Stimulus Frequency Research Articles

Test-retest reliability of distortion-product thresholds compared to behavioral auditory thresholds

When referred to baseline measures, serial monitoring of pure-tone behavioral thresholds and distortion-product otoacoustic emissions (DPOAEs) can be used to detect the progression of cochlear damage. Semi-logarithmic DPOAE input-output (I/O) functions enable the computation of estimated distortion-product thresholds (EDPTs) by means of linear regression, a metric that provides a quantitative estimate of hearing loss due to cochlear-amplifier degradation. DPOAE wave interference and a suboptimal choice of stimulus levels limit the accuracy of EDPTs. This work identifies the test-retest reliability of EDPTs derived from short-pulse DPOAE level maps (EDPTLM), a method that circumvents limitations associated with both wave interference and suboptimal choice of stimulus levels. The test-retest reliability was compared to that of EDPTs derived from semi-logarithmic I/O functions (EDPTI/O) and that of behavioral thresholds acquired with pure-tone audiometry (PTA) and modified Békésy tracking audiometry (TA) to provide a foundation for identifying and interpreting significant threshold shifts.The DPOAE-based auditory thresholds (EDPTLM and EDPTI/O) and behavioral thresholds (PTA and TA) were recorded seven times within three months at 14 frequencies with f2 = 1–14 kHz in 20 ears from ten subjects with normal hearing (4PTA0.5–4kHz < 20 dB HL). To obtain EDPTLM, short-pulse DPOAEs were recorded using 21 L1,L2 pairs. Reconstruction of DPOAE growth behavior as a function of L1 and L2 using nonlinear curve fitting enabled the derivation of EDPTLM for each frequency.Test-retest reliability was determined using three different approaches: 1) centered thresholds, 2) average threshold differences, and 3) average absolute threshold differences, between each possible test session (N = 21). Test-retest reliability based on centered thresholds and average threshold differences showed no statistically significant difference between EDPTLM, EDPTI/O, PTA, and TA for the pooled analysis incorporating all stimulus frequencies. Average absolute threshold differences presented small but significant differences in test-retest reliability with median values of 3.00 dB for PTA, 3.20 dB for TA, 3.34 dB for EDPTLM, and 3.51 dB for EDPTI/O. A considerable frequency dependence of test-retest reliability was found; namely, the highest test-retest reliability was for EDPTLM at f2 = 11 – 14 kHz. Otherwise, at lower frequencies, the highest test-retest reliability was for TA at f2 =1 – 2 kHz.Overall, the test-retest reliability of EDPTLM was better than that of EDPTI/O and was similar to that for behavioral thresholds. Hence, deriving EDPTLM from individual level maps is a promising and sensitive method for objectively monitoring the state of the cochlea. Furthermore, the detection of an equidirectional threshold change at a single frequency in both EDPTLM and TA might allow reducing the threshold shift as indication of a follow-up examination from the clinical standard of 10 dB down to 5 dB. This stricter indicator might be beneficial when monitoring cochlear damage, for example ototoxicity, in the presence of (remnant) cochlear amplification at baseline.

Is the Focal Muscle Vibration an Effective Motor Conditioning Intervention? A Systematic Review.

Mechanical vibration, applied to single or few muscles, can be a selective stimulus for muscle spindles, able to modify neuromuscular management, inducing short and long-term effects, are now mainly employed in clinic studies. Several studies reported as treatments with focal vibratory (FVT) can influence neuromuscular parameters also in healthy people. However, the application modalities and the consequent effects are remarkably fragmented. This paper aims to review these studies and to characterize the FVT effectiveness on long-term conditional capacities in relation to FVT characteristics. A systematic search of studies published from 1985 to 2020 in English on healthcare databases was performed. Articles had to meet the following criteria: (1) treatment based on a locally applied vibration on muscle belly or tendon; (2) healthy adults involved; (3) outcomes time analysis enduring for more than 24 h. Twelve studies were found, all of them presented an excellent quality score of ≥75%. All selected papers reported positive changes, comparable with traditional long-lasting training effects. Muscle force and power were the most investigated parameters. The after-effects persisted for up to several months. Among the different FV administration modalities, the most effective seems to show a stimulus frequency of ≈100 Hz, repeated more times within three-five days on a voluntary contracted muscle.

Blind Visualization of Task-Related Networks From Visual Oddball Simultaneous EEG-fMRI Data: Spectral or Spatiospectral Model?

Various disease conditions can alter EEG event-related responses and fMRI-BOLD signals. We hypothesized that event-related responses and their clinical alterations are imprinted in the EEG spectral domain as event-related (spatio)spectral patterns (ERSPat). We tested four EEG-fMRI fusion models utilizing EEG power spectra fluctuations (i.e., absolute spectral model - ASM; relative spectral model - RSM; absolute spatiospectral model - ASSM; and relative spatiospectral model - RSSM) for fully automated and blind visualization of task-related neural networks. Two (spatio)spectral patterns (high δ4 band and low β1 band) demonstrated significant negative linear relationship (pFWE < 0.05) to the frequent stimulus and three patterns (two low δ2 and δ3 bands, and narrow θ1 band) demonstrated significant positive relationship (p < 0.05) to the target stimulus. These patterns were identified as ERSPats. EEG-fMRI F-map of each δ4 model showed strong engagement of insula, cuneus, precuneus, basal ganglia, sensory-motor, motor and dorsal part of fronto-parietal control (FPCN) networks with fast HRF peak and noticeable trough. ASM and RSSM emphasized spatial statistics, and the relative power amplified the relationship to the frequent stimulus. For the δ4 model, we detected a reduced HRF peak amplitude and a magnified HRF trough amplitude in the frontal part of the FPCN, default mode network (DMN) and in the frontal white matter. The frequent-related β1 patterns visualized less significant and distinct suprathreshold spatial associations. Each θ1 model showed strong involvement of lateralized left-sided sensory-motor and motor networks with simultaneous basal ganglia co-activations and reduced HRF peak and amplified HRF trough in the frontal part of the FPCN and DMN. The ASM θ1 model preserved target-related EEG-fMRI associations in the dorsal part of the FPCN. For δ4, β1, and θ1 bands, all models provided high local F-statistics in expected regions. The most robust EEG-fMRI associations were observed for ASM and RSSM.

Local administration of genistein as a local anesthetic agent inhibits the trigeminal nociceptive neuronal activity in rats

A modulatory role has been reported for the isoflavone, genistein, on voltage-gated Na+ channels in the trigeminal ganglion in vitro. However, the acute effects of genistein in vivo, particularly on nociceptive transmission in the trigeminal system, remain to be determined. The aim of the present study was to examine whether acute local genistein administration to rats attenuates the excitability of wide-dynamic range (WDR) spinal trigeminal nucleus caudalis (SpVc) neurons in response to nociceptive and non-nociceptive mechanical stimulation in vivo.Extracellular single unit recordings were made from SpVc WDR neurons in response to orofacial non-noxious and noxious mechanical stimulation of pentobarbital-anesthetized rats. The effects of local administration of genistein, lidocaine, and lidocaine with genistein to the receptive field on the discharge frequency of SpVc neurons were evaluated. The mean firing frequency of SpVc WDR neurons in response to both non-noxious and noxious mechanical stimuli was significantly and dose-dependently (0.1−10 mM) inhibited by genistein, and maximum inhibition of the discharge frequency of both non-noxious and noxious mechanical stimuli was seen within 10 min. The inhibitory effect of genistein lasted for 20 min and was reversible. No significant difference was seen between the relative magnitude of inhibition by genistein on the SpVc WDR neuronal discharge frequency for noxious and non-noxious stimulation. The mean magnitude of inhibition by genistein (10 mM) on SpVc neuronal discharge frequency was almost equal to that of the local anesthetic, 1 % lidocaine (37 mM). Local injection of half-dose of lidocaine replaced the half-dose of genistein. These results suggest that local injection of genistein into the peripheral receptive field suppresses the excitability of SpVc neurons, possibly via inhibition of voltage-gated Na+ channels in the nociceptive nerve terminals of trigeminal ganglion. Therefore, administration of genistein as a local anesthetic may provide relief from trigeminal nociceptive pain without side effects, thus contributing to the area of complementary and alternative medicines.

Examining the Factors that Contribute to Non-Monotonic Growth of the [Formula: see text]Otoacoustic Emission in Humans.

Cubic distortion product otoacoustic emission input-output functions in humans show a complex pattern of growth. To further investigate the growth of the [Formula: see text] otoacoustic emission, magnitude and phase input-output functions were obtained from human subjects using a range of stimulus levels, frequencies, and frequency ratios. Three factors related to cochlear nonlinearity may produce non-monotonic input-output functions: a two-component interaction, an operating point shift, and two-tone suppression. To complement data interpretation, a local model of distortion product otoacoustic emission generation was fit to the magnitude spectrum of the averaged ear canal sound pressure recording to quantify operating point shift. Results obtained are consistent with non-monotonic growth occurring primarily as a result of two-tone suppression and/or a two-component interaction. These two mechanisms are expected to operate at different stimulus levels, with different signature magnitude and phase patterns, and are unlikely to overlap in producing non-monotonic growth. An operating point shift was suggested in three cases. These results support multiple factors contributing to the complexity of growth of the [Formula: see text] otoacoustic emission in humans and highlight the importance of looking at phase in addition to magnitude when interpreting distortion product otoacoustic emission growth.

A case-control study of visual, auditory and audio-visual sensory interactions in children with autism spectrum disorder.

To assess the relative integrity of early visual and auditory processes in autism spectrum disorder (ASD), we used frequency-tagged visual and auditory stimulation and high-density electroencephalogram recordings of unimodal and dual-modality responses in a case–control design. To test for the specificity of effects on ASD, we recorded from a smaller group of children with attention-deficit hyperactivity disorder (ADHD). Horizontal 3 cycle per degree (cpd) gratings were presented at 5 Hz, and a random stream of /ba/, /da/, /ga/ syllables was presented at 6 Hz. Grating contrast response functions were measured unimodally and in the presence of a 64-dB auditory input. Auditory response functions were measured unimodally and in the presence of a 40% contrast grating. Children with ASD (n = 34) and ADHD (n = 13) showed a common lack of audio–visual interaction compared to typically developing children (n = 40) when measured at the first harmonic of the visual stimulus frequency. Both patient groups also showed depressed first harmonic responses at low contrast, but the ADHD group had consistently higher first-harmonic responses at high contrast. Children with ASD had a preferential loss of second-harmonic (transient) responses. The alteredtransient responses in ASD are likely to arise very early in the visual pathway and could thus have downstream consequences for many other visual mechanisms and processes. The alteration in audio–visual interaction could be a signature of a comorbid phenotype shared by ASD and ADHD, possibly due to alterations in attentional selection systems.

Cortical network effects of subthalamic deep brain stimulation in a thalamo-cortical microcircuit model

Objective. High frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) suppresses excessive beta band (∼13–30 Hz) activity of the motor cortex in Parkinson’s disease (PD). While the mechanisms of action of STN DBS are not well-understood, strong evidence supports a role for cortical network modulating effects elicited by antidromic activation of cortical axons via the hyperdirect pathway. Approach. A spiking model of the thalamo-cortical microcircuit was developed to examine modulation of cortical network activity by antidromic STN DBS, mediated by direct activation of deep pyramidal neurons (PNs) and subsequent indirect activation of other thalamo-cortical structures. Main results. Increasing synaptic coupling strength from cortical granular to superficial layers, from inhibitory neurons to deep PNs, and from thalamus reticular to relay cells, along with thalamocortical connection strength, accompanied by reduced coupling from cortical superficial to granular layers, from thalamus relay cells to reticular neurons, and corticothalamic connection strength, led to increased beta activity and neural synchrony, as observed in PD. High frequency DBS desynchronized correlated neural activity, resulting in clusters of both excited and inhibited deep cortical PNs. The emergence of additional frequency components in the local field potential (LFP), and increased power at subharmonics of the DBS frequency as observed in patients with dyskinesia during DBS, occurred under different stimulus amplitudes and frequencies. While high-frequency (>100 Hz) DBS suppressed the LFP beta power, low-frequency (<40 Hz) DBS increased beta power when more than 10% of PNs were activated, but reduced the total beta power at lower levels of neural activation. Significance. The results suggest a potential mechanism for experimentally observed alterations in cortical neural activity during DBS via the propagation of DBS stimuli throughout the cortical network, modulated by short-term synaptic plasticity, and the emergence of resonance due to interaction of DBS with existing M1 rhythms by engaging feedforward-feedback loops.

Neurophysiological improvements in speech-in-noise task after short-term choir training in older adults.

Perceiving speech in noise (SIN) is important for health and well-being and decreases with age. Musicians show improved speech-in-noise abilities and reduced age-related auditory decline, yet it is unclear whether short term music engagement has similar effects. In this randomized control trial we used a pre-post design to investigate whether a 12-week music intervention in adults aged 50-65 without prior music training and with subjective hearing loss improves well-being, speech-in-noise abilities, and auditory encoding and voluntary attention as indexed by auditory evoked potentials (AEPs) in a syllable-in-noise task, and later AEPs in an oddball task. Age and gender-matched adults were randomized to a choir or control group. Choir participants sang in a 2-hr ensemble with 1-hr home vocal training weekly; controls listened to a 3-hr playlist weekly, attended concerts, and socialized online with fellow participants. From pre- to post-intervention, no differences between groups were observed on quantitative measures of well-being or behavioral speech-in-noise abilities. In the choir group, but not the control group, changes in the N1 component were observed for the syllable-in-noise task, with increased N1 amplitude in the passive condition and decreased N1 latency in the active condition. During the oddball task, larger N1 amplitudes to the frequent standard stimuli were also observed in the choir but not control group from pre to post intervention. Findings have implications for the potential role of music training to improve sound encoding in individuals who are in the vulnerable age range and at risk of auditory decline.

Establishing Reproducibility and Correlation of Cochlear Microphonic Amplitude to Implant Electrode Position Using Intraoperative Electrocochleography and Postoperative Cone Beam Computed Tomography.

The primary objective of this study was to establish the reproducibility of cochlear microphonic (CM) recordings obtained from a cochlear implant (CI) electrode contact during and immediately after insertion. This was achieved by evaluating the insertion angle and calculating the position of the apical electrode contact during insertion, using postoperative cone beam computed tomography (CBCT). The secondary objective was to create individualized patient maps of electrode contacts located within acoustically sensitive regions by correlating the CM amplitude to the electrode position determined using CBCT. CMs were recorded from a CI electrode contact during and immediately after insertion in 12 patients (n = 14 ears). Intraoperative recordings were made for a 0.5 kHz tone burst stimulus and were recorded from the apical electrode contact. Postinsertion recordings were made from the odd-numbered electrode contacts (1-15) along the array, using a range of stimulus frequencies (from 0.125 to 2 kHz). The time point at which each electrode contact passed through the round window was noted throughout the insertion, and the CM amplitude at this point was correlated to postoperative CBCT. This correlation was then used to estimate the CM amplitude at particular points within the cochlea, which was in turn compared with the amplitudes recorded from each electrode postoperatively to assess the reproducibility of the recordings. Significant correlation was shown between intraoperative insertion and postinsertion angles at two amplitude events (maximum amplitude: 29° mean absolute error, r = 0.77, p = 0.006; 10% of maximum amplitude: 52° mean absolute error, r = 0.85, p = 0.002). We have developed a novel method to demonstrate the reproducibility of the CM responses recorded from a CI electrode during insertion. By correlating the CM amplitude with the postoperative CBCT, we have also been able to create individualized maps of CM responses, categorizing the cochlea into acoustically responsive and unresponsive regions. If the electrode contacts within the acoustically sensitive regions are shown to be associated with improved loudness discrimination, it could have implications for optimal electrode mapping and placement.

Effect of Spectrally Modified Speech on Speech Perception of Native Speakers of Marathi

Objective: We investigated the effect of spectrally modified speech on speech perception of native speakers of Marathi. Methods: A total of eight word-lists with each list consisting of 25 words in Marathi were used as speech stimuli. The speech stimuli in List 1, List 2, List 3, List 4, List 5, List 6, and List 7 were spectrally modified by filtering them at 500 Hz, 1000 Hz, 1500 Hz, 2000 Hz, 2500 Hz, 3000 Hz, and 3500 Hz cutoff frequencies, respectively. The speech stimuli in List 8 were unfiltered. The speech identification score (SIS) testing was performed as a measure of speech perception using eight word-lists on a total of 125 normal hearing native speakers of Marathi in the age range between 18 and 25 years. Results: The results revealed that there was a statistically significant effect of spectral modification on speech perception. An increase in cutoff frequency of speech stimuli was analogous to increase in speech perception performance. The normal range of SIS (90%–100%) was achieved for speech stimuli filtered at 2500 Hz cutoff frequency. Conclusion: Although speech is a broadband signal, the findings of this study suggest that the spectral information till 2500 Hz is sufficient for optimum perception of speech of Marathi.

Age-differences in interpreting the valence of ambiguous facial expressions: evidence for multiple contributing processes

ABSTRACT Surprised facial expressions, which are ambiguous in valence, are interpreted more positively by older adults than by younger adults. To evaluate the processes contributing to this age difference, we varied the spatial frequency of the surprised-face stimuli. When faces were presented in a low-spatial-frequency band, it biased participants to rate them negatively. Although this occurred for both younger and older adults, the older adults’ ratings of the low-spatial-frequency faces were more positive than that of the younger adults. This suggests that there is an age-related reduction in the default negativity of interpretations. We also found that older adults, as a whole, rated the high-spatial-frequency faces more positively than did younger adults. However, this effect was eliminated for the subset of older adults with poor high-spatial-frequency perception abilities for whom these faces were difficult to perceive. Thus, older adults’ more positive interpretations of surprised faces may also reflect cognitively-effortful regulatory processes.

The "Missing 6 dB" Revisited: Influence of Room Acoustics and Binaural Parameters on the Loudness Mismatch Between Headphones and Loudspeakers.

Generations of researchers observed a mismatch between headphone and loudspeaker presentation: the sound pressure level at the eardrum generated by a headphone has to be about 6 dB higher compared to the level created by a loudspeaker that elicits the same loudness. While it has been shown that this effect vanishes if the same waveforms are generated at the eardrum in a blind comparison, the origin of the mismatch is still unclear. We present new data on the issue that systematically characterize this mismatch under variation of the stimulus frequency, presentation room, and binaural parameters of the headphone presentation. Subjects adjusted the playback level of a headphone presentation to equal loudness as loudspeaker presentation, and the levels at the eardrum were determined through appropriate transfer function measurements. Identical experiments were conducted at Oldenburg and Aachen with 40 normal-hearing subjects including 14 that passed through both sites. Our data verify a mismatch between loudspeaker and binaural headphone presentation, especially at low frequencies. This mismatch depends on the room acoustics, and on the interaural coherence in both presentation modes. It vanishes for high frequencies and broadband signals if individual differences in the sound transfer to the eardrums are accounted for. Moreover, small acoustic and non-acoustic differences in an anechoic reference environment (Oldenburg vs. Aachen) exert a large effect on the recorded loudness mismatch, whereas not such a large effect of the respective room is observed across moderately reverberant rooms at both sites. Hence, the non-conclusive findings from the literature appear to be related to the experienced disparity between headphone and loudspeaker presentation, where even small differences in (anechoic) room acoustics significantly change the response behavior of the subjects. Moreover, individual factors like loudness summation appear to be only loosely connected to the observed mismatch, i.e., no direct prediction is possible from individual binaural loudness summation to the observed mismatch. These findings – even though not completely explainable by the yet limited amount of parameter variations performed in this study – have consequences for the comparability of experiments using loudspeakers with conditions employing headphones or other ear-level hearing devices.

A four-state adaptive Hopf oscillator.

Adaptive oscillators (AOs) are nonlinear oscillators with plastic states that encode information. Here, an analog implementation of a four-state adaptive oscillator, including design, fabrication, and verification through hardware measurement, is presented. The result is an oscillator that can learn the frequency and amplitude of an external stimulus over a large range. Notably, the adaptive oscillator learns parameters of external stimuli through its ability to completely synchronize without using any pre- or post-processing methods. Previously, Hopf oscillators have been built as two-state (a regular Hopf oscillator) and three-state (a Hopf oscillator with adaptive frequency) systems via VLSI and FPGA designs. Building on these important implementations, a continuous-time, analog circuit implementation of a Hopf oscillator with adaptive frequency and amplitude is achieved. The hardware measurements and SPICE simulation show good agreement. To demonstrate some of its functionality, the circuit’s response to several complex waveforms, including the response of a square wave, a sawtooth wave, strain gauge data of an impact of a nonlinear beam, and audio data of a noisy microphone recording, are reported. By learning both the frequency and amplitude, this circuit could be used to enhance applications of AOs for robotic gait, clock oscillators, analog frequency analyzers, and energy harvesting.

Oscillatory Entrainment of the Frequency-following Response in Auditory Cortical and Subcortical Structures.

There is much debate about the existence and function of neural oscillatory mechanisms in the auditory system. The frequency-following response (FFR) is an index of neural periodicity encoding that can provide a vehicle to study entrainment in frequency ranges relevant to speech and music processing. Criteria for entrainment include the presence of poststimulus oscillations and phase alignment between stimulus and endogenous activity. To test the hypothesis of entrainment, in experiment 1 we collected FFR data for a repeated syllable using magnetoencephalography (MEG) and electroencephalography in 20 male and female human adults. We observed significant oscillatory activity after stimulus offset in auditory cortex and subcortical auditory nuclei, consistent with entrainment. In these structures, the FFR fundamental frequency converged from a lower value over 100 ms to the stimulus frequency, consistent with phase alignment, and diverged to a lower value after offset, consistent with relaxation to a preferred frequency. In experiment 2, we tested how transitions between stimulus frequencies affected the MEG FFR to a train of tone pairs in 30 people. We found that the FFR was affected by the frequency of the preceding tone for up to 40 ms at subcortical levels, and even longer durations at cortical levels. Our results suggest that oscillatory entrainment may be an integral part of periodic sound representation throughout the auditory neuraxis. The functional role of this mechanism is unknown, but it could serve as a fine-scale temporal predictor for frequency information, enhancing stability and reducing susceptibility to degradation that could be useful in real-life noisy environments.SIGNIFICANCE STATEMENT Neural oscillations are proposed to be a ubiquitous aspect of neural function, but their contribution to auditory encoding is not clear, particularly at higher frequencies associated with pitch encoding. In a magnetoencephalography experiment, we found converging evidence that the frequency-following response has an oscillatory component according to established criteria: poststimulus resonance, progressive entrainment of the neural frequency to the stimulus frequency, and relaxation toward the original state on stimulus offset. In a second experiment, we found that the frequency and amplitude of the frequency-following response to tones are affected by preceding stimuli. These findings support the contribution of intrinsic oscillations to the encoding of sound, and raise new questions about their functional roles, possibly including stabilization and low-level predictive coding.

The Vagus Nerve Somatosensory-evoked Potential in Neural Disorders: Systematic Review and Illustrative Vignettes.

Objective. To review the scientific publications reporting vagal nerve somatosensory-evoked potential (VSEP) findings from individuals with brain disorders, and present novel physiological explanations on the VSEP origin. Methods. We did a systematic review on the papers reporting VSEP findings from individuals with brain disorders and their controls. We evaluated papers published from 2003 to date indexed in PubMed, Web of Science, and Scielo databases. We extracted the following information: number of patients and controls, type of neural disorder, age, gender, stimulating/recording and grounding electrodes as well as stimulus side, intensity, duration, frequency, and polarity. Information about physiological parameters, neurobiological variables, and correlation studies was also reviewed. Representative vignettes were included to add support to our conclusions. Results. The VSEP was studied in 297 patients with neural disorders such as Parkinson's disease (PD), Alzheimer's disease, vascular dementia, mild cognitive impairment, subjective memory impairment, major depression, and multiple sclerosis. Scalp responses marked as the VSEP showed high variability, low validity, and poor reproducibility. VSEP latencies and amplitudes did not correlate with disease duration, unified PD rating scale score, or heart function in PD patients nor with cerebrospinal fluid β amyloid, phosphor-τ, and cognitive tests from patients with mental disorders. Vignettes demonstrated that the VSEP was volume conduction propagating from muscles surrounding the scalp recording electrodes. Conclusion. The VSEP is not a brain-evoked potential of neural origin but muscle activity induced by electrical stimulation of the tragus region of the ear. This review and illustrative vignettes argue against assessing the parasympathetic system using the so-called VSEP.

Multichannel Electrochemical Impedance Spectroscopy and equivalent circuit synthesis of a large-scale vanadium redox flow battery

An original multichannel Electrochemical Impedance Spectroscopy (EIS) system operating at high bias current and suitable for kW-class Vanadium Redox Flow Batteries (VRFBs) is presented. Power and signal connections, whose stray parameters affected measurements, required a careful optimization and calibration in the implementation of the measurement chain. In any cases, electromagnetic interferences set an upper limit to the applied stimulus frequency that limited the set of measurement data at each bias point. The paper provides early results obtained with this EIS system, which were used to identify an equivalent circuit of the whole stack in which each cell is represented with a dynamic Thévenin equivalent, i.e. the series of a voltage source, a variable resistor and a variable RC loop. The dependence of the equivalent parameters on the operating conditions has been experimentally analyzed, confirming that only the RC-loop resistance is strongly affected by mass transport. To our knowledge, this is the first dynamic equivalent circuit of a whole stack that has been validated against EIS measurements taken on a real industrial-scale VRFB. Building on the measurement methodology here presented, advanced online state of health of industrial flow batteries can be developed and implemented.

Broad frequency sensitivity and complex neural coding in the larval zebrafish auditory system

Most animals have complex auditory systems that identify salient features of the acoustic landscape to direct appropriate responses. In fish, these features include the volume, frequency, complexity, and temporal structure of acoustic stimuli transmitted through water. Larval fish have simple brains compared to adults but swim freely and depend on sophisticated sensory processing for survival.1-5 Zebrafish larvae, an important model for studying brain-wide neural networks, have thus far been found to possess a rudimentary auditory system, sensitive to a narrow range of frequencies and without evident sensitivity to acoustic features that are salient and ethologically important to adult fish.6,7 Here, we have combined a novel method for delivering water-borne sounds, a diverse assembly of acoustic stimuli, and whole-brain calcium imaging to describe the responses of individual auditory-responsive neurons across the brains of zebrafish larvae. Our results reveal responses to frequencies ranging from 100Hz to 4 kHz, with evidence of frequency discrimination from 100Hz to 2.5 kHz. Frequency-selective neurons are located in numerous regions of the brain, and neurons responsive to the same frequency are spatially grouped in some regions. Using functional clustering, we identified categories of neurons that are selective for a single pure-tone frequency, white noise, the sharp onset of acoustic stimuli, and stimuli involving a gradual crescendo. These results suggest a more nuanced auditory system than has previously been described in larval fish and provide insights into how a young animal's auditory system can both function acutely and serve as the scaffold for a more complex adult system.

Axon-glia interactions in the ascending auditory system.

The auditory system detects and encodes sound information with high precision to provide a high-fidelity representation of the environment and communication. In mammals, detection occurs in the peripheral sensory organ (the cochlea) containing specialized mechanosensory cells (hair cells) that initiate the conversion of sound-generated vibrations into action potentials in the auditory nerve. Neural activity in the auditory nerve encodes information regarding the intensity and frequency of sound stimuli, which is transmitted to the auditory cortex through the ascending neural pathways. Glial cells are critical for precise control of neural conduction and synaptic transmission throughout the pathway, allowing for the precise detection of the timing, frequency, and intensity of sound signals, including the sub-millisecond temporal fidelity is necessary for tasks such as sound localization, and in humans, for processing complex sounds including speech and music. In this review, we focus on glia and glia-like cells that interact with hair cells and neurons in the ascending auditory pathway and contribute to the development, maintenance, and modulation of neural circuits and transmission in the auditory system. We also discuss the molecular mechanisms of these interactions, their impact on hearing and on auditory dysfunction associated with pathologies of each cell type.

Cochlear tuning estimates from level ratio functions of distortion product otoacoustic emissions

Objective: Distortion product otoacoustic emission (DPOAE) levels plotted as a function of stimulus frequency ratio demonstrate a bandpass shape. This bandpass shape is narrower at higher frequencies compared to lower frequencies and thus has been thought to be related to cochlear mechanical tuning. Design: However, the frequency- and level-dependence of these functions above 8 kHz is largely unknown. Furthermore, how tuning estimates from these functions are related to behavioural tuning is not fully understood. Study Sample: From experiment 1, we report DPOAE level ratio functions (LRF) from seven normal-hearing, young-adults for f2 = 0.75–16 kHz and two stimulus levels of 62/52 and 52/37 dB FPL. We found that LRFs became narrower as a function of increasing frequency and decreasing level. Results: Tuning estimates from these functions increased as expected from 1-8 kHz. In experiment 2, we compared tuning estimates from DPOAE LRF to behavioural tuning in 24 normal-hearing, young adults for 1 and 4 kHz and found that behavioural tuning generally predicted DPOAE LRF estimated tuning. Conclusions: Our findings suggest that DPOAE LRFs generally reflect the tuning profile consistent with basilar membrane, neural, and behavioural tuning. However, further investigations are warranted to fully determine the use of DPOAE LRF as a clinical measure of cochlear tuning.

Repetitive Peripheral Magnetic Stimulation of Wrist Extensors Enhances Cortical Excitability and Motor Performance in Healthy Individuals.

Repetitive peripheral magnetic stimulation (rPMS) may improve motor function following central nervous system lesions, but the optimal parameters of rPMS to induce neural plasticity and mechanisms underlying its action remain unclear. We examined the effects of rPMS over wrist extensor muscles on neural plasticity and motor performance in 26 healthy volunteers. In separate experiments, the effects of rPMS on motor evoked potentials (MEPs), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), direct motor response (M-wave), Hoffmann-reflex, and ballistic wrist extension movements were assessed before and after rPMS. First, to examine the effects of stimulus frequency, rPMS was applied at 50, 25, and 10 Hz by setting a fixed total number of stimuli. A significant increase in MEPs of wrist extensors was observed following 50 and 25 Hz rPMS, but not 10 Hz rPMS. Next, we examined the time required to induce plasticity by increasing the number of stimuli, and found that at least 15 min of 50 and 25 Hz rPMS was required. Based on these parameters, lasting effects were evaluated following 15 min of 50 or 25 Hz rPMS. A significant increase in MEP was observed up to 60 min following 50 and 25 Hz rPMS; similarly, an attenuation of SICI and enhancement of ICF were also observed. The maximal M-wave and Hoffmann-reflex did not change, suggesting that the increase in MEP was due to plastic changes at the motor cortex. This was accompanied by increasing force and electromyograms during wrist ballistic extension movements following 50 and 25 Hz rPMS. These findings suggest that 15 min of rPMS with 25 Hz or more induces an increase in cortical excitability of the relevant area rather than altering the excitability of spinal circuits, and has the potential to improve motor output.