Frequency Auditory Steady-state Response Research Articles

Auditory steady-state responses in the auditory cortex of mice during estrus cycle

Auditory-steady state responses (ASSRs) disclose the brain’s potency to oscillate and have been suggested to serve as biomarkers in various psychiatric disorders. GABAergic neurotransmission, a critical component of brain oscillations, is strongly influenced by sex hormones. In line, the severity of symptoms in psychiatric disorders has been linked to changes in sex hormones during the menstrual cycle. However, how these sex hormones affect ASSRs remain largely unknown. This was addressed by performing chronic recordings of ASSRs in mice while monitoring its estrus cycle. Here, the stability of ASSRs during long-term recordings was validated and showed good reliability. 40 Hz ASSRs showed changes throughout the estrus cycle where it decreased in the metestrus phase compared to the diestrus phase. In contrast, other frequency ASSRs did not show significant changes throughout the estrus cycle. Taken together, our findings illustrate that the estrus cycle may influence the generation of ASSRs and that the phase of the estrus cycle should be taken into consideration when ASSRs are recorded in females.

Envelope Following Response to 440 Hz Carrier Chirp-Modulated Tones Show Clinically Relevant Changes in Schizophrenia.

The 40 Hz auditory steady-state response (ASSR) impairment is suggested as an electrophysiological biomarker of schizophrenia; however, existing data also points to the deficiency of low and high frequency ASSR responses. In order to obtain the full picture of potential impairment in schizophrenia, it is important to test responses at different frequencies. The current study aims to evaluate a wide frequency range (1–120 Hz) in response to brief low-frequency carrier chirp-modulated tones in a group of patients with schizophrenia. The EEG-derived envelope following responses (EFRs) were obtained in a group of male patients with schizophrenia (N = 18) and matched controls (N = 18). While subjects were watching silent movies, 440 Hz carrier chirp-modulated at 1–120 Hz tones were presented. Phase-locking index and evoked amplitude in response to stimulation were assessed and compared on point-to-point basis. The peak frequency of the low gamma response was estimated. Measures were correlated with psychopathology—positive, negative, total scores of the Positive and Negative Syndrome Scale (PANSS), and hallucination subscale scores. In comparison to controls, patients showed (1) reduced power of theta-beta (4–18 Hz) responses, (2) intact but slower low gamma (30–60 Hz), and (3) reduced high gamma (95–120 Hz) responses. No correlation survived the Bonferroni correction, but a sign of positive association between low gamma phase-locking and the prevalence of hallucinations, and a sign of negative association between high gamma phase-locking and the total PANSS scores were observed. Brain networks showed impaired capabilities to generate EFRs at different frequencies in schizophrenia; moreover, even when responses of patients did not significantly differ from controls on the group level, they still showed potentially clinically relevant variability.

Low and medium frequency auditory steady-state responses decrease during NREM sleep.

Previous research on auditory steady-state responses (ASSRs) demonstrated sensitivity of 40 Hz ASSR to changes in the level of arousal, both in sleep and in general anaesthesia. In this study we extended the range of stimulation frequencies, using also low and medium stimulation frequencies (4, 6, 8, 12, 20, 40 Hz) and studied their susceptibility to the loss of consciousness in NREM sleep (N2 and N3 stages). Effects of NREM sleep were examined in power domain with relative power (RP), and in phase domain using inter-trial phase coherence (PC) parameter. The activity in power domain was also compared to no-stimulation data. Regions displaying significant waking-NREM sleep differences were selected using non-parametric suprathreshold cluster test. For 4, 6, 20 and 40 Hz stimulation relative power of ASSRs was lower in NREM sleep, with maximal change for 40 Hz stimulation. This decrease was not seen in no-stimulation condition. For all stimulation frequencies (except 12 Hz) we observed decrease of phase coherence of ASSR during NREM sleep. Our results demonstrate that low and medium frequency ASSRs are state-sensitive, thus susceptible to loss of consciousness during NREM sleep. Diminishing of power and phase coherence may result from cortical down states and/or thalamic inhibition. Our results support possible use of low- and medium-frequency ASSRs for discrimination between states of altered consciousness and emphasize the role of the auditory system in determining these variations.

Delta Vs Gamma Auditory Steady State Synchrony in Schizophrenia.

Delta band (1-4 Hz) neuronal responses support the precision and stability of auditory processing, and a deficit in delta band synchrony may be relevant to auditory domain symptoms in schizophrenia patients. Delta band synchronization elicited by a 2.5 Hz auditory steady state response (ASSR) paradigm, along with those from theta (5 Hz), alpha (10 Hz), beta (20 Hz), gamma (40 Hz), and high gamma (80 Hz) frequency ASSR, were compared in 128 patients with schizophrenia, 108 healthy controls, and 55 first-degree relatives (FDR) of patients. Delta band synchronization was significantly impaired in patients compared with controls (F = 18.3, P < .001). There was a significant 2.5 Hz by 40 Hz ASSR interaction (P = .023), arising from a greater reduction of 2.5 Hz ASSR than of 40 Hz ASSR, in patients compared with controls. Greater deficit in delta ASSR was associated with auditory perceptual abnormality (P = .007) and reduced verbal working memory (P < .001). Gamma frequency ASSR impairment was also significant but more modest (F = 8.7, P = .004), and this deficit was also present in FDR (P = .022). The ability to sustain delta band oscillation entrainment in the auditory pathway is significantly reduced in schizophrenia patients and appears to be clinically relevant.

Phencyclidine Disrupts the Auditory Steady State Response in Rats.

The Auditory Steady-State Response (ASSR) in the electroencephalogram (EEG) is usually reduced in schizophrenia (SZ), particularly to 40 Hz stimulation. The gamma frequency ASSR deficit has been attributed to N-methyl-D-aspartate receptor (NMDAR) hypofunction. We tested whether the NMDAR antagonist, phencyclidine (PCP), produced similar ASSR deficits in rats. EEG was recorded from awake rats via intracranial electrodes overlaying the auditory cortex and at the vertex of the skull. ASSRs to click trains were recorded at 10, 20, 30, 40, 50, and 55 Hz and measured by ASSR Mean Power (MP) and Phase Locking Factor (PLF). In Experiment 1, the effect of different subcutaneous doses of PCP (1.0, 2.5 and 4.0 mg/kg) on the ASSR in 12 rats was assessed. In Experiment 2, ASSRs were compared in PCP treated rats and control rats at baseline, after acute injection (5 mg/kg), following two weeks of subchronic, continuous administration (5 mg/kg/day), and one week after drug cessation. Acute administration of PCP increased PLF and MP at frequencies of stimulation below 50 Hz, and decreased responses at higher frequencies at the auditory cortex site. Acute administration had a less pronounced effect at the vertex site, with a reduction of either PLF or MP observed at frequencies above 20 Hz. Acute effects increased in magnitude with higher doses of PCP. Consistent effects were not observed after subchronic PCP administration. These data indicate that acute administration of PCP, a NMDAR antagonist, produces an increase in ASSR synchrony and power at low frequencies of stimulation and a reduction of high frequency (> 40 Hz) ASSR activity in rats. Subchronic, continuous administration of PCP, on the other hand, has little impact on ASSRs. Thus, while ASSRs are highly sensitive to NMDAR antagonists, their translational utility as a cross-species biomarker for NMDAR hypofunction in SZ and other disorders may be dependent on dose and schedule.

Auditory steady-state response and auditory brainstem response thresholds in children

The inclusion of the auditory steady-state response (ASSR) into test-batteries for objective audiometry has allowed for clinical comparisons with the most widely used procedure, the auditory brainstem response (ABR). The current study describes ASSR and ABR thresholds for a group of infants and young children with various types and degrees of hearing loss. A sample of 48 subjects (23 female) with a mean age of 2.8+/-1.9 years SD were assessed with a comprehensive test-battery and classified according to type and degree of hearing loss. Thresholds were determined with a broadband click-evoked ABR and single frequency ASSR evoked with continuous tones (0.25-4 kHz) amplitude modulated (67-95 Hz). Mean difference scores (+/-SD) between the ABR and high frequency ASSR thresholds were 9.8 (+/-11), 3.6 (+/-12) and 10.5 (+/-12) dB at 1, 2 and 4 kHz, respectively. An ASSR mean threshold for 2-4 and 1-4 kHz compared to the ABR threshold revealed an average difference of 7 (+/-9) and 7.9 (+/-8) dB, respectively. The overall correlation between the ABR and ASSR thresholds was highest for the mean ASSR thresholds of 2-4 and 1-4 kHz (r=0.92 for both conditions). Correlations between the ABR and individual ASSR frequencies were slightly less (0.82-0.86). The average of the 2-4 kHz ASSR thresholds correlated best with the click-evoked ABR for all categories of hearing loss except for the sensorineural hearing loss category for which the 1-4 kHz ASSR average was better correlated to ABR thresholds. Findings demonstrate the reliability of verifying high frequency ASSR thresholds with a click-evoked ABR as an important cross-check in infants for whom behavioural audiometry may not be possible.

Auditory steady-state responses and clinical applications

The auditory steady-state responses to single continuous tones modulated in amplitude have been proposed as an alternative to objective frequency-specific audiometry. The aim of this study was to compare thresholds obtained by pure-tone audiometry (PTA) and by auditory steady-state responses in normal hearing or affected by hearing loss in adults and in order to evaluate the applicability of this objective test in no collaborative hearing-impaired subjects. Eleven people, 6 normal hearing and 5 with hearing loss, underwent PTA and multiple frequency auditory steady-state responses; simultaneous carrier tones (0.5, 1, 2 and 4 KHz) modulated in amplitude at different rates (77-105 Hz) were presented monaurally (TDH 49 earphones) at variable intensities (110-20 dB SPL). The mean threshold difference between PTA and multiple frequency auditory steady-state responses was 28 dB (standard deviation=14.2) and R correlation value at 0.5-1-2-4 kHz was 0.71 (P=0.0012) at the Pearson's test. These differences were significantly smaller considering the hearing-impaired separately (11.7 dB, standard deviation=2.9). The results of this study confirm previous reports showing that the multiple auditory steady-state response method is an accurate predictor of the behavioural audiogram in patients with sensory-neural hearing impairments and can be used as a valid support for behavioural evaluations.

Predicting Pure-Tone Thresholds with Dichotic Multiple Frequency Auditory Steady State Responses

The accuracy of dichotic multiple frequency auditory steady state in predicting pure-tone thresholds at 0.5, 1, 2, and 4.0 kHz compared to an ABR protocol (click and tone burst at 0.5 kHz) were explored in a group of 25 hearing-impaired subjects across the degree and configuration spectrum. Mean steady state thresholds were within 14, 18, 15, and 14 dB of the pure tones at 0.5, 1, 2, and 4 kHz, compared to the tone-burst ABR at 0.5 kHz pure-tone difference of 24 dB, and a click-evoked pure-tone (2-4 kHz) difference of 9 dB. Recording time for the steady state protocol was 28 minutes (+/- 11) compared to 24 minutes (+/- 9) of the ABR protocol. Degree of loss had a significant effect on steady state; configuration of hearing loss had a limited effect. Mf ASSR predicted thresholds with relative accuracy although some configurations showed discrepancies for low-frequency estimates.

Steady state responses to multiple amplitude-modulated tones: an optimized method to test frequency-specific thresholds in hearing-impaired children and normal-hearing subjects.

To evaluate, using statistical methods, the usefulness of the binaural multiple frequency auditory steady state responses (MF SSRs) for objective, frequency-specific audiometry in a large sample of hearing-impaired children and normal-hearing subjects. The MF SSRs were recorded in a sample of 43 hearing-impaired children (86 ears) and 40 normal-hearing young adults (80 ears). Simultaneous carrier tones (0.5, 1, 2, and 4 kHz) modulated in amplitude at different rates (77 to 105 Hz) were presented binaurally (TDH 49 earphones) at variable intensities (110 to 20 dB SPL). For each subject the response thresholds (RTHs) at 0.5, 1, 2, and 4 kHz, were determined automatically (F test) and compared with the corresponding behavioral thresholds (BTHs). In the normal-hearing subjects, RTHs were detectable, on average, between 11 and 15 dB above the BTH. These differences were significantly smaller in the hearing-impaired (5 to 13 dB). Also a close correspondence was found between the subjective and objective audiogram curves in both groups. The within subject Spearman correlation coefficients calculated between the two curves, were in most cases above the significance cut off point (p < 0.05). Also in 1-way repeated measures analysis of variance, the overall error in the estimation of the audiogram (vector across frequency of absolute distances between the curves) did not differ significantly from zero. The binaural MF SSR was proven to be a valid technique for the estimation of an objective audiogram, in a large sample of hearing-impaired children and normal-hearing subjects. With this method, frequency-specific thresholds at 0.5, 1, 2, and 4 kHz could be determined in all subjects (and both ears) with no appreciable loss in accuracy and a considerable reduction in testing time (average recording time = 21 minutes) when compared with other frequency-specific techniques.

The Low and High Frequency Auditory Steady State Responses Mature at Different Rates

The age-related changes in the fast rate (70–110 Hz) auditory steady state response elicited by multiple-frequency tones (MSSR) that were amplitude-modulated (AM) are reported here. The MSSR was recorded in a sample of 64 well babies distributed into three age groups: 0–29 days (n = 25); 1–6 months (n = 26); 7–12 months (n = 13). Four simultaneously presented AM tones (0.5, 1, 2 and 4 kHz) were delivered monaurally through TDH 49 earphones, at different intensities (between 90 and 30 dB SPL). Clear developmental changes were found between birth and 12 months of age in response threshold, amplitude and detectability. Statistical analysis revealed that these changes occurred at different rates for low- and high- frequency responses. Nonetheless adult-like hearing thresholds were estimated reasonably well in most newborns and well babies, for all frequencies tested. Therefore the MSSR technique could be useful for objective frequency-specific audiometry beginning at birth.