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The auditory steady state response (ASSR) arises when periodic sounds evoke stable responses in auditory networks that reflect the acoustic characteristics of the stimuli, such as the amplitude of the sound envelope. Larger for some stimulus rates than others, the ASSR in the human electroencephalogram (EEG) is notably maximal for sounds modulated in amplitude at 40 Hz. To investigate the local circuit underpinnings of the large ASSR to 40 Hz amplitude-modulated (AM) sounds, we acquired skull EEG and local field potential (LFP) recordings from primary auditory cortex (A1) in the rat during the presentation of 20, 30, 40, 50, and 80 Hz AM tones. 40 Hz AM tones elicited the largest ASSR from the EEG acquired above auditory cortex and the LFP acquired from each cortical layer in A1. The large ASSR in the EEG to 40 Hz AM tones was not due to larger instantaneous amplitude of the signals or to greater phase alignment of the LFP across the cortical layers. Instead, it resulted from decreased latency variability (or enhanced temporal consistency) of the 40 Hz response. Statistical models indicate the EEG signal was best predicted by LFPs in either the most superficial or deep cortical layers, suggesting deep layer coordinators of the ASSR. Overall, our results indicate that the recruitment of non-uniform but more temporally consistent responses across A1 layers underlie the larger ASSR to amplitude-modulated tones at 40 Hz.

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.

Melody is a core component of music in which discrete pitches are serially arranged to convey emotion and meaning. Perception varies along several pitch-based dimensions: (i) the absolute pitch of notes, (ii) the difference in pitch between successive notes, and (iii) the statistical expectation of each note given prior context. How the brain represents these dimensions and whether their encoding is specialized for music remains unknown. We recorded high-density neurophysiological activity directly from the human auditory cortex while participants listened to Western musical phrases. Pitch, pitch-change, and expectation were selectively encoded at different cortical sites, indicating a spatial map for representing distinct melodic dimensions. The same participants listened to spoken English, and we compared responses to music and speech. Cortical sites selective for music encoded expectation, while sites that encoded pitch and pitch-change in music used the same neural code to represent equivalent properties of speech. Findings reveal how the perception of melody recruits both music-specific and general-purpose sound representations.

Understanding the neural basis of speech perception requires that we study the human brain both at the scale of the fundamental computational unit of neurons and in their organization across the depth of cortex. Here we used high-density Neuropixels arrays1-3 to record from 685 neurons across cortical layers at nine sites in a high-level auditory region that is critical for speech, the superior temporal gyrus4,5, while participants listened to spoken sentences. Single neurons encoded a wide range of speech sound cues, including features of consonants and vowels, relative vocal pitch, onsets, amplitude envelope and sequence statistics. Neurons at each cross-laminar recording exhibited dominant tuning to a primary speech feature while also containing a substantial proportion of neurons that encoded other features contributing to heterogeneous selectivity. Spatially, neurons at similar cortical depths tended to encode similar speech features. Activity across all cortical layers was predictive of high-frequency field potentials (electrocorticography), providing a neuronal origin for macroelectrode recordings from the cortical surface. Together, these results establish single-neuron tuning across the cortical laminae as an important dimension of speech encoding in human superior temporal gyrus.

Tau rhythms are largely defined by sound responsive alpha band (~8-13 Hz) oscillations generated largely within auditory areas of the superior temporal gyri. Studies of tau have mostly employed magnetoencephalography or intracranial recording because of taus elusiveness in the electroencephalogram. Here, we demonstrate that independent component analysis (ICA) decomposition can be an effective way to identify tau sources and study tau source activities in EEG recordings. Subjects (N = 18) were passively exposed to complex acoustic stimuli while the EEG was recorded from 68 electrodes across the scalp. Subjects data were split into 60 parallel processing pipelines entailing use of five levels of high-pass filtering (passbands of 0.1, 0.5, 1, 2, and 4 Hz), three levels of low-pass filtering (25, 50, and 100 Hz), and four different ICA algorithms (fastICA, infomax, adaptive mixture ICA [AMICA], and multi-model AMICA [mAMICA]). Tau-related independent component (IC) processes were identified from this data as being localized near the superior temporal gyri with a spectral peak in the 8-13 Hz alpha band. These tau ICs showed alpha suppression during sound presentations that was not seen for other commonly observed IC clusters with spectral peaks in the alpha range (e.g., those associated with somatomotor mu, and parietal or occipital alpha). The choice of analysis parameters impacted the likelihood of obtaining tau ICs from an ICA decomposition. Lower cutoff frequencies for high-pass filtering resulted in significantly fewer subjects showing a tau IC than more aggressive high-pass filtering. Decomposition using the fastICA algorithm performed the poorest in this regard, while mAMICA performed best. The best combination of filters and ICA model choice was able to identify at least one tau IC in the data of ~94% of the sample. Altogether, the data reveal close similarities between tau EEG IC dynamics and tau dynamics observed in MEG and intracranial data. Use of relatively aggressive high-pass filters and mAMICA decomposition should allow researchers to identify and characterize tau rhythms in a majority of their subjects. We believe adopting the ICA decomposition approach to EEG analysis can increase the rate and range of discoveries related to auditory responsive tau rhythms.

The brain produces diverse functions, from perceiving sounds to producing arm reaches, through the collective activity of populations of many neurons. Determining if and how the features of these exogenous variables (e.g., sound frequency, reach angle) are reflected in population neural activity is important for understanding how the brain operates. Often, high-dimensional neural population activity is confined to low-dimensional latent spaces. However, many current methods fail to extract latent spaces that are clearly structured by exogenous variables. This has contributed to a debate about whether or not brains should be thought of as dynamical systems or representational systems. Here, we developed a new latent process Bayesian regression framework, the orthogonal stochastic linear mixing model (OSLMM) which introduces an orthogonality constraint amongst time-varying mixture coefficients, and provide Markov chain Monte Carlo inference procedures. We demonstrate superior performance of OSLMM on latent trajectory recovery in synthetic experiments and show superior computational efficiency and prediction performance on several real-world benchmark data sets. We primarily focus on demonstrating the utility of OSLMM in two neural data sets: μECoG recordings from rat auditory cortex during presentation of pure tones and multi-single unit recordings form monkey motor cortex during complex arm reaching. We show that OSLMM achieves superior or comparable predictive accuracy of neural data and decoding of external variables (e.g., reach velocity). Most importantly, in both experimental contexts, we demonstrate that OSLMM latent trajectories directly reflect features of the sounds and reaches, demonstrating that neural dynamics are structured by neural representations. Together, these results demonstrate that OSLMM will be useful for the analysis of diverse, large-scale biological time-series datasets.

• Auditory and frontal cortex responses were recorded after hearing loss. • Mice show recovery of evoked responses and temporal processing in the absence of ABR. • Temporal processing recovery is cortical region-specific after hearing loss. • Poor recovery in frontal cortex may link hearing loss and cognitive decline. Noise-induced hearing loss (NIHL) studies have focused on the lemniscal auditory pathway, but little is known about how NIHL impacts different cortical regions. Here we compared response recovery trajectories in the auditory and frontal cortices (AC, FC) of mice following NIHL. We recorded EEG responses from awake mice (male n = 15, female n = 14) before and following NIHL (longitudinal design) to quantify event related potentials and gap-in-noise temporal processing. Hearing loss was verified by measuring the auditory brainstem response (ABR) before and at 1-, 10-, 23–, and 45-days after noise-exposure. Resting EEG, event related potentials (ERP) and auditory steady state responses (ASSR) were recorded at the same time-points after NIHL. The inter-trial phase coherence (ITPC) of the ASSR was measured to quantify the ability of AC and FC to synchronize responses to short gaps embedded in noise. Despite the absence of click-evoked ABRs up to 90 dB SPL and up to 45-days post-exposure, ERPs from the AC and FC showed full recovery in ∼ 50 % of the mice to pre-NIHL levels in both AC and FC. The ASSR ITPC was reduced following NIHL in AC and FC in all the mice on day 1 after NIHL. The AC showed full recovery of ITPC over 45-days. Despite ERP amplitude recovery, the FC does not show recovery of ASSR ITPC. These results indicate post-NIHL plasticity with similar response amplitude recovery across AC and FC, but cortical region-specific trajectories in temporal processing recovery. [ABSTRACT FROM AUTHOR]

The cerebral cortex comprises many distinct regions that differ in structure, function, and patterns of connectivity. Current approaches to parcellating these regions often take advantage of functional neuroimaging approaches that can identify regions involved in a particular process with reasonable spatial resolution. However, neuroanatomical biomarkers are also very useful in identifying distinct cortical regions either in addition to, or in place of functional measures. For example, differences in myelin density are thought to relate to functional differences between regions, are sensitive to individual patterns of experience, and have been shown to vary across functional hierarchies in a predictable manner. Accordingly, the current study provides quantitative stereological estimates of myelin density for each of the 13 regions that make up the feline auditory cortex. We demonstrate that significant differences can be observed between auditory cortical regions, with the highest myelin density observed in the regions that comprise the auditory core (i.e., the primary auditory cortex and anterior auditory field). Moreover, our myeloarchitectonic map suggests that myelin density varies in a hierarchical fashion that conforms to the traditional model of spatial organization in auditory cortex. Taken together, these results establish myelin as a useful biomarker for parcellating auditory cortical regions, and provide detailed estimates against which other, less invasive methods of quantifying cortical myelination may be compared. [ABSTRACT FROM AUTHOR]

Research suggests a potential of gamma oscillation entrainment for enhancing memory in Alzheimer's disease and healthy subjects. Gamma entrainment can be accomplished with oscillatory electrical, but also sensory stimulation. However, comparative studies between sensory stimulation and transcranial alternating current stimulation (tACS) effects on memory processes are lacking. This study examined the effects of rhythmic gamma auditory stimulation (rAS) and temporal gamma‐tACS on verbal long‐term memory (LTM) and working memory (WM) in 74 healthy individuals. Participants were assigned to two groups according to the stimulation techniques (rAS or tACS). Memory was assessed in three experimental blocks, in which each participant was administered with control, 40, and 60 Hz stimulation in counterbalanced order. All interventions were well‐tolerated, and participants reported mostly comparable side effects between real stimulation (40 and 60 Hz) and the control condition. LTM immediate and delayed recall remained unaffected by stimulations, while immediate recall intrusions decreased during 60 Hz stimulation. Notably, 40 Hz interventions improved WM compared to control stimulations. These results highlight the potential of 60 and 40 Hz temporal cortex stimulation for reducing immediate LTM recall intrusions and improving WM performance, respectively, probably due to the entrainment of specific gamma oscillations in the auditory cortex. The results also shed light on the comparative effects of these neuromodulation tools on memory functions, and their potential applications for cognitive enhancement and in clinical trials. We compared the effects of a single session online gamma‐rhythmic auditory stimulation (rAS) and temporal gamma‐transcranial alternating current stimulation (tACS) on memory processes in healthy individuals. Findings reveal that 40 Hz stimulation enhances verbal working memory (i.e., digit span backward score), while 60 Hz stimulation reduces immediate recall intrusions rate during a declarative long‐term memory task. These frequency‐specific effects suggest a potential role for auditory cortex activity in immediate cognitive demands, shedding light on the mechanisms of gamma frequency neuromodulation. [ABSTRACT FROM AUTHOR]

• Induction of a cortical inflammatory lesion affects the excitability of ipsilateral thalamic neurons in the EAE model of MS. • K v 7.3 channels regulate the firing pattern of thalamic neurons and are crucial for auditory-stimulus discrimination. • RTG treatment rescues inflammation-induced hyperexcitability of vMGN neurons and preserves auditory information processing. Multiple Sclerosis (MS) is an autoimmune neurodegenerative disease, whose primary hallmark is the occurrence of inflammatory lesions in white and grey matter structures. Increasing evidence in MS patients and respective murine models reported an impaired ionic homeostasis driven by inflammatory-demyelination, thereby profoundly affecting signal propagation. However, the impact of a focal inflammatory lesion on single-cell and network functionality has hitherto not been fully elucidated. In this study, we sought to determine the consequences of a localized cortical inflammatory lesion on the excitability and firing pattern of thalamic neurons in the auditory system. Moreover, we tested the neuroprotective effect of Retigabine (RTG), a specific K v 7 channel opener, on disease outcome. To resemble the human disease, we focally administered pro-inflammatory cytokines, TNF-α and IFN-γ, in the primary auditory cortex (A1) of MOG 35-55 immunized mice. Thereafter, we investigated the impact of the induced inflammatory milieu on afferent thalamocortical (TC) neurons, by performing ex vivo recordings. Moreover, we explored the effect of K v 7 channel modulation with RTG on auditory information processing, using in vivo electrophysiological approaches. Our results revealed that a cortical inflammatory lesion profoundly affected the excitability and firing pattern of neighboring TC neurons. Noteworthy, RTG restored control-like values and TC tonotopic mapping. Our results suggest that RTG treatment might robustly mitigate inflammation-induced altered excitability and preserve ascending information processing. [ABSTRACT FROM AUTHOR]

Harmonics are an integral part of music, speech, and vocalizations of animals. Since the rest of the auditory environment is primarily made up of nonharmonic sounds, the auditory system needs to perceptually separate the above two kinds of sounds. In mice, harmonics, generally with two-tone components (two-tone harmonic complexes, TTHCs), form an important component of vocal communication. Communication by pups during isolation from the mother and by adult males during courtship elicits typical behaviors in female mice—dams and adult courting females, respectively. Our study shows that the processing of TTHC is specialized in mice providing neural basis for perceptual differences between tones and TTHCs and also nonharmonic sounds. Investigation of responses in the primary auditory cortex (Au1) from in vivo extracellular recordings and two-photon Ca2+ imaging of excitatory and inhibitory neurons to TTHCs exhibit enhancement, suppression, or no-effect with respect to tones. Irrespective of neuron type, harmonic enhancement is maximized, and suppression is minimized when the fundamental frequencies (F0 ) match the neuron’s best fundamental frequency (BF0 ). Sex-specific processing of TTHC is evident from differences in the distributions of neurons’ best frequency (BF) and best fundamental frequency (BF0) in single units, differences in harmonic suppressed cases re-BF0, independent of neuron types, and from pairwise noise correlations among excitatory and parvalbumin inhibitory interneurons. Furthermore, TTHCs elicit a higher response compared with two-tone nonharmonics in females, but not in males. Thus, our study shows specialized neural processing of TTHCs over tones and nonharmonics, highlighting local network specialization among different neuronal types. [ABSTRACT FROM AUTHOR]

The integration of visual letters and speech sounds is a crucial part of learning to read. Previous studies investigating this integration have revealed a modulation by audiovisual (AV) congruency, commonly known as the congruency effect. To investigate the cortical oscillations of the congruency effects across different oscillatory frequency bands, we conducted a Japanese priming task in which a visual letter was followed by a speech sound. We analyzed the power and phase properties of oscillatory activities in the theta and beta bands between congruent and incongruent letter‐speech sound (L‐SS) pairs. Our results revealed stronger theta‐band (5–7 Hz) power in the congruent condition and cross‐modal phase resetting within the auditory cortex, accompanied by enhanced inter‐trial phase coherence (ITPC) in the auditory‐related areas in response to the congruent condition. The observed congruency effect of theta‐band power may reflect increased neural activities in the left auditory region during L‐SS integration. Additionally, theta ITPC findings suggest that visual letters amplify neuronal responses to the following corresponding auditory stimulus, which may reflect the differential cross‐modal influences in the primary auditory cortex. In contrast, decreased beta‐band (20–35 Hz) oscillatory power was observed in the right centroparietal regions for the congruent condition. The reduced beta power seems to be unrelated to the processing of AV integration, but may be interpreted as the brain response to predicting auditory sounds during language processing. Our data provide valuable insights by indicating that oscillations in different frequency bands contribute to the disparate aspects of L‐SS integration. [ABSTRACT FROM AUTHOR]

Perceptual segregation of complex sounds such as speech and music simultaneously emanating from multiple sources is a remarkable ability that is common in humans and other animals alike. Unlike animal physiological experiments with simplified sounds or human investigations with spatially broad imaging techniques, this study combines insights from animal single-unit recordings with segregation of speech-like sound mixtures. Ferrets are trained to attend to a female voice and detect a target word, both in presence and absence of a concurrent equally salient male voice. Recordings are made in primary and secondary auditory cortical fields, and in frontal cortex. During task performance, representation of the female words becomes enhanced relative to the male in all, but especially in higher cortical regions. Analysis of the temporal and spectral response characteristics during task performance reveals how speech segregation gradually emerges in the auditory cortex. A computational model evaluated on the same voice mixtures replicates and extends these results to different attentional targets (attention to female or male voices). These findings underscore the role of the principle of temporal coherence whereby attention to a target voice binds together all neural responses coherently modulated with the target, thus ultimately forming and extracting a common auditory stream. Ferrets learned to attend and react to words of a female voice embedded in a speech mixture with a male. Recordings in auditory cortex reveal rapidly enhanced responses to the attended female voice and a simultaneous suppression of the male distractor. [ABSTRACT FROM AUTHOR]

The mammalian cerebral cortex is composed of a rich diversity of cell types. Sensory cortical cells are organized into networks that rely on their functional diversity to ultimately carry out a variety of sophisticated cognitive functions for perception, learning, and memory. The auditory cortex (AC) has been most extensively studied for its experience-dependent effects, including for perceptual learning and associative memory. Here, we used single-nucleus RNA sequencing (snRNA-seq) in the AC of the adult rat to investigate the breadth of transcriptionally diverse cell types that likely support the role of AC in experience-dependent functions. A variety of unique excitatory and inhibitory neuron subtypes were identified that harbor unique transcriptional profiles of genes with putative relevance for the adaptive neuroplasticity of cortical microcircuits. In addition, we report for the first time a diversity of astrocytes in AC that may represent functionally unique subtypes, including those that could integrate experience-dependent adult neuroplasticity at cortical synapses. Together, these results pave the way for building models of how cortical neurons work in concert with astrocytes to fulfill dynamic and experience-dependent cognitive functions. [ABSTRACT FROM AUTHOR]

Humans perceive continuous speech signals as discrete sequences. To clarify the temporal segmentation window of speech information processing in the human auditory cortex, the relationship between speech perception and cortical responses was investigated using auditory evoked magnetic fields (AEFs). AEFs were measured while participants heard synthetic Japanese words /atataka/. There were eight types of /atataka/ with different speech rates. The durations of the words ranged from 75 to 600 ms. The results revealed a clear correlation between the AEFs and syllables. Specifically, when the durations of the words were between 375 and 600 ms, the evoked responses exhibited four clear responses from the superior temporal area, M100, that corresponded not only to the onset of speech but also to each group of consonant/vowel syllable units. The number of evoked M100 responses was correlated to the duration of the stimulus as well as the number of perceived syllables. The approximate range of the temporal segmentation window limit of speech perception was considered to be between 75 and 94 ms. This finding may contribute to optimizing the temporal performance of high-speed synthesized speech generation systems. [ABSTRACT FROM AUTHOR]

Most scientists agree that subjective tinnitus is the pathological result of an interaction of damage to the peripheral auditory system and central neuroplastic adaptations. Here we investigate such tinnitus related adaptations in the primary auditory cortex (AC) 7 and 13 days after noise trauma induction of tinnitus by quantifying the density of the extracellular matrix (ECM) in the AC of Mongolian gerbils (Meriones unguiculatus). The ECM density has been shown to be relevant for neuroplastic processes and synaptic stability within the cortex. We utilized a mild monaural acoustic noise trauma in overall 22 gerbils to induce tinnitus and a sham exposure in 16 control (C) animals. Tinnitus was assessed by a behavioral response paradigm. Animals were separated for a presence (T) or absence (NT) of a tinnitus percept by a behavioral task. The ECM density 7 and 13 days after trauma was quantified using immunofluorescence luminance of Wisteria floribunda lectin-fluoresceine-5-isothiocyanate (WFA-FITC) on histological slices of the primary AC, relative to the non-auditory brainstem as a reference area. At both timepoints, we found that the WFA-FITC luminance of the AC of NT animals was not significantly different from that of C animals. However, we found a significant increase of luminance in T animals' ACs compared to NT or C animals' cortices. This effect was found exclusively on the AC side contralateral to the trauma ear. These results point to a hemisphere specific process of stabilization of synaptic connections in primary AC, which may be involved in the chronic manifestation of tinnitus. [ABSTRACT FROM AUTHOR]

Offset responses are traditionally viewed as indicators of sound cessation. Here, we investigate offset responses to auditory click trains, examining how they are modulated by inter-click intervals (ICIs) and train duration. Using extracellular recordings and electrocorticography (ECoG) in non-human primates, alongside electroencephalography (EEG) in humans, we show that offset responses are significantly influenced by both ICI and train length, thereby establishing them as markers of temporal integration. We introduce the concept of the 'Neuronal Integrative Window' (NIW), defined as the temporal span during which neurons integrate stimuli to produce or modulate the temporal integration signal. Our data reveal that on the neuronal level, the auditory cortex (AC) exhibits a more expansive NIW than the medial geniculate body (MGB), integrating stimuli over longer durations and showing a preference for larger ICIs. Furthermore, our results indicate that offset responses could serve as potential biomarkers for neurological and psychiatric conditions, highlighted by their sensitivity to pharmacological modulation with ketamine. This study advances our understanding of auditory temporal processing and proposes a novel approach for assessing and monitoring brain health. Offset responses to auditory click trains reveal temporal integration in the auditory cortex, introducing the 'Neuronal Integrative Window' concept and suggesting offset responses as potential biomarkers for assessing and monitoring brain health. [ABSTRACT FROM AUTHOR]

Tinnitus has been identified as a potential contributor to anxiety. Thalamo-cortical pathway plays a crucial role in the transmission of auditory and emotional information, but its casual link to tinnitus-associated anxiety remains unclear. In this study, we explore the neural activities in the thalamus and cortex of the sodium salicylate (NaSal)-treated mice, which exhibit both hyperacusis and anxiety-like behaviors. We find an increase in gamma band oscillations (GBO) in both auditory cortex (AC) and prefrontal cortex (PFC), as well as phase-locking between cortical GBO and thalamic neural activity. These changes are attributable to a suppression of GABAergic neuron activity in thalamic reticular nucleus (TRN), and optogenetic activation of TRN reduces NaSal-induced hyperacusis and anxiety-like behaviors. The elevation of endocannabinoid (eCB)/ cannabinoid receptor 1 (CB1R) transmission in TRN contributes to the NaSal-induced abnormalities. Our results highlight the regulative role of TRN in the auditory and limbic thalamic-cortical pathways. Sodium salicylate enhances endocannabinoid signaling, reducing GABAergic activity in the thalamic reticular nucleus. This increases gamma oscillations in the auditory cortex and prefrontal cortex, causing hyperacusis and anxiety-like behaviors. [ABSTRACT FROM AUTHOR]

Neural activity cannot be directly observed using fMRI; rather it must be inferred from the hemodynamic responses that neural activity causes. Solving this inverse problem is made possible through the use of forward models, which generate predicted hemodynamic responses given hypothesised underlying neural activity. Commonly‐used hemodynamic models were developed to explain data from healthy young participants; however, studies of ageing and dementia are increasingly shifting the focus toward elderly populations. We evaluated the validity of a range of hemodynamic models across the healthy adult lifespan: from basis sets for the linear convolution models commonly used to analyse fMRI studies, to more advanced models including nonlinear fitting of a parameterised hemodynamic response function (HRF) and nonlinear fitting of a biophysical generative model (hemodynamic modelling, HDM). Using an exceptionally large sample of participants, and a sensorimotor task optimized for detecting the shape of the BOLD response to brief stimulation, we first characterised the effects of age on descriptive features of the response (e.g., peak amplitude and latency). We then compared these to features from more complex nonlinear models, fit to four regions of interest engaged by the task, namely left auditory cortex, bilateral visual cortex, left (contralateral) motor cortex and right (ipsilateral) motor cortex. Finally, we validated the extent to which parameter estimates from these models have predictive validity, in terms of how well they predict age in cross‐validated multiple regression. We conclude that age‐related differences in the BOLD response can be captured effectively by models with three free parameters. Furthermore, we show that biophysical models like the HDM have predictive validity comparable to more common models, while additionally providing insights into underlying mechanisms, which go beyond descriptive features like peak amplitude or latency, and include estimation of nonlinear effects. Here, the HDM revealed that most of the effects of age on the BOLD response could be explained by an increased rate of vasoactive signal decay and decreased transit rate of blood, rather than changes in neural activity per se. However, in the absence of other types of neural/hemodynamic data, unique interpretation of HDM parameters is difficult from fMRI data alone, and some brain regions in some tasks (e.g., ipsilateral motor cortex) can show responses that are more difficult to capture using current models. [ABSTRACT FROM AUTHOR]

Age‐related hearing impairment (ARHI) is commonly associated with decreased auditory temporal resolution caused by auditory neurodegeneration. Age‐related deterioration in gap detection ability, resulting in poor temporal auditory processing, is often attributed to pathophysiological changes in both the peripheral and central auditory systems. This study aimed to investigate whether the gap detection ability declines in the early stages of ageing and to determine its usefulness in detecting peripheral and central auditory degeneration. The study used 1‐month‐old (1 M), 6‐month‐old (6 M) and 12‐month‐old (12 M) mice to examine changes in gap detection ability and associated auditory pathophysiology. Although hearing thresholds did not significantly differ between the groups, the amplitude of auditory brainstem response (ABR) wave I decreased significantly in an age‐dependent manner, consistent with age‐related cochlear synaptopathy. The relative ABR amplitude ratio of waves 2 and 5 to wave 1 was significantly increased in 12 M mice, indicating that the central auditory system had increased in relative neuroactivity. A significant increase in gap detection thresholds was observed in 12 M mice compared to 1 M mice. Although cochlear synaptopathy and central hyperactivity were positively correlated with gap detection thresholds, central hyperactivity strongly influenced gap detection ability. In the cochlear nucleus and auditory cortex, the inhibitory synaptic expression of GAD65 and the expression of parvalbumin were significantly decreased in 12 M mice, consistent with central hyperactivity. Evaluating gap detection performance may allow the identification of decreased auditory temporal resolution in the early stages of ARHI, which is strongly associated with auditory neurodegeneration. [ABSTRACT FROM AUTHOR]

Thousands of species use vocal signals to communicate with one another. Vocalizations carry rich information, yet characterizing and analyzing these complex, high-dimensional signals is difficult and prone to human bias. Moreover, animal vocalizations are ethologically relevant stimuli whose representation by auditory neurons is an important subject of research in sensory neuroscience. A method that can efficiently generate naturalistic vocalization waveforms would offer an unlimited supply of stimuli with which to probe neuronal computations. Although unsupervised learning methods allow for the projection of vocalizations into low-dimensional latent spaces learned from the waveforms themselves, and generative modeling allows for the synthesis of novel vocalizations for use in downstream tasks, we are not aware of any model that combines these tasks to synthesize naturalistic vocalizations in the waveform domain for stimulus playback. In this paper, we demonstrate BiWaveGAN: a bidirectional generative adversarial network (GAN) capable of learning a latent representation of ultrasonic vocalizations (USVs) from mice. We show that BiWaveGAN can be used to generate, and interpolate between, realistic vocalization waveforms. We then use these synthesized stimuli along with natural USVs to probe the sensory input space of mouse auditory cortical neurons. We show that stimuli generated from our method evoke neuronal responses as effectively as real vocalizations, and produce receptive fields with the same predictive power. BiWaveGAN is not restricted to mouse USVs but can be used to synthesize naturalistic vocalizations of any animal species and interpolate between vocalizations of the same or different species, which could be useful for probing categorical boundaries in representations of ethologically relevant auditory signals. NEW & NOTEWORTHY: A new type of artificial neural network is presented that can be used to generate animal vocalization waveforms and interpolate between them to create new vocalizations. We find that our synthetic naturalistic stimuli drive auditory cortical neurons in the mouse equally well and produce receptive field features with the same predictive power as those obtained with natural mouse vocalizations, confirming the quality of the stimuli produced by the neural network. [ABSTRACT FROM AUTHOR]

Introduction The use of functional near-infrared light spectroscopy (fNIRS) may be applied to study cortical responses in children and could offer insight into auditory and speech perception during the early stages of life. Some literature suggests that babies are already able to identify familiar voices at birth, and fNIRS is a non-invasive technique that can be used to study this population. Objective To characterize the cortical responses of infants during their first trimester of life to infant-directed speech using near-infrared light spectroscopy and to verify whether there is a difference in responses when infant-directed speech is performed by their mother compared with an unknown person. Methods Twenty-three children between 0 and 3 months, healthy, without risk indicators for hearing loss, and with results considered normal in the audiological evaluation were tested with near-infrared spectroscopy using infant-directed speech as an auditory stimulus produced by their own mother and by an unknown source. Results Bilateral cortical activation was observed. The responses were present in the temporal, frontal, and parietal regions. Regarding the familiarity aspect, no significant difference was observed for the mother's voice compared with an unknown voice. Conclusion Infant-directed speech has prosodic characteristics capable of activating several cortical regions in the infant's first trimester of life, especially the temporal region. The familiarity effect needs to be better defined for this type of stimulus during this period. [ABSTRACT FROM AUTHOR]

Introduction Mismatch negativity (MMN) represents a negative component of event-related potentials, which is mentioned by guidelines as an important tool to provide measurable data regarding the functionality of the auditory system in acoustic processing. However, the literature still lacks reliable data that can support the clinical use of this potential in the complementary diagnosis of central auditory processing (CAP) disorder (CAPD). Objectives To analyze whether MMN assessment might be associated with the CAP behavioral test battery, as well as to assess the effects of auditory ability deficits on MMN responses in the pediatric population. Methods In total, 45 age-matched children participated in the study. They were submitted to the CAP behavior assessment and to MMN. The children were tested with a combination of speech contrast consisting of acoustic syllables [da] versus [ta], governed by the oddball paradigm. Results Mismatch negativity did not show a direct association with a single test but with the combination of the four tests used as a behavioral test battery to identify CAPD. The results also indicated that the auditory ability deficits influenced the measurement of MMN latency (p = 0.003*), but not the amplitude (p = 0.857) or the area (p = 0.577). Conclusion Mismatch negativity was shown to be statistically associated with the battery of tests used to identify deficits in auditory abilities in the studied sample rather than with a single behavioral test. The deficits in auditory abilities were observed in the MMN latency. Mismatch negativity can be used to assess children with CAPD. [ABSTRACT FROM AUTHOR]

Stimulus-specific adaptation is a hallmark of sensory processing in which a repeated stimulus results in diminished successive neuronal responses, but a deviant stimulus will still elicit robust responses from the same neurons. Recent work has established that synaptically released zinc is an endogenous mechanism that shapes neuronal responses to sounds in the auditory cortex. Here, to understand the contributions of synaptic zinc to deviance detection of specific neurons, we performed wide-field and 2-photon calcium imaging of multiple classes of cortical neurons. We find that intratelencephalic (IT) neurons in both layers 2/3 and 5 as well as corticocollicular neurons in layer 5 all demonstrate deviance detection; however, we find a specific enhancement of deviance detection in corticocollicular neurons that arises from ZnT3-dependent synaptic zinc in layer 2/3 IT neurons. Genetic deletion of ZnT3 from layer 2/3 IT neurons removes the enhancing effects of synaptic zinc on corticocollicular neuron deviance detection and results in poorer acuity of detecting deviant sounds by behaving mice. [ABSTRACT FROM AUTHOR]

Distinguishing reality from hallucinations requires efficient monitoring of agency. It has been hypothesized that a copy of motor signals, termed efference copy (EC) or corollary discharge (CD), suppresses sensory responses to yield a sense of agency; impairment of the inhibitory function leads to hallucinations. However, how can the sole absence of inhibition yield positive symptoms of hallucinations? We hypothesize that selective impairments in functionally distinct signals of CD and EC during motor-to-sensory transformation cause the positive symptoms of hallucinations. In an electroencephalography (EEG) experiment with a delayed articulation paradigm in schizophrenic patients with (AVHs) and without auditory verbal hallucinations (non-AVHs), we found that preparing to speak without knowing the contents (general preparation) did not suppress auditory responses in both patient groups, suggesting the absent of inhibitory function of CD. Whereas, preparing to speak a syllable (specific preparation) enhanced the auditory responses to the prepared syllable in non-AVHs, whereas AVHs showed enhancement in responses to unprepared syllables, opposite to the observations in the normal population, suggesting that the enhancement function of EC is not precise in AVHs. A computational model with a virtual lesion of an inhibitory inter-neuron and disproportional sensitization of auditory cortices fitted the empirical data and further quantified the distinct impairments in motor-to-sensory transformation in AVHs. These results suggest that "broken" CD plus "noisy" EC causes erroneous monitoring of the imprecise generation of internal auditory representation and yields auditory hallucinations. Specific impairments in functional granularity of motor-to-sensory transformation mediate positivity symptoms of agency abnormality in mental disorders. Can the absence of inhibition lead to auditory hallucinations? This study shows that the impairment of motor-based sensory predictions causes erroneous monitoring of imprecise internal auditory representations, thus causing auditory hallucinations. [ABSTRACT FROM AUTHOR]

• Nonlinear maturation of auditory cortex function and structure during infancy and toddlerhood. • Increased myelination in auditory radiations contributes to decreases in auditory evoked response latencies during infancy. • Associations between white-matter structure and speed of auditory response can be observed at the level of individual child. In school-age children, the myelination of the auditory radiation thalamocortical pathway is associated with the latency of auditory evoked responses, with the myelination of thalamocortical axons facilitating the rapid propagation of acoustic information. Little is known regarding this auditory system function-structure association in infants and toddlers. The present study tested the hypothesis that maturation of auditory radiation white-matter microstructure (e.g., fractional anisotropy (FA); measured using diffusion-weighted MRI) is associated with the latency of the infant auditory response (the P2m response, measured using magnetoencephalography, MEG) in a cross-sectional (N = 47, 2 to 24 months, 19 females) as well as longitudinal cohort (N = 18, 2 to 29 months, 8 females) of typically developing infants and toddlers. Of 18 longitudinal infants, 2 infants had data from 3 timepoints and 16 infants had data from 2 timepoints. In the cross-sectional sample, non-linear maturation of P2m latency and auditory radiation diffusion measures were observed. Auditory radiation diffusion accounted for significant variance in P2m latency, even after removing the variance associated with age in both P2m latency and auditory radiation diffusion measures. In the longitudinal sample, latency and FA associations could be observed at the level of a single child. Findings provide strong support for the hypothesis that an increase in thalamocortical neural conduction velocity, due to increased axon diameter and/or myelin maturation, contributes to a decrease in the infant P2m auditory evoked response latency. Infant multimodal brain imaging identifies brain mechanisms contributing to the rapid changes in neural circuit activity during the first two years of life. [ABSTRACT FROM AUTHOR]

[Display omitted] • Suppression of N1 event-related potential during speech was significantly reduced in schizophrenia patients. • Bipolar disorder patients exhibited intermediate sensory attenuation between the schizophrenia and control group. • The extent of N1 suppression inversely correlated with the severity of Anomalous Self-Experiences in schizophrenia, but not in bipolar disorder. The Corollary Discharge (CD) mechanism inhibits self-generated speech sound perception, appearing disrupted in schizophrenia and potentially contributing to Anomalous Self-Experiences (ASEs). However, it remains unclear if this alteration and its correlation with ASEs extend to other psychotic disorders. Electroencephalography was used to study the N1 Event-Related Potential (ERP) as an index of CD-mediated suppression in the auditory cortex across thirty-five participants with schizophrenia, twenty-six with bipolar disorder, and thirty healthy controls. Auditory N1 was elicited by two conditions: real-time listening to self-pronounced vowels while speaking through connected microphone and earphones (listen/talk −or talk condition in previous literature-) and passive listening to the same previously recorded self-uttered vowels (listen/no talk −or listen condition-). N1 ERP amplitude was lower in the listen/talk condition compared to listen/no talk across all groups. However, N1 suppression was significantly reduced in schizophrenia, with bipolar patients showing intermediate attenuation between both groups (i.e., non-significantly different from controls). Furthermore, N1 suppression inversely correlated with ASEs severity only in schizophrenia. Dysfunction of the CD mechanism may be a defining feature of schizophrenia, where it is connected to ASEs. These results corroborate previous findings linking auditory N1 ERP suppression with disrupted CD mechanism in schizophrenia, but not in bipolar disorder. [ABSTRACT FROM AUTHOR]

In the auditory cortex, synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), plays crucial roles in information processing and adaptation to the auditory environment. Previous rodent studies have shown lifelong cortical map plasticity, even beyond the critical period of development. While thalamocortical synapses exhibit LTD during the critical period, little is known about LTD in the cortico-cortical connections of the adult mouse auditory cortex. Here, we investigated the transient response dynamics of LTD in layers 2-5 of the mouse auditory cortex following tetanic stimulation (TS) to layer 4. To characterize LTD properties, we developed a recording protocol to monitor activity levels at multiple sites, including those more than 0.45 mm from the TS site. This allowed us to distinguish LTD-induced reductions in neural excitability from other types, including neural activity depletion. Our findings revealed that LTD induced in layer 4 persisted for over 40-min post-TS, indicating robust cortico-cortical LTD. Using electrophysiological data and a modified synaptic model, we identified key receptors involved in synaptic plasticity and their effects on response dynamics, proposing a method for studying LTD in the mature mouse auditory cortex. Particularly, by employing a simple dynamical model, we analyzed and discussed the involvement of key receptors during the transient period of LTD. This study expands our understanding of synaptic plasticity in the mature mouse auditory cortex beyond the critical period, potentially informing future treatments for hearing disorders. [ABSTRACT FROM AUTHOR]

Background: Cochlear implants made a great impact in the management of severe-to-profound hearing loss in both children and adults. Its greatest impact is in helping children born with a profound hearing loss and implanted early to attend mainstream education and using spoken language to communicate. However, the final outcome in pediatric implantation is not predictable as there are large number of factors which will affect the outcome of cochlear implantation. Studying these determinants increases the ability of clinicians to offer educated preoperative prognosis and might potentially allow for manipulation of variables in an attempt to achieve the best possible outcome. Objective: The aim of this study was to assess the preoperative factors affecting the audiological, speech, and language outcomes achieved by the recipients of cochlear implants. Methodology: A total of 39 children with severe-to-profound sensory neural hearing loss were implanted with cochlear implants. Children had received their implants before age of 5 years. Tests of receptive, expressive language quotient, aided cortical auditory-evoked potential using speech stimulus, aided free field audiometry, and aided speech reception thresholds were administered. Characteristics of the child and the family (age before implant and duration of implant use, cause of hearing loss, preimplant use of hearing aids and language therapy, and sociodemographic characteristics of their families) were the preoperative variables. These variables were considered predictors of audiological and language outcomes achieved by children and were determined using statistical analysis by univariate and multivariate analyses. Results: Age of the studied children at time of cochlear implantation was statistically significant predictor for CI outcome as regard receptive language quotient and also for N1 latency. Hearing age of the studied children was a statistically significant predictor for CI outcome as regards P1 latency. Conclusion: Based on our findings, two most important factors affecting outcome of cochlear implantation were the age at implantation and the hearing age. Other factors were important but did not affect the outcome significantly. [ABSTRACT FROM AUTHOR]

This study aimed to investigate integration of alternating speech, a stimulus which classically produces a V-shaped speech intelligibility function with minimum at 2–6 Hz in typical-hearing (TH) listeners. We further studied how degraded speech impacts intelligibility across alternating rates (2, 4, 8, and 32 Hz) using vocoded speech, either in the right ear or bilaterally, to simulate single-sided deafness with a cochlear implant (SSD-CI) and bilateral CIs (BiCI), respectively. To assess potential cortical signatures of across-ear integration, we recorded activity in the bilateral auditory cortices (AC) and dorsolateral prefrontal cortices (DLPFC) during the task using functional near-infrared spectroscopy (fNIRS). For speech intelligibility, the V-shaped function was reproduced only in the BiCI condition; TH (with ceiling scores) and SSD-CI conditions had significantly higher scores across all alternating rates compared to the BiCI condition. For fNIRS, the AC and DLPFC exhibited significantly different activity across alternating rates in the TH condition, with altered activity patterns in both regions in the SSD-CI and BiCI conditions. Our results suggest that degraded speech inputs in one or both ears impact across-ear integration and that different listening strategies were employed for speech integration manifested as differences in cortical activity across conditions. [ABSTRACT FROM AUTHOR]

Objective: Tinnitus may be associated with various brain changes. However, the degenerative changes in patients with tinnitus have not been extensively investigated. We aimed to evaluate degenerative, structural, and functional brain changes in patients with mild cognitive impairment (MCI) who also suffer from tinnitus. Materials and methods: This study included participants aged 60 to 80 years with MCI and a hearing level better than 40 dB. The participants were classified into two groups: MCI with tinnitus (MCI-T) and MCI without tinnitus (MCI-NT). All patients underwent Tinnitus Handicap Inventory (THI), 3 T brain MRI, F18-florapronol PET, and F18-FDG PET. Results: The MCI-T group exhibited higher ß-amyloid deposition in the superior temporal gyrus, temporal pole, and middle temporal gyrus compared to the MCI-NT group (p < 0.05 for all). Additionally, the MCI-T group showed increased metabolism in the inferior frontal gyrus, insula, and anterior cingulate cortex (ACC) (p < 0.005 for all). The THI score was strongly correlated with increased volume in the insula, ACC, superior frontal gyrus, supplementary motor area, white matter near the hippocampus, and precentral gyrus (p < 0.05 for all). Moreover, the MCI-T group demonstrated higher metabolic activity in the default mode network (DMN) and lower activity in the executive control network (ECN) (p < 0.05 for all). In the MCI-T group, the posterior DMN was positively correlated with the visual network and negatively with the ECN, whereas in the MCI-NT group, it correlated positively with the ECN. Conclusion: The MCI-T group exhibited greater ß-amyloid accumulation in the auditory cortex and more extensive changes across various brain networks compared with the MCI-NT group, potentially leading to diverse clinical symptoms such as dementia with semantic deficits or depression. Tinnitus in MCI patients may serve as a biomarker for degenerative changes in the temporal lobe and alterations in brain network dynamics. [ABSTRACT FROM AUTHOR]

Perceptual systems heavily rely on prior knowledge and predictions to make sense of the environment. Predictions can originate from multiple sources of information, including contextual short-term priors, based on isolated temporal situations, and context-independent long-term priors, arising from extended exposure to statistical regularities. While the effects of short-term predictions on auditory perception have been well-documented, how long-term predictions shape early auditory processing is poorly understood. To address this, we recorded magnetoencephalography data from native speakers of two languages with different word orders (Spanish: functor-initial vs Basque: functor-final) listening to simple sequences of binary sounds alternating in duration with occasional omissions. We hypothesized that, together with contextual transition probabilities, the auditory system uses the characteristic prosodic cues (duration) associated with the native language’s word order as an internal model to generate long-term predictions about incoming non-linguistic sounds. Consistent with our hypothesis, we found that the amplitude of the mismatch negativity elicited by sound omissions varied orthogonally depending on the speaker’s linguistic background and was most pronounced in the left auditory cortex. Importantly, listening to binary sounds alternating in pitch instead of duration did not yield group differences, confirming that the above results were driven by the hypothesized long-term ‘duration’ prior. These findings show that experience with a given language can shape a fundamental aspect of human perception – the neural processing of rhythmic sounds – and provides direct evidence for a long-term predictive coding system in the auditory cortex that uses auditory schemes learned over a lifetime to process incoming sound sequences. [ABSTRACT FROM AUTHOR]

Cinema, a modern titan of entertainment, holds power to move people with the artful manipulation of auditory and visual stimuli. Despite this, the mechanisms behind how sensory stimuli elicit emotional responses are unknown. Thus, this study evaluated which brain regions were involved when sensory stimuli evoke auditory- or visual-driven emotions during film viewing. Using functional magnetic resonance imaging (fMRI) decoding techniques, we found that brain activities in the auditory area and insula represent the stimuli that evoke emotional response. The observation of brain activities in these regions could provide further insights to these mechanisms for the improvement of film-making, as well as the development of novel neural techniques in neuroscience. In near feature, such a "neuro-designed" products/ applications might gain in popularity. [ABSTRACT FROM AUTHOR]

Extensive research with musicians has shown that instrumental musical training can have a profound impact on how acoustic features are processed in the brain. However, less is known about the influence of singing training on neural activity during voice perception, particularly in response to salient acoustic features, such as the vocal vibrato in operatic singing. To address this gap, the present study employed functional magnetic resonance imaging (fMRI) to measure brain responses in trained opera singers and musically untrained controls listening to recordings of opera singers performing in two distinct styles: a full operatic voice with vibrato, and a straight voice without vibrato. Results indicated that for opera singers, perception of operatic voice led to differential fMRI activations in bilateral auditory cortical regions and the default mode network. In contrast, musically untrained controls exhibited differences only in bilateral auditory cortex. These results suggest that operatic singing training triggers experience-dependent neural changes in the brain that activate self-referential networks, possibly through embodiment of acoustic features associated with one's own singing style. [ABSTRACT FROM AUTHOR]

During infancy and adolescence, language develops from a predominantly interhemispheric control--through the corpus callosum (CC)--to a predominantly intrahemispheric control, mainly subserved by the left arcuate fasciculus (AF). Using multimodal neuroimaging, we demonstrate that human left-handers (both male and female) with an atypical language lateralization show a rightward participation of language areas from the auditory cortex to the inferior frontal cortex when contrasting speech to tone perception and an enhanced interhemispheric anatomical and functional connectivity. Crucially, musicianship determines two different structural pathways to this outcome. Nonmusicians present a relation between atypical lateralization and intrahemispheric underdevelopment across the anterior AF, hinting at a dysregulation of the ontogenetic shift from an interhemispheric to an intrahemispheric brain. Musicians reveal an alternative pathway related to interhemispheric overdevelopment across the posterior CC and the auditory cortex. We discuss the heterogeneity in reaching atypical language lateralization and the relevance of early musical training in altering the normal development of language cognitive functions. [ABSTRACT FROM AUTHOR]

Although the locus ceruleus (LC) is recognized as a crucial modulator for attention and perception by releasing norepinephrine into various cortical regions, the impact of LC-noradrenergic (LC-NE) modulation on auditory discrimination behavior remains elusive. In this study, we firstly recorded local field potential and single-unit activity in multiple cortical regions associated with auditory- motor processing, including the auditory cortex, posterior parietal cortex, secondary motor cortex, anterior cingulate cortex, prefrontal cortex, and orbitofrontal cortex (OFC), in response to optogenetic activation (40 Hz and 0.5 s) of the LC-NE neurons in awake mice (male). We found that phasic LC stimulation induced a persistent high gamma oscillation (50-80 Hz) in the OFC. Phasic activation of LC-NE neurons also resulted in a corresponding increase in norepinephrine levels in the OFC, accompanied by a pupillary dilation response. Furthermore, when mice were performing a go/no-go auditory discrimination task, we optogeneticaly activated the neural projections from LC to OFC and revealed a shortened latency in behavioral responses to sound stimuli and an increased false alarm rate. These impulsive behavioral responses may be associated with the gamma neural activity in the OFC. These findings have broadened our understanding of the neural mechanisms involved in the role of LC in auditory-motor processing. [ABSTRACT FROM AUTHOR]

Objective: The aim of this is to explore changes in cross-modal reorganization within the auditory–visual cortex after cochlear implantation, examining their influence on auditory and speech functions along with their underlying mechanisms. Methods: Twenty prelingually deaf children who received cochlear implantation and rehabilitation training at our hospital between February 2022 and February 2023 comprised the prelingual deaf group. Simultaneously, 20 healthy children served as the control group. The prelingual deaf group underwent brain cortical activity assessment and evaluation of auditory-speech recovery pre-surgery, at postoperative weeks 1 and 2, and at months 1, 3, 6, 9, and 12. The control group underwent parallel assessments and evaluations. We analyzed the correlation between cortical activity in the auditory–visual cortex of patients and their auditory-speech functional recovery. Results: The group with prelingual deafness displayed elevated levels of auditory and visual cortical electromagnetic intensity compared to the control group, both prior to and 9  months after surgery. However, by the 12-month mark postsurgery, there was no discernible distinction between the two groups. Following surgery, the prelingually deaf group exhibited a progressive improvement in both Categories of Auditory Performance (CAP) and Speech Intelligibility Rate (SIR), initially lagging behind the control group. Notably, a negative correlation emerged between auditory and visual cortical electromagnetic intensity values and CAP/SIR scores at the 12-month post-surgery assessment. Conclusion: Cochlear implantation in prelingually deaf children results in elevated activity within the auditory and visual cortices, demonstrated by heightened electromagnetic intensity readings. Cross-modal reorganization is observed temporarily at 3  months post-surgery, which resolves to baseline levels by 12  months post-surgery. This phenomenon of reversal correlates with the restoration of auditory and speech functions in these children. [ABSTRACT FROM AUTHOR]

Aims: Resting state functional magnetic resonance imaging (rs‐fMRI) has been widely used in studying default mode network (DMN) changes in postoperative delirium (POD). Reproducibility and interpretability of the analyzing results remain insufficiently studied. Methods: Delirium‐like behavior was induced by tibial fixation surgery under isoflurane anesthesia. Firstly, we evaluated delirium‐like behavior and inflammatory responses in hippocampus and systemic level. Then the expressions of microRNA (miRNA) and target gene were sequenced and validated. Afterwards the functional connectivity (FC) in DMN was analyzed. Finally, results were correlated with DMN changes. Results: POD‐like behavior caused significant changes of miR‐34b‐5p, miR‐328‐5p, and miR‐3505 in miRNA level and Nos1, Tubb3, and Gys1 in the gene level. The FC in left and right hippocampus (L‐Hip and R‐Hip) and right auditory cortex (R‐AC) was found significantly changed. Significant correlations were found in FCL‐Hip/R‐AC and FCR‐Hip/R‐AC for miR‐34b‐5p and miR‐3505, as well as Nos1 and Tubb3. For miR‐328‐5p, no significant correlations were found. Conclusion: Our study demonstrates that POD‐like behavior induced significant miRNA and gene expression changes were associated with hippocampus related long‐term FC disruption in DMN. The results increased reproducibility and interpretability for standardized rs‐fMRI data analysis, as well as providing potential targets for postoperative delirium treatment. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to evaluate the effectiveness of a visual rehabilitation method for anisometropic amblyopia that uses visual evoked potential (VEP) parameters and sound biofeedback to increase objectiveness. Design: an observational, case-controlled trial. Setting: Ophthalmology Clinic, Emergency County Hospital, Cluj-Napoca, Romania. Participants: Sixteen subjects with amblyopic anisometropia, aged 15–57, and sixteen controls, aged 24–33, were included. Interventions: Subjects were divided into two groups. The control group, composed of normal-vision subjects, and the amblyopic group received 10 training sessions. The rehabilitation program lasted 10 min, took place twice a week, and ran over five consecutive weeks. During each session, the subjects were asked to fixate on a target on the computer screen and were instructed to keep the fixation and maintain the sound of the biofeedback at high frequency. Main Measures: The study assessed the main visual parameters at baseline, after 10 sessions, and 1, 3, 6, and 12 months after treatment. Performance was evaluated by measuring visual acuity, contrast sensitivity, and reading velocity (words/minute). Results: In the experimental group, mean BCVA improved with two rows, which means an improvement in the LogMARLogMAR scale with an average of nine letters. These values tended to be maintained over time. Both groups showed better reading velocities after training, but this parameter has undergone large variability during follow-ups. Contrast sensitivity was also improved and stable. Conclusions: Visual rehabilitation with the Retimax Vision Trainer can improve visual performance in patients with amblyopia after the critical period, an improvement that is maintained in most cases for at least one year after treatment. [ABSTRACT FROM AUTHOR]

Sound‐source localization is based on spatial cues arising due to interactions of sound waves with the torso, head and ears. Here, we evaluated neural responses to free‐field sound sources in the central nucleus of the inferior colliculus (CIC), the medial geniculate body (MGB) and the primary auditory cortex (A1) of Mongolian gerbils. Using silicon probes we recorded from anaesthetized gerbils positioned in the centre of a sound‐attenuating, anechoic chamber. We measured rate‐azimuth functions (RAFs) with broad‐band noise of varying levels presented from loudspeakers spanning 210° in azimuth and characterized RAFs by calculating spatial centroids, Equivalent Rectangular Receptive Fields (ERRFs), steepest slope locations and spatial‐separation thresholds. To compare neuronal responses with behavioural discrimination thresholds from the literature we performed a neurometric analysis based on signal‐detection theory. All structures demonstrated heterogeneous spatial tuning with a clear dominance of contralateral tuning. However, the relative amount of contralateral tuning decreased from the CIC to A1. In all three structures spatial tuning broadened with increasing sound‐level. This effect was strongest in CIC and weakest in A1. Neurometric spatial‐separation thresholds compared well with behavioural discrimination thresholds for locations directly in front of the animal. Our findings contrast with those reported for another rodent, the rat, which exhibits homogenous and sharply delimited contralateral spatial tuning. Spatial tuning in gerbils resembles more closely the tuning reported in A1 of cats, ferrets and non‐human primates. Interestingly, gerbils, in contrast to rats, share good low‐frequency hearing with carnivores and non‐human primates, which may account for the observed spatial tuning properties. [ABSTRACT FROM AUTHOR]

Background: Magnetoencephalography (MEG) is a non-invasive imaging technique for directly measuring the external magnetic field generated from synchronously activated pyramidal neurons in the brain. The optically pumped magnetometer (OPM) is known for its less expensive, non-cryogenic, movable and user-friendly custom-design provides the potential for a change in functional neuroimaging based on MEG. Methods: An array of OPMs covering the opposite sides of a subject's head is placed inside a magnetically shielded room (MSR) and responses evoked from the auditory cortices are measured. Results: High signal-to-noise ratio auditory evoked response fields (AEFs) were detected by a wearable OPM-MEG system in a MSR, for which a flexible helmet was specially designed to minimize the sensor-to-head distance, along with a set of bi-planar coils developed for background field and gradient nulling. Neuronal current sources activated in AEF experiments were localized and the auditory cortices showed the highest activities. Performance of the hybrid optically pumped magnetometer-magnetoencephalography/electroencephalography (OPM-MEG/EEG) system was also assessed. Conclusions: The multi-channel OPM-MEG system performs well in a custom built MSR equipped with bi-planar coils and detects human AEFs with a flexible helmet. Moreover, the similarities and differences of auditory evoked potentials (AEPs) and AEFs are discussed, while the operation of OPM-MEG sensors in conjunction with EEG electrodes provides an encouraging combination for the exploration of hybrid OPM-MEG/EEG systems. [ABSTRACT FROM AUTHOR]

The human auditory system extracts rich linguistic abstractions from speech signals. Traditional approaches to understanding this complex process have used linear feature-encoding models, with limited success. Artificial neural networks excel in speech recognition tasks and offer promising computational models of speech processing. We used speech representations in state-of-the-art deep neural network (DNN) models to investigate neural coding from the auditory nerve to the speech cortex. Representations in hierarchical layers of the DNN correlated well with the neural activity throughout the ascending auditory system. Unsupervised speech models performed at least as well as other purely supervised or fine-tuned models. Deeper DNN layers were better correlated with the neural activity in the higher-order auditory cortex, with computations aligned with phonemic and syllabic structures in speech. Accordingly, DNN models trained on either English or Mandarin predicted cortical responses in native speakers of each language. These results reveal convergence between DNN model representations and the biological auditory pathway, offering new approaches for modeling neural coding in the auditory cortex.

Abstract The mammalian cerebral cortex is composed of a rich diversity of cell types. Sensory cortical cells are organized into networks that rely on their functional diversity to ultimately carry out a variety of sophisticated cognitive functions for perception, learning, and memory. The auditory cortex (AC) has been most extensively studied for its experience-dependent effects, including for perceptual learning and associative memory. Here, we used single-nucleus RNA sequencing (snRNA-seq) in the AC of the adult rat to investigate the breadth of transcriptionally diverse cell types that likely support the role of AC in experience-dependent functions. A variety of unique excitatory and inhibitory neuron subtypes were identified that harbor unique transcriptional profiles of genes with putative relevance for the adaptive neuroplasticity of cortical microcircuits. In addition, we report for the first time a diversity of astrocytes in AC that may represent functionally unique subtypes, including those that could integrate experience-dependent adult neuroplasticity at cortical synapses. Together, these results pave the way for building models of how cortical neurons work in concert with astrocytes to fulfill dynamic and experience-dependent cognitive functions.

Abstract Most scientists agree that subjective tinnitus is the pathological result of an interaction of damage to the peripheral auditory system and central neuroplastic adaptations. Here we investigate such tinnitus related adaptations in the primary auditory cortex (AC) 7 and 13 days after noise trauma induction of tinnitus by quantifying the density of the extracellular matrix (ECM) in the AC of Mongolian gerbils (Meriones unguiculatus). The ECM density has been shown to be relevant for neuroplastic processes and synaptic stability within the cortex. We utilized a mild monaural acoustic noise trauma in overall 22 gerbils to induce tinnitus and a sham exposure in 16 control (C) animals. Tinnitus was assessed by a behavioral response paradigm. Animals were separated for a presence (T) or absence (NT) of a tinnitus percept by a behavioral task. The ECM density 7 and 13 days after trauma was quantified using immunofluorescence luminance of Wisteria floribunda lectin-fluoresceine-5-isothiocyanate (WFA-FITC) on histological slices of the primary AC, relative to the non-auditory brainstem as a reference area. At both timepoints, we found that the WFA-FITC luminance of the AC of NT animals was not significantly different from that of C animals. However, we found a significant increase of luminance in T animals’ ACs compared to NT or C animals’ cortices. This effect was found exclusively on the AC side contralateral to the trauma ear. These results point to a hemisphere specific process of stabilization of synaptic connections in primary AC, which may be involved in the chronic manifestation of tinnitus.

Brains can gracefully weed out irrelevant stimuli to guide behavior. This feat is believed to rely on a progressive selection of task-relevant stimuli across the cortical hierarchy, but the specific across-area interactions enabling stimulus selection are still unclear. Here, we propose that population gating, occurring within primary auditory cortex (A1) but controlled by top-down inputs from prelimbic region of medial prefrontal cortex (mPFC), can support across-area stimulus selection. Examining single-unit activity recorded while rats performed an auditory context-dependent task, we found that A1 encoded relevant and irrelevant stimuli along a common dimension of its neural space. Yet, the relevant stimulus encoding was enhanced along an extra dimension. In turn, mPFC encoded only the stimulus relevant to the ongoing context. To identify candidate mechanisms for stimulus selection within A1, we reverse-engineered low-rank RNNs trained on a similar task. Our analyses predicted that two context-modulated neural populations gated their preferred stimulus in opposite contexts, which we confirmed in further analyses of A1. Finally, we show in a two-region RNN how population gating within A1 could be controlled by top-down inputs from PFC, enabling flexible across-area communication despite fixed inter-areal connectivity.

Effective task execution requires the representation of multiple task-related variables that determine how stimuli lead to correct responses. Even the primary visual cortex (V1) represents other task-related variables such as expectations, choice, and context. However, it is unclear how V1 can flexibly accommodate these variables without interfering with visual representations. We trained mice on a context-switching cross-modal decision task, where performance depends on inferring task context. We found that the context signal that emerged in V1 was behaviorally relevant as it strongly covaried with performance, independent from movement. Importantly, this signal was integrated into V1 representation by multiplexing visual and context signals into orthogonal subspaces. In addition, auditory and choice signals were also multiplexed as these signals were orthogonal to the context representation. Thus, multiplexing allows V1 to integrate visual inputs with other sensory modalities and cognitive variables to avoid interference with the visual representation while ensuring the maintenance of task-relevant variables.

Direct neural recordings from human auditory cortex have demonstrated encoding for acoustic-phonetic features of consonants and vowels. Neural responses also encode distinct acoustic amplitude cues related to timing, such as those that occur at the onset of a sentence after a silent period or the onset of the vowel in each syllable. Here, we used a group reduced rank regression model to show that distributed cortical responses support a low-dimensional latent state representation of temporal context in speech. The timing cues each capture more unique variance than all other phonetic features and exhibit rotational or cyclical dynamics in latent space from activity that is widespread over the superior temporal gyrus. We propose that these spatially distributed timing signals could serve to provide temporal context for, and possibly bind across time, the concurrent processing of individual phonetic features, to compose higher-order phonological (e.g. word-level) representations.

Background: Auditory electrophysiological tests of the cortex, which are processed in or close to the auditory cortex, are brain reactions to sound. A variation in a continuous stimulus causes the acoustic change complex potential (ACC), which is a wave following the P1-N1-P2 response. Objective: To measure the amplitude and latency of different components of ACC in normal subjects and across individuals with mild and moderate degrees of sensorineural hearing loss (SNHL). Patients and methods: The study includes 100 individuals with the age ranged from 10 to 50 years with different degrees of SNHL. The ACC was evoked by a change of second formant in the middle of ongoing steady-state synthetic, 3 formant vowels (ooee). The total duration was 500 ms. Changing occurred at 250 ms. Results: The SNHL subgroups showed statistically significantly longer P1 and N1 latencies. N1 and P2 amplitudes of ACC onset response were larger with a statistical significance as compared to controls. Post hoc analysis revealed no statistically significant difference between mild and moderate SNHL on ACC parameters. Age showed a significant negative correlation with ACC N1 and P2 latency, ACC P1 and N1 amplitude, and onset P2 latency. Onset response P1 latency was significantly higher in children than adults. Median ACC P1 amplitude significantly increased in children than adults. Conclusion: ACC is a reliable tool for testing the auditory cortex function of detecting difference in sounds presented that can be recorded readily in patients with mild and moderate SNHL. [ABSTRACT FROM AUTHOR]

Aging is often associated with decline in brain processing power and neural predictive capabilities. To challenge this notion, we used magnetoencephalography (MEG) and magnetic resonance imaging (MRI) to record the whole-brain activity of 39 older adults (over 60 years old) and 37 young adults (aged 18–25 years) during recognition of previously memorised and varied musical sequences. Results reveal that when recognising memorised sequences, the brain of older compared to young adults reshapes its functional organisation. In fact, it shows increased early activity in sensory regions such as the left auditory cortex (100 ms and 250 ms after each note), and only moderate decreased activity (350 ms) in medial temporal lobe and prefrontal regions. When processing the varied sequences, older adults show a marked reduction of the fast-scale functionality (250 ms after each note) of higher-order brain regions including hippocampus, ventromedial prefrontal and inferior temporal cortices, while no differences are observed in the auditory cortex. Accordingly, young outperform older adults in the recognition of novel sequences, while no behavioural differences are observed with regards to memorised ones. Our findings show age-related neural changes in predictive and memory processes, integrating existing theories on compensatory neural mechanisms in non-pathological aging. MEG shows that the aging brain reshapes its functional organisation during musical sequence recognition, with increased sensory regions activity and reduced memory regions functionality, indicating novel neural compensatory mechanisms in aging. [ABSTRACT FROM AUTHOR]

The physiological interactions between the peripheral and central auditory systems are crucial for auditory information transmission and perception, while reliable models for auditory neural circuits are currently lacking. To address this issue, mouse and human neural pathways are generated by utilizing a carbon nanotube nanofiber system. The super‐aligned pattern of the scaffold renders the axons of the bipolar and multipolar neurons extending in a parallel direction. In addition, the electrical conductivity of the scaffold maintains the electrophysiological activity of the primary mouse auditory neurons. The mouse and human primary neurons from peripheral and central auditory units in the system are then co‐cultured and showed that the two kinds of neurons form synaptic connections. Moreover, neural progenitor cells of the cochlea and auditory cortex are derived from human embryos to generate region‐specific organoids and these organoids are assembled in the nanofiber‐combined 3D system. Using optogenetic stimulation, calcium imaging, and electrophysiological recording, it is revealed that functional synaptic connections are formed between peripheral neurons and central neurons, as evidenced by calcium spiking and postsynaptic currents. The auditory circuit model will enable the study of the auditory neural pathway and advance the search for treatment strategies for disorders of neuronal connectivity in sensorineural hearing loss. [ABSTRACT FROM AUTHOR]