Sound Level Changes the Auditory Cortical Activation Detected with Functional Near-Infrared Spectroscopy.

BACKGROUND: Functional near-infrared spectroscopy (fNIRS) is a viable non-invasive technique for functional neuroimaging in the cochlear implant (CI) population; however, the effects of acoustic stimulus features on the fNIRS signal have not been thoroughly examined. This study examined the effect of stimulus level on fNIRS responses in adults with normal hearing or bilateral CIs. We hypothesized that fNIRS responses would correlate with both stimulus level and subjective loudness ratings, but that the correlation would be weaker with CIs due to the compression of acoustic input to electric output. METHODS: Thirteen adults with bilateral CIs and 16 with normal hearing (NH) completed the study. Signal-correlated noise, a speech-shaped noise modulated by the temporal envelope of speech stimuli, was used to determine the effect of stimulus level in an unintelligible speech-like stimulus between the range of soft to loud speech. Cortical activity in the left hemisphere was recorded. RESULTS: Results indicated a positive correlation of cortical activation in the left superior temporal gyrus with stimulus level in both NH and CI listeners with an additional correlation between cortical activity and perceived loudness for the CI group. The results are consistent with the literature and our hypothesis. CONCLUSIONS: These results support the potential of fNIRS to examine auditory stimulus level effects at a group level and the importance of controlling for stimulus level and loudness in speech recognition studies. Further research is needed to better understand cortical activation patterns for speech recognition as a function of both stimulus presentation level and perceived loudness.

Divergent auditory activation in relation to inhibition task performance in children and adults.

Adults and children show remarkable differences in cortical auditory activation which, in children, have shown relevance for cognitive performance, specifically inhibitory control. However, it has not been tested whether these differences translate to functional differences in response inhibition between adults and children. We recorded auditory responses of adults and school-aged children (6-14 years) using combined magneto- and electroencephalography (M/EEG) during passive listening conditions and an auditory Go/No-go task. The associations between auditory cortical responses and inhibition performance measures diverge between adults and children; while in children the brain-behavior associations are not significant, or stronger responses are beneficial, adults show negative associations between auditory cortical responses and inhibitory performance. Furthermore, we found differences in brain responses between adults and children; the late (~200 ms post stimulation) adult peak activation shifts from auditory to frontomedial areas. In contrast, children show prolonged obligatory responses in the auditory cortex. Together this likely translates to a functional difference between adults and children in the cortical resources for performance consistency in auditory-based cognitive tasks.

Dual-stream cortical pathways mediate sensory prediction.

Predictions are constantly generated from diverse sources to optimize cognitive functions in the ever-changing environment. However, the neural origin and generation process of top-down induced prediction remain elusive. We hypothesized that motor-based and memory-based predictions are mediated by distinct descending networks from motor and memory systems to the sensory cortices. Using functional magnetic resonance imaging (fMRI) and a dual imagery paradigm, we found that motor and memory upstream systems activated the auditory cortex in a content-specific manner. Moreover, the inferior and posterior parts of the parietal lobe differentially relayed predictive signals in motor-to-sensory and memory-to-sensory networks. Dynamic causal modeling of directed connectivity revealed selective enabling and modulation of connections that mediate top-down sensory prediction and ground the distinctive neurocognitive basis of predictive processing.

Temporal hierarchy of cortical responses reflects core-belt-parabelt organization of auditory cortex in musicians.

Human auditory cortex (AC) organization resembles the core-belt-parabelt organization in nonhuman primates. Previous studies assessed mostly spatial characteristics; however, temporal aspects were little considered so far. We employed co-registration of functional magnetic resonance imaging (fMRI) and magnetoencephalography (MEG) in musicians with and without absolute pitch (AP) to achieve spatial and temporal segregation of human auditory responses. First, individual fMRI activations induced by complex harmonic tones were consistently identified in four distinct regions-of-interest within AC, namely in medial Heschl's gyrus (HG), lateral HG, anterior superior temporal gyrus (STG), and planum temporale (PT). Second, we analyzed the temporal dynamics of individual MEG responses at the location of corresponding fMRI activations. In the AP group, the auditory evoked P2 onset occurred ~25 ms earlier in the right as compared with the left PT and ~15 ms earlier in the right as compared with the left anterior STG. This effect was consistent at the individual level and correlated with AP proficiency. Based on the combined application of MEG and fMRI measurements, we were able for the first time to demonstrate a characteristic temporal hierarchy ("chronotopy") of human auditory regions in relation to specific auditory abilities, reflecting the prediction for serial processing from nonhuman studies.

Decoding subject's own name in the primary auditory cortex.

Current studies have shown that perception of subject's own name (SON) involves multiple multimodal brain regions, while activities in unimodal sensory regions (i.e., primary auditory cortex) and their interaction with multimodal regions during the self-processing remain unclear. To answer this, we combined multivariate pattern analysis and dynamic causal modelling analysis to explore the regional activation pattern and inter-region effective connection during the perception of SON. We found that SON and other names could be decoded from the activation pattern in the primary auditory cortex. In addition, we found an excitatory effect of SON on connections from the anterior insula/inferior frontal gyrus to the primary auditory cortex, and to the temporoparietal junction. Our findings extended the current knowledge of self-processing by showing that primary auditory cortex could discriminate SON from other names. Furthermore, our findings highlighted the importance of influence of the insula on the primary auditory cortex during self-processing.

Neuroimaging evidence for the direct role of auditory scene analysis in object perception.

Auditory Scene Analysis (ASA) refers to the grouping of acoustic signals into auditory objects. Previously, we have shown that perceived musicality of auditory sequences varies with high-level organizational features. Here, we explore the neural mechanisms mediating ASA and auditory object perception. Participants performed musicality judgments on randomly generated pure-tone sequences and manipulated versions of each sequence containing low-level changes (amplitude; timbre). Low-level manipulations affected auditory object perception as evidenced by changes in musicality ratings. fMRI was used to measure neural activation to sequences rated most and least musical, and the altered versions of each sequence. Next, we generated two partially overlapping networks: (i) a music processing network (music localizer) and (ii) an ASA network (base sequences vs. ASA manipulated sequences). Using Representational Similarity Analysis, we correlated the functional profiles of each ROI to a model generated from behavioral musicality ratings as well as models corresponding to low-level feature processing and music perception. Within overlapping regions, areas near primary auditory cortex correlated with low-level ASA models, whereas right IPS was correlated with musicality ratings. Shared neural mechanisms that correlate with behavior and underlie both ASA and music perception suggests that low-level features of auditory stimuli play a role in auditory object perception.

Dog and human neural sensitivity to voicelikeness: A comparative fMRI study.

Voice-sensitivity in the auditory cortex of a range of mammals has been proposed to be determined primarily by tuning to conspecific auditory stimuli, but recent human findings indicate a role for a more general tuning to voicelikeness. Vocal emotional valence, a central characteristic of vocalisations, has been linked to the same basic acoustic parameters across species. Comparative neuroimaging revealed that during voice perception, such acoustic parameters modulate emotional valence-sensitivity in auditory cortical regions in both family dogs and humans. To explore the role of voicelikeness in auditory emotional valence-sensitivity across species, here we constructed artificial emotional sounds in two sound categories: voice-like vs. sine-wave sounds, parametrically modulating two main acoustic parameters, f0 and call length. We hypothesised that if mammalian auditory systems are characterised by a general tuning to voicelikeness, voice-like sounds will be processed preferentially, and acoustic parameters for voice-like sounds will be processed differently than for sine-wave sounds - both in dogs and humans. We found cortical areas in both species that responded stronger to voice-like than to sine-wave stimuli, while there were no regions responding stronger to sine-wave sounds in either species. Additionally, we found that in bilateral primary and emotional valence-sensitive auditory regions of both species, the processing of voice-like and sine-wave sounds are modulated by f0 in opposite ways. These results reveal functional similarities between evolutionarily distant mammals for processing voicelikeness and its effect on processing basic acoustic cues of vocal emotions.

Sleep Problems in Preschoolers With Autism Spectrum Disorder Are Associated With Sensory Sensitivities and Thalamocortical Overconnectivity.

BACKGROUND: Projections between the thalamus and sensory cortices are established early in development and play an important role in regulating sleep as well as in relaying sensory information to the cortex. Atypical thalamocortical functional connectivity frequently observed in children with autism spectrum disorder (ASD) might therefore be linked to sensory and sleep problems common in ASD. METHODS: Here, we investigated the relationship between auditory-thalamic functional connectivity measured during natural sleep functional magnetic resonance imaging, sleep problems, and sound sensitivities in 70 toddlers and preschoolers (1.5-5 years old) with ASD compared with a matched group of 46 typically developing children. RESULTS: In children with ASD, sleep problems and sensory sensitivities were positively correlated, and increased sleep latency was associated with overconnectivity between the thalamus and auditory cortex in a subsample with high-quality magnetic resonance imaging data (n = 29). In addition, auditory cortex blood oxygen level-dependent signal amplitude was elevated in children with ASD, potentially reflecting reduced sensory gating or a lack of auditory habituation during natural sleep. CONCLUSIONS: These findings indicate that atypical thalamocortical functional connectivity can be detected early in development and may play a crucial role in sleep problems and sensory sensitivities in ASD.

Cortical depth profiles of auditory and visual 7 T functional MRI responses in human superior temporal areas.

Invasive neurophysiological studies in nonhuman primates have shown different laminar activation profiles to auditory vs. visual stimuli in auditory cortices and adjacent polymodal areas. Means to examine the underlying feedforward vs. feedback type influences noninvasively have been limited in humans. Here, using 1-mm isotropic resolution 3D echo-planar imaging at 7 T, we studied the intracortical depth profiles of functional magnetic resonance imaging (fMRI) blood oxygenation level dependent (BOLD) signals to brief auditory (noise bursts) and visual (checkerboard) stimuli. BOLD percent-signal-changes were estimated at 11 equally spaced intracortical depths, within regions-of-interest encompassing auditory (Heschl's gyrus, Heschl's sulcus, planum temporale, and posterior superior temporal gyrus) and polymodal (middle and posterior superior temporal sulcus) areas. Effects of differing BOLD signal strengths for auditory and visual stimuli were controlled via normalization and statistical modeling. The BOLD depth profile shapes, modeled with quadratic regression, were significantly different for auditory vs. visual stimuli in auditory cortices, but not in polymodal areas. The different depth profiles could reflect sensory-specific feedforward versus cross-sensory feedback influences, previously shown in laminar recordings in nonhuman primates. The results suggest that intracortical BOLD profiles can help distinguish between feedforward and feedback type influences in the human brain. Further experimental studies are still needed to clarify how underlying signal strength influences BOLD depth profiles under different stimulus conditions.

Task-modulated Sensitivity to Vocal Pitch in the Dorsal Premotor Cortex during Multitalker Speech Recognition.

It has long been known that listening to speech activates inferior frontal (pre-)motor regions in addition to a more dorsal premotor site (dPM). Recent work shows that dPM, located adjacent to laryngeal motor cortex, responds to low-level acoustic speech cues including vocal pitch, and the speech envelope, in addition to higher-level cues such as phoneme categories. An emerging hypothesis is that dPM is part of a general auditory-guided laryngeal control circuit that plays a role in producing speech and other voluntary auditory-vocal behaviors. We recently reported a study in which dPM responded to vocal pitch during a degraded speech recognition task, but only when speech was rated as unintelligible; dPM was more robustly modulated by the categorical difference between intelligible and unintelligible speech. Contrary to the general auditory-vocal hypothesis, this suggests intelligible speech is the primary driver of dPM. However, the same pattern of results was observed in pitch-sensitive auditory cortex. Crucially, vocal pitch was not relevant to the intelligibility judgment task, which may have facilitated processing of phonetic information at the expense of vocal pitch cues. The present fMRI study (n = 25) tests the hypothesis that, for a multitalker task that emphasizes pitch for talker segregation, left dPM and pitch-sensitive auditory regions will respond to vocal pitch regardless of overall speech intelligibility. This would suggest that pitch processing is indeed a primary concern of this circuit, apparent during perception only when the task demands it. Spectrotemporal modulation distortion was used to independently modulate vocal pitch and phonetic content in two-talker (male/female) utterances across two conditions (Competing, Unison), only one of which required pitch-based segregation (Competing). A Bayesian hierarchical drift-diffusion model was used to predict speech recognition performance from patterns of spectrotemporal distortion imposed on each trial. The model's drift rate parameter, a d'-like measure of performance, was strongly associated with vocal pitch for Competing but not Unison. Using a second Bayesian hierarchical model, we identified regions where behaviorally relevant acoustic features were related to fMRI activation in dPM. We regressed the hierarchical drift-diffusion model's posterior predictions of trial-wise drift rate, reflecting the relative presence or absence of behaviorally relevant acoustic features from trial to trial, against trial-wise activation amplitude. A significant positive association with overall drift rate, reflecting vocal pitch and phonetic cues related to overall intelligibility, was observed in left dPM and bilateral auditory cortex in both conditions. A significant positive association with "pitch-restricted" drift rate, reflecting only the relative presence or absence of behaviorally relevant pitch cues, regardless of the presence or absence of phonetic content (intelligibility), was observed in left dPM, but only in the Competing condition. Interestingly, the same effect was observed in bilateral auditory cortex but in both conditions. A post hoc mediation analysis ruled out the possibility that decision load was responsible for the observed pitch effects. These findings suggest that processing of vocal pitch is a primary concern of the auditory-cortex-dPM circuit, although during perception core pitch, processing is carried out by auditory cortex with a potential modulatory influence from dPM.

Developmental organization of neural dynamics supporting auditory perception.

PURPOSE: A prominent view of language acquisition involves learning to ignore irrelevant auditory signals through functional reorganization, enabling more efficient processing of relevant information. Yet, few studies have characterized the neural spatiotemporal dynamics supporting rapid detection and subsequent disregard of irrelevant auditory information, in the developing brain. To address this unknown, the present study modeled the developmental acquisition of cost-efficient neural dynamics for auditory processing, using intracranial electrocorticographic responses measured in individuals receiving standard-of-care treatment for drug-resistant, focal epilepsy. We also provided evidence demonstrating the maturation of an anterior-to-posterior functional division within the superior-temporal gyrus (STG), which is known to exist in the adult STG. METHODS: We studied 32 patients undergoing extraoperative electrocorticography (age range: eight months to 28 years) and analyzed 2,039 intracranial electrode sites outside the seizure onset zone, interictal spike-generating areas, and MRI lesions. Patients were given forward (normal) speech sounds, backward-played speech sounds, and signal-correlated noises during a task-free condition. We then quantified sound processing-related neural costs at given time windows using high-gamma amplitude at 70-110 Hz and animated the group-level high-gamma dynamics on a spatially normalized three-dimensional brain surface. Finally, we determined if age independently contributed to high-gamma dynamics across brain regions and time windows. RESULTS: Group-level analysis of noise-related neural costs in the STG revealed developmental enhancement of early high-gamma augmentation and diminution of delayed augmentation. Analysis of speech-related high-gamma activity demonstrated an anterior-to-posterior functional parcellation in the STG. The left anterior STG showed sustained augmentation throughout stimulus presentation, whereas the left posterior STG showed transient augmentation after stimulus onset. We found a double dissociation between the locations and developmental changes in speech sound-related high-gamma dynamics. Early left anterior STG high-gamma augmentation (i.e., within 200 ms post-stimulus onset) showed developmental enhancement, whereas delayed left posterior STG high-gamma augmentation declined with development. CONCLUSIONS: Our observations support the model that, with age, the human STG refines neural dynamics to rapidly detect and subsequently disregard uninformative acoustic noises. Our study also supports the notion that the anterior-to-posterior functional division within the left STG is gradually strengthened for efficient speech-sound perception after birth.

Activity level in left auditory cortex predicts behavioral performance in inhibition tasks in children.

Sensory processing during development is important for the emerging cognitive skills underlying goal-directed behavior. Yet, it is not known how auditory processing in children is related to their cognitive functions. Here, we utilized combined magneto- and electroencephalographic (M/EEG) measurements in school-aged children (6-14y) to show that child auditory cortical activity at ∼250 ms after auditory stimulation predicts the performance in inhibition tasks. While unaffected by task demands, the amplitude of the left-hemisphere activation pattern was significantly correlated with the variability of behavioral response time. Since this activation pattern is typically not present in adults, our results suggest divergent brain mechanisms in adults and children for consistent performance in auditory-based cognitive tasks. This difference can be explained as a shift in cortical resources for cognitive control from sensorimotor associations in the auditory cortex of children to top-down regulated control processes involving (pre)frontal and cingulate areas in adults.

Imagined Musical Scale Relationships Decoded from Auditory Cortex.

Notes in a musical scale convey different levels of stability or incompleteness, forming what is known as a tonal hierarchy. Levels of stability conveyed by these scale degrees are partly responsible for generating expectations as a melody proceeds, for emotions deriving from fulfillment (or not) of those expectations, and for judgments of overall melodic well-formedness. These functions can be extracted even during imagined music. We investigated whether patterns of neural activity in fMRI could be used to identify heard and imagined notes, and if patterns associated with heard notes could identify notes that were merely imagined. We presented trained musicians with the beginning of a scale (key and timbre were varied). The next note in the scale was either heard or imagined. A probe tone task assessed sensitivity to the tonal hierarchy, and state and trait measures of imagery were included as predictors. Multivoxel classification yielded above-chance results in primary auditory cortex (Heschl's gyrus) for heard scale-degree decoding. Imagined scale-degree decoding was successful in multiple cortical regions spanning bilateral superior temporal, inferior parietal, precentral, and inferior frontal areas. The right superior temporal gyrus yielded successful cross-decoding of heard-to-imagined scale-degree, indicating a shared pathway between tonal-hierarchy perception and imagery. Decoding in right and left superior temporal gyrus and right inferior frontal gyrus was more successful in people with more differentiated tonal hierarchies and in left inferior frontal gyrus among people with higher self-reported auditory imagery vividness, providing a link between behavioral traits and success of neural decoding. These results point to the neural specificity of imagined auditory experiences-even of such functional knowledge-but also document informative individual differences in the precision of that neural response.

Evidence of cortical thickness increases in bilateral auditory brain structures following piano learning in older adults.

Morphological differences in the auditory brain of musicians compared to nonmusicians are often associated with life-long musical activity. Cross-sectional studies, however, do not allow for any causal inferences, and most experimental studies testing music-driven adaptations investigated children. Although the importance of the age at which musical training begins is widely recognized to impact neuroplasticity, there have been few longitudinal studies examining music-related changes in the brains of older adults. Using magnetic resonance imaging, we measured cortical thickness (CT) of 12 auditory-related regions of interest before and after 6 months of musical instruction in 134 healthy, right-handed, normal-hearing, musically-naive older adults (64-76 years old). Prior to the study, all participants were randomly assigned to either piano training or to a musical culture/music listening group. In five regions-left Heschl's gyrus, left planum polare, bilateral superior temporal sulcus, and right Heschl's sulcus-we found an increase in CT in the piano training group compared with the musical culture group. Furthermore, CT of the right Heschl's gyrus could be identified as a morphological substrate supporting speech in noise perception. The results support the conclusion that playing an instrument is an effective stimulator for cortical plasticity, even in older adults.

Multi-modal imaging of the auditory-larynx motor network for voicing perception.

Voicing is one of the most important characteristics of phonetic speech sounds. Despite its importance, voicing perception mechanisms remain largely unknown. To explore auditory-motor networks associated with voicing perception, we firstly examined the brain regions that showed common activities for voicing production and perception using functional magnetic resonance imaging. Results indicated that the auditory and speech motor areas were activated with the operculum parietale 4 (OP4) during both voicing production and perception. Secondly, we used a magnetoencephalography and examined the dynamical functional connectivity of the auditory-motor networks during a perceptual categorization task of /da/-/ta/ continuum stimuli varying in voice onset time (VOT) from 0 to 40 ms in 10 ms steps. Significant functional connectivities from the auditory cortical regions to the larynx motor area via OP4 were observed only when perceiving the stimulus with VOT 30 ms. In addition, regional activity analysis showed that the neural representation of VOT in the auditory cortical regions was mostly correlated with categorical perception of voicing but did not reflect the perception of stimulus with VOT 30 ms. We suggest that the larynx motor area, which is considered to play a crucial role in voicing production, contributes to categorical perception of voicing by complementing the temporal processing in the auditory cortical regions.

The Representation of Time Windows in Primate Auditory Cortex.

Whether human and nonhuman primates process the temporal dimension of sound similarly remains an open question. We examined the brain basis for the processing of acoustic time windows in rhesus macaques using stimuli simulating the spectrotemporal complexity of vocalizations. We conducted functional magnetic resonance imaging in awake macaques to identify the functional anatomy of response patterns to different time windows. We then contrasted it against the responses to identical stimuli used previously in humans. Despite a similar overall pattern, ranging from the processing of shorter time windows in core areas to longer time windows in lateral belt and parabelt areas, monkeys exhibited lower sensitivity to longer time windows than humans. This difference in neuronal sensitivity might be explained by a specialization of the human brain for processing longer time windows in speech.

Faster Repetition Rate Sharpens the Cortical Representation of Echo Streams in Echolocating Bats.

There is consensus that primary auditory cortex (A1) utilizes a combination of rate codes and temporally precise population codes to represent discreet auditory objects. During the response to auditory streams, forward suppression constrains cortical rate coding strategies, but it may also be well positioned to enhance temporal coding strategies that rely on synchronized firing across neural ensembles. Here, we exploited the rapid temporal dynamics of bat echolocation to investigate how forward suppression modulates the cortical ensemble representation of complex acoustic signals embedded in echo streams. We recorded from auditory cortex of anesthetized free-tailed bats while stimulating the auditory system with naturalistic biosonar pulse-echo sequences covering a range of pulse emission rates. As expected, increasing pulse repetition rate significantly reduced the number of spikes per echo stimulus, but it also increased spike timing precision and doubled the information gain. This increased spike-timing precision translated into more robust inter-neuronal synchronization patterns with >10-dB higher signal-to-noise ratios (SNRs) at the ensemble level. We propose that forward suppression dynamically mediates a trade-off between the sensitive detection of isolated sounds versus precise spatiotemporal encoding of ongoing sound sequences in auditory cortex.

Distinct Representations of Tonotopy and Pitch in Human Auditory Cortex.

Frequency-to-place mapping, or tonotopy, is a fundamental organizing principle throughout the auditory system, from the earliest stages of auditory processing in the cochlea to subcortical and cortical regions. Although cortical maps are referred to as tonotopic, it is unclear whether they simply reflect a mapping of physical frequency inherited from the cochlea, a computation of pitch based on the fundamental frequency, or a mixture of these two features. We used high-resolution functional magnetic resonance imaging (fMRI) to measure BOLD responses as male and female human participants listened to pure tones that varied in frequency or complex tones that varied in either spectral content (brightness) or fundamental frequency (pitch). Our results reveal evidence for pitch tuning in bilateral regions that partially overlap with the traditional tonotopic maps of spectral content. In general, primary regions within Heschl's gyri (HGs) exhibited more tuning to spectral content, whereas areas surrounding HGs exhibited more tuning to pitch.SIGNIFICANCE STATEMENT Tonotopy, an orderly mapping of frequency, is observed throughout the auditory system. However, it is not known whether the tonotopy observed in the cortex simply reflects the frequency spectrum (as in the ear) or instead represents the higher-level feature of fundamental frequency, or pitch. Using carefully controlled stimuli and high-resolution functional magnetic resonance imaging (fMRI), we separated these features to study their cortical representations. Our results suggest that tonotopy in primary cortical regions is driven predominantly by frequency, but also reveal evidence for tuning to pitch in regions that partially overlap with the tonotopic gradients but extend into nonprimary cortical areas. In addition to resolving ambiguities surrounding cortical tonotopy, our findings provide evidence that selectivity for pitch is distributed bilaterally throughout auditory cortex.

Mapping cortico-subcortical sensitivity to 4 Hz amplitude modulation depth in human auditory system with functional MRI.

Temporal modulations in the envelope of acoustic waveforms at rates around 4 Hz constitute a strong acoustic cue in speech and other natural sounds. It is often assumed that the ascending auditory pathway is increasingly sensitive to slow amplitude modulation (AM), but sensitivity to AM is typically considered separately for individual stages of the auditory system. Here, we used blood oxygen level dependent (BOLD) fMRI in twenty human subjects (10 male) to measure sensitivity of regional neural activity in the auditory system to 4 Hz temporal modulations. Participants were exposed to AM noise stimuli varying parametrically in modulation depth to characterize modulation-depth effects on BOLD responses. A Bayesian hierarchical modeling approach was used to model potentially nonlinear relations between AM depth and group-level BOLD responses in auditory regions of interest (ROIs). Sound stimulation activated the auditory brainstem and cortex structures in single subjects. BOLD responses to noise exposure in core and belt auditory cortices scaled positively with modulation depth. This finding was corroborated by whole-brain cluster-level inference. Sensitivity to AM depth variations was particularly pronounced in the Heschl's gyrus but also found in higher-order auditory cortical regions. None of the sound-responsive subcortical auditory structures showed a BOLD response profile that reflected the parametric variation in AM depth. The results are compatible with the notion that early auditory cortical regions play a key role in processing low-rate modulation content of sounds in the human auditory system.

Encoding of acquired sound-sequence salience by auditory cortical offset responses.

Behaviorally relevant sounds are often composed of distinct acoustic units organized into specific temporal sequences. The meaning of such sound sequences can therefore be fully recognized only when they have terminated. However, the neural mechanisms underlying the perception of sound sequences remain unclear. Here, we use two-photon calcium imaging in the auditory cortex of behaving mice to test the hypothesis that neural responses to termination of sound sequences ("Off-responses") encode their acoustic history and behavioral salience. We find that auditory cortical Off-responses encode preceding sound sequences and that learning to associate a sound sequence with a reward induces enhancement of Off-responses relative to responses during the sound sequence ("On-responses"). Furthermore, learning enhances network-level discriminability of sound sequences by Off-responses. Last, learning-induced plasticity of Off-responses but not On-responses lasts to the next day. These findings identify auditory cortical Off-responses as a key neural signature of acquired sound-sequence salience.