Auditory Sensory Processing Research Articles

Neurophysiology of Effortful Listening: Decoupling Motivational Modulation from Task Demands.

In demanding listening situations, a listener's motivational state may affect their cognitive investment. Here, we aim to delineate how domain-specific sensory processing, domain-general neural alpha power, and pupil size as a proxy for cognitive investment encode influences of motivational state under demanding listening. Participants (male and female) performed an auditory gap-detection task while the pupil size and the magnetoencephalogram were simultaneously recorded. Task demand and a listener's motivational state were orthogonally manipulated through changes in gap duration and monetary-reward prospect, respectively. Whereas task difficulty impaired performance, reward prospect enhanced it. The pupil size reliably indicated the modulatory impact of an individual's motivational state. At the neural level, the motivational state did not affect auditory sensory processing directly but impacted attentional postprocessing of an auditory event as reflected in the late evoked-response field and alpha-power change. Both pregap pupil dilation and higher parietal alpha power predicted better performance at the single-trial level. The current data support a framework wherein the motivational state acts as an attentional top-down neural means of postprocessing the auditory input in challenging listening situations.

Probing a neural unreliability account of auditory sensory processing atypicalities in Rett Syndrome

BackgroundIn the search for objective tools to quantify neural function in Rett Syndrome (RTT), which are crucial in the evaluation of therapeutic efficacy in clinical trials, recordings of sensory-perceptual functioning using event-related potential (ERP) approaches have emerged as potentially powerful tools. Considerable work points to highly anomalous auditory evoked potentials (AEPs) in RTT. However, an assumption of the typical signal-averaging method used to derive these measures is “stationarity” of the underlying responses – i.e. neural responses to each input are highly stereotyped. An alternate possibility is that responses to repeated stimuli are highly variable in RTT. If so, this will significantly impact the validity of assumptions about underlying neural dysfunction, and likely lead to overestimation of underlying neuropathology. To assess this possibility, analyses at the single-trial level assessing signal-to-noise ratios (SNR), inter-trial variability (ITV) and inter-trial phase coherence (ITPC) are necessary.MethodsAEPs were recorded to simple 100 Hz tones from 18 RTT and 27 age-matched controls (Ages: 6–22 years). We applied standard AEP averaging, as well as measures of neuronal reliability at the single-trial level (i.e. SNR, ITV, ITPC). To separate signal-carrying components from non-neural noise sources, we also applied a denoising source separation (DSS) algorithm and then repeated the reliability measures.ResultsSubstantially increased ITV, lower SNRs, and reduced ITPC were observed in auditory responses of RTT participants, supporting a “neural unreliability” account. Application of the DSS technique made it clear that non-neural noise sources contribute to overestimation of the extent of processing deficits in RTT. Post-DSS, ITV measures were substantially reduced, so much so that pre-DSS ITV differences between RTT and TD populations were no longer detected. In the case of SNR and ITPC, DSS substantially improved these estimates in the RTT population, but robust differences between RTT and TD were still fully evident.ConclusionsTo accurately represent the degree of neural dysfunction in RTT using the ERP technique, a consideration of response reliability at the single-trial level is highly advised. Non-neural sources of noise lead to overestimation of the degree of pathological processing in RTT, and denoising source separation techniques during signal processing substantially ameliorate this issue.

Mismatch Negativity in Schizophrenia, Unaffected First-degree Relatives, and Healthy Controls

BackgroundMismatch negativity (MMN) amplitude is attenuated in schizophrenia patients (SZ). However, variability in illness course among SZ samples and types of deviant stimuli used in MMN paradigms have contributed to inconsistent findings across studies. Though MMN is suggested to be impaired in schizotypy, the potential link between the two is yet to be systematically examined in unaffected first-degree relatives of schizophrenia patients (FDR). MethodsThe SZ sample had twenty-two drug-naïve or drug-free patients (dSZ) and thirty chronic/medicated patients (cSZ). dSZ and cSZ patients were compared with thirty-six unaffected FDR and thirty-two healthy controls (HC) using a two-tone passive auditory oddball MMN paradigm in an event-related potential experiment with two conditions (presented as separate blocks)–duration-deviant (duration-MMN) and frequency-deviant (frequency-MMN). Schizotypy scores and MMN indices were examined for correlation in FDR. ResultsDuration-MMN amplitude was significantly attenuated in both dSZ and cSZ compared to other groups. dSZ and cSZ did not differ on MMN indices. Psychopathology scores and features of illness (illness duration, medication dosage, etc.) did not correlate with MMN indices. In FDR, Schizotypal trait measures did not correlate with MMN indices. ConclusionsDuration-MMN emerged as a more robust indicator of prediction error signalling deficit in SZ. Frequency-MMN amplitude did not significantly differ among the groups, and MMN indices did not correlate with state and trait measures of schizophrenia-related psychopathology. These findings reiterates that auditory sensory processing captured by MMN is likely reflective of dynamic cognitive functions at the point of testing, and is unlikely to be an expression of enduring symptomatology.

EEG-based hierarchical classification of level of demand and modality of auditory and visual sensory processing

Objective. To date, most research on electroencephalography (EEG)-based mental workload detection for passive brain-computer interface (pBCI) applications has focused on identifying the overall level of cognitive resources required, such as whether the workload is high or low. We propose, however, that being able to determine the specific type of cognitive resources being used, such as visual or auditory, would also be useful. This would enable the pBCI to take more appropriate action to reduce the overall level of cognitive demand on the user. For example, if a high level of workload was detected and it is determined that the user is primarily engaged in visual information processing, then the pBCI could cause some information to be presented aurally instead. In our previous work we showed that EEG could be used to differentiate visual from auditory processing tasks when the level of processing is high, but the two modalities could not be distinguished when the level of cognitive processing demand was very low. The current study aims to build on this work and move toward the overall objective of developing a pBCI that is capable of predicting both the level and the type of cognitive resources being used. Approach. Fifteen individuals undertook carefully designed visual and auditory tasks while their EEG data was being recorded. In this study, we incorporated a more diverse range of sensory processing conditions including not only single-modality conditions (i.e. those requiring one of either visual or auditory processing) as in our previous study, but also dual-modality conditions (i.e. those requiring both visual and auditory processing) and no-task/baseline conditions (i.e. when the individual is not engaged in either visual or auditory processing). Main results. Using regularized linear discriminant analysis within a hierarchical classification algorithm, the overall cognitive demand was predicted with an accuracy of more than 86%, while the presence or absence of visual and auditory sensory processing were each predicted with an accuracy of approximately 70%. Significance. The findings support the feasibility of establishing a pBCI that can determine both the level and type of attentional resources required by the user at any given moment. This pBCI could assist in enhancing safety in hazardous jobs by triggering the most effective and efficient adaptation strategies when high workload conditions are detected.

Assessing the integrity of auditory sensory memory processing in CLN3 disease (Juvenile Neuronal Ceroid Lipofuscinosis (Batten disease)): an auditory evoked potential study of the duration-evoked mismatch negativity (MMN)

BackgroundWe interrogated auditory sensory memory capabilities in individuals with CLN3 disease (juvenile neuronal ceroid lipofuscinosis), specifically for the feature of “duration” processing. Given decrements in auditory processing abilities associated with later-stage CLN3 disease, we hypothesized that the duration-evoked mismatch negativity (MMN) of the event related potential (ERP) would be a marker of progressively atypical cortical processing in this population, with potential applicability as a brain-based biomarker in clinical trials.MethodsWe employed three stimulation rates (fast: 450 ms, medium: 900 ms, slow: 1800 ms), allowing for assessment of the sustainability of the auditory sensory memory trace. The robustness of MMN directly relates to the rate at which the regularly occurring stimulus stream is presented. As presentation rate slows, robustness of the sensory memory trace diminishes. By manipulating presentation rate, the strength of the sensory memory trace is parametrically varied, providing greater sensitivity to detect auditory cortical dysfunction. A secondary hypothesis was that duration-evoked MMN abnormalities in CLN3 disease would be more severe at slower presentation rates, resulting from greater demand on the sensory memory system.ResultsData from individuals with CLN3 disease (N = 21; range 6–28 years of age) showed robust MMN responses (i.e., intact auditory sensory memory processes) at the medium stimulation rate. However, at the fastest rate, MMN was significantly reduced, and at the slowest rate, MMN was not detectable in CLN3 disease relative to neurotypical controls (N = 41; ages 6–26 years).ConclusionsResults reveal emerging insufficiencies in this critical auditory perceptual system in individuals with CLN3 disease.

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.

Exploratory evidence for differences in GABAergic regulation of auditory processing in autism spectrum disorder

Altered reactivity and responses to auditory input are core to the diagnosis of autism spectrum disorder (ASD). Preclinical models implicate ϒ-aminobutyric acid (GABA) in this process. However, the link between GABA and auditory processing in humans (with or without ASD) is largely correlational. As part of a study of potential biosignatures of GABA function in ASD to inform future clinical trials, we evaluated the role of GABA in auditory repetition suppression in 66 adults (n = 28 with ASD). Neurophysiological responses (temporal and frequency domains) to repetitive standard tones and novel deviants presented in an oddball paradigm were compared after double-blind, randomized administration of placebo, 15 or 30 mg of arbaclofen (STX209), a GABA type B (GABAB) receptor agonist. We first established that temporal mismatch negativity was comparable between participants with ASD and those with typical development (TD). Next, we showed that temporal and spectral responses to repetitive standards were suppressed relative to responses to deviants in the two groups, but suppression was significantly weaker in individuals with ASD at baseline. Arbaclofen reversed weaker suppression of spectral responses in ASD but disrupted suppression in TD. A post hoc analysis showed that arbaclofen-elicited shift in suppression was correlated with autistic symptomatology measured using the Autism Quotient across the entire group, though not in the smaller sample of the ASD and TD group when examined separately. Thus, our results confirm: GABAergic dysfunction contributes to the neurophysiology of auditory sensory processing alterations in ASD, and can be modulated by targeting GABAB activity. These GABA-dependent sensory differences may be upstream of more complex autistic phenotypes.

Normative Intercorrelations Between EEG Microstate Characteristics

EEG microstates are brief, recurring periods of stable brain activity that reflect the activation of large-scale neural networks. The temporal characteristics of these microstates, including their average duration, number of occurrences, and percentage contribution have been shown to serve as biomarkers of mental and neurological disorders. However, little is known about how microstate characteristics of prototypical network types relate to each other. Normative intercorrelations among these parameters are necessary to help researchers better understand the functions and interactions of underlying networks, interpret and relate results, and generate new hypotheses. Here, we present a systematic analysis of intercorrelations between EEG microstate characteristics in a large sample representative of western working populations (n = 583). Notably, we find that microstate duration is a general characteristic that varies across microstate types. Further, microstate A and B show mutual reinforcement, indicating a relationship between auditory and visual sensory processing at rest. Microstate C appears to play a special role, as it is associated with longer durations of all other microstate types and increased global field power, suggesting a relationship of these parameters with the anterior default mode network. All findings could be confirmed using independent EEG recordings from a retest-session (n = 542).

Effects of transcutaneous auricular vagus nerve stimulation paired with tones on electrophysiological markers of auditory perception

BackgroundTranscutaneous auricular vagus nerve stimulation (taVNS) has been introduced as a non-invasive alternative to invasive vagus nerve stimulation (iVNS). While iVNS paired with tones has been highlighted as a potential effective therapy for the treatment of auditory disorders such as tinnitus, there is still scarce data available confirming the efficacy of non-invasive taVNS. Here, we assessed the effect of taVNS paired with acoustic stimuli on sensory-related electrophysiological responses. MethodsA total of 22 healthy participants were investigated with a taVNS tone-pairing paradigm using a within-subjects design. In a single session pure tones paired with either active taVNS or sham taVNS were repeatedly presented. Novel tones without electrical stimulation served as control condition. Auditory event related potentials and auditory cortex oscillations were compared before and after the tone pairing procedure between stimulation conditions. ResultsFrom pre to post pairing, we observed a decrease in the N1 amplitude and in theta power to tones paired with sham taVNS while these electrophysiological measures remained stable for tones paired with active taVNS a pattern mirroring auditory sensory processing of novel, unpaired control tones. ConclusionOur results demonstrate the efficacy of a short-term application of non-invasive taVNS to modulate auditory processing in healthy individuals and, thereby, have potential implications for interventions in auditory processing deficits.

Neurophysiological measures of auditory sensory processing are associated with adaptive behavior in children with Autism Spectrum Disorder

BackgroundAtypical auditory cortical processing is consistently found in scalp electrophysiological and magnetoencephalographic studies of Autism Spectrum Disorder (ASD), and may provide a marker of neuropathological brain development. However, the relationship between atypical cortical processing of auditory information and adaptive behavior in ASD is not yet well understood.MethodsWe sought to test the hypothesis that early (100-175 ms) auditory processing in ASD is related to everyday adaptive behavior through the examination of auditory event-related potentials (AEPs) in response to simple tones and Vineland Adaptive Behavior Scales in a large cohort of children with ASD (N = 84), aged 6–17, and in age- and IQ- matched neurotypically (NT) developing controls (N = 132).ResultsStatistical analyses revealed significant group differences in early AEPs over temporal scalp regions (150-175 ms), and the expected rightward lateralization of the AEP (100-125 ms and 150-175 ms) to tonal stimuli in both groups. Lateralization of the AEP (150-175 ms) was significantly associated with adaptive functioning in the socialization domain.ConclusionsThese results lend support to the hypothesis that atypical processing of sensory information is related to everyday adaptive behavior in autism.

No Differences in Auditory Steady-State Responses in Children with Autism Spectrum Disorder and Typically Developing Children.

Auditory steady-state response (ASSR) has been studied as a potential biomarker for abnormal auditory sensory processing inautism spectrum disorder (ASD), with mixed results. Motivated by prior somatosensory findings of group differences in inter-trial coherence (ITC) between ASD and typically developing (TD) individuals at twice the steady-state stimulation frequency, we examined ASSR at 25 and 50 as well as 43 and 86Hz in response to 25-Hz and 43-Hz auditory stimuli, respectively, using magnetoencephalography. Data were recorded from 22 ASD and 31 TD children, ages 6-17years. ITC measures showed prominent ASSRs at the stimulation and double frequencies, without significant group differences. These results do not support ASSR as a robust ASD biomarkerof abnormal auditory processing in ASD. Furthermore, the previously observed atypical double-frequency somatosensory response in ASD did not generalize to the auditory modality.Thus, the hypothesis about modality-independent abnormal local connectivityin ASD was not supported.

Mismatch negativity as an early biomarker of cognitive impairment in schizophrenia

BackgroundDue to its disturbance in schizophrenic patients, mismatch negativity (MMN) generation is believed to be a potential biomarker for recognizing primary impairments in auditory sensory processing during the course of the disease. However, great controversy exists regarding the type and onset of MMN-related impairments, with the deficits to frequency deviants is more debatable. This cross-sectional, case–control study was conducted to assess the cognitive functions among 33 eligible Egyptian schizophrenics (15 early and 18 chronic), and 30 matched healthy controls by assessing their psychometric tests and correlating them to the coexisting frequency deviant MMN responses (using both tone and speech stimuli).ResultsDeficits in frequency MMN and neuropsychological tests were evident among early and chronic schizophrenics compared to their matched control counterparts, and also between early versus chronic schizophrenia in favor of the later. MMN deficits to speech stimuli were more elicited than tone stimuli among schizophrenics. Moreover, significant correlations were identified between MMN parameters and the results of psychiatric cognitive scales.ConclusionsWe demonstrated that frequency-deviant MMN deficits are evident feature among the enrolled Egyptian schizophrenics. The cognitive functions as indexed by MMN seem affected early, with the striking decrease of MMN amplitude and delay of latency point towards the progression of the illness. The normal lateralization of MMN was absent in chronic schizophrenia. These findings could be helpful in using the MMN as an additional objective tool for confirming cognitive impairments among schizophrenics and to differentiate between early- and chronic-schizophrenic patients for medico-legal purposes and clinical implication for medications.

EEG-based detection of modality-specific visual and auditory sensory processing

Objective. A passive brain–computer interface (pBCI) is a system that enhances a human–machine interaction by monitoring the mental state of the user and, based on this implicit information, making appropriate modifications to the interaction. Key to the development of such a system is the ability to reliably detect the mental state of interest via neural signals. Many different mental states have been investigated, including fatigue, attention and various emotions, however one of the most commonly studied states is mental workload, i.e. the amount of attentional resources required to perform a task. The emphasis of mental workload studies to date has been almost exclusively on detecting and predicting the ‘level’ of cognitive resources required (e.g. high vs. low), but we argue that having information regarding the specific ‘type’ of resources (e.g. visual or auditory) would allow the pBCI to apply more suitable adaption techniques than would be possible knowing just the overall workload level. Approach. 15 participants performed carefully designed visual and auditory tasks while electroencephalography (EEG) data was recorded. The tasks were designed to be as similar as possible to one another except for the type of attentional resources required. The tasks were performed at two different levels of demand. Using traditional machine learning algorithms, we investigated, firstly, if EEG can be used to distinguish between auditory and visual processing tasks and, secondly, what effect level of sensory processing demand has on the ability to distinguish between auditory and visual processing tasks. Main results. The results show that at the high level of demand, the auditory vs. visual processing tasks could be distinguished with an accuracy of 77.1% on average. However, in the low demand condition in this experiment, the tasks were not classified with an accuracy exceeding chance. Significance. These results support the feasibility of developing a pBCI for detecting not only the level, but also the type, of attentional resources being required of the user at a given time. Further research is required to determine if there is a threshold of demand under which the type of sensory processing cannot be detected, but even if that is the case, these results are still promising since it is the high end of demand that is of most concern in safety critical scenarios. Such a BCI could help improve safety in high risk occupations by initiating the most effective and efficient possible adaptation strategies when high workload conditions are detected.

A comparative study of the cortical function during the interpretation of algorithms in pseudocode and the solution of first-order algebraic equations.

This study intends to determine whether similarities of the functioning of the cerebral cortex exist, modeled as a graph, during the execution of mathematical tasks and programming related tasks. The comparison is done using network parameters and during the development of computer programming tasks and the solution of first-order algebraic equations. For that purpose, electroencephalographic recordings (EEG) were made with a volunteer group of 16 students of systems engineering of Universidad del Norte in Colombia, while they were performing computer programming tasks and solving first-order algebraic equations with three levels of difficulty. Then, based on the Synchronization Likelihood method, graph models of functional cortical networks were developed, whose parameters of Small-Worldness (SWN), global(Eg) and local (El) efficiency were compared between both types of tasks. From this study, it can be highlighted, first, the novelty of studying cortical function during the solution of algebraic equations and during programming tasks; second, significant differences between both types of tasks observed only in the delta and theta bands. Likewise, the differences between simpler mathematical tasks with the other levels in both types of tasks; third, the Brodmann areas 21 and 42, associated with auditory sensory processing, can be considered as differentiating elements of programming tasks; as well as Brodmann area 8, during equation solving.

A study of the relationship between auditory sensory processing specificity Listening difficulties (LiD)

A study of the relationship between auditory sensory processing specificity Listening difficulties (LiD)

Psychopathic and autistic traits differentially influence the neural mechanisms of social cognition from communication signals

Psychopathy is associated with severe deviations in social behavior and cognition. While previous research described such cognitive and neural alterations in the processing of rather specific social information from human expressions, some open questions remain concerning central and differential neurocognitive deficits underlying psychopathic behavior. Here we investigated three rather unexplored factors to explain these deficits, first, by assessing psychopathy subtypes in social cognition, second, by investigating the discrimination of social communication sounds (speech, non-speech) from other non-social sounds, and third, by determining the neural overlap in social cognition impairments with autistic traits, given potential common deficits in the processing of communicative voice signals. The study was exploratory with a focus on how psychopathic and autistic traits differentially influence the function of social cognitive and affective brain networks in response to social voice stimuli. We used a parametric data analysis approach from a sample of 113 participants (47 male, 66 female) with ages ranging between 18 and 40 years (mean 25.59, SD 4.79). Our data revealed four important findings. First, we found a phenotypical overlap between secondary but not primary psychopathy with autistic traits. Second, primary psychopathy showed various neural deficits in neural voice processing nodes (speech, non-speech voices) and in brain systems for social cognition (mirroring, mentalizing, empathy, emotional contagion). Primary psychopathy also showed deficits in the basal ganglia (BG) system that seems specific to the social decoding of communicative voice signals. Third, neural deviations in secondary psychopathy were restricted to social mirroring and mentalizing impairments, but with additional and so far undescribed deficits at the level of auditory sensory processing, potentially concerning deficits in ventral auditory stream mechanisms (auditory object identification). Fourth, high autistic traits also revealed neural deviations in sensory cortices, but rather in the dorsal auditory processing streams (communicative context encoding). Taken together, social cognition of voice signals shows considerable deviations in psychopathy, with differential and newly described deficits in the BG system in primary psychopathy and at the neural level of sensory processing in secondary psychopathy. These deficits seem especially triggered during the social cognition from vocal communication signals.

Largely unaffected auditory and visual sensory processing phenotypes in the evoked potentials of Fmr1 KO2 mice.

Sensory sensitivity symptoms are common in autism spectrum disorders and fragile X syndrome. Mainly in the auditory modality, disturbed processing has been found in both fragile X patients and the corresponding genetic mouse model, the Fmr1 knockout mouse. Here, we tried to replicate the auditory deficits and assess whether also visual processing is affected, using electroencephalography readouts under freely behaving conditions in the second-generation Fmr1 knockout mice. No differences between wild-type and knockout animals were found in single auditory and visual evoked potentials in response to pure sine tones and full-field light flashes. Visual sensory gating was enhanced in the early but not the late components of the evoked potentials, but no changes were found in auditory sensory gating. The higher harmonics of the synchronisation response to flickering visual stimuli seemed to be reduced with 10, but not 20 or 40 Hz, stimulation. However, this effect was not reproduced in an independent second cohort of animals. No synchronisation differences were found in response to a chirp stimulus, of which the frequency steadily increased. Taken together, this study could not reproduce earlier reported increased amplitudes in auditory responses, nor could it convincingly show that synchronisation deficits found to be present in the auditory modality also existed in the visual modality. The discrepancies within this study as well as between various studies assessing sensory processing in the Fmr1 KO raise questions about the external validity of these phenotypes and warrant careful interpretation of these phenotypes.

Increased rate of listening difficulties in autistic children

IntroductionAuditory challenges are both common and disruptive for autistic children and evidence suggests that listening difficulties may be linked to academic underachievement (Ashburner, Ziviani & Rodger, 2008). Such deficits may also contribute to issues with attention, behavior, and communication (Ashburner et al., 2008; Riccio, Cohen, Garrison & Smith, 2005). The present study aims to summarize the auditory challenges of autistic children with normal pure-tone hearing thresholds, and perceived listening difficulties, seen at auditory-ASD clinics in the US and Australia. MethodsData were compiled on a comprehensive, auditory-focused test battery in a large clinical sample of school-age autistic children with normal pure-tone hearing to date (N = 71, 6–14 years). Measures included a parent-reported auditory sensory processing questionnaire and tests of speech recognition in noise, binaural integration, attention, auditory memory and listening comprehension. Individual test performance was compared to normative data from children with no listening difficulties. ResultsOver 40% of patients exhibited significantly reduced speech recognition in noise and abnormal dichotic integration that were not attributed to deficits in attention. The majority of patients (86%) performed abnormally on at least one auditory measure, suggesting that functional auditory issues can exist in autistic patients despite normal pure-tone sensitivity. ConclusionIncluding functional listening measures during audiological evaluations may improve clinicians’ ability to detect and manage the auditory challenges impacting this population. Learner Outcomes: 1) Readers will be able to describe the auditory difficulties experienced by some autistic patients (ASD). 2) Readers will be able to describe clinical measures potentially useful for detecting listening difficulties in high-functioning autistic children.

ДИНАМІКА ЯКОСТІ МУЗИЧНИХ СЕНСОРНИХ УМІНЬ МОЛОДШИХ УЧНІВ: РЕЗУЛЬТАТИ ФОРМУВАЛЬНОГО ЕКСПЕРИМЕНТУ

The importance of forming primary school children’s musical perception is justified by the introduction of the new version of the educational standard and educational programs as well as by teaching Arts on the basis of an integrative methodological approach. The purpose of the article is to scientifically ground the system of didactic influences on musical perceptual processes of younger school children focusing on the following research tasks: a) to define sensory ability as a unit of functioning of musical perception; b) to characterize the levels of pupils’ musical sensory skills formed in the mass experience of primary education; c) to disclose the specifics of variable experimental effects which differ in the degree of intensity of intermodal connections of sensory channels; d) to compare the quality dynamics of musical sensory skills formation in different versions of the pedagogical experiment. Musical sensory ability is defined as the performance of a system of auditory interiorized perceptual familiarizing and cognitive actions based on the mastered standards of music sounds and skills of applying these standards in the examination of musical phenomena. It has been found that in the mass experience of primary education pupils master musical sensory skills at elementary, intermediate and sufficient quality levels where the intermediate one prevails. The system of exercises and game tasks has been developed on the basis of intermodality with coordination of musical and phonemic auditory, musical auditory and color visual, musical auditory and spatial visual sensory processes. The system is aimed at expanding and systematizing pupils' reference ideas about music sounds as well as forming rational ways of their examining musical phenomena. The effectiveness of the introduced didactic influences has been proved: in comparison with the control group the participants of experimental groups, especially the first one, have demonstrated both the highest efficiency of distinguishing and systematizing music sounds and a variety of skills to reproduce them in singing, spatial modelling and instrumental game. The following changes have taken place in the structure of experimental groups: the respondents with an elementary level of musical perception development have not been identified, but a level gradation with intermediate, sufficient, high and consistently high levels of mastery of musical sensory processes. Key words: musical sensory ability, standards of musical sounds, methods of examination of musical sounds, game tasks, exercises, younger students.

Effects of the Glycine Transporter-1 Inhibitor Iclepertin (BI 425809) on Sensory Processing, Neural Network Function, and Cognition in Animal Models Related to Schizophrenia.

N-methyl-D-aspartate (NMDA) receptor hypofunction leading to neural network dysfunction is thought to play an important role in the pathophysiology of cognitive impairment associated with schizophrenia (CIAS). Increasing extracellular concentrations of the NMDA receptor co-agonist glycine through inhibition of glycine transporter-1 (GlyT1) has the potential to treat CIAS by improving cortical network function through enhanced glutamatergic signaling. Indeed, the novel GlyT1 inhibitor iclepertin (BI 425809) improved cognition in a recent clinical study in patients with schizophrenia. The present study tested the ability of iclepertin to reverse deficits in auditory sensory processing and cortical network function induced by the uncompetetive NMDA receptor antagonist, MK-801, using electroencephalography (EEG) to measure auditory event-related potentials (AERPs) and 40 Hz auditory steady-state response (ASSR). In addition, improvements in memory performance with iclepertin were evaluated using the T-maze spontaneous alternation test in MK-801-treated mice and the social recognition test in naïve rats. Iclepertin reversed MK-801-induced deficits in the AERP readouts N1 amplitude and N1 gating, as well as reversing deficits in 40 Hz ASSR power and intertrial coherence. Additionally, iclepertin significantly attenuated an MK-801-induced increase in basal gamma power. Furthermore, iclepertin reversed MK-801-induced working memory deficits in mice and improved social recognition memory performance in rats. Overall, this study demonstrates that inhibition of GlyT1 is sufficient to attenuate MK-801-induced deficits in translatable EEG parameters relevant to schizophrenia. Moreover, iclepertin showed memory-enhancing effects in rodent cognition tasks, further demonstrating the potential for GlyT1 inhibition to treat CIAS. SIGNIFICANCE STATEMENT: Despite the significant patient burden caused by cognitive impairment associated with schizophrenia, there are currently no approved pharmacotherapies. In this preclinical study, the novel glycine transporter inhibitor iclepertin (BI 425809) reversed sensory processing deficits and neural network dysfunction evoked by inhibition of N-methyl-D-aspartate receptors and enhanced working memory performance and social recognition in rodents. These findings support previous clinical evidence for the procognitive effects of iclepertin.