliability of these measures in patients with schizophrenia has not been determined.MethodsASSRs were obtained by recording EEG data during presentation of repeated 20-Hz, 30-Hz and 40-Hz auditory click trains from nine schizophrenia patients (SZ) and nine healthy controls (HC) tested on two occasions. Similar ASSR data were collected from a separate group of 30 HC on two to three test occasions. A subset of these HC subjects had EEG recordings during two tasks, passively listening and actively attending to click train stimuli. Evoked power, total power, PLF, and PLA were calculated following Morlet wavelet time-frequency decomposition of EEG data and test-retest generalizability (G) coefficients were calculated for each ASSR condition, time-frequency measure, and subject group.ResultsG-coefficients ranged from good to excellent (> 0.6) for most 40-Hz time-frequency measures and participant groups, whereas 20-Hz G-coefficients were much more variable. Importantly, test-retest reliability was excellent for the various 40-Hz ASSR measures in SZ, similar to reliabilities in HC. Active attention to click train stimuli modestly reduced G-coefficients in HC relative to the passive listening condition.DiscussionThe excellent test-retest reliability of 40-Hz ASSR measures replicates previous EEG and MEG studies. PLA, a relatively new time-frequency measure, was shown for the first time to have excellent reliability, comparable to power and PLF measures. Excellent reliability of 40 Hz ASSR measures in SZ supports their use in clinical trials and longitudinal observational studies.

Comparison of frequency-Specific hearing thresholds between pure-tone audiometry and auditory steady-state response

Introduction: Hearing assessment in difficult to assess persons gives inconsistent response in free field hearing and pure-tone audiometry (PTA). We have been performing brainstem evoked response audiometry (BERA) as an objective assessment in such cases. BERA has limitations that it is not frequency specific, measures thresholds in higher frequencies only, signal intensity levels cannot be higher than 90 dB and presents the data in waveform which needs to be interpreted by experienced audiologist to deduce correct information. All these limitations can be negated with use of auditory steady-state response (ASSR) which can present intensity levels till 120 dB, is frequency specific, even for lower frequencies and has automated response and deduction analysis. The aim of our study was to compare pure-tone thresholds with ASSR thresholds in normal hearing and hearing loss subjects with an objective to validate the ASSR as a tool for objective hearing assessment. Materials and Methods: In this prospective cross-sectional study of 70 adults (n = 140 ears) of both genders, with and without hearing complaints, Group 1 consisted of 24 individuals of normal hearing, Group 2 consisted of 25 individuals of sensorineural hearing loss, and 21 individuals with conductive hearing loss in Group 3. The patients were evaluated with PTA and ASSR test. The mean pure tone and ASSR thresholds for each frequency were calculated and analyzed using the SPSS IBM software. Results: The mean difference of ASSR with PTA was noted at 9.92 dB in the right ear and 10 dB in the left ear. A high significant correlation was noted between ASSR and PTA with P(0.0005) across all the three groups. The relationship between the PTA and ASSR measurement for measuring average hearing threshold levels is described by the equation: PTA = ASSR mean × 0.99–9.92. Conclusion: ASSR is an excellent tool to predict accurate level of frequency-specific hearing threshold. It has constant relationship with pure tone thresholds. ASSR can predict true hearing thresholds in “difficult to assess” patients such as children and malingerers. This can also be used in the prediction of disability assessment objectively.

Auditory steady state response deficits are associated with symptom severity and poor functioning in patients with psychotic disorder

ObjectivesGamma oscillation is important for cortico-cortical coordination and the integration of information across neural networks. The 40 Hz auditory steady-state response (ASSR), which reflects neural synchrony in the gamma band (30–100 Hz), is abnormal in patients with schizophrenia (SZ). The present study used the ASSR at multiple frequencies to examine (1) gamma dysfunction in patients with SZ, schizoaffective (SA), and bipolar disorder (BD) compared with controls, (2) the relationship between ASSR measures and clinical symptom severity, and (3) the relationship between ASSR measures and real-life community functioning. MethodsEEG was recorded from 75 controls, 52 SZ, 55 SA, and 89 BD patients during 20–30-40-Hz binaural click trains. ANCOVA was used to compare ASSR measures between groups controlling for age, sex, and education. Associations between ASSR measures, symptom severity, and community functioning were examined using linear regression and Pearson partial correlations. ResultsASSR deficits at gamma frequency were observed in all patient groups. SA patients showed additional specific deficit in the 20 Hz ASSR. Severity of manic, depressive, and anxiety symptoms mediated ASSR deficits. Severity of hallucinatory symptom and community functioning, particularly independent living/meaningful activity, were significantly and independently associated with the 40 Hz ASSR. ConclusionsSZ, SA and BD patients are likely to share the same abnormalities in neural processes that generate gamma oscillations. 40 Hz ASSR are associated with community functioning across patients and may serve as a biomarker for predicting functional outcome.

On the Cost of Introducing Speech-Like Properties to a Stimulus for Auditory Steady-State Response Measurements.

Validating hearing-aid fittings in prelingual infants is challenging because typical measures (aided audiometry, etc.) are impossible with infants. One objective alternative uses an aided auditory steady-state response (ASSR) measurement. To make an appropriate measurement, the hearing aid’s signal-processing features must be activated (or deactivated) as if the ASSR stimulus was real speech. Rather than manipulating the hearing-aid settings to achieve this, an ASSR stimulus with speech-like properties was developed. This promotes clinical simplicity and face validity of the validation. The stimulus consists of narrow-band CE-Chirps®, modified to mimic the International Speech Test Signal (ISTS). This study examines the cost of introducing the speech-like features into the ASSR stimulus. Thus, 90 to 100 Hz ASSRs were recorded to the ISTS-modified stimulus as well as an equivalent stimulus without the ISTS modification, presented through insert phones to 10 young normal-hearing subjects. Noise-corrected ASSR magnitudes and clinically relevant detection times were estimated and analyzed with mixed-model analyses of variance. As a supplement, the observed changes to the ASSR magnitudes were compared with an objective characterization of the stimuli based on modulation power. The main findings were a reduction in ASSR magnitude of 4 dB and an increase in detection time by a factor of 1.5 for the ISTS-modified stimulus compared with the standard. Detection rates were unaffected given sufficient recording time. For clinical use of the hearing-aid validation procedure, the key metric is the detection time. While this varied considerably across subjects, the observed 50% mean increase corresponds to less than 1 min of additional recording time.

Independent component analysis for cochlear implant artifacts attenuation from electrically evoked auditory steady-state response measurements

Objective. Electrically evoked auditory steady-state responses (EASSRs) are potentially useful for objective cochlear implant (CI) fitting and follow-up of the auditory maturation in infants and children with a CI. EASSRs are recorded in the electro-encephalogram (EEG) in response to electrical stimulation with continuous pulse trains, and are distorted by significant CI artifacts related to this electrical stimulation. The aim of this study is to evaluate a CI artifacts attenuation method based on independent component analysis (ICA) for three EASSR datasets. Approach. ICA has often been used to remove CI artifacts from the EEG to record transient auditory responses, such as cortical evoked auditory potentials. Independent components (ICs) corresponding to CI artifacts are then often manually identified. In this study, an ICA based CI artifacts attenuation method was developed and evaluated for EASSR measurements with varying CI artifacts and EASSR characteristics. Artifactual ICs were automatically identified based on their spectrum. Main results. For 40 Hz amplitude modulation (AM) stimulation at comfort level, in high SNR recordings, ICA succeeded in removing CI artifacts from all recording channels, without distorting the EASSR. For lower SNR recordings, with 40 Hz AM stimulation at lower levels, or 90 Hz AM stimulation, ICA either distorted the EASSR or could not remove all CI artifacts in most subjects, except for two of the seven subjects tested with low level 40 Hz AM stimulation. Noise levels were reduced after ICA was applied, and up to 29 ICs were rejected, suggesting poor ICA separation quality. Significance. We hypothesize that ICA is capable of separating CI artifacts and EASSR in case the contralateral hemisphere is EASSR dominated. For small EASSRs or large CI artifact amplitudes, ICA separation quality is insufficient to ensure complete CI artifacts attenuation without EASSR distortion.

Intraoperative auditory steady-state monitoring during surgery in the cerebellopontine angle for estimation of postoperative hearing classes.

OBJECTIVE Brainstem auditory evoked potentials (BAEPs) have been used for intraoperative monitoring of the auditory nerve for many years. However, BAEPs yield limited information about the expected postoperative hearing quality and speech perception. The auditory steady-state response (ASSR) enables objective audiograms to be obtained in patients under anesthesia. These ASSRs could be used for intraoperative estimation of hearing classes to improve the postoperative outcome and quality of life. Studies investigating the clinical use of ASSRs during total intravenous anesthesia are currently lacking. The work presented in this article therefore investigates the application of ASSRs for intraoperative estimation of hearing classes. METHODS In 43 patients undergoing surgery for vestibular schwannoma, ASSR measurements were performed at the beginning and end of the surgical procedure. ASSR stimuli consisted of 80-dB hearing level amplitude-modulated tones with 5-minute duration, 90-Hz modulation, and 3 different carrier frequencies: 500, 1000, and 2000 Hz. Stimulation was performed unilaterally with and without contralateral masking, using single and combined carriers. Evoked responses were recorded and analyzed in the frequency domain. ASSRs were compared with extraoperative hearing classes and BAEPs using ANOVA, correlation, and receiver operating characteristic statistics. RESULTS ASSRs yielded high and consistent area under the curve (AUC) values (mean 0.83) and correlation values (mean -0.63), indicating reliable prediction of hearing classes. Analysis of BAEP amplitude changes showed lower AUC (mean 0.79) and correlation values (0.63, 0.37, and 0.50 for Waves I, III, and V, respectively). Latencies showed low AUC values (mean 0.6) and no significant correlation. Combination of several carriers for simultaneous evaluation reduced ASSR amplitudes and respective AUC values. Contralateral masking did not show a significant effect. CONCLUSIONS ASSRs robustly estimate hearing class in patients under total intravenous anesthesia, even when using short measurement durations. The method provides a diagnostic performance that exceeds conventional BAEP monitoring and enables objective and automated evaluation. On the basis of these findings, continuous intraoperative auditory monitoring could become a promising alternative or adjunct to BAEPs.

Differentiation between major depressive disorder and bipolar disorder by auditory steady-state responses

BackgroundThe auditory steady-state response (ASSR) elicited by gamma band neural oscillations has received considerable interest as a biomarker of psychiatric disorders. Although recent ASSR studies have reported that patients with bipolar disorder (BD) show altered ASSRs, little is known about ASSRs in patients with major depressive disorder (MDD). The aim of this study was to evaluate whether ASSRs in MDD subjects differed from those in BD subjects or normal controls (NC). MethodWe analyzed ASSRs in 14 MDD patients, 19 BD patients, and 29 normal control subjects. We used whole-head 306-channel magnetoencephalography to evaluate ASSR power and phase-locking factors (PLF) elicited by 20-, 30-, 40-, and 80-Hz click trains. We determined optimal sensitivity and specificity of ASSR power and PLF for the diagnosis of MDD or BD via receiver operating characteristic (ROC) curve analysis using a nonparametric approach. ResultsMDD patients exhibited no significant differences in ASSR power or PLF compared with NC subjects, while BD patients showed deficits on the ASSR measures. MDD patients showed significantly larger ASSR power and PLF for 30-, 40-, and 80-Hz stimuli compared with BD patients. The area under the curve (AUC) for the ROC analysis (MDD vs. BD) was 0.81 [95% CI=0.66–0.96, p=0.003] concerning 40-Hz ASSR power. LimitationsWe could not exclude the effect of medication and the sample size of the current study is relatively small. ConclusionsWe could differentiate between MDD and BD subjects in terms of gamma band ASSR. Our data suggest that the 40-Hz ASSR may be a potential biomarker for differentiation between MDD and BD patients.

Auditory steady state response in bipolar disorder: relation to clinical state, cognitive performance, medication status, and substance disorders

Abnormalities in auditory steady state response (ASSR) at gamma range frequencies have been found in bipolar disorder, but the relationship of these neurophysiological disturbances to clinical factors has not been well characterized. We therefore evaluated the ASSR in bipolar disorder and examined its sensitivity to clinical symptoms, cognitive function, and pharmacological treatment. A total of 68 patients with bipolar disorder and 77 control participants were evaluated. Click trains presented at 20, 30, 40, and 50 Hz evoked ASSRs. Mean trial power (MTP) and phase locking factor (PLF) measured response magnitude and phase synchronization of the ASSR at each stimulation frequency. Clinical state, pharmacological treatment, and neuropsychological performance were assessed, and their respective relationships with ASSR measures were evaluated. Patients with bipolar disorder showed reduced MTP and PLF compared to control participants. Bipolar disorder patients taking psychotropic medications had decreased PLF relative to patients withdrawn from medications. Control participants performed better on neuropsychological tests than bipolar disorder patients; however, test scores did not correlate with ASSR measures. Deficits in the generation and maintenance of ASSR are present in bipolar disorder, implicating disturbances in auditory pathways. ASSR may be sensitive to medication status. Other clinical features, including mood state, psychotic features, cognitive performance, smoking, or history of substance use disorder, were unrelated to MTP or PLF.

Intraoperative Auditory Steady State Response Measurements During Vibrant Soundbridge Middle Ear Implantation in Patients With Mixed Hearing Loss

To optimize intraoperatively the coupling of the floating mass transducer (FMT) of the Vibrant Soundbridge middle ear implant to the round or oval cochlear window in patients with mixed hearing loss. Intraoperative measurement of objective hearing thresholds using auditory steady state responses (ASSRs). Radboud University Nijmegen Medical Centre, tertiary referral hospital. Four individuals with mixed hearing loss and, at least no incus, in need for a middle ear implant. Surgical placement of the Vibrant Soundbridge. ASSR thresholds were measured intraoperatively, whereas FMT coupling to the cochlea was manipulated to find the most effective coupling of the FMT. Differences in ASSR thresholds between different FMT coupling options within patients. With ASSR, we assessed placement of the FMT in the round window niche, loosely or tightly packed in the niche; creation of a mobile window in case of a fixed stapes footplate; and FMT position coupled to the stapes that afforded vibration in the natural vibration direction or perpendicular to it. Furthermore, test-retest variations in ASSR thresholds were studied. It was shown that differences in ASSR thresholds could be detected, while manipulating the FMT couplings, which were statistically significant. Intraoperative ASSR measurement is a good method to study different positions of the FMT and to determine the best position of the FMT for a patient.

Test-Retest Reliability of Bone-Conducted Auditory Steady-State Response

Auditory steady-state response (ASSR) are used for estimating hearing sensitivity of those who cannot be subjectively tested. Recently, bone-conducted (BC) ASSR are also available on clinical systems but the test-retest reliability of BC ASSR has not been reported. The purpose of this study was to investigate the test-retest reliability of BC ASSR in adults with normal hearing and with sensorineural hearing loss (SNHL). Data were obtained from 22 ears with normal hearing and 11 ears with SNHL. The BC ASSR measurement was performed at carrier frequencies of 500, 1,000, 2,000 and 4,000 Hz using the Audera system. All procedures for measuring the BC ASSR were repeated within 15 days. There were no significant differences in BC ASSR thresholds between the test and the retest for both groups (p>.05). The correlation coefficients of the BC ASSR thresholds ranged from poor (0.34, 0.38) for 500, 1,000 Hz to moderate (0.58, 0.62) for 2,000, 4,000 Hz in normal hearing adults. The correlation coefficients in SNHL adults were 0.33, 0.90, 0.93 and 0.68 for each test frequency. Results demonstrated moderately strong reliability for 1,000, 2,000 and 4,000 Hz, although the reliability for 500 Hz was low. It is suggested, therefore, that the BC ASSR measurement be a clinically reliable test especially in high frequencies. KEY WORDS：Bone-conducted ASSR·Reliability.

Adults with Auditory Neuropathy: Comparison of Auditory Steady-State Response and Pure-Tone Audiometry

The relation between the auditory steady-state response (ASSR) and behavioral audiometric thresholds requires further clarification in the case of adults with auditory neuropathy/auditory dys-synchrony (AN/AD). The aim of this study was to compare pure-tone audiometric threshold (PTAT) and ASSR in adults with AN/AD. Sixteen adult participants (32 ears) with AN/AD, ranging in age from 14 to 34 years. PTAT and ASSR with high-rate stimulus modulation were measured at four octave frequencies, 500, 1000, 2000, and 4000 Hz, in each ear. The behavioral auditory thresholds were compared with ASSR estimated thresholds at each frequency. Analyses included comparison of group means and coefficients of correlation. The average pure-tone thresholds revealed a moderate hearing loss in the AN/AD patients with a focus on the low frequencies. Low-frequency loss audiograms were observed in almost two-thirds of the participants. The estimated auditory thresholds measured by ASSR at all frequencies were substantially higher than the PTAT measures. There were no significant correlations between the PTAT and ASSR measurements at the 1000, 2000, and 4000 Hz frequencies (p > .05); the correlation between the two measures at 500 Hz (p = .029, r = 0.39) was weak but significant. There was no significant correlation between the PTAT and ASSR results at the majority of the frequencies usually tested in adults with AN/AD. Although ASSR is not a suitable method to estimate auditory thresholds in this group of patients, perhaps it can be utilized as an adjunct technique for the differential diagnosis of this disorder.

Effects of Contralateral Noise on 40-Hz and 80-Hz Auditory Steady-State Responses

The amplitude of 40-Hz auditory steady-state response (ASSR) in response to repeated click or tone pips at levels of 45 to 60 dB SL is reduced by up to 50% by the central masking mechanism if white noise at levels of 40 to 60 dB SL is applied contralaterally. However, the effect of contralateral noise on the elevation of the threshold of ASSR is unknown. The present study investigated the effects of contralateral noise on the threshold measurements of ASSR for 40- and 80-Hz amplitude modulated tones that are widely used in clinical examinations. The effects of contralateral noise on the 40- and 80-Hz ASSRs for amplitude modulated tones at 500 Hz and 2000 Hz were examined in 11 healthy volunteers (10 men and 1 woman, mean age 26.1 years). Contralateral noise consisted of white noise low-pass filtered at 700 and 4000 Hz in the measurements of ASSR at a carrier frequency of 500 and 2000 Hz, respectively. Contralateral noise at a level of 40 dB SL caused no significant psychophysical threshold elevation, caused significant threshold elevation of the 40-Hz ASSR (average 10 to 15 dB), and caused no significant threshold elevation of the 80-Hz ASSR. The different effects on the 40- and 80-Hz ASSRs were probably related to the differences in sources because the 40-Hz ASSR contains more components from the upper auditory pathway that are affected by contralateral masking, whereas the 80-Hz ASSR contains more components from the brain stem. The present results suggest that threshold elevation of the 40-Hz ASSR may occur during clinical measurements using binaural presentation of sounds and cause a possible discrepancy between psychophysical threshold and 40-Hz ASSR measurements.