Determination and evaluation of clinically efficient stopping criteria for the multiple auditory steady-state response technique

Background: Although the auditory steady-state response (ASSR) technique utilizes objective statistical detection algorithms to estimate behavioural hearing thresholds, the audiologist still has to decide when to terminate ASSR recordings introducing once more a certain degree of subjectivity. Aims: The present study aimed at establishing clinically efficient stopping criteria for a multiple 80-Hz ASSR system. Methods: In Experiment 1, data of 31 normal hearing subjects were analyzed off-line to propose stopping rules. Consequently, ASSR recordings will be stopped when (1) all 8 responses reach significance and significance can be maintained for 8 consecutive sweeps; (2) the mean noise levels were ≤ 4 nV (if at this “≤ 4-nV” criterion, p-values were between 0.05 and 0.1, measurements were extended only once by 8 sweeps); and (3) a maximum amount of 48 sweeps was attained. In Experiment 2, these stopping criteria were applied on 10 normal hearing and 10 hearing-impaired adults to asses the efficiency. Results: The application of these stopping rules resulted in ASSR threshold values that were comparable to other multiple-ASSR research with normal hearing and hearing-impaired adults. Furthermore, in 80% of the cases, ASSR thresholds could be obtained within a time-frame of 1 hour. Investigating the significant response-amplitudes of the hearing-impaired adults through cumulative curves indicated that probably a higher noise-stop criterion than “≤ 4 nV” can be used. Conclusions: The proposed stopping rules can be used in adults to determine accurate ASSR thresholds within an acceptable time-frame of about 1 hour. However, additional research with infants and adults with varying degrees and configurations of hearing loss is needed to optimize these criteria

Validation of the 40 Hz Auditory Steady State Response as a Pharmacodynamic Biomarker of Evoked Neural Synchrony

Schizophrenia is a troubling and severe mental illness that is only incompletely treated by currently available drugs. New drug development is hindered by a scarcity of functionally relevant pharmacodynamic biomarkers that are translatable across preclinical and human subjects. Although psychosis is a major feature of schizophrenia, cognitive and negative symptoms determine the long-term functional outcomes for patients. Stimulus-evoked neural synchrony at gamma (~ 40 Hz) frequency plays an important role in the processing and integration of sensory information. Not surprisingly, schizophrenia patients show deficits in gamma oscillations. NMDA receptor (NMDAR) activation on fast-spiking parvalbumin-positive interneurons is deemed important for the generation of gamma oscillations. NMDA hypofunction has been proposed as an alternative hypothesis to the well-known dopamine dysregulation to explain the neurochemical abnormalities associated with schizophrenia. For this dissertation, we validated a preclinical model to pharmacologically probe NMDA-mediated gamma oscillations by further characterizing the auditory-steady state response (ASSR) in female Sprague Dawley rats. The ASSR is a measure of cortical neural synchrony evoked in response to periodic auditory stimuli. ASSR at 40 Hz is consistently disrupted in patients. First, we established the reliability of click train-evoked 40 Hz ASSR and tone-evoked gamma oscillations in 6 separate sessions, spread over a 3-week period. Then we established the sensitivity of these neural synchrony measures to acute NMDAR blockade using the high affinity NMDA channel blocker MK-801, using a repeated measures design. Next, we compared the reliability and sensitivity of the 40 Hz ASSR from two distinct recording sites. Results from this study showed that as compared to vertex, temporal recording showed a greater gamma synchrony. However, the temporal recording had poor test-retest reliability and lower sensitivity to MK-801-induced disruption. Lastly, we characterized the dose-response profiles of an NMDA co-agonist D-serine, an atypical (clozapine) and a typical (haloperidol) antipsychotic, on the 40 Hz ASSR. Results from these studies showed that only clozapine was effective in robustly augmenting 40 Hz ASSR. Furthermore, only clozapine pretreatment had partial protective effect against MK-801 induced ASSR disruption. Overall, this work establishes that vertex recorded 40 Hz ASSR is a reliable neural synchrony biomarker in female SD rats that is amenable for bidirectional pharmacodynamic modulation

Real-time detection of auditory : steady-state brainstem potentials evoked by auditory stimuli

The auditory steady-state response (ASSR) is advantageous against other hearing techniques because of its capability in providing objective and frequency specific information. The objectives are to reduce the lengthy test duration, and improve the signal detection rate and the robustness of the detection against the background noise and unwanted artefacts.Two prominent state estimation techniques of Luenberger observer and Kalman filter have been used in the development of the autonomous ASSR detection scheme. Both techniques are real-time implementable, while the challenges faced in the application of the observer and Kalman filter techniques are the very poor SNR (could be as low as −30dB) of ASSRs and unknown statistics of the noise. Dual-channel architecture is proposed, one is for the estimate of sinusoid and the other for the estimate of the background noise. Simulation and experimental studies were also conducted to evaluate the performances of the developed ASSR detection scheme, and to compare the new method with other conventional techniques. In general, both the state estimation techniques within the detection scheme produced comparable results as compared to the conventional techniques, but achieved significant measurement time reduction in some cases. A guide is given for the determination of the observer gains, while an adaptive algorithm has been used for adjustment of the gains in the Kalman filters.In order to enhance the robustness of the ASSR detection scheme with adaptive Kalman filters against possible artefacts (outliers), a multisensory data fusion approach is used to combine both standard mean operation and median operation in the ASSR detection algorithm. In addition, a self-tuned statistical-based thresholding using the regression technique is applied in the autonomous ASSR detection scheme. The scheme with adaptive Kalman filters is capable of estimating the variances of system and background noise to improve the ASSR detection rate

Effects of age on amplitude-modulated cVEMP temporal modulation transfer function

With the aging population on the rise, the need for effective assessment tools to identify risk factors for falls among the elderly is paramount. One independent risk factor for falls is vestibular impairment, but the available vestibular diagnostic tests have limitations. A promising new methodology: amplitude-modulated tones to elicit a vestibular-evoked myogenic potential (AMcVEMP), offers a more detailed examination of vestibular (sacculo-collic reflex) functions. This method assesses non-linearities, synchrony, and magnitude, providing a more thorough evaluation compared to the conventional transient cVEMP. So far, AMcVEMP has only been utilized in young adults. The current study aimed to investigate the impact of age on the AMcVEMP temporal modulation transfer function (TMTF), determine the shape and limit of the AMcVEMP TMTF, and assess non-linearity across a range of modulation frequencies. The study included 49 healthy participants, categorized into three age groups. AMcVEMP responses were elicited using a carrier-frequency of 500 Hz and 10 modulation frequencies. An FFT-based approach was employed to analyze the responses, focusing on amplitude, signal-to-noise ratio (SNR), phase coherence (PC), and non-linearity. To measure non-linearity, harmonics of the modulation frequencies were analyzed. The AMcVEMP responses exhibited characteristics consistent with saccular rectification. The AMcVEMP amplitude, SNR, and PC reduced with increasing age. The effects of age were less pronounced for PC, showing 100% response rates among older adults. Further, AMcVEMP TMTF range reduced with age for all measures. The shape of the AMcVEMP TMTF resembled bandpass filter among young adults and got narrower with age. Lastly, for the non-linearity measures, harmonics were robust in most young, some middle-aged and fewer older adults, indicating loss of non-linearity with aging. AMcVEMP offers several advantages in assessing older adults compared to conventional cVEMP: higher response rates and the ability to examine and quantify the magnitude, synchrony, and non-linearity from the sacculo-collic reflex. This study advances our overall understanding of age-related changes in the vestibular system. Further utility of AMcVEMP in clinical populations will advance our comprehension of vestibular pathophysiology. Furthermore, linking vestibular non-linearity with functional balance may facilitate the development of strategies to mitigate the risk of falls among older adults

Effects of theta-frequency binaural beats on post-exercise recovery and stress responsivity

Binaural beats are an auditory illusion perceived when two or more pure tones of similar frequencies are presented dichotically through stereo headphones. This phenomenon is thought to have the potential to facilitate changes in arousal. The present study investigated the effects of 7 Hz binaural beating on post-exercise recovery and stress responsivity in college-aged students (n = 21; 18-29 years old).Theta binaural beats failed to outperform placebo in altering post-exercise recovery or stress responsivity. However, after listening to binaural beats, participants reported feeling more relaxed (6.4% change) and less stressed (11.5% change). Findings from the present study suggest that listening to binaural beats may have subtle psychological effects

A Preliminary Study on the Safety of Elastography during Pregnancy: Hypoacusia, Anthropometry, and Apgar Score in Newborns

Transient or acoustic radiation force elastography (ARFE) is becoming the most extended technology to assess cervical effacement, additionally to the Bishop test and conventional ultrasound. However, a debate on the fetal safety has been opened due to the high intensity focused beam emitted to produce shear waves. This work is aimed at providing preliminary data to assess clinical effects of fetal exposure. A follow-up study in newborns of 42 women exposed to ARFE during pregnancy was carried out to explore neonatal hypoacusia, Apgar test, and anthropometry. No hypoacusia cases attributable to ARFE were observed. The Apgar test at five minutes scored normally in all the newborns. Comparisons between anthropometric measurements showed no significant statistically differences. The results preclude to state the harmfulness nor the safety of ARFE. However, given the concern on the high level of energy and the potential risk of harmful bioeffects, larger studies are recommended.Ministry of Education DPI2017-85359-R UNGR15-CE-3664 PI16/00339Carlos III Feder fundJunta de Andalucía PIN-0030-2017 PI-0107-2017Spanish Government TEC2014-57394-PMNat Scientific Unit of Excellence UCE.PP2017.0

Bewusstseinsverlust unter Propofol Anästhesie

In dieser Arbeit wurden verschiedene hirnelektrische Parameter und Verhaltensmaße im Wachzustand und während Anästhesie analysiert. Die übergreifende Hauptfragestellung lautete hierbei: Welche Veränderungen treten in Hirnprozessen unter tiefer Propofol-Anästhesie auf und mit Hilfe welcher Indikatoren ist es möglich, diese abzubilden? An der Untersuchung nahmen 21 VPN teil, die mit Hilfe unterschiedlicher EEG-Paradigmen (akustischer passiver Oddball, akustisches Klickreizparadigma, Paradigma mit noxischer Reizung) und einigen postnarkotischen Gedächtnistests untersucht wurden. Die Gedächtnistests lieferten keinen Hinweis auf explizite oder implizite Erinnerungen aus der Narkosezeit. Dies in Verbindung mit der Veränderung der Kennwerte im Klickreizparadigma wird als Nachweis einer vollständigen Bewusstseinsausschaltung unter Anästhesie gewertet. In diesem Zustand konnten zahlreiche modalitätsabhängige Veränderungen hirnelektrischer Prozesse festgestellt werden. Diese Resultate werden dargestellt, in den Forschungskontext eingereiht und mit Blick auf ihren Beitrag für ein besseres Verständnis von Anästhesie-induzierten Zuständen der Bewusstlosigkeit und von Bewusstsein allgemein interpretiert