Salient sounds distort time perception and production.

The auditory world is often cacophonous, with some sounds capturing attention and distracting us from our goals. Despite the universality of this experience, many questions remain about how and why sound captures attention, how rapidly behavior is disrupted, and how long this interference lasts. Here, we use a novel measure of behavioral disruption to test predictions made by models of auditory salience. Models predict that goal-directed behavior is disrupted immediately after points in time that feature a high degree of spectrotemporal change. We find that behavioral disruption is precisely time-locked to the onset of distracting sound events: Participants who tap to a metronome temporarily increase their tapping speed 750 ms after the onset of distractors. Moreover, this response is greater for more salient sounds (larger amplitude) and sound changes (greater pitch shift). We find that the time course of behavioral disruption is highly similar after acoustically disparate sound events: Both sound onsets and pitch shifts of continuous background sounds speed responses at 750 ms, with these effects dying out by 1,750 ms. These temporal distortions can be observed using only data from the first trial across participants. A potential mechanism underlying these results is that arousal increases after distracting sound events, leading to an expansion of time perception, and causing participants to misjudge when their next movement should begin.

Generalization of auditory expertise in audio engineers and instrumental musicians.

From auditory perception to general cognition, the ability to play a musical instrument has been associated with skills both related and unrelated to music. However, it is unclear if these effects are bound to the specific characteristics of musical instrument training, as little attention has been paid to other populations such as audio engineers and designers whose auditory expertise may match or surpass that of musicians in specific auditory tasks or more naturalistic acoustic scenarios. We explored this possibility by comparing students of audio engineering (n = 20) to matched conservatory-trained instrumentalists (n = 24) and to naive controls (n = 20) on measures of auditory discrimination, auditory scene analysis, and speech in noise perception. We found that audio engineers and performing musicians had generally lower psychophysical thresholds than controls, with pitch perception showing the largest effect size. Compared to controls, audio engineers could better memorise and recall auditory scenes composed of non-musical sounds, whereas instrumental musicians performed best in a sustained selective attention task with two competing streams of tones. Finally, in a diotic speech-in-babble task, musicians showed lower signal-to-noise-ratio thresholds than both controls and engineers; however, a follow-up online study did not replicate this musician advantage. We also observed differences in personality that might account for group-based self-selection biases. Overall, we showed that investigating a wider range of forms of auditory expertise can help us corroborate (or challenge) the specificity of the advantages previously associated with musical instrument training.

Quantitative MRI maps of human neocortex explored using cell type-specific gene expression analysis.

Quantitative magnetic resonance imaging (qMRI) allows extraction of reproducible and robust parameter maps. However, the connection to underlying biological substrates remains murky, especially in the complex, densely packed cortex. We investigated associations in human neocortex between qMRI parameters and neocortical cell types by comparing the spatial distribution of the qMRI parameters longitudinal relaxation rate (${R_{1}}$), effective transverse relaxation rate (${R_{2}}^{\ast }$), and magnetization transfer saturation (MTsat) to gene expression from the Allen Human Brain Atlas, then combining this with lists of genes enriched in specific cell types found in the human brain. As qMRI parameters are magnetic field strength-dependent, the analysis was performed on MRI data at 3T and 7T. All qMRI parameters significantly covaried with genes enriched in GABA- and glutamatergic neurons, i.e. they were associated with cytoarchitecture. The qMRI parameters also significantly covaried with the distribution of genes enriched in astrocytes (${R_{2}}^{\ast }$ at 3T, ${R_{1}}$ at 7T), endothelial cells (${R_{1}}$ and MTsat at 3T), microglia (${R_{1}}$ and MTsat at 3T, ${R_{1}}$ at 7T), and oligodendrocytes and oligodendrocyte precursor cells (${R_{1}}$ at 7T). These results advance the potential use of qMRI parameters as biomarkers for specific cell types.

Slow phase-locked modulations support selective attention to sound.

To make sense of complex soundscapes, listeners must select and attend to task-relevant streams while ignoring uninformative sounds. One possible neural mechanism underlying this process is alignment of endogenous oscillations with the temporal structure of the target sound stream. Such a mechanism has been suggested to mediate attentional modulation of neural phase-locking to the rhythms of attended sounds. However, such modulations are compatible with an alternate framework, where attention acts as a filter that enhances exogenously-driven neural auditory responses. Here we attempted to test several predictions arising from the oscillatory account by playing two tone streams varying across conditions in tone duration and presentation rate; participants attended to one stream or listened passively. Attentional modulation of the evoked waveform was roughly sinusoidal and scaled with rate, while the passive response did not. However, there was only limited evidence for continuation of modulations through the silence between sequences. These results suggest that attentionally-driven changes in phase alignment reflect synchronization of slow endogenous activity with the temporal structure of attended stimuli.

Dissociating the functions of three left posterior superior temporal regions that contribute to speech perception and production.

Prior studies have shown that the left posterior superior temporal sulcus (pSTS) and left temporo-parietal junction (TPJ) both contribute to phonological short-term memory, speech perception and speech production. Here, by conducting a within-subjects multi-factorial fMRI study, we dissociate the response profiles of these regions and a third region - the anterior ascending terminal branch of the left superior temporal sulcus (atSTS), which lies dorsal to pSTS and ventral to TPJ. First, we show that each region was more activated by (i) 1-back matching on visually presented verbal stimuli (words or pseudowords) compared to 1-back matching on visually presented non-verbal stimuli (pictures of objects or non-objects), and (ii) overt speech production than 1-back matching, across 8 types of stimuli (visually presented words, pseudowords, objects and non-objects and aurally presented words, pseudowords, object sounds and meaningless hums). The response properties of the three regions dissociated within the auditory modality. In left TPJ, activation was higher for auditory stimuli that were non-verbal (sounds of objects or meaningless hums) compared to verbal (words and pseudowords), irrespective of task (speech production or 1-back matching). In left pSTS, activation was higher for non-semantic stimuli (pseudowords and hums) than semantic stimuli (words and object sounds) on the dorsal pSTS surface (dpSTS), irrespective of task. In left atSTS, activation was not sensitive to either semantic or verbal content. The contrasting response properties of left TPJ, dpSTS and atSTS was cross-validated in an independent sample of 59 participants, using region-by-condition interactions. We also show that each region participates in non-overlapping networks of frontal, parietal and cerebellar regions. Our results challenge previous claims about functional specialisation in the left posterior superior temporal lobe and motivate future studies to determine the timing and directionality of information flow in the brain networks involved in speech perception and production.

Dimension-selective attention and dimensional salience modulate cortical tracking of acoustic dimensions.

Some theories of auditory categorization suggest that auditory dimensions that are strongly diagnostic for particular categories - for instance voice onset time or fundamental frequency in the case of some spoken consonants - attract attention. However, prior cognitive neuroscience research on auditory selective attention has largely focused on attention to simple auditory objects or streams, and so little is known about the neural mechanisms that underpin dimension-selective attention, or how the relative salience of variations along these dimensions might modulate neural signatures of attention. Here we investigate whether dimensional salience and dimension-selective attention modulate the cortical tracking of acoustic dimensions. In two experiments, participants listened to tone sequences varying in pitch and spectral peak frequency; these two dimensions changed at different rates. Inter-trial phase coherence (ITPC) and amplitude of the EEG signal at the frequencies tagged to pitch and spectral changes provided a measure of cortical tracking of these dimensions. In Experiment 1, tone sequences varied in the size of the pitch intervals, while the size of spectral peak intervals remained constant. Cortical tracking of pitch changes was greater for sequences with larger compared to smaller pitch intervals, with no difference in cortical tracking of spectral peak changes. In Experiment 2, participants selectively attended to either pitch or spectral peak. Cortical tracking was stronger in response to the attended compared to unattended dimension for both pitch and spectral peak. These findings suggest that attention can enhance the cortical tracking of specific acoustic dimensions rather than simply enhancing tracking of the auditory object as a whole.

Attentional modulation of neural entrainment to sound streams in children with and without ADHD.

To extract meaningful information from complex auditory scenes like a noisy playground, rock concert, or classroom, children can direct attention to different sound streams. One means of accomplishing this might be to align neural activity with the temporal structure of a target stream, such as a specific talker or melody. However, this may be more difficult for children with ADHD, who can struggle with accurately perceiving and producing temporal intervals. In this EEG study, we found that school-aged children's attention to one of two temporally-interleaved isochronous tone 'melodies' was linked to an increase in phase-locking at the melody's rate, and a shift in neural phase that aligned the neural responses with the attended tone stream. Children's attention task performance and neural phase alignment with the attended melody were linked to performance on temporal production tasks, suggesting that children with more robust control over motor timing were better able to direct attention to the time points associated with the target melody. Finally, we found that although children with ADHD performed less accurately on the tonal attention task than typically developing children, they showed the same degree of attentional modulation of phase locking and neural phase shifts, suggesting that children with ADHD may have difficulty with attentional engagement rather than attentional selection.

Primate auditory prototype in the evolution of the arcuate fasciculus.

The human arcuate fasciculus pathway is crucial for language, interconnecting posterior temporal and inferior frontal areas. Whether a monkey homolog exists is controversial and the nature of human-specific specialization unclear. Using monkey, ape and human auditory functional fields and diffusion-weighted MRI, we identified homologous pathways originating from the auditory cortex. This discovery establishes a primate auditory prototype for the arcuate fasciculus, reveals an earlier phylogenetic origin and illuminates its remarkable transformation.

Effects of auditory selective attention on neural phase: individual differences and short-term training.

How does the brain follow a sound that is mixed with others in a noisy environment? One possible strategy is to allocate attention to task-relevant time intervals. Prior work has linked auditory selective attention to alignment of neural modulations with stimulus temporal structure. However, since this prior research used relatively easy tasks and focused on analysis of main effects of attention across participants, relatively little is known about the neural foundations of individual differences in auditory selective attention. Here we investigated individual differences in auditory selective attention by asking participants to perform a 1-back task on a target auditory stream while ignoring a distractor auditory stream presented 180° out of phase. Neural entrainment to the attended auditory stream was strongly linked to individual differences in task performance. Some variability in performance was accounted for by degree of musical training, suggesting a link between long-term auditory experience and auditory selective attention. To investigate whether short-term improvements in auditory selective attention are possible, we gave participants 2 â€‹h of auditory selective attention training and found improvements in both task performance and enhancements of the effects of attention on neural phase angle. Our results suggest that although there exist large individual differences in auditory selective attention and attentional modulation of neural phase angle, this skill improves after a small amount of targeted training.

Tailored perception: Individuals' speech and music perception strategies fit their perceptual abilities.

Perception involves integration of multiple dimensions that often serve overlapping, redundant functions, for example, pitch, duration, and amplitude in speech. Individuals tend to prioritize these dimensions differently (stable, individualized perceptual strategies), but the reason for this has remained unclear. Here we show that perceptual strategies relate to perceptual abilities. In a speech cue weighting experiment (trial N = 990), we first demonstrate that individuals with a severe deficit for pitch perception (congenital amusics; N = 11) categorize linguistic stimuli similarly to controls (N = 11) when the main distinguishing cue is duration, which they perceive normally. In contrast, in a prosodic task where pitch cues are the main distinguishing factor, we show that amusics place less importance on pitch and instead rely more on duration cues-even when pitch differences in the stimuli are large enough for amusics to discern. In a second experiment testing musical and prosodic phrase interpretation (N = 16 amusics; 15 controls), we found that relying on duration allowed amusics to overcome their pitch deficits to perceive speech and music successfully. We conclude that auditory signals, because of their redundant nature, are robust to impairments for specific dimensions, and that optimal speech and music perception strategies depend not only on invariant acoustic dimensions (the physical signal), but on perceptual dimensions whose precision varies across individuals. Computational models of speech perception (indeed, all types of perception involving redundant cues e.g., vision and touch) should therefore aim to account for the precision of perceptual dimensions and characterize individuals as well as groups. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Speech-in-speech perception, nonverbal selective attention, and musical training.

Speech is more difficult to understand when it is presented concurrently with a distractor speech stream. One source of this difficulty is that competing speech can act as an attentional lure, requiring listeners to exert attentional control to ensure that attention does not drift away from the target. Stronger attentional control may enable listeners to more successfully ignore distracting speech, and so individual differences in selective attention may be one factor driving the ability to perceive speech in complex environments. However, the lack of a paradigm for measuring nonverbal sustained selective attention to sound has made this hypothesis difficult to test. Here we find that individuals who are better able to attend to a stream of tones and respond to occasional repeated sequences while ignoring a distractor tone stream are also better able to perceive speech masked by a single distractor talker. We also find that participants who have undergone more musical training show better performance on both verbal and nonverbal selective attention tasks, and this musician advantage is greater in older participants. This suggests that one source of a potential musician advantage for speech perception in complex environments may be experience or skill in directing and maintaining attention to a single auditory object. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Pupil-linked phasic arousal evoked by violation but not emergence of regularity within rapid sound sequences.

The ability to track the statistics of our surroundings is a key computational challenge. A prominent theory proposes that the brain monitors for unexpected uncertainty - events which deviate substantially from model predictions, indicating model failure. Norepinephrine is thought to play a key role in this process by serving as an interrupt signal, initiating model-resetting. However, evidence is from paradigms where participants actively monitored stimulus statistics. To determine whether Norepinephrine routinely reports the statistical structure of our surroundings, even when not behaviourally relevant, we used rapid tone-pip sequences that contained salient pattern-changes associated with abrupt structural violations vs. emergence of regular structure. Phasic pupil dilations (PDR) were monitored to assess Norepinephrine. We reveal a remarkable specificity: When not behaviourally relevant, only abrupt structural violations evoke a PDR. The results demonstrate that Norepinephrine tracks unexpected uncertainty on rapid time scales relevant to sensory signals.

Rapid Ocular Responses Are Modulated by Bottom-up-Driven Auditory Salience.

Despite the prevalent use of alerting sounds in alarms and human-machine interface systems and the long-hypothesized role of the auditory system as the brain's "early warning system," we have only a rudimentary understanding of what determines auditory salience-the automatic attraction of attention by sound-and which brain mechanisms underlie this process. A major roadblock has been the lack of a robust, objective means of quantifying sound-driven attentional capture. Here we demonstrate that: (1) a reliable salience scale can be obtained from crowd-sourcing (N = 911), (2) acoustic roughness appears to be a driving feature behind this scaling, consistent with previous reports implicating roughness in the perceptual distinctiveness of sounds, and (3) crowd-sourced auditory salience correlates with objective autonomic measures. Specifically, we show that a salience ranking obtained from online raters correlated robustly with the superior colliculus-mediated ocular freezing response, microsaccadic inhibition (MSI), measured in naive, passively listening human participants (of either sex). More salient sounds evoked earlier and larger MSI, consistent with a faster orienting response. These results are consistent with the hypothesis that MSI reflects a general reorienting response that is evoked by potentially behaviorally important events regardless of their modality.SIGNIFICANCE STATEMENT Microsaccades are small, rapid, fixational eye movements that are measurable with sensitive eye-tracking equipment. We reveal a novel, robust link between microsaccade dynamics and the subjective salience of brief sounds (salience rankings obtained from a large number of participants in an online experiment): Within 300 ms of sound onset, the eyes of naive, passively listening participants demonstrate different microsaccade patterns as a function of the sound's crowd-sourced salience. These results position the superior colliculus (hypothesized to underlie microsaccade generation) as an important brain area to investigate in the context of a putative multimodal salience hub. They also demonstrate an objective means for quantifying auditory salience.

Non-invasive laminar inference with MEG: Comparison of methods and source inversion algorithms.

Magnetoencephalography (MEG) is a direct measure of neuronal current flow; its anatomical resolution is therefore not constrained by physiology but rather by data quality and the models used to explain these data. Recent simulation work has shown that it is possible to distinguish between signals arising in the deep and superficial cortical laminae given accurate knowledge of these surfaces with respect to the MEG sensors. This previous work has focused around a single inversion scheme (multiple sparse priors) and a single global parametric fit metric (free energy). In this paper we use several different source inversion algorithms and both local and global, as well as parametric and non-parametric fit metrics in order to demonstrate the robustness of the discrimination between layers. We find that only algorithms with some sparsity constraint can successfully be used to make laminar discrimination. Importantly, local t-statistics, global cross-validation and free energy all provide robust and mutually corroborating metrics of fit. We show that discrimination accuracy is affected by patch size estimates, cortical surface features, and lead field strength, which suggests several possible future improvements to this technique. This study demonstrates the possibility of determining the laminar origin of MEG sensor activity, and thus directly testing theories of human cognition that involve laminar- and frequency-specific mechanisms. This possibility can now be achieved using recent developments in high precision MEG, most notably the use of subject-specific head-casts, which allow for significant increases in data quality and therefore anatomically precise MEG recordings. SECTION: Analysis methods. CLASSIFICATIONS: Source localization: inverse problem; Source localization: other.

Whole-Brain In-vivo Measurements of the Axonal G-Ratio in a Group of 37 Healthy Volunteers.

The g-ratio, quantifying the ratio between the inner and outer diameters of a fiber, is an important microstructural characteristic of fiber pathways and is functionally related to conduction velocity. We introduce a novel method for estimating the MR g-ratio non-invasively across the whole brain using high-fidelity magnetization transfer (MT) imaging and single-shell diffusion MRI. These methods enabled us to map the MR g-ratio in vivo across the brain's prominent fiber pathways in a group of 37 healthy volunteers and to estimate the inter-subject variability. Effective correction of susceptibility-related distortion artifacts was essential before combining the MT and diffusion data, in order to reduce partial volume and edge artifacts. The MR g-ratio is in good qualitative agreement with histological findings despite the different resolution and spatial coverage of MRI and histology. The MR g-ratio holds promise as an important non-invasive biomarker due to its microstructural and functional relevance in neurodegeneration.

Audio-visual speech perception: a developmental ERP investigation.

Being able to see a talking face confers a considerable advantage for speech perception in adulthood. However, behavioural data currently suggest that children fail to make full use of these available visual speech cues until age 8 or 9. This is particularly surprising given the potential utility of multiple informational cues during language learning. We therefore explored this at the neural level. The event-related potential (ERP) technique has been used to assess the mechanisms of audio-visual speech perception in adults, with visual cues reliably modulating auditory ERP responses to speech. Previous work has shown congruence-dependent shortening of auditory N1/P2 latency and congruence-independent attenuation of amplitude in the presence of auditory and visual speech signals, compared to auditory alone. The aim of this study was to chart the development of these well-established modulatory effects over mid-to-late childhood. Experiment 1 employed an adult sample to validate a child-friendly stimulus set and paradigm by replicating previously observed effects of N1/P2 amplitude and latency modulation by visual speech cues; it also revealed greater attenuation of component amplitude given incongruent audio-visual stimuli, pointing to a new interpretation of the amplitude modulation effect. Experiment 2 used the same paradigm to map cross-sectional developmental change in these ERP responses between 6 and 11 years of age. The effect of amplitude modulation by visual cues emerged over development, while the effect of latency modulation was stable over the child sample. These data suggest that auditory ERP modulation by visual speech represents separable underlying cognitive processes, some of which show earlier maturation than others over the course of development.

LXCXE-independent chromatin remodeling by Rb/E2f mediates neuronal quiescence.

Neuronal survival is dependent upon the retinoblastoma family members, Rb1 (Rb) and Rb2 (p130). Rb is thought to regulate gene repression, in part, through direct recruitment of chromatin modifying enzymes to its conserved LXCXE binding domain. We sought to examine the mechanisms that Rb employs to mediate cell cycle gene repression in terminally differentiated cortical neurons. Here, we report that Rb loss converts chromatin at the promoters of E2f-target genes to an activated state. We established a mouse model system in which Rb-LXCXE interactions could be induciblely disabled. Surprisingly, this had no effect on survival or gene silencing in neuronal quiescence. Absence of the Rb LXCXE-binding domain in neurons is compatible with gene repression and long-term survival, unlike Rb deficiency. Finally, we are able to show that chromatin activation following Rb deletion occurs at the level of E2fs. Blocking E2f-mediated transcription downstream of Rb loss is sufficient to maintain chromatin in an inactive state. Taken together our results suggest a model whereby Rb-E2f interactions are sufficient to maintain gene repression irrespective of LXCXE-dependent chromatin remodeling.

Speech versus song: multiple pitch-sensitive areas revealed by a naturally occurring musical illusion.

It is normally obvious to listeners whether a human vocalization is intended to be heard as speech or song. However, the 2 signals are remarkably similar acoustically. A naturally occurring boundary case between speech and song has been discovered where a spoken phrase sounds as if it were sung when isolated and repeated. In the present study, an extensive search of audiobooks uncovered additional similar examples, which were contrasted with samples from the same corpus that do not sound like song, despite containing clear prosodic pitch contours. Using functional magnetic resonance imaging, we show that hearing these 2 closely matched stimuli is not associated with differences in response of early auditory areas. Rather, we find that a network of 8 regions, including the anterior superior temporal gyrus (STG) just anterior to Heschl's gyrus and the right midposterior STG, respond more strongly to speech perceived as song than to mere speech. This network overlaps a number of areas previously associated with pitch extraction and song production, confirming that phrases originally intended to be heard as speech can, under certain circumstances, be heard as song. Our results suggest that song processing compared with speech processing makes increased demands on pitch processing and auditory-motor integration.

Adenovirus E1A directly targets the E2F/DP-1 complex.

Deregulation of the cell cycle is of paramount importance during adenovirus infection. Adenovirus normally infects quiescent cells and must initiate the cell cycle in order to propagate itself. The pRb family of proteins controls entry into the cell cycle by interacting with and repressing transcriptional activation by the E2F transcription factors. The viral E1A proteins indirectly activate E2F-dependent transcription and cell cycle entry, in part, by interacting with pRb and family members to free the E2Fs. We report here that an E1A 13S isoform can unexpectedly activate E2F-responsive gene expression independently of binding to the pRb family of proteins. We demonstrate that E1A binds to E2F/DP-1 complexes through a direct interaction with DP-1. E1A appears to utilize this binding to recruit itself to E2F-regulated promoters, and this allows the E1A 13S protein, but not the E1A 12S protein, to activate transcription independently of interaction with pRb. Importantly, expression of E1A 13S, but not E1A 12S, led to significant enhancement of E2F4 occupancy of E2F sites of two E2F-regulated promoters. These observations identify a novel mechanism by which adenovirus deregulates the cell cycle and suggest that E1A 13S may selectively activate a subset of E2F-regulated cellular genes during infection.

Critical roles for non-pRb targets of human papillomavirus type 16 E7 in cervical carcinogenesis.

High-risk human papillomaviruses (HPV) encode two oncogenes, E6 and E7, expressed in nearly all cervical cancers. In vivo, HPV-16 E7 has been shown to induce multiple phenotypes in the context of transgenic mice, including cervical cancer. E7 is a multifunctional protein known best for its ability to inactivate the tumor suppressor pRb. To determine the importance of pRb inactivation by E7 in cervical cancer, we pursued studies with genetically engineered mice. E7 expression in estrogen-treated murine cervix induced dysplasia and invasive cancers as reported previously, but targeted Rb inactivation in cervical epithelium was not sufficient to induce any cervical dysplasia or neoplasia. Furthermore, E7 induced cervical cancer formation even when the E7-pRb interaction was disrupted by the use of a knock-in mouse carrying an E7-resistant mutant Rb allele. pRb inactivation was necessary but not sufficient for E7 to overcome differentiation-induced or DNA damage-induced cell cycle arrest, and expression patterns of the E2F-responsive genes Mcm7 and cyclin E indicate that other E2F regulators besides pRb are important targets of E7. Together, these data indicate that non-pRb targets of E7 play critical roles in cervical carcinogenesis.