Low-frequency Stimuli Research Articles

Dynamical effects of low-frequency and high-frequency current stimuli in a memristive Morris–Lecar neuron model

This paper deduces that the potassium and calcium ion currents in the two-dimensional (2D) Morris–Lecar neuron model can be respectively characterized by a passive memristor and a locally active memristor. Then a memristive Morris–Lecar neuron model with an equivalent circuit scheme is first constructed. The equilibrium trajectory and its stability are analyzed, which displays fold and Hopf bifurcations with proper model parameters. Bursting behavior and mixed-mode oscillations with after-depolarizing potential for low-frequency current stimulus are numerically disclosed. Besides, the bifurcation mechanisms for bursting behavior and mixed-mode oscillations are theoretically deduced. Furthermore, the firing patterns and antimonotonicity phenomenon for high-frequency current stimulus are numerically discovered. This study provides a new concept for building memristive bionic circuits from neuron models with well-defined ion channel currents.

Proteins required for stereocilia elongation during mammalian hair cell development ensure precise and steady heights during adult life

The hair bundle, or stereocilia bundle, is the mechanosensory compartment of hair cells (HCs) in the inner ear. To date, most mechanistic studies have focused on stereocilia bundle morphogenesis, and it remains unclear how this organelle critical for hearing preserves its precise dimensions during life in mammals. The GPSM2-GNAI complex occupies the distal tip of stereocilia in the tallest row and is required for their elongation during development. Here, we ablate GPSM2-GNAI in adult mouse HCs after normal stereocilia elongation is completed. We observe a progressive height reduction of the tallest row stereocilia totaling ~600 nm after 12 wk in Gpsm2 mutant inner HCs. To measure GPSM2 longevity at tips, we generated a HaloTag-Gpsm2 mouse strain and performed pulse-chase experiments in vivo. Estimates using pulse-chase or tracking loss of GPSM2 immunolabeling following Gpsm2 inactivation suggest that GPSM2 is relatively long-lived at stereocilia tips with a half-life of 9 to 10 d. Height reduction coincides with dampened auditory brainstem responses evoked by low-frequency stimuli in particular. Finally, GPSM2 is required for normal tip enrichment of elongation complex (EC) partners MYO15A, WHRN, and EPS8, mirroring their established codependence during development. Taken together, our results show that the EC is also essential in mature HCs to ensure precise and stable stereocilia height and for sensitive detection of a full range of sound frequencies.

Firing patterns and fast–slow dynamics in an N-type LAM-based FitzHugh–Nagumo circuit

The diversity of firing patterns and their bifurcation mechanisms of a neuron circuit are crucial for exploiting bionic applications. This paper constructs an N-type locally active memristor (LAM)-based FitzHugh–Nagumo (FHN) circuit by replacing the tunnel-diode in the original FHN circuit. Numerical simulations and hardware measurements reveal that the N-type LAM-based FHN circuit can reproduce rich neuromorphic firing patterns of quasi-periodic/periodic bursting behaviors and chaotic/periodic spiking behaviors. The bursting and spiking behaviors are triggered by a low-frequency stimulus and a high-frequency one, respectively. Besides, the fold and Hopf bifurcation sets are depicted. Then, the bifurcation mechanisms for the quasi-periodic and periodic bursting behaviors via Hopf/Hopf and Hopf/fold bifurcations are theoretically deduced by time-domain waveform and equilibrium trajectory. The numerical results and hardware experiments exhibit the effectiveness of the proposed memristive FHN circuit in reproducing abundant firing patterns of bursting and spiking behaviors.

The role of pannexin/purinergic signaling in intervascular communication from capillaries during skeletal muscle contraction in male Golden hamsters.

We sought to determine the physiological relevance of pannexin/purinergic-dependent signaling in mediating conducted vasodilation elicited by capillary stimulation through skeletal muscle contraction. Using hamster cremaster muscle and intravital microscopy we stimulated capillaries through local muscle contraction while observing the associated upstream arteriole. Capillaries were stimulated with muscle contraction at low and high contraction (6 and 60CPM) and stimulus frequencies (4 and 40 Hz) in the absence and presence of pannexin blocker mefloquine (MEF; 10-5 M), purinergic receptor antagonist suramin (SUR 10-5 M) and gap-junction uncoupler halothane (HALO, 0.07%) applied between the capillary stimulation site and the upstream arteriolar observation site. Conducted vasodilations elicited at 6CPM were inhibited by HALO while vasodilations at 60CPM were inhibited by MEF and SUR. The conducted response elicited at 4 Hz was inhibited by MEF while the vasodilation at 40 Hz was unaffected by any blocker. Therefore, upstream vasodilations resulting from capillary stimulation via muscle contraction are dependent upon a pannexin/purinergic-dependent pathway that appears to be stimulation parameter-dependent. Our data highlight a physiological importance of the pannexin/purinergic pathway in facilitating communication between capillaries and upstream arteriolar microvasculature and, consequently, indicating that this pathway may play a crucial role in regulating blood flow in response to skeletal muscle contraction.

Sound-Evoked Neural Activity in Normal-Hearing Tinnitus: Effects of Frequency and Stimulated Ear Side.

Tinnitus is a common phantom auditory percept believed to be related to plastic changes in the brain due to hearing loss. However, tinnitus can also occur in the absence of any clinical hearing loss. In this case, since there is no hearing loss, the mechanisms that drive plastic changes remain largely enigmatic. Previous studies showed subtle differences in sound-evoked brain activity associated with tinnitus in subjects with tinnitus and otherwise normal hearing, but the results are not consistent across studies. Here, we aimed to investigate these differences using monaural rather than binaural stimuli. Sound-evoked responses were measured using functional magnetic resonance imaging (MRI) in participants with and without tinnitus. All participants had clinically normal audiograms. The stimuli were pure tones with frequencies between 353 and 8000 Hz, presented monaurally. A Principal Component Analysis (PCA) of the response in the auditory cortex revealed no difference in tonotopic organization, which confirmed earlier studies. A GLM analysis showed hyperactivity in the lateral areas of the bilateral auditory cortex. Consistent with the tonotopic map, this hyperactivity mainly occurred in response to low stimulus frequencies. This may be related to hyperacusis. Furthermore, there was an interaction between stimulation side and tinnitus in the parahippocampus. This may reflect an interference between tinnitus and spatial orientation.

Intense Short-Video-Based Social Media Use reduces the P300 Event-Related Potential Component in a Visual Oddball Experiment: A Sign for Reduced Attention.

The birth and following growth of social media platforms has influenced a lot. In addition to beneficial features, it has long-been noticed that heavy consumption of social media can have negative effects beyond a simple lack of time for other things. Of particular interest is the idea that consuming short videos lasting only fractions of a minute and watched one after another can lead to deficits in concentration and attention. Completing the existing literature that already reports evidence for attention deficits related to heavy social media use, the present study aims to contribute to this acute topic by adding neurophysiological data to it. In particular, this study made use of a well-known experimental paradigm, which is able to detect attention-related changes on a neurophysiological level. The so-called oddball paradigm was applied and the hypothesis that heavy social media users mainly consuming short videos show a reduced P300 event-related potential (ERP) component was tested, which has been found to reflect attention-related brain functions. For this, we invited twenty-nine participants and designed a visual oddball experiment including a white circle on black background as the low-frequency target stimulus and a white triangle on black background as the high-frequency non-target stimulus. On the basis of their self-reported short-video-based social media usage habits, all participants were grouped into heavy (more than 4 h daily usage) and regular (below 3 h daily usage) users, and finally data from 14 heavy and 15 regular users were further analyzed. It was found that only regular users show a clear P300 ERP component, while this particular brain potential amplitude reflecting attentional processes was significantly reduced in heavy users. This result provides empirical brain imaging evidence that heavy short-video-based social media use indeed affects attentional brain processes in a negative way.

Assessment of Interaural Attenuation in Infants and Young Children Using Bone-Conducted Auditory Brainstem Response.

In hearing assessment, the term interaural attenuation (IAA) is used to quantify the reduction in test signal intensity as it crosses from the side of the test ear to the nontest ear. In the auditory brainstem response (ABR) testing of infants and young children, the size of the IAA of bone-conducted (BC) stimuli is essential for the appropriate use of masking, which is needed for the accurate measurement of BC ABR thresholds. This study aimed to assess the IAA for BC ABR testing using 0.5 to 4 kHz narrowband (NB) CE-chirp LS stimuli in infants and toddlers with normal hearing from birth to three years of age and to examine the effects of age and frequency on IAA. A total of 55 infants and toddlers with normal hearing participated in the study. They were categorized into three age groups: the young group (n = 31, infants from birth to 3 mo), middle-aged group (n = 13, infants aged 3-12 mo), and older group (n = 11, toddlers aged 12-36 mo). The participants underwent BC ABR threshold measurements for NB CE-chirp LS stimuli at 0.5 to 4 kHz. For each participant, one ear was randomly defined as the "test ear" and the other as the "nontest ear." BC ABR thresholds were measured under two conditions. In both conditions, traces were recorded from the channel ipsilateral to the test ear, whereas masking was delivered to the nontest ear. In condition A, the bone oscillator was placed on the mastoid of the test ear, whereas in condition B, the bone oscillator was placed on the mastoid contralateral to the test ear. The difference between the thresholds obtained under conditions A and B was calculated to assess IAA. The means of IAA (and range) in the young age group for the frequencies 0.5, 1, 2, and 4 kHz were 5.38 (0-15) dB, 11.67 (0-30) dB, 21.15 (10-40) dB, and 23.53 (15-35) dB, respectively. Significant effects were observed for both age and frequency on BC IAA. BC IAA levels decreased with age from birth to 36 mo. In all age groups, smaller values were observed at lower frequencies and increased values were observed at higher frequencies. BC IAA levels were both age and frequency dependent. The study found that the BC IAA values for lower stimulus frequencies were smaller than previously assumed, even in infants younger than 3 mo. These results suggest that masking should be applied in BC ABR threshold assessments for NB CE-chirp LS stimuli at 0.5, 1, and 2 kHz, even in young infants. Masking may not be necessary for testing at 4 kHz if a clear response is obtained at 15 dB normal-hearing level (nHL) in infants younger than 3 mo.

Localization of Low- and High-Frequency Sounds in Cochlear Implant Recipients Using a Contralateral Hearing Aid.

The ability to localize sounds is partly recovered in patients using a cochlear implant (CI) in one ear and a hearing aid (HA) on the contralateral side. Binaural processing seems effective at least to some extent, despite the difference between electric and acoustic stimulation in each ear. To obtain further insights into the mechanisms of binaural hearing in these listeners, localization of low- and high-frequency sounds was tested. The study used a within-subject design, where participants were tasked with localizing sound sources in the horizontal plane. The experiment was conducted in an anechoic chamber, where an array of seven loudspeakers was mounted along the 24 azimuthal angle span from -90° to +90°. Stimuli were applied with different frequencies: broadband noise and high- and low-frequency noise. Ten CI recipients participated in the study. All had an asymmetric hearing loss with a CI in the poorer ear and an HA on the contralateral side. Accuracy of sound localization in terms of angular error and percentage of correct localization scores. The median angular error was 40° in bimodal conditions for both broadband noise and high-frequency noise stimuli. The angular error increased to 47° for low-frequency noise stimuli. In the unilaterally aided condition with an HA, only a median angular error of 78° was observed. Irrespective of the frequency composition of the stimuli, this group of bimodal listeners showed some ability to localize sounds. Angular errors were larger than those reported in the literature for bilateral CI users or single-sided deaf listeners with a CI. In the unilateral listening condition with HA, only localization of sounds was not possible for most subjects.

A Guinea Pig Model Suggests That Objective Assessment of Acoustic Hearing Preservation in Human Ears With Cochlear Implants Is Confounded by Shifts in the Spatial Origin of Acoustically Evoked Potential Measurements Along the Cochlear Length.

Our recent empirical findings have shown that the auditory nerve compound action potential (CAP) evoked by a low-level tone burst originates from a narrow cochlear region tuned to the tone burst frequency. At moderate to high sound levels, the origins shift to the most sensitive audiometric regions rather than the extended high-frequency regions of the cochlear base. This means that measurements evoked from extended high-frequency sound stimuli can shift toward the apex with increasing level. Here we translate this study to understand the spatial origin of acoustically evoked responses from ears that receive cochlear implants, an emerging area of research and clinical practice that is not completely understood. An essential step is to first understand the influence of the cochlear implant in otherwise naive ears. Our objective was to understand how function of the high-frequency cochlear base, which can be excited by the intense low-frequency sounds that are frequently used for objective intra- and postoperative monitoring, can be influenced by the presence of the cochlear implant. We acoustically evoked responses and made measurements with an electrode placed near the guinea pig round window. The cochlear implant was not utilized for either electrical stimulation or recording purposes. With the cochlear implant in situ, CAPs were acoustically evoked from 2 to 16 kHz tone bursts of various levels while utilizing the slow perfusion of a kainic acid solution from the cochlear apex to the cochlear aqueduct in the base, which sequentially reduced neural responses from finely spaced cochlear frequency regions. This cochlear perfusion technique reveals the spatial origin of evoked potential measurements and provides insight on what influence the presence of an implant has on acoustical hearing. Threshold measurements at 3 to 11 kHz were elevated by implantation. In an individual ear, thresholds were elevated and lowered as cochlear implant was respectively inserted and removed, indicative of "conductive hearing loss" induced by the implant. The maximum threshold elevation occurred at most sensitive region of the naive guinea pig ear (33.66 dB at 8 kHz), making 11 kHz the most sensitive region to acoustic sounds for guinea pig ears with cochlear implants. Conversely, the acute implantation did not affect the low-frequency, 500 Hz thresholds and suprathreshold function, as shown by the auditory nerve overlapped waveform. As the sound pressure level of the tone bursts increased, mean data show that the spatial origin of CAPs along the cochlear length shifted toward the most sensitive cochlear region of implanted ears, not the extended high-frequency cochlear regions. However, data from individual ears showed that after implantation, measurements from moderate to high sound pressure levels originate in places that are unique to each ear. Alterations to function of the cochlear base from the in situ cochlear implant may influence objective measurements of implanted ears that are frequently made with intense low-frequency sound stimuli. Our results from guinea pigs advance the interpretation of measurements used to understand how and when residual acoustic hearing is lost in human ears receiving a cochlear implant.

Hyperthyroidism-Induced Upregulation of Neurodegeneration-Related Gene Expression in Metaplasticity-Induced Hippocampus

Introduction: Thyroid hormones, which produce critical changes in our bodies even when their physiological levels alter slightly, are crucial hormones that influence gene transcription. Neuronal plasticity, on the other hand, requires both the activation of local proteins as well as protein translation and transcription in response to external signals. So far, no study has examined metaplastic long-term potentiation (LTP) and related gene expression levels in a hyperthyroid experimental model. Methods: The Wistar male rats were administered 0.2 mg/kg/day of <sc>l</sc>-thyroxine for 21 days to induce hyperthyroidism. Perforant path was primed with 1-Hz low-frequency stimuli (LFS) for 900 s to investigate metaplasticity responses. The LFS was followed by high-frequency stimuli (HFS, 100 Hz) after 5 min. Excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude were recorded from the granule cell layer of the dentate gyrus. The mRNA levels of genes related to neurodegeneration (Gsk-3β, Cdk5, Akt1, Mapt, p35, Capn1, Bace1, and Psen2) were measured using the RT-PCR method for the stimulated hippocampus. Results: Similar to euthyroid rats, hyperthyroid animals had a lower EPSP slope and PS after LFS. Depression of EPSP prevented subsequently induced EPSP-LTP, although HFS was able to elicit PS-LTP despite depression of PS amplitude in both groups. Despite similarities in metaplastic LTP responses, these electrophysiological findings were accompanied by increased Akt, Bace1, Cdk5, and p35-mRNA expressions and decreased Gsk-3β mRNA expression in hyperthyroid rats’ hippocampus. Conclusion: These data support the view that in thyroid hormone excess, the mechanism that keeps synaptic efficacy within a dynamic range occurs concurrently with increased mRNA expression of neurodegeneration-related genes. Our study encourages further examination of the increased risk of neurodegenerative disease in hyperthyroidism.

Lever Mechanism for Diaphragm-Type Vibrators to Enhance Vibrotactile Intensity.

Thin and light vibrators that leverage the inverse piezoelectric effect with a diaphragm mechanism are promising vibrotactile actuators owing to their form factors and high temporal and frequency response. However, generating perceptually sufficient displacement in the low-frequency domain is challenging. This study presents a lever mechanism mounted on a diaphragm vibrator to enhance the vibrotactile intensity of low-frequency vibrotactile stimuli. The lever mechanism is inspired by the tactile contact lens consisting of an array of cylinders held against the skin on a sheet that enhances micro-bump tactile detection. We built an experimental apparatus including our previously developed thin-film diaphragm-type vibrator, which reproduced the common characteristic of piezoelectric vibrators: near-threshold displacement (10 to 20 μm) at low frequency. Experiments demonstrated enhanced vibrotactile intensity at frequencies less than 100 Hz with the lever mechanism. Although the arrangement and material of the mechanism can be improved, our findings can help improve the expressiveness of diaphragm-type vibrators.

Defining the Boundaries of Patient Perception in Spinal Cord Stimulation Programming

ObjectivesRecent developments in spinal cord stimulation (SCS) programming have initiated new modalities of imperceptible stimulation. However, the boundaries of sensory perception are not well defined. The BEnchtop NEuromodulation Following endIng of Trial study aimed to create a map of perceptual threshold responses across a broad range of SCS parameters and programming to inform subperception therapy design. Materials and MethodsThis multicenter study was conducted at seven US sites. A total of 43 patients with low back and/or leg pain who completed a percutaneous commercial SCS trial were enrolled. Test stimulation was delivered through trial leads for approximately 90 minutes before removal. SCS parameters, including amplitude, frequency, pulse width (PW), electrode configuration, cycling, and multifrequency stimulation were varied during testing. Paresthesia threshold (PT), comfort level (CL), perceptual coverage area, and paresthesia quality (through patient selection of keywords) were collected. Differences were evaluated with analysis of variance followed by post hoc multiple comparisons using t-tests with Bonferroni correction. ResultsPT was primarily determined by PW and was insensitive to frequency for constant frequency stimulation (range: 20 Hz–10 kHz; F(1284) = 69.58, p < 0.0001). For all tests, CL was approximately 25% higher than PT. The dominant variable that influenced paresthesia quality was frequency. Sensations described as comfortable and tingling were most common for frequencies between 60 Hz and 2.4 kHz; unpleasant sensations were generally more common outside this range. Increasing distance between active electrodes from 7 mm to 14 mm, or cycling the SCS waveform at 1 Hz, decreased PT (p < 0.0001). Finally, PT for a low-frequency stimulus (ie, 60 Hz) was unaffected by mixing with a sub-PT high-frequency stimulus. ConclusionsIn contrast to previous work investigating narrower ranges, PW primarily influenced PT, independently of frequency. Paresthesia quality was primarily influenced by pulse frequency. These findings advance our understanding of SCS therapy and may be used to improve future novel neuromodulation paradigms.

Transmembrane Channel-Like (Tmc) Subunits Contribute to Frequency Sensitivity in the Zebrafish Utricle.

Information about dynamic head motion is conveyed by a central "striolar" zone of vestibular hair cells and afferent neurons in the inner ear. How vestibular hair cells are tuned to transduce dynamic stimuli at the molecular level is not well understood. Here we take advantage of the differential expression pattern of tmc1, tmc2a, and tmc2b, which encode channel subunits of the mechanotransduction complex in zebrafish vestibular hair cells. To test the role of various combinations of Tmc subunits in transducing dynamic head movements, we measured reflexive eye movements induced by high-frequency stimuli in single versus double tmc mutants. Wefound that Tmc2a function correlates with the broadest range of frequency sensitivity, whereas Tmc2b mainly contributes to lower-frequency responses. Tmc1, which is largely excluded from the striolar zone, plays a minor role in sensing lower-frequency stimuli. Our study suggests that the Tmc subunits impart functional differences to the mechanotransduction of dynamic stimuli.Significance Statement Information about dynamic head movements is transmitted by sensory receptors, known as hair cells, in the labyrinth of the inner ear. The sensitivity of hair cells to fast or slow movements of the head differs according to cell type. Whether the mechanotransduction complex that converts mechanical stimuli into electrical signals in hair cells participates in conveying frequency information is not clear. Here we find that the transmembrane channel-like 1/2 genes, which encode a central component of the complex, are differentially expressed in the utricle and contribute to frequency sensitivity in zebrafish.

Unveiling weak auditory evoked potentials using data-driven filtering

Auditory evoked potentials (AEPs) are commonly used to objectively evaluate sound perception in humans. Close to the hearing threshold and for low frequencies, efficient filtering of AEP from other brain activities is of major concern due to weak potentials and the requirement of long averaging times. Filtered AEP data are well-interpretable and useful, especially in medical and psychological diagnostics. Here, we present two data-driven approaches for efficient AEP filtering. First, neural networks of different architectures trained for EEG denoising are used to extract weak late-response AEP for low-frequency and infrasonic stimuli. During the design of the networks, we leveraged knowledge of the specific characteristics of the expected AEP data. Second, a singular value decomposition (SVD) of EEG data is evaluated, attempting to create classifiers for the presence of weak late-response AEP modes. We anticipate that the evaluation of AEP with data-driven methods can support researchers and scientists, for example, with real-time evaluation and diagnosis of acoustic-induced discomfort.

Effect of electrical and chemical (activation versus inactivation) stimulation of the infralimbic division of the medial prefrontal cortex in rats with chronic neuropathic pain.

Neuropathic pain (NP) represents a complex disorder with sensory, cognitive, and emotional symptoms. The medial prefrontal cortex (mPFC) takes critical regulatory roles and may change functionally and morphologically during chronic NP. There needs to be a complete understanding of the neurophysiological and psychopharmacological bases of the NP phenomenon. This study aimed to investigate the participation of the infralimbic division (IFL) of the mPFC in chronic NP, as well as the role of the N-methyl-D-aspartic acid receptor (NMDAr) in the elaboration of chronic NP. Male Wistar rats were submitted to the von Frey and acetone tests to assess mechanical and cold allodynia after 21days of chronic constriction injury (CCI) of the sciatic nerve or Sham-procedure ("false operated"). Electrical neurostimulation of the IFL/mPFC was performed by low-frequency stimuli (20 μA, 100Hz) applied for 15s by deep brain stimulation (DBS) device 21days after CCI. Either cobalt chloride (CoCl2 at 1.0mM/200 nL), NMDAr agonist (at 0.25, 1.0, and 2.0nmol/200 nL) or physiological saline (200 nL) was administered into the IFL/mPFC. CoCl2 administrationin the IFL cortex did not alter either mechanical or cold allodynia. DBS stimulation of the IFL cortex decreased mechanical allodynia in CCI rats. Chemical stimulation of the IFL cortex by an NMDA agonist (at 2.0nmol) decreased mechanical allodynia. NMDA at any dose (0.25, 1.0, and 2.0nmol) reduced the flicking/licking duration in the cold test. These findings suggest that the IFL/mPFC and the NMDAr of the neocortex are involved in attenuating chronic NP in rats.

Poster Session: Oculomotor influences on retinal input signals in myopia.

Studies of emmetropization have traditionally focused on the spatial characteristics of visual input signals. Yet the input to the retina is not a two-dimensional pattern but a temporally-varying luminance flow. The temporal structure of this flow is predominately determined by eye movements, as the human eyes move incessantly. Even when fixating on a single point, a persistent motion known as ocular drift reformats the luminance flow in a way that counterbalances the spectra of natural scenes. It is established that emmetropes are highly sensitive to these luminance modulations. However, their visual consequences in myopia and hyperopia are unknown. Here, we first review how the temporal-frequency distribution of retinal input signals varies with the amount of ocular drift. We then use a detailed optical/geometrical model of the eye to study how the eye movements jointly shape retinal input as a function of refraction. We show that, within the temporal range of sensitivity of the retina, the spatial frequency distribution of the input signals conveys signed information about defocus. Specifically, for a given degree of defocus, myopic retinas experience more power from low spatial frequency stimuli than hyperopic retinas. These redistribution of input power may have a consequence during eye growth supporting the proposal that eye movements should be taken into consideration in the process of emmetropization.

A high-density EEG and structural MRI source analysis of the frequency following response to missing fundamental stimuli reveals subcortical and cortical activation to low and high frequency stimuli

Pitch is a perceptual rather than physical phenomenon, important for spoken language use, musical communication, and other aspects of everyday life. Auditory stimuli can be designed to probe the relationship between perception and physiological responses to pitch-evoking stimuli. One technique for measuring physiological responses to pitch-evoking stimuli is the frequency following response (FFR). The FFR is an electroencephalographic (EEG) response to periodic auditory stimuli. The FFR contains nonlinearities not present in the stimuli, including correlates of the amplitude envelope of the stimulus; however, these nonlinearities remain undercharacterized. The FFR is a composite response reflecting multiple neural and peripheral generators, and their contributions to the scalp-recorded FFR vary in ill-understood ways depending on the electrode montage, stimulus, and imaging technique. The FFR is typically assumed to be generated in the auditory brainstem; there is also evidence both for and against a cortical contribution to the FFR. Here a methodology is used to examine the FFR correlates of pitch and the generators of the FFR to stimuli with different pitches. Stimuli were designed to tease apart biological correlates of pitch and amplitude envelope. FFRs were recorded with 256-electrode EEG nets, in contrast to a typical FFR setup which only contains a single active electrode. Structural MRI scans were obtained for each participant to co-register with the electrode locations and constrain a source localization algorithm. The results of this localization shed light on the generating mechanisms of the FFR, including providing evidence for both cortical and subcortical auditory sources.

Comparison of the Components of Brainstem Auditory Responses Using Click and Chirp Stimuli in Premature Infants

Background and Objectives: Prematurity means that the baby is born before 37 months of age, which leads to various problems, including hearing defects. Timely detection of hearing loss with the help of tools that facilitate this identification, can have a significant impact on the child’s personal, social, and educational development. The aim of the present study was to achieve better responses using the chirp stimulus along with the click. The chirp stimulus can compensate for the time delay caused by low-frequency stimuli and increases the simultaneous presentation of high and low frequencies in the cochlea. Therefore, the morphology of the waves is improved, and the amplitude of responses increases; thus, the waves can be better identified despite the prematurity of the infants. Methods: Eighy newborns were examined in four groups, which were divided into term and preterm groups based on gestational age (including late preterm, moderate, and very preterm). The intensity of the click and chirp stimuli was fixed at 40 and 80 dB. The amplitude and latency of waves I, III, and V, the inter-peak latencies of I-III, III-V, and I-V, as well as the ratio of the amplitude of wave V/I were among the compared parameters. It should be mentioned in tables paired t-test was used in cases marked with *. Wilcoxon test was used in other cases. Results: The chirp stimulus mainly had less latency than the click stimulus and created a larger amplitude at a high intensity (80 dB). In the intensity close to the threshold, i.e. 40 dB, these findings were slightly different. The more developed the infants, the stronger the responses and the more effective the chirp stimulus in eliciting responses. Conclusion: The chirp stimulus was more effective in obtaining multiple components of brainstem-evoked responses in infants, especially preterm infants, and investigating the status of their auditory system. The use of a higher sample size could lead to an increase in the growth of clinical use and better efficiency of diagnostic protocols and responses.

Differences between children and adults in the neural encoding of voice fundamental frequency in the presence of noise and reverberation.

Environmental noise and reverberation challenge speech understanding more significantly in children than in adults. However, the neural/sensory basis for the difference is poorly understood. We evaluated the impact of noise and reverberation on the neural processing of the fundamental frequency of voice (f0 )-an important cue to tag or recognize a speaker. In a group of 39 6-15-year-old children and 26 adults with normal hearing, envelope following responses (EFRs) were elicited by a male-spoken/i/in quiet, noise, reverberation, and both noise and reverberation. Due to increased resolvability of harmonics at lower than higher vowel formants that may affect susceptibility to noise and/or reverberation, the/i/was modified to elicit two EFRs: one initiated by the low frequency first formant (F1) and the other initiated by mid to high frequency second and higher formants (F2+) with predominantly resolved and unresolved harmonics, respectively. F1 EFRs were more susceptible to noise whereas F2+ EFRs were more susceptible to reverberation. Reverberation resulted in greater attenuation of F1 EFRs in adults than children, and greater attenuation of F2+ EFRs in older than younger children. Reduced modulation depth caused by reverberation and noise explained changes in F2+ EFRs but was not the primary determinant for F1 EFRs. Experimental data paralleled modelled EFRs, especially for F1. Together, data suggest that noise or reverberation influences the robustness of f0 encoding depending on the resolvability of vowel harmonics, and that maturation of processing temporal/envelope information of voice is delayed in reverberation, particularly for low frequency stimuli.

Modulation of potassium conductances optimizes fidelity of auditory information.

Potassium channels in auditory neurons are rapidly modified by changes in the auditory environment. In response to elevated auditory stimulation, short-term mechanisms such as protein phosphorylation and longer-term mechanisms such as accelerated channel synthesis increase the amplitude of currents that promote high-frequency firing. It has been suggested that this allows neurons to fire at high rates in response to high sound levels. We have carried out simple simulations of the response to postsynaptic neurons to patterns of neurotransmitter release triggered by auditory stimuli. These demonstrate that the amplitudes of potassium currents required for optimal encoding of a low-amplitude auditory signal differ from those for louder sounds. Specifically, the cross-correlation of the output of a neuron with an auditory stimulus is improved by increasing potassium currents as sound amplitude increases. Temporal fidelity for low-frequency stimuli is improved by increasing potassium currents that activate at negative potentials, while that for high-frequency stimuli requires increases in currents that activate at positive membrane potentials. These effects are independent of the firing rate. Moreover, levels of potassium currents that maximize the fidelity of the output of an ensemble of neurons differ from those that maximize fidelity for a single neuron. This suggests that the modulatory mechanisms must coordinate channel activity in groups of neurons or an entire nucleus. The simulations provide an explanation for the modulation of the intrinsic excitability of auditory brainstem neurons by changes in environmental sound levels, and the results may extend to information processing in other neural systems.