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.

Processing of auditory novelty in human cortex during a semantic categorization task.

Auditory semantic novelty - a new meaningful sound in the context of a predictable acoustical environment - can probe neural circuits involved in language processing. Aberrant novelty detection is a feature of many neuropsychiatric disorders. This large-scale human intracranial electrophysiology study examined the spatial distribution of gamma and alpha power and auditory evoked potentials (AEP) associated with responses to unexpected words during performance of semantic categorization tasks. Participants were neurosurgical patients undergoing monitoring for medically intractable epilepsy. Each task included repeatedly presented monosyllabic words from different talkers ("common") and ten words presented only once ("novel"). Targets were words belonging to a specific semantic category. Novelty effects were defined as differences between neural responses to novel and common words. Novelty increased task difficulty and was associated with augmented gamma, suppressed alpha power, and AEP differences broadly distributed across the cortex. Gamma novelty effect had the highest prevalence in planum temporale, posterior superior temporal gyrus (STG) and pars triangularis of the inferior frontal gyrus; alpha in anterolateral Heschl's gyrus (HG), anterior STG and middle anterior cingulate cortex; AEP in posteromedial HG, lower bank of the superior temporal sulcus, and planum polare. Gamma novelty effect had a higher prevalence in dorsal than ventral auditory-related areas. Novelty effects were more pronounced in the left hemisphere. Better novel target detection was associated with reduced gamma novelty effect within auditory cortex and enhanced gamma effect within prefrontal and sensorimotor cortex. Alpha and AEP novelty effects were generally more prevalent in better performing participants. Multiple areas, including auditory cortex on the superior temporal plane, featured AEP novelty effect within the time frame of P3a and N400 scalp-recorded novelty-related potentials. This work provides a detailed account of auditory novelty in a paradigm that directly examined brain regions associated with semantic processing. Future studies may aid in the development of objective measures to assess the integrity of semantic novelty processing in clinical populations.

Altered hierarchical auditory predictive processing after lesions to the orbitofrontal cortex.

Orbitofrontal cortex (OFC) is classically linked to inhibitory control, emotion regulation, and reward processing. Recent perspectives propose that the OFC also generates predictions about perceptual events, actions, and their outcomes. We tested the role of the OFC in detecting violations of prediction at two levels of abstraction (i.e., hierarchical predictive processing) by studying the event-related potentials (ERPs) of patients with focal OFC lesions (n = 12) and healthy controls (n = 14) while they detected deviant sequences of tones in a local-global paradigm. The structural regularities of the tones were controlled at two hierarchical levels by rules defined at a local (i.e., between tones within sequences) and at a global (i.e., between sequences) level. In OFC patients, ERPs elicited by standard tones were unaffected at both local and global levels compared to controls. However, patients showed an attenuated mismatch negativity (MMN) and P3a to local prediction violation, as well as a diminished MMN followed by a delayed P3a to the combined local and global level prediction violation. The subsequent P3b component to conditions involving violations of prediction at the level of global rules was preserved in the OFC group. Comparable effects were absent in patients with lesions restricted to the lateral PFC, which lends a degree of anatomical specificity to the altered predictive processing resulting from OFC lesion. Overall, the altered magnitudes and time courses of MMN/P3a responses after lesions to the OFC indicate that the neural correlates of detection of auditory regularity violation are impacted at two hierarchical levels of rule abstraction.

Sensory Gating in the Auditory System: Classical and Novel Stimulus Paradigms.

PURPOSE: Sensory gating is a phenomenon where the cortical response to the second stimulus in a pair of identical stimuli is inhibited. It is most often assessed in a conditioning-testing paradigm. Both active and passive neuronal mechanisms have been implicated in sensory gating. The present study aimed to assess if sensory gating is caused by an active neural mechanism associated with stimulus redundancy. METHOD: The study was carried out on 20 young neurotypical adults. We assessed the gating phenomenon using identical and nonidentical stimuli pairs presented in an electrophysiological conditioning-testing paradigm. We hypothesized that the novel stimulus in the nonidentical stimulus pair would not exhibit the sensory gating effects (reduction in the amplitude of cortical potentials to the second stimuli in the pair), owing to stimulus novelty. RESULTS: Contrary to our expectations, the response analyses of the cortical auditory evoked potentials revealed that adults gated repetitive and novel stimuli similarly. CONCLUSIONS: The findings are discussed in relation to the significance of methodological factors in evaluating sensory gating. We believe that additional research using oddball presentation of novel stimuli along with appropriate analysis methods is necessary before drawing any conclusions on the mechanisms underlying sensory gating.

Exploring the neural underpinnings of chord prediction uncertainty: an electroencephalography (EEG) study.

Predictive processing in the brain, involving interaction between interoceptive (bodily signal) and exteroceptive (sensory) processing, is essential for understanding music as it encompasses musical temporality dynamics and affective responses. This study explores the relationship between neural correlates and subjective certainty of chord prediction, focusing on the alignment between predicted and actual chord progressions in both musically appropriate chord sequences and random chord sequences. Participants were asked to predict the final chord in sequences while their brain activity was measured using electroencephalography (EEG). We found that the stimulus preceding negativity (SPN), an EEG component associated with predictive processing of sensory stimuli, was larger for non-harmonic chord sequences than for harmonic chord progressions. Additionally, the heartbeat evoked potential (HEP), an EEG component related to interoceptive processing, was larger for random chord sequences and correlated with prediction certainty ratings. HEP also correlated with the N5 component, found while listening to the final chord. Our findings suggest that HEP more directly reflects the subjective prediction certainty than SPN. These findings offer new insights into the neural mechanisms underlying music perception and prediction, emphasizing the importance of considering auditory prediction certainty when examining the neural basis of music cognition.

Order effects in task-free learning: Tuning to information-carrying sound features.

Event-related potentials (ERPs) acquired during task-free passive listening can be used to study how sensitivity to common pattern repetitions and rare deviations changes over time. These changes are purported to represent the formation and accumulation of precision in internal models that anticipate future states based on probabilistic and/or statistical learning. This study features an unexpected finding; a strong order-dependence in the speed with which deviant responses are elicited that anchors to first learning. Participants heard four repetitions of a sequence in which an equal number of short (30 msec) and long (60 msec) pure tones were arranged into four blocks in which one was common (the standard, p = .875) and the other rare (the deviant, p = .125) with probabilities alternating across blocks. Some participants always heard the sequences commencing with the 30 msec deviant block, and others always with the 60 msec deviant block first. A deviance-detection component known as mismatch negativity (MMN) was extracted from responses and the point in time at which MMN reached maximum amplitude was used as the dependent variable. The results show that if participants heard sequences commencing with the 60 msec deviant block first, the MMN to the 60 msec and 30 msec deviant peaked at an equivalent latency. However, if participants heard sequences commencing with the 30 msec deviant first, the MMN peaked earlier to the 60 msec deviant. Furthermore, while the 30 msec MMN latency did not differ as a function of sequence composition, the 60 msec MMN latency did and was earlier when the sequences began with a 30 msec deviant first. By examining MMN latency effects as a function of age and hearing level it was apparent that the differentiation in 30 msec and 60 msec MMN latency expands with older age and raised hearing threshold due to prolongation of the time taken for the 30 msec MMN to peak. The observations are discussed with reference to how the initial sound composition may tune the auditory system to be more sensitive to different cues (i.e., offset responses vs perceived loudness). The order-effect demonstrates a remarkably powerful anchoring to first learning that might reflect initial tuning to the most valuable discriminating feature within a given listening environment, an effect that defies explanation based on statistical information alone.

Auditory prediction and prediction error responses evoked through a novel cascade roving paradigm: a human ECoG study.

Auditory sensory processing is assumed to occur in a hierarchical structure including the primary auditory cortex (A1), superior temporal gyrus, and frontal areas. These areas are postulated to generate predictions for incoming stimuli, creating an internal model of the surrounding environment. Previous studies on mismatch negativity have indicated the involvement of the superior temporal gyrus in this processing, whereas reports have been mixed regarding the contribution of the frontal cortex. We designed a novel auditory paradigm, the "cascade roving" paradigm, which incorporated complex structures (cascade sequences) into a roving paradigm. We analyzed electrocorticography data from six patients with refractory epilepsy who passively listened to this novel auditory paradigm and detected responses to deviants mainly in the superior temporal gyrus and inferior frontal gyrus. Notably, the inferior frontal gyrus exhibited broader distribution and sustained duration of deviant-elicited responses, seemingly differing in spatio-temporal characteristics from the prediction error responses observed in the superior temporal gyrus, compared with conventional oddball paradigms performed on the same participants. Moreover, we observed that the deviant responses were enhanced through stimulus repetition in the high-gamma range mainly in the superior temporal gyrus. These features of the novel paradigm may aid in our understanding of auditory predictive coding.

Inhibitory Deficits of Insomnia Disorder: A Meta-Analysis on Event Related Potentials in Auditory Oddball Task.

BACKGROUND: Despite numerous studies on auditory event-related potentials (ERPs) in insomnia disorder (ID), the results are inconsistent across different ERP components (e.g. N1, P2, P3, and N350), types of auditory stimuli (e.g. standard and deviant), and stages of sleep (e.g. wakefulness, NREM sleep, and REM sleep). In light of this variability, we conducted a systematic meta-analysis of previous auditory ERP studies in ID to provide a quantitative review of the existing literature. METHODS: Relevant literatures were searched on the Embase, PubMed/MEDLINE, PsycINFO and Cochrane Library. A total of 12 studies comprising 497 participants were finally included in this meta-analysis. The study protocol was registered with PROSPERO under the registration number CRD42022308348. RESULTS: We found that patients with ID have significantly decreased N1 (Hedges' g = 0.34, 95%CI [0.04, 0.65]) and P3 (Hedges'g = -1.21, 95%CI [-2.37, -0.06]) amplitudes during wakefulness. In addition, decreases in P2 (Hedges'g = -0.57, 95%CI [-0.96, -0.17]) amplitude during wakefulness and N350 (Hedges' g = 0.73, 95%CI [0.36, 1.09]) amplitude during NREM. CONCLUSIONS: This meta-analysis represents the first systematic investigation of ERP features across different stages of sleep in individuals with ID. Our results suggest that in patients with insomnia, the absence or deficiency of arousal inhibition during the nighttime sleep initiation or maintenance process may interfere with the normal process of sleep.

Making sense of music: Insights from neurophysiology and connectivity analyses in naturalistic listening conditions.

According to the latest frameworks, auditory perception and memory involve the constant prediction of future sound events by the brain, based on the continuous extraction of feature regularities from the environment. The neural hierarchical mechanisms for predictive processes in perception and memory for sounds are typically studied in relation to simple acoustic features in isolated sounds or sound patterns inserted in highly certain contexts. Such studies have identified reliable prediction formation and error signals, e.g., the N100 or the mismatch negativity (MMN) evoked responses. In real life, though, individuals often face situations in which uncertainty prevails and where making sense of sounds becomes a hard challenge. In music, not only deviations from predictions are masterly set up by composers to induce emotions but sometimes the sheer uncertainty of sound scenes is exploited for aesthetic purposes, especially in compositional styles such as Western atonal classical music. In very recent magnetoencephalography (MEG) and electroencephalography (EEG) studies, experimental and technical advances in stimulation paradigms and analysis approaches have permitted the identification of prediction-error responses from highly uncertain, atonal contexts and the extraction of prediction-related responses from real, continuous music. Moreover, functional connectivity analyses revealed the emergence of cortico-hippocampal interactions during the formation of auditory memories for more predictable vs. less predictable patterns. These findings contribute to understanding the general brain mechanisms that enable us to predict even highly uncertain sound environments and to possibly make sense of and appreciate even atonal music.

Delirium is associated with loss of feedback cortical connectivity.

INTRODUCTION: Post-operative delirium (POD) is associated with increased morbidity and mortality but is bereft of treatments, largely due to our limited understanding of the underlying pathophysiology. We hypothesized that delirium reflects a disturbance in cortical connectivity that leads to altered predictions of the sensory environment. METHODS: High-density electroencephalogram recordings during an oddball auditory roving paradigm were collected from 131 patients. Dynamic causal modeling (DCM) analysis facilitated inference about the neuronal connectivity and inhibition-excitation dynamics underlying auditory-evoked responses. RESULTS: Mismatch negativity amplitudes were smaller in patients with POD. DCM showed that delirium was associated with decreased left-sided superior temporal gyrus (l-STG) to auditory cortex feedback connectivity. Feedback connectivity also negatively correlated with delirium severity and systemic inflammation. Increased inhibition of l-STG, with consequent decreases in feed-forward and feed-back connectivity, occurred for oddball tones during delirium. DISCUSSION: Delirium is associated with decreased feedback cortical connectivity, possibly resulting from increased intrinsic inhibitory tone. HIGHLIGHTS: Mismatch negativity amplitude was reduced in patients with delirium. Patients with postoperative delirium had increased feedforward connectivity before surgery. Feedback connectivity was diminished from left-side superior temporal gyrus to left primary auditory sensory area during delirium. Feedback connectivity inversely correlated with inflammation and delirium severity.

That sounds awful! Does sound unpleasantness modulate the mismatch negativity and its habituation?

There are sounds that most people perceive as highly unpleasant, for instance, the sound of rubbing pieces of polystyrene together. Previous research showed larger physiological and neural responses for such aversive compared to neutral sounds. Hitherto, it remains unclear whether habituation, i.e., diminished responses to repeated stimulus presentation, which is typically reported for neutral sounds, occurs to the same extent for aversive stimuli. We measured the mismatch negativity (MMN) in response to rare occurrences of aversive or neutral deviant sounds within an auditory oddball sequence in 24 healthy participants, while they performed a demanding visual distractor task. Deviants occurred as single events (i.e., between two standards) or as double deviants (i.e., repeating the identical deviant sound in two consecutive trials). All deviants elicited a clear MMN, and amplitudes were larger for aversive than for neutral deviants (irrespective of their position within a deviant pair). This supports the claim of preattentive emotion evaluation during early auditory processing. In contrast to our expectations, MMN amplitudes did not show habituation, but increased in response to deviant repetition-similarly for aversive and neutral deviants. A more fine-grained analysis of individual MMN amplitudes in relation to individual arousal and valence ratings of each sound item revealed that stimulus-specific MMN amplitudes were best predicted by the interaction of deviant position and perceived arousal, but not by valence. Deviants with perceived higher arousal elicited larger MMN amplitudes only at the first deviant position, indicating that the MMN reflects preattentive processing of the emotional content of sounds.

Limiting parameter range for cortical-spherical mapping improves activated domain estimation for attention modulated auditory response.

BACKGROUND: Attention is one of the factors involved in selecting input information for the brain. We applied a method for estimating domains with clear boundaries using magnetoencephalography (the domain estimation method) for auditory-evoked responses (N100m) to evaluate the effects of attention in milliseconds. However, because the surface around the auditory cortex is folded in a complicated manner, it is unknown whether the activity in the auditory cortex can be estimated. NEW METHOD: The parameter range to express current sources was set to include the auditory cortex. Their search region was expressed as a direct product of the parameter ranges used in the adaptive diagonal curves. RESULTS: Without a limitation of the range, activity was estimated in regions other than the auditory cortex in all cases. However, with the limitation of the range, the activity was estimated in the primary or higher auditory cortex. Further analysis of the limitation of the range showed that the domains activated during attention included the regions activated during no attention for the participants whose amplitudes of N100m were higher during attention. COMPARISON WITH EXISTING METHOD: We proposed a method for effectively limiting the search region to evaluate the extent of the activated domain in regions with complex folded structures. CONCLUSION: To evaluate the extent of activated domains in regions with complex folded structures, it is necessary to limit the parameter search range. The area of the activated domains in the auditory cortex may increase by attention on the millisecond timescale.

Probing the Neurophysiology of Temporal Sensitivity in the Somatosensory System Using the Mismatch Negativity (MMN) Sensory Memory Paradigm.

Duration is an amodal feature common to all sensory experiences, but low-level processing of the temporal qualities of somatosensation remains poorly understood. The goal of the present study was to evaluate electrophysiological discrimination of parametric somatosensory stimuli to better understand how the brain processes the duration of tactile information. This research used a somatosensory mismatch negativity (sMMN) paradigm to evaluate electrophysiological sensitivity to differences in the duration of vibrotactile stimuli in healthy young adults. Specifically, a 100 ms standard vibration was presented 80% of the time while the remaining 20% of presentations were made up of deviant stimuli with one of the following durations: 115, 130, 145, or 160 ms. When a deviation from the anticipated tactile input is detected, the distinct electrophysiological signature of the sMMN is present. A companion behavioral task assessed individual thresholds for cognizant awareness of the standard and deviant vibrotactile stimuli. The results of the present study demonstrated a sMMN response when deviant stimuli were 130, 145, and 160 ms, but not when they were 115 ms. This suggests that on average the participants did not electrophysiologically discriminate between the 100 and 115 ms. Future work may apply this paradigm to better understand atypical tactile sensitivity in various clinical conditions.

Relationship between schematic and dynamic expectations of melodic patterns in music perception.

Prediction is fundamental in music listening. Two types of expectations have been proposed: schematic expectations, which arise from knowledge of tonal regularities (e.g., harmony and key) acquired through long-term plasticity and learning, and dynamic expectations, which arise from short-term regularity representations (e.g., rhythmic patterns and melodic contours) extracted from ongoing musical contexts. Although both expectations are indispensable in music listening, how they interact with each other in music prediction remains unclear. The present study examined the relationship between schematic and dynamic expectations in music processing using event-related potentials (ERPs). At the ending note of the melodies, the schematic expectation was violated by presenting a note with music-syntactic irregular (i.e., outof- key note), while the dynamic expectation was violated by presenting a contour deviant based on online statistical learning of melodic patterns. Schematic and dynamic expectations were manipulated to predict the same note. ERPs were recorded for the music-syntactic irregularity and the contour deviant, which occurred independently or simultaneously. The results showed that the music-syntactic irregularity elicited an early right anterior negativity (ERAN), reflecting the prediction error in the schematic expectation, while the contour deviant elicited a mismatch negativity (MMN), reflecting the prediction error in the dynamic expectation. Both components occurred within a similar latency range. Moreover, the ERP amplitude was multiplicatively increased when the irregularity and deviance occurred simultaneously. These findings suggest that schematic and dynamic expectations function concurrently in an interactive manner when both expectations predict the same note.

Abrupt phase changes coupled with waning in amplitude of neural oscillation lead to phase-locking in the auditory evoked responses.

Neural oscillations on the human auditory cortex measured with the magnetoencephalography were band-pass filtered between 3 and 16 Hz and then divided into instantaneous phases and amplitudes by the Hilbert transformation. Spontaneously, the amplitudes fluctuated, i.e. waxed and waned; The phases rotated at around 6 Hz most of the time, but abruptly accelerated or decelerated when the amplitudes waned close to zero. After auditory stimuli, the amplitudes and the phases were coupled in the same way as spontaneously. Amounts and directions of the accelerations or decelerations were thereby specific so that the phases subsequently took mostly the same value, i.e. were locked, at around the time of N100 peaks in the auditory evoked responses. In short, the auditory evoked responses emerged from spontaneous oscillations by abrupt phase changes coupled with waning in amplitudes and phase-locking thereafter.

Time-resolved dynamic computational modeling of human EEG recordings reveals gradients of generative mechanisms for the MMN response.

Despite attempts to unify the different theoretical accounts of the mismatch negativity (MMN), there is still an ongoing debate on the neurophysiological mechanisms underlying this complex brain response. On one hand, neuronal adaptation to recurrent stimuli is able to explain many of the observed properties of the MMN, such as its sensitivity to controlled experimental parameters. On the other hand, several modeling studies reported evidence in favor of Bayesian learning models for explaining the trial-to-trial dynamics of the human MMN. However, direct comparisons of these two main hypotheses are scarce, and previous modeling studies suffered from methodological limitations. Based on reports indicating spatial and temporal dissociation of physiological mechanisms within the timecourse of mismatch responses in animals, we hypothesized that different computational models would best fit different temporal phases of the human MMN. Using electroencephalographic data from two independent studies of a simple auditory oddball task (n = 82), we compared adaptation and Bayesian learning models' ability to explain the sequential dynamics of auditory deviance detection in a time-resolved fashion. We first ran simulations to evaluate the capacity of our design to dissociate the tested models and found that they were sufficiently distinguishable above a certain level of signal-to-noise ratio (SNR). In subjects with a sufficient SNR, our time-resolved approach revealed a temporal dissociation between the two model families, with high evidence for adaptation during the early MMN window (from 90 to 150-190 ms post-stimulus depending on the dataset) and for Bayesian learning later in time (170-180 ms or 200-220ms). In addition, Bayesian model averaging of fixed-parameter models within the adaptation family revealed a gradient of adaptation rates, resembling the anatomical gradient in the auditory cortical hierarchy reported in animal studies.

Competing influence of visual speech on auditory neural adaptation.

Visual information from a speaker's face enhances auditory neural processing and speech recognition. To determine whether auditory memory can be influenced by visual speech, the degree of auditory neural adaptation of an auditory syllable preceded by an auditory, visual, or audiovisual syllable was examined using EEG. Consistent with previous findings and additional adaptation of auditory neurons tuned to acoustic features, stronger adaptation of N1, P2 and N2 auditory evoked responses was observed when the auditory syllable was preceded by an auditory compared to a visual syllable. However, although stronger than when preceded by a visual syllable, lower adaptation was observed when the auditory syllable was preceded by an audiovisual compared to an auditory syllable. In addition, longer N1 and P2 latencies were then observed. These results further demonstrate that visual speech acts on auditory memory but suggest competing visual influences in the case of audiovisual stimulation.

Neural signatures of automatic repetition detection in temporally regular and jittered acoustic sequences.

Detection of repeating patterns within continuous sound streams is crucial for efficient auditory perception. Previous studies demonstrated a remarkable sensitivity of the human auditory system to periodic repetitions in unfamiliar, meaningless sounds. Automatic repetition detection was reflected in different EEG markers, including sustained activity, neural synchronisation, and event-related responses to pattern occurrences. The current study investigated how listeners' attention and the temporal regularity of a sound modulate repetition perception, and how this influence is reflected in different EEG markers that were previously suggested to subserve dissociable functions. We reanalysed data of a previous study in which listeners were presented with sequences of unfamiliar artificial sounds that either contained repetitions of a certain sound segment or not. Repeating patterns occurred either regularly or with a temporal jitter within the sequences, and participants' attention was directed either towards the pattern repetitions or away from the auditory stimulation. Across both regular and jittered sequences during both attention and in-attention, pattern repetitions led to increased sustained activity throughout the sequence, evoked a characteristic positivity-negativity complex in the event-related potential, and enhanced inter-trial phase coherence of low-frequency oscillatory activity time-locked to repeating pattern onsets. While regularity only had a minor (if any) influence, attention significantly strengthened pattern repetition perception, which was consistently reflected in all three EEG markers. These findings suggest that the detection of pattern repetitions within continuous sounds relies on a flexible mechanism that is robust against in-attention and temporal irregularity, both of which typically occur in naturalistic listening situations. Yet, attention to the auditory input can enhance processing of repeating patterns and improve repetition detection.

Investigating the optimal stimulus to evoke the binaural interaction component of the auditory brainstem response.

Objective assessment of spatial and binaural hearing deficits remains a major clinical challenge. The binaural interaction component (BIC) of the auditory brainstem response (ABR) holds promise as a non-invasive biomarker for diagnosing such deficits. However, while comparative studies have reported robust BIC in animal models, BIC in humans can sometimes be unreliably evoked even in subjects with normal hearing. Here we explore the hypothesis that the standard methodology for collecting monaural ABRs may not be ideal for electrophysiological assessment of binaural hearing. This study aims to improve ABR BIC measurements by determining more optimal stimuli to evoke it. Building on previous methodology demonstrated to enhance peak amplitude of monaural ABRs, we constructed a series of level-dependent chirp stimuli based on empirically derived latencies of monaural-evoked ABR waves I, IV and the binaural-evoked BIC DN1, the most prominent BIC peak, in a cohort of ten chinchillas. We hypothesized that chirps designed based on BIC DN1 latency would specifically enhance across-frequency temporal synchrony in the afferent inputs leading to the binaural circuits that produce the BIC and would thus produce a larger DN1 than either traditional clicks or chirps designed to optimize monaural ABRs. Compared to clicks, we found that level-specific chirp stimuli evoked significantly greater BIC DN1 amplitudes, and that this effect persisted across all stimulation levels tested. However, we found no significant differences between BICs resulting from chirps created using binaural-evoked BIC DN1 latencies and those using monaural-evoked ABR waves I or IV. These data indicate that existing level-specific, monaural-based chirp stimuli may improve BIC detectability and reduce variability in human BIC measurements.