Sex differences during development in cortical temporal processing and event related potentials in wild-type and fragile X syndrome model mice.

BACKGROUND: Autism spectrum disorder (ASD) is currently diagnosed in approximately 1 in 44 children in the United States, based on a wide array of symptoms, including sensory dysfunction and abnormal language development. Boys are diagnosed ~ 3.8 times more frequently than girls. Auditory temporal processing is crucial for speech recognition and language development. Abnormal development of temporal processing may account for ASD language impairments. Sex differences in the development of temporal processing may underlie the differences in language outcomes in male and female children with ASD. To understand mechanisms of potential sex differences in temporal processing requires a preclinical model. However, there are no studies that have addressed sex differences in temporal processing across development in any animal model of ASD. METHODS: To fill this major gap, we compared the development of auditory temporal processing in male and female wildtype (WT) and Fmr1 knock-out (KO) mice, a model of Fragile X Syndrome (FXS), a leading genetic cause of ASD-associated behaviors. Using epidural screw electrodes, we recorded auditory event related potentials (ERP) and auditory temporal processing with a gap-in-noise auditory steady state response (ASSR) paradigm at young (postnatal (p)21 and p30) and adult (p60) ages from both auditory and frontal cortices of awake, freely moving mice. RESULTS: The results show that ERP amplitudes were enhanced in both sexes of Fmr1 KO mice across development compared to WT counterparts, with greater enhancement in adult female than adult male KO mice. Gap-ASSR deficits were seen in the frontal, but not auditory, cortex in early development (p21) in female KO mice. Unlike male KO mice, female KO mice show WT-like temporal processing at p30. There were no temporal processing deficits in the adult mice of both sexes. CONCLUSIONS: These results show a sex difference in the developmental trajectories of temporal processing and hypersensitive responses in Fmr1 KO mice. Male KO mice show slower maturation of temporal processing than females. Female KO mice show stronger hypersensitive responses than males later in development. The differences in maturation rates of temporal processing and hypersensitive responses during various critical periods of development may lead to sex differences in language function, arousal and anxiety in FXS.

Distributed representations of prediction error signals across the cortical hierarchy are synergistic.

A relevant question concerning inter-areal communication in the cortex is whether these interactions are synergistic. Synergy refers to the complementary effect of multiple brain signals conveying more information than the sum of each isolated signal. Redundancy, on the other hand, refers to the common information shared between brain signals. Here, we dissociated cortical interactions encoding complementary information (synergy) from those sharing common information (redundancy) during prediction error (PE) processing. We analyzed auditory and frontal electrocorticography (ECoG) signals in five common awake marmosets performing two distinct auditory oddball tasks and investigated to what extent event-related potentials (ERP) and broadband (BB) dynamics encoded synergistic and redundant information about PE processing. The information conveyed by ERPs and BB signals was synergistic even at lower stages of the hierarchy in the auditory cortex and between auditory and frontal regions. Using a brain-constrained neural network, we simulated the synergy and redundancy observed in the experimental results and demonstrated that the emergence of synergy between auditory and frontal regions requires the presence of strong, long-distance, feedback, and feedforward connections. These results indicate that distributed representations of PE signals across the cortical hierarchy can be highly synergistic.

Frequency-dependent temporary threshold shifts in the Eastern painted turtle (Chrysemys picta picta).

Testudines are a highly threatened group facing an array of stressors, including alteration of their sensory environment. Underwater noise pollution has the potential to induce hearing loss and disrupt detection of biologically important acoustic cues and signals. To examine the conditions that induce temporary threshold shifts (TTS) in hearing in the freshwater Eastern painted turtle (Chrysemys picta picta), three individuals were exposed to band limited continuous white noise (50-1000 Hz) of varying durations and amplitudes (sound exposure levels ranged from 151 to 171 dB re 1 µPa2 s). Control and post-exposure auditory thresholds were measured and compared at 400 and 600 Hz using auditory evoked potential methods. TTS occurred in all individuals at both test frequencies, with shifts of 6.1-41.4 dB. While the numbers of TTS occurrences were equal between frequencies, greater shifts were observed at 600 Hz, a frequency of higher auditory sensitivity, compared to 400 Hz. The onset of TTS occurred at 154 dB re 1 µPa2 s for 600 Hz, compared to 158 dB re 1 µPa2 s at 400 Hz. The 400-Hz onset and patterns of TTS growth and recovery were similar to those observed in previously studied Trachemys scripta elegans, suggesting TTS may be comparable across Emydidae species.

Exploring the relationship between auditory late latency response and language age in children using cochlear implant.

AIM & OBJECTIVES: The study aimed to compare P1 latency and P1-N1 amplitude with receptive and expressive language ages in children using cochlear implant (CI) in one ear and a hearing aid (HA) in non-implanted ear. METHODS: The study included 30 children, consisting of 18 males and 12 females, aged between 48 and 96 months. The age at which the children received CI ranged from 42 to 69 months. A within-subject research design was utilized and participants were selected through purposive sampling. Auditory late latency responses (ALLR) were assessed using the Intelligent hearing system to measure P1 latency and P1-N1 amplitude. The assessment checklist for speech-language skills (ACSLS) was employed to evaluate receptive and expressive language age. Both assessments were conducted after cochlear implantation. RESULTS: A total of 30 children participated in the study, with a mean implant age of 20.03 months (SD: 8.14 months). The mean P1 latency and P1-N1 amplitude was 129.50 ms (SD: 15.05 ms) and 6.93 µV (SD: 2.24 µV) respectively. Correlation analysis revealed no significant association between ALLR measures and receptive or expressive language ages. However, there was significant negative correlation between the P1 latency and implant age (Spearman's rho = -0.371, p = 0.043). CONCLUSIONS: The study suggests that P1 latency which is an indicative of auditory maturation, may not be a reliable marker for predicting language outcomes. It can be concluded that language development is likely to be influenced by other factors beyond auditory maturation alone.

Auditory Encoding of Natural Speech at Subcortical and Cortical Levels Is Not Indicative of Cognitive Decline.

More and more patients worldwide are diagnosed with dementia, which emphasizes the urgent need for early detection markers. In this study, we built on the auditory hypersensitivity theory of a previous study-which postulated that responses to auditory input in the subcortex as well as cortex are enhanced in cognitive decline-and examined auditory encoding of natural continuous speech at both neural levels for its indicative potential for cognitive decline. We recruited study participants aged 60 years and older, who were divided into two groups based on the Montreal Cognitive Assessment, one group with low scores (n = 19, participants with signs of cognitive decline) and a control group (n = 25). Participants completed an audiometric assessment and then we recorded their electroencephalography while they listened to an audiobook and click sounds. We derived temporal response functions and evoked potentials from the data and examined response amplitudes for their potential to predict cognitive decline, controlling for hearing ability and age. Contrary to our expectations, no evidence of auditory hypersensitivity was observed in participants with signs of cognitive decline; response amplitudes were comparable in both cognitive groups. Moreover, the combination of response amplitudes showed no predictive value for cognitive decline. These results challenge the proposed hypothesis and emphasize the need for further research to identify reliable auditory markers for the early detection of cognitive decline.

Rate dependent neural responses of interaural-time-difference cues in fine-structure and envelope.

Advancements in cochlear implants (CIs) have led to a significant increase in bilateral CI users, especially among children. Yet, most bilateral CI users do not fully achieve the intended binaural benefit due to potential limitations in signal processing and/or surgical implant positioning. One crucial auditory cue that normal hearing (NH) listeners can benefit from is the interaural time difference (ITD), i.e., the time difference between the arrival of a sound at two ears. The ITD sensitivity is thought to be heavily relying on the effective utilization of temporal fine structure (very rapid oscillations in sound). Unfortunately, most current CIs do not transmit such true fine structure. Nevertheless, bilateral CI users have demonstrated sensitivity to ITD cues delivered through envelope or interaural pulse time differences, i.e., the time gap between the pulses delivered to the two implants. However, their ITD sensitivity is significantly poorer compared to NH individuals, and it further degrades at higher CI stimulation rates, especially when the rate exceeds 300 pulse per second. The overall purpose of this research thread is to improve spatial hearing abilities in bilateral CI users. This study aims to develop electroencephalography (EEG) paradigms that can be used with clinical settings to assess and optimize the delivery of ITD cues, which are crucial for spatial hearing in everyday life. The research objective of this article was to determine the effect of CI stimulation pulse rate on the ITD sensitivity, and to characterize the rate-dependent degradation in ITD perception using EEG measures. To develop protocols for bilateral CI studies, EEG responses were obtained from NH listeners using sinusoidal-amplitude-modulated (SAM) tones and filtered clicks with changes in either fine structure ITD (ITDFS) or envelope ITD (ITDENV). Multiple EEG responses were analyzed, which included the subcortical auditory steady-state responses (ASSRs) and cortical auditory evoked potentials (CAEPs) elicited by stimuli onset, offset, and changes. Results indicated that acoustic change complex (ACC) responses elicited by ITDENV changes were significantly smaller or absent compared to those elicited by ITDFS changes. The ACC morphologies evoked by ITDFS changes were similar to onset and offset CAEPs, although the peak latencies were longest for ACC responses and shortest for offset CAEPs. The high-frequency stimuli clearly elicited subcortical ASSRs, but smaller than those evoked by lower carrier frequency SAM tones. The 40-Hz ASSRs decreased with increasing carrier frequencies. Filtered clicks elicited larger ASSRs compared to high-frequency SAM tones, with the order being 40 > 160 > 80> 320 Hz ASSR for both stimulus types. Wavelet analysis revealed a clear interaction between detectable transient CAEPs and 40-Hz ASSRs in the time-frequency domain for SAM tones with a low carrier frequency.

Modulatory Effects on Laminar Neural Activity Induced by Near-Infrared Light Stimulation with a Continuous Waveform to the Mouse Inferior Colliculus In Vivo.

Infrared neural stimulation (INS) is a promising area of interest for the clinical application of a neuromodulation method. This is in part because of its low invasiveness, whereby INS modulates the activity of the neural tissue mainly through temperature changes. Additionally, INS may provide localized brain stimulation with less tissue damage. The inferior colliculus (IC) is a crucial auditory relay nucleus and a potential target for clinical application of INS to treat auditory diseases and develop artificial hearing devices. Here, using continuous INS with low to high-power density, we demonstrate the laminar modulation of neural activity in the mouse IC in the presence and absence of sound. We investigated stimulation parameters of INS to effectively modulate the neural activity in a facilitatory or inhibitory manner. A mathematical model of INS-driven brain tissue was first simulated, temperature distributions were numerically estimated, and stimulus parameters were selected from the simulation results. Subsequently, INS was administered to the IC of anesthetized mice, and the modulation effect on the neural activity was measured using an electrophysiological approach. We found that the modulatory effect of INS on the spontaneous neural activity was bidirectional between facilitatory and inhibitory effects. The modulatory effect on sound-evoked responses produced only an inhibitory effect to all examined stimulus intensities. Thus, this study provides important physiological evidence on the response properties of IC neurons to INS. Overall, INS can be used for the development of new therapies for neurological disorders and functional support devices for auditory central processing.

Auditory oddball responses in the human subthalamic nucleus and substantia nigra pars reticulata.

The auditory oddball is a mainstay in research on attention, novelty, and sensory prediction. How this task engages subcortical structures like the subthalamic nucleus and substantia nigra pars reticulata is unclear. We administered an auditory OB task while recording single unit activity (35 units) and local field potentials (57 recordings) from the subthalamic nucleus and substantia nigra pars reticulata of 30 patients with Parkinson's disease undergoing deep brain stimulation surgery. We found tone modulated and oddball modulated units in both regions. Population activity differentiated oddball from standard trials from 200 ms to 1000 ms after the tone in both regions. In the substantia nigra, beta band activity in the local field potential was decreased following oddball tones. The oddball related activity we observe may underlie attention, sensory prediction, or surprise-induced motor suppression.

Phenotypic analysis of multielectrode array EEG biomarkers in developing and adult male Fmr1 KO mice.

Fragile X Syndrome (FXS) is a leading known genetic cause of intellectual disability with symptoms that include increased anxiety and social and sensory processing deficits. Recent electroencephalographic (EEG) studies in humans with FXS have identified neural oscillation deficits that include increased resting state gamma power, increased amplitude of auditory evoked potentials, and reduced phase locking of sound-evoked gamma oscillations. Similar EEG phenotypes are present in mouse models of FXS, but very little is known about the development of such abnormal responses. In the current study, we employed a 30-channel mouse multielectrode array (MEA) system to record and analyze resting and stimulus-evoked EEG signals in male P21 and P91 WT and Fmr1 KO mice. This led to several novel findings. First, P91, but not P21, Fmr1 KO mice have significantly increased resting EEG power in the low- and high-gamma frequency bands. Second, both P21 and P91 Fmr1 KO mice have markedly attenuated inter-trial phase coherence (ITPC) to spectrotemporally dynamic auditory stimuli as well as to 40 Hz and 80 Hz auditory steady-state response (ASSR) stimuli. This suggests abnormal temporal processing from early development that may lead to abnormal speech and language function in FXS. Third, we found hemispheric asymmetry of fast temporal processing in the mouse auditory cortex in WT but not Fmr1 KO mice. Together, these findings define a set of EEG phenotypes in young and adult mice that can serve as translational targets for genetic and pharmacological manipulation in phenotypic rescue studies.

Developmental Windows for Effects of Choline and Folate on Excitatory and Inhibitory Neurotransmission During Human Gestation.

Choline and folate are critical nutrients for fetal brain development, but the timing of their influence during gestation has not been previously characterized. At different periods during gestation, choline stimulation of α7-nicotinic receptors facilitates conversion of γ-aminobutyric acid (GABA) receptors from excitatory to inhibitory and recruitment of GluR1-R2 receptors for faster excitatory responses to glutamate. The outcome of the fetal development of inhibition and excitation was assessed in 159 newborns by P50 cerebral auditory-evoked responses. Paired stimuli, S1, S2, were presented 500 msec apart. Higher P50 amplitude in response to S1 (P50S1microV) assesses excitation, and lower P50S2microV assesses inhibition in this paired-stimulus paradigm. Development of inhibition was related solely to maternal choline plasma concentration and folate supplementation at 16 weeks' gestation. Development of excitation was related only to maternal choline at 28 weeks. Higher maternal choline concentrations later in gestation did not compensate for earlier lower concentrations. At 4 years of age, increased behavior problems on the Child Behavior Checklist 1½-5yrs were related to both newborn inhibition and excitation. Incomplete development of inhibition and excitation associated with lower choline and folate during relatively brief periods of gestation thus has enduring effects on child development.

[A study of mismatched negative in normal hearing patients of different ages].

Objective:To study the characteristics of Mismatch negativity（MMN） in normal hearing patients of different ages, and to compare the MMN of normal hearing subjects at different ages to explore the differences in MMN between different ages. Methods:MMN test was performed on both ears using the classic Oddball mode. A frequency of 1 000 Hz（standard stimuli） and 2 000 Hz（deviant stimuli） was used to evoked the MMN. According to different age groups: the juvenile group（7-17 years old）, the youth group（18-44 years old）, the middle-aged group（45-59 years old）, and the elderly group（60-75 years old）, with 25 cases in each group. The MMN characteristics of normal hearing subjects in different age groups were analyzed statistically and the differences between groups were compared. All subjects underwent pure tone threshold test, tympanic reactance test and ABR test before MMN test. Results:MMN waveform could be elicited from both ears of 100 subjects. Among them, the average latency of the juvenile group was（159.70±20.34） ms while the average amplitude was（4.34±2.26） µV, For the youth group, the average latency was（166.01±28.67） ms and the average amplitude was（3.70±2.28） µV. Then in the middle-aged group, the average latency was（175.16±37.24） ms, meanwhile, the average amplitude was（2.69±0.84） µV. Finally, the elderly group has an average latency of（178.03±14.37） ms and an average amplitude of（2.11±0.70） µV. Therefore, there was no statistical difference in latency and amplitude between all groups（P>0.05）, and there was no statistical difference in latency and amplitude between left and right ears among all subjects as a whole（P>0.05）. However, when the left and right ears of all groups were compared, it was found that the latency between the left and right ears of the Juvenile group had statistical significance（P<0.05）, and the amplitude difference was not statistically significant（P>0.05）, while the latency and amplitude differences between the left and right ears of other groups had no statistical significance（P>0.05）. There were also no significant differences in latency and amplitude between men and women（P>0.05）. Conclusion:There was no statistically significant difference in the latency and amplitude of mismatched negative among normal hearing subjects of different ages, and no statistically significant difference in the MMN latency and amplitude between the left and right ears of subjects and between men and women. Therefore, the study inferred that the auditory cerebral cortex of subjects aged 7-75 years old maintained a stable state for a long time after maturity, and the latency and amplitude of mismatched negative waves were relatively stable. It is not affected by age, gender and ear side, and can stably reflect the auditory cortex function of the subjects. It has broad application prospects in clinical practice, and provides a reliable detection means for future research on the changes of the auditory cerebral cortex of patients, which is worthy of our further research and clinical promotion.

Psychoacoustic and electroencephalographic responses to changes in amplitude modulation depth and frequency in relation to speech recognition in cochlear implantees.

Temporal envelope modulations (TEMs) are one of the most important features that cochlear implant (CI) users rely on to understand speech. Electroencephalographic assessment of TEM encoding could help clinicians to predict speech recognition more objectively, even in patients unable to provide active feedback. The acoustic change complex (ACC) and the auditory steady-state response (ASSR) evoked by low-frequency amplitude-modulated pulse trains can be used to assess TEM encoding with electrical stimulation of individual CI electrodes. In this study, we focused on amplitude modulation detection (AMD) and amplitude modulation frequency discrimination (AMFD) with stimulation of a basal versus an apical electrode. In twelve adult CI users, we (a) assessed behavioral AMFD thresholds and (b) recorded cortical auditory evoked potentials (CAEPs), AMD-ACC, AMFD-ACC, and ASSR in a combined 3-stimulus paradigm. We found that the electrophysiological responses were significantly higher for apical than for basal stimulation. Peak amplitudes of AMFD-ACC were small and (therefore) did not correlate with speech-in-noise recognition. We found significant correlations between speech-in-noise recognition and (a) behavioral AMFD thresholds and (b) AMD-ACC peak amplitudes. AMD and AMFD hold potential to develop a clinically applicable tool for assessing TEM encoding to predict speech recognition in CI users.

Basic Properties of Coordinated Neuronal Ensembles in the Auditory Thalamus.

Coordinated neuronal activity has been identified to play an important role in information processing and transmission in the brain. However, current research predominantly focuses on understanding the properties and functions of neuronal coordination in hippocampal and cortical areas, leaving subcortical regions relatively unexplored. In this study, we use single-unit recordings in female Sprague Dawley rats to investigate the properties and functions of groups of neurons exhibiting coordinated activity in the auditory thalamus-the medial geniculate body (MGB). We reliably identify coordinated neuronal ensembles (cNEs), which are groups of neurons that fire synchronously, in the MGB. cNEs are shown not to be the result of false-positive detections or by-products of slow-state oscillations in anesthetized animals. We demonstrate that cNEs in the MGB have enhanced information-encoding properties over individual neurons. Their neuronal composition is stable between spontaneous and evoked activity, suggesting limited stimulus-induced ensemble dynamics. These MGB cNE properties are similar to what is observed in cNEs in the primary auditory cortex (A1), suggesting that ensembles serve as a ubiquitous mechanism for organizing local networks and play a fundamental role in sensory processing within the brain.

Lower Childhood Socioeconomic Status Is Associated with Greater Neural Responses to Ambient Auditory Changes in Adulthood.

Humans' early life experience varies by socioeconomic status (SES), raising the question of how this difference is reflected in the adult brain. An important aspect of brain function is the ability to detect salient ambient changes while focusing on a task. Here, we ask whether subjective social status during childhood is reflected by the way young adults' brain detecting changes in irrelevant information. In two studies (total n = 58), we examine electrical brain responses in the frontocentral region to a series of auditory tones, consisting of standard stimuli (80%) and deviant stimuli (20%) interspersed randomly, while participants were engaged in various visual tasks. Both studies showed stronger automatic change detection indexed by MMN in lower SES individuals, regardless of the unattended sound's feature, attended emotional content, or study type. Moreover, we observed a larger MMN in lower-SES participants, although they did not show differences in brain and behavior responses to the attended task. Lower-SES people also did not involuntarily orient more attention to sound changes (i.e., deviant stimuli), as indexed by the P3a. The study indicates that individuals with lower subjective social status may have an increased ability to automatically detect changes in their environment, which may suggest their adaptation to their childhood environments.

Audiovisual speech asynchrony asymmetrically modulates neural binding.

Previous psychophysical and neurophysiological studies in young healthy adults have provided evidence that audiovisual speech integration occurs with a large degree of temporal tolerance around true simultaneity. To further determine whether audiovisual speech asynchrony modulates auditory cortical processing and neural binding in young healthy adults, N1/P2 auditory evoked responses were compared using an additive model during a syllable categorization task, without or with an audiovisual asynchrony ranging from 240 ms visual lead to 240 ms auditory lead. Consistent with previous psychophysical findings, the observed results converge in favor of an asymmetric temporal integration window. Three main findings were observed: 1) predictive temporal and phonetic cues from pre-phonatory visual movements before the acoustic onset appeared essential for neural binding to occur, 2) audiovisual synchrony, with visual pre-phonatory movements predictive of the onset of the acoustic signal, was a prerequisite for N1 latency facilitation, and 3) P2 amplitude suppression and latency facilitation occurred even when visual pre-phonatory movements were not predictive of the acoustic onset but the syllable to come. Taken together, these findings help further clarify how audiovisual speech integration partly operates through two stages of visually-based temporal and phonetic predictions.

Exploring the Differences Between an Immature and a Mature Human Auditory System Through Auditory Late Responses in Quiet and in Noise.

Children are disadvantaged compared to adults when they perceive speech in a noisy environment. Noise reduces their ability to extract and understand auditory information. Auditory-Evoked Late Responses (ALRs) offer insight into how the auditory system can process information in noise. This study investigated how noise, signal-to-noise ratio (SNR), and stimulus type affect ALRs in children and adults. Fifteen participants from each group with normal hearing were studied under various conditions. The findings revealed that both groups experienced delayed latencies and reduced amplitudes in noise but that children had fewer identifiable waves than adults. Babble noise had a significant impact on both groups, limiting the analysis to one condition: the /da/ stimulus at +10 dB SNR for the P1 wave. P1 amplitude was greater in quiet for children compared to adults, with no stimulus effect. Children generally exhibited longer latencies. N1 latency was longer in noise, with larger amplitudes in white noise compared to quiet for both groups. P2 latency was shorter with the verbal stimulus in quiet, with larger amplitudes in children than adults. N2 latency was shorter in quiet, with no amplitude differences between the groups. Overall, noise prolonged latencies and reduced amplitudes. Different noise types had varying impacts, with the eight-talker babble noise causing more disruption. Children's auditory system responded similarly to adults but may be more susceptible to noise. This research emphasizes the need to understand noise's impact on children's auditory development, given their exposure to noisy environments, requiring further exploration of noise parameters in children.

Visual modulation of auditory evoked potentials in the cat.

Visual modulation of the auditory system is not only a neural substrate for multisensory processing, but also serves as a backup input underlying cross-modal plasticity in deaf individuals. Event-related potential (ERP) studies in humans have provided evidence of a multiple-stage audiovisual interactions, ranging from tens to hundreds of milliseconds after the presentation of stimuli. However, it is still unknown if the temporal course of visual modulation in the auditory ERPs can be characterized in animal models. EEG signals were recorded in sedated cats from subdermal needle electrodes. The auditory stimuli (clicks) and visual stimuli (flashes) were timed by two independent Poison processes and were presented either simultaneously or alone. The visual-only ERPs were subtracted from audiovisual ERPs before being compared to the auditory-only ERPs. N1 amplitude showed a trend of transiting from suppression-to-facilitation with a disruption at ~ 100-ms flash-to-click delay. We concluded that visual modulation as a function of SOA with extended range is more complex than previously characterized with short SOAs and its periodic pattern can be interpreted with "phase resetting" hypothesis.

Predicting early auditory evoked potentials using a computational model of auditory-nerve processing.

Non-invasive electrophysiological measures, such as auditory evoked potentials (AEPs), play a crucial role in diagnosing auditory pathology. However, the relationship between AEP morphology and cochlear degeneration remains complex and not well understood. Dau [J. Acoust. Soc. Am. 113, 936-950 (2003)] proposed a computational framework for modeling AEPs that utilized a nonlinear auditory-nerve (AN) model followed by a linear unitary response function. While the model captured some important features of the measured AEPs, it also exhibited several discrepancies in response patterns compared to the actual measurements. In this study, an enhanced AEP modeling framework is presented, incorporating an improved AN model, and the conclusions from the original study were reevaluated. Simulation results with transient and sustained stimuli demonstrated accurate auditory brainstem responses (ABRs) and frequency-following responses (FFRs) as a function of stimulation level, although wave-V latencies remained too short, similar to the original study. When compared to physiological responses in animals, the revised model framework showed a more accurate balance between the contributions of auditory-nerve fibers (ANFs) at on- and off-frequency regions to the predicted FFRs. These findings emphasize the importance of cochlear processing in brainstem potentials. This framework may provide a valuable tool for assessing human AN models and simulating AEPs for various subtypes of peripheral pathologies, offering opportunities for research and clinical applications.

Artifact removal by template subtraction enables recordings of the frequency following response in cochlear-implant users.

Electrically evoked frequency-following responses (eFFRs) provide insight in the phase-locking ability of brainstem of cochlear-implant (CI) users. eFFRs can potentially be used to gain insight in the individual differences in the biological limitation on temporal encoding of the electrically stimulated auditory pathway, which can be inherent to the electrical stimulation itself and/or the degenerative processes associated with hearing loss. One of the major challenge of measuring eFFRs in CI users is the process of isolating the stimulation artifact from the neural response, as both the response and the artifact overlap in time and have similar frequency characteristics. Here we introduce a new artifact removal method based on template subtraction that successfully removes the stimulation artifacts from the recordings when CI users are stimulated with pulse trains from 128 to 300 pulses per second in a monopolar configuration. Our results show that, although artifact removal was successful in all CI users, the phase-locking ability of the brainstem to the different pulse rates, as assessed with the eFFR differed substantially across participants. These results show that the eFFR can be measured, free from artifacts, in CI users and that they can be used to gain insight in individual differences in temporal processing of the electrically stimulated auditory pathway.

Aberrant thalamocortical connectivity and shifts between the resting state and task state in patients with schizophrenia.

Prominent pathological hypotheses for schizophrenia include auditory processing deficits and dysconnectivity within cerebral networks. However, most neuroimaging studies have focused on impairments in either resting-state or task-related functional connectivity in patients with schizophrenia. The aims of our study were to examine (1) blood oxygen level-dependent (BOLD) signals during auditory steady-state response (ASSR) tasks, (2) functional connectivity during the resting-state and ASSR tasks and (3) state shifts between the resting-state and ASSR tasks in patients with schizophrenia. To reduce the functional consequences of scanner noise, we employed resting-state and sparse sampling auditory fMRI paradigms in 25 schizophrenia patients and 25 healthy controls. Auditory stimuli were binaural click trains at frequencies of 20, 30, 40 and 80 Hz. Based on the detected ASSR-evoked BOLD signals, we examined the functional connectivity between the thalamus and bilateral auditory cortex during both the resting state and ASSR task state, as well as their alterations. The schizophrenia group exhibited significantly diminished BOLD signals in the bilateral auditory cortex and thalamus during the 80 Hz ASSR task (corrected p < 0.05). We observed a significant inverse relationship between the resting state and ASSR task state in altered functional connectivity within the thalamo-auditory network in schizophrenia patients. Specifically, our findings demonstrated stronger functional connectivity in the resting state (p < 0.004) and reduced functional connectivity during the ASSR task (p = 0.048), which was mediated by abnormal state shifts, within the schizophrenia group. These results highlight the presence of abnormal thalamocortical connectivity associated with deficits in the shift between resting and task states in patients with schizophrenia.