The effects of propofol on the 40-Hz auditory steady-state response and on the electroencephalogram in humans.

The auditory steady state response (ASSR) is an oscillatory brain response, which is phase locked to the rhythm of an auditory stimulus. ASSRs have been recorded in response to a wide frequency range of modulation and/or repetition, but the physiological features of the ASSRs are somewhat different depending on the modulation frequency. Recently, the 20-Hz ASSR has been emphasized in clinical examinations, especially in the area of psychiatry. However, little is known about the physiological properties of the 20-Hz ASSR, compared to those of the 40-Hz and 80-Hz ASSRs. The effects of contralateral noise on the ASSR are known to depend on the modulation frequency to evoke ASSR. However, the effects of contralateral noise on the 20-Hz ASSR are not known. Here we assessed the effects of contralateral white noise at a level of 70 dB SPL on the 20-Hz and 40-Hz ASSRs using a helmet-shaped magnetoencephalography system in 9 healthy volunteers (8 males and 1 female, mean age 31.2 years). The ASSRs were elicited by monaural 1000-Hz 5-s tone bursts amplitude-modulated at 20 and 39 Hz and presented at 80 dB SPL. Contralateral noise caused significant suppression of both the 20-Hz and 40-Hz ASSRs, although suppression was significantly smaller for the 20-Hz ASSRs than the 40-Hz ASSRs. Moreover, the greatest suppression of both 20-Hz and 40-Hz ASSRs occurred in the right hemisphere when stimuli were presented to the right ear with contralateral noise. The present study newly showed that 20-Hz ASSRs are suppressed by contralateral noise, which may be important both for characterization of the 20-Hz ASSR and for interpretation in clinical situations. Physicians must be aware that the 20-Hz ASSR is significantly suppressed by sound (e.g. masking noise or binaural stimulation) applied to the contralateral ear.

40-Hz multiple auditory steady-state responses to narrow-band chirps in sedated and anaesthetized infants

The 40-Hz auditory steady state response (ASSR) signals recorded from human subjects during sleep and wakefulness are investigated in this study for the purpose of monitoring sleep. The ASSR signals extracted from stimulated electro encephalogram (EEG), explored in search for differentiating and robust to noise features. Choosing appropriate features in time and frequency domain, the performance of linear and quadratic discriminant analysis in classifying signals in different scenarios are studied. While the developed method itself is novel in sleep monitoring, due to similarities between N3 stage of sleep and anesthesia, the method will pave the way for later analysis on monitoring consciousness with 40-Hz ASSR. The 40-Hz ASSR extraction and noise cancellation methods presented in this paper can also be used for extracting 40-Hz ASSR from its background EEG signal in general.

Sound presented to the contralateral ear suppresses the amplitude of the 40-Hz auditory steady-state response (ASSR). The frequency characteristics of this suppression of the 40-Hz ASSR for amplitude modulated (AM) tones at 1,000 Hz (79-dB SPL) were examined in 12 healthy volunteers (10 males and 2 females, mean age 32.3 years) using contralateral AM tones (500, 1,000, 2,000, and 4,000 Hz) and 1/3 octave-band noise (500, 1,000, 2,000, and 4,000 Hz). The 40-Hz ASSR at 1,000 Hz was suppressed by a relatively wide frequency range of contralateral sound than expected from the known characteristics of psychophysical central masking by contralateral sound: the greatest suppression was obtained with 500- and 1,000-Hz sounds, but considerable suppression was also obtained with 2,000- and 4,000-Hz sounds. Substantial differences in the suppression pattern were not observed between two types of contra-suppressors; i.e., AM tones and 1/3 octave-band noise. Therefore, any sound presented to the contralateral ear, regardless of the frequency, can suppress the 40-Hz ASSR. Moreover, the different frequency characteristics of the contralateral sound effects between the psychophysical central masking and the 40-Hz ASSR would support the idea that the 40-Hz ASSR has an additive role in the processing of auditory signals to simple threshold judgment. Investigation of the type of psychophysical measurement using the AM signal showing similar suppression patterns by the presentation of contralateral sound would be helpful to reveal the functional relevance of ASSRs.

T159. Hemispheric difference in temporal perception between 40- and 80-Hz auditory steady-state responses: MEG and ECoG studies

Two-channel auditory steady-state response (ASSR) recording at high and low MF (modulation frequency) most likely provides an insight about the response amplitude and latency from different directions at the brainstem level and at the thalamus or cortical level. Little is known about the combined relationship between MF (39 and 79 Hz) and electrode montages (ipsilateral and contralateral) to single AM (amplitude modulation) tones on the ASSR amplitude and latency. To determine if ipsilateral versus contralateral response asymmetries are present at the brainstem level (79 Hz ASSR) and at the thalamus or cortical levels (39 Hz ASSR). Descriptive and inferential statistics for interchannel ipsilateral and contralateral ASSR amplitude and latency to 79 and 39 Hz. Twenty-five normal-hearing, right-handed young female adults participated in the study. All participants were right-handed, and their age ranged between 18 to 28 years (mean 24.5 +/- 1.6 years). Ipsilateral and contralateral ASSR to 39 and 79 Hz MF and 100% AM stimuli were recorded at 500, 2000, and 4000 Hz carrier frequencies at 65 dB SPL. The ASSR amplitudes and phases were determined for each MF across Fc (carrier frequency) for the two channels to the test (right) ear. ASSR amplitude and latency between recording montages for each MF and across carrier frequency were compared by computing two-way repeated measures ANOVA. The mean ipsilateral ASSR amplitudes to 39 Hz across frequency were slightly larger (228.6 +/- 61.6 microV) than the contralateral response amplitude (223.2 +/- 78 microV) while the mean ipsilateral 79 Hz amplitudes were smaller (127.3 +/- 114.8) compared to contralateral 79 Hz amplitude (154.6 +/- 112.7 microV). For latency response, the mean ipsilateral/contralateral latency difference, on average, was 1 msec or less for both MFs. Results, in normal female adults, indicated no significant interchannel ASSR asymmetries for amplitude and latency (p > 0.05) at the brainstem (79 Hz ASSR) and at the thalamus or cortical levels (39 Hz ASSR). Interchannel ipsilateral and contralateral ASSR amplitude and latency to 79 and 39 Hz are not significantly different in normal, young female adults. Two-channel recording of ASSR to different MFs may be of clinical value in otoneurologic assessment.

Background: The 40 Hz auditory steady state response (ASSR) is robustly impaired in chronic schizophrenia which could reflect impaired GABAergic neurotransmission in auditory cortex. However, little is known about the presence of alterations in the 40 Hz ASSR in early and at-risk stages of psychosis. In the current study, we aimed to explore the 40 Hz ASSR impairments in individuals at ultra-high risk (UHR) of psychosis and the possible relationship of deficits in gamma-band entrainment to dysfunctional GABAergic neurotransmission through measurements of cortical GABA-levels. Methods: Fifty UHR participants recruited from the general public, NHS primary care and mental health services and 25 healthy controls were included as part of the MRC-funded Youth Mental Health Risk and Resilience (YouR)-study. MEG data were recorded while participants were passively presented with a series of 1000 Hz carrier tones amplitude modulated at 40 Hz. These data were analyzed at source-level by reconstruction in the frequency-domain using 98 nodes defined from the AAL-atlas and LCMV beamformer source-analysis algorithms. This approach was employed in order to estimate ASSR responses directly from their generating sources while suppressing sensor-level noise and activity in neighboring brain areas. Finally, GABA/Cr ratios were measured, using 1H-MRS at 3T and 2 × 2 × 2 cm voxels placed in the right visual and bilateral auditory cortices. Results: Across groups, the ASSR stimulus significantly activated 15 AAL nodes (FDR corrected), including auditory areas such as right superior temporal gyrus, right heschl’s gyrus, right medial temporal gyrus and left supramarginal gyrus. Subsequent group comparisons revealed impaired 40 Hz ASSR spectral power in secondary auditory areas in UHR participants, which was maximal at 250–750 ms post-stimulus onset in the left supramarginal gyrus. Furthermore, a significant difference was found for GABA/Cr levels in the right auditory cortex (UHR > controls). Conclusion: These results indicate that the 40 Hz ASSR is impaired in UHR participants, which could be related to aberrant GABAergic neurotransmission in auditory cortex. Accordingly, the 40 Hz ASSR could potentially constitute a biomarker for early detection and diagnosis reflecting changes in the balance between excitation and inhibition in auditory areas.

An algorithm for predicting the amplitude of 40-Hz auditory steady state response (ASSR), which is an indicative of depth of anaesthesia, is presented in this paper. The amplitude of 40-Hz ASSR is an indicative of the depth of anaesthesia. Predicting this amplitude will help anesthesiologists in choosing the dose of the anaesthetic agents and have an estimation of the patients' next depth of anaesthesia state. The method is applied to the 40-Hz ASSR signals recorded from 20 human subjects during surgical operation. The algorithm uses sequential feature selection and multi-linear regression for choosing the most informative features and estimating the amplitude of ASSR on the next cycle and at the end of induction stage, when the patient looses his/her eyelash reflex. The algorithm uses the dose of anaesthetic drug, some of the demographics and medical parameters of the patients and their previous ASSR cycles for prediction. As the system provided with more ASSR cycles, the error in prediction decreases and estimation gets more accurate. The method is applied on the induction phase where patients' depth of anaesthesia changes very fast but it is applicable to all other stages of anaesthesia as well.

An auditory steady-state response (ASSR) is an electrophysiological response to periodic stimuli that reflects the synchronization of endogenous oscillations. The 40-Hz ASSR is reduced in patients with schizophrenia, bipolar disorder, and autism spectrum disorder, making it a candidate biomarker for these psychiatric disorders. Previous studies have revealed that experimental conditions such as stimulus duration and inter-stimulus interval tend to affect ASSR, suggesting that novelty detection may play an important role in determining the magnitude of ASSR. The present study is the first to investigate the effect of novelty detection on 20- and 40-Hz ASSRs in healthy individuals. Magnetoencephalography recordings were obtained from 30 healthy adults exposed to auditory stimuli at 20 and 40 Hz. The stimuli were presented in three paradigms: 20- and 40-Hz repetitive presentations and random presentation, the latter being categorized by whether the preceding stimulus was the same (S trials) or different (D trials). The ASSR amplitude and inter-trial phase coherence (ITPC) were assessed via time-frequency analysis. The results revealed that the 20-Hz ASSR was suppressed with increased novelty, with the highest amplitude and ITPC observed during repetitive presentation. In contrast, the 40-Hz ASSR was enhanced by increased novelty, with the greatest measures observed during the D trials. These findings show that novelty detection modulates 20- and 40-Hz ASSRs in opposite directions, highlighting its critical role in shaping stimulus-induced oscillatory responses. This frequency-specific modulation pattern may provide a novel perspective for understanding ASSR abnormalities in psychiatric disorders.

The auditory middle-latency response (transient) and the 40-Hz auditory steady state response (ASSR) are modulated by anesthetics. However, the quantitative relation between these evoked responses is difficult to obtain because of technical limitations of the recording methods used to obtain transients at high stimulation rates. This study uses continuous-loop averaging deconvolution to fill this technical gap and to study the relation between the transient and ASSR waveform during general anesthesia. The authors recorded 5- and 40-Hz transients and 40-Hz ASSRs in 13 subjects during general anesthesia. The 5- and 40-Hz transients were used to predict the 40-Hz ASSR by linearly superimposing the transient waveforms. The predicted and recorded ASSRs were analyzed and compared using phasor and Hotelling T(2) analyses. Grand-averaged recordings revealed differences in the early middle-latency peaks between 5- and 40-Hz transients, e.g., the peak P(x) was present only in 5-Hz transient. Only the predicted 40-Hz ASSR derived from the 40-Hz transient matched the actual ASSR. Phasor analysis showed that the early peaks contribute significantly to the steady state waveform, and this explains why 5-Hz transient does not predict the 40-Hz ASSR. Oscillations in both the 5- and 40-Hz transients were observed during anesthesia. The 40-Hz ASSR represents a composite waveform and arises when transient waveforms elicited with a 40-Hz stimulation rate are overlapped and superimposed. During general anesthesia, the morphology of the transient is dependent on the rate of stimulus presentation. The composite nature of the ASSR may explain nonmonotonic anesthetic dose-response relations observed by others.

This study describes the history, stimulus tones, detection techniques, source generators and clinical applications of auditory steady-state responses (ASSR). The most important benefit of ASSR in objective audiometry is that it can provide an accurate assessment of hearing at different audiometric frequencies in a frequency specific manner, if sinusoidally amplitude-modulated tones are used as tonal stimuli. Power spectrum analysis and phase coherence using fast Fourier transform are useful for the automatic detection of threshold because of the sinusoidal response waveform configuration. Because the detectability of ASSR changes under different arousal states, 40-Hz ASSR is suitable for waking adults and 80-Hz ASSR for sleeping children in the assessment of hearing. Regarding the sources of those responses, 40-Hz ASSR is considered the steady-state version of the middle latency response and 80-Hz ASSR is considered the steady-state version of auditory brainstem response (ABR). Bone conduction stimuli are also useful in the assessment of conductive hearing loss, though the responses are not reliable at the intensity level of 60dB or higher. The difficulty in predicting a hearing level of 500Hz or less using the 80-Hz ASSR threshold can be explained by auditory filter. Its advantage is that the thresholds at 4 different frequencies in both ears can be predicted more rapidly than ABR using the multiple simultaneous stimulation technique. In addition, the ASSR to clicks may provide a rapid screening technique. Finally, it may be helpful in assessing suprathreshold hearing to use ASSRs to sounds that sweep their intensity (sweep technique) or actual speech sounds. In this respect, ASSRs may contribute to the objective fitting of hearing aids in young children.

Background. The auditory steady state response (ASSR) is generated in bilateral auditory cortex and is the most used electroencephalographic (EEG) or magnetoencephalographic measure of gamma band abnormalities in schizophrenia. While the finding of reduced 40-Hz ASSR power and phase consistency in schizophrenia have been replicated many times, the 40-Hz ASSR phase locking angle (PLA), which assesses oscillation latency or phase delay, has rarely been examined. Furthermore, whether 40-Hz ASSR phase delay in schizophrenia is lateralized or common to left and right auditory cortical generators is unknown. Methods. Previously analyzed EEG data recorded from 24 schizophrenia patients and 24 healthy controls presented with 20-, 30-, and 40-Hz click trains to elicit ASSRs were re-analyzed to assess PLA in source space. Dipole moments in the right and left hemisphere were used to assess both frequency and hemisphere specificity of ASSR phase delay in schizophrenia. Results. Schizophrenia patients exhibited significantly reduced (ie, phase delayed) 40-Hz PLA in the left, but not the right, hemisphere, but their 20- and 30-Hz PLA values were normal. This left-lateralized 40-Hz phase delay was unrelated to symptoms or to previously reported left-lateralized PLF reductions in the schizophrenia patients. Conclusions. Consistent with sensor-based studies, the 40-Hz ASSR source-localized to left, but not right, auditory cortex was phase delayed in schizophrenia. Consistent with prior studies showing left temporal lobe volume deficits in schizophrenia, our findings suggest sluggish entrainment to 40-Hz auditory stimulation specific to left auditory cortex that are distinct from well-established deficits in gamma ASSR power and phase synchrony.

Aberrant attentional modulation of the auditory steady state response (ASSR) is related to auditory hallucination severity in the first-episode schizophrenia-spectrum

The early detection of autistic tendencies in children is essential for providing proper care and education. The auditory steady-state response (ASSR) provides a passive, non-invasive technique for assessing neural synchrony at specific response frequencies in many mental disorders, including autism spectrum disorder (ASD), but few studies have investigated its use in young children. This study investigated the ASSR at 20 Hz and 40 Hz in typically developing (TD) children and children with ASD aged 5-7 years. The participants were 23 children with ASD and 32 TD children aged 5-7 years. Using a custom-made magnetoencephalography device, we measured ASSR at 20 Hz and 40 Hz, compared the results between groups, and evaluated the association with intellectual function as measured by Kaufmann Assessment Battery for Children. Responses to 20 Hz and 40 Hz were clearly detected in both groups with no significant difference identified. Consistent with previous findings, right dominance of the 40-Hz ASSR was observed in both groups. In the TD children, the right-side 40-Hz ASSR was correlated with age. The Kaufmann Assessment Battery for Children score was correlated with the left-side 40-Hz ASSR in both groups. Right-dominant ASSR was successfully detected in young TD children and children with ASD. No difference in ASSR was observed between the children with ASD and the TD children, although the right-side 40-Hz ASSR increased with age only in the TD children. Left-side 40-Hz ASSR was associated with intelligence score in both groups.

A new design based on wavelet analysis for the objective audiometry devices is proposed. The auditory brainstem response and 80-Hz auditory steady-state response (ASSR) are used in the objective audiometry devices for infants. For the aged, an objective audiometry device is used in anti-aging investigations, which enables the hearing acuity of awake adults to be tested with the 40-Hz ASSR. The ASSR evoked by an amplitude modulated tone is recorded as a waveform. However, the evoked potential response is very small. Therefore, it is difficult to decide a threshold of the response and whether a significant response exists when it is mixed with noise such as the background brain waves. To cope with this problem, we need to average the evoked response waveforms. In particular, the 40-Hz ASSR has a large amount of noise caused by the background brain waves in comparison with the 80-Hz ASSR. In this paper, we apply waveform analysis using the wavelet transform in order to extract the 40-Hz ASSR from a signal mixed with a large amount of noise. Subjects with normal hearing participated in this study.