Left Motor δ Oscillations Reflect Asynchrony Detection in Multisensory Speech Perception.

During multisensory speech perception, slow δ oscillations (∼1-3 Hz) in the listener's brain synchronize with the speech signal, likely engaging in speech signal decomposition. Notable fluctuations in the speech amplitude envelope, resounding speaker prosody, temporally align with articulatory and body gestures and both provide complementary sensations that temporally structure speech. Further, δ oscillations in the left motor cortex seem to align with speech and musical beats, suggesting their possible role in the temporal structuring of (quasi)-rhythmic stimulation. We extended the role of δ oscillations to audiovisual asynchrony detection as a test case of the temporal analysis of multisensory prosody fluctuations in speech. We recorded Electroencephalograph (EEG) responses in an audiovisual asynchrony detection task while participants watched videos of a speaker. We filtered the speech signal to remove verbal content and examined how visual and auditory prosodic features temporally (mis-)align. Results confirm (1) that participants accurately detected audiovisual asynchrony, and (2) increased δ power in the left motor cortex in response to audiovisual asynchrony. The difference of δ power between asynchronous and synchronous conditions predicted behavioral performance, and (3) decreased δ-ß coupling in the left motor cortex when listeners could not accurately map visual and auditory prosodies. Finally, both behavioral and neurophysiological evidence was altered when a speaker's face was degraded by a visual mask. Together, these findings suggest that motor δ oscillations support asynchrony detection of multisensory prosodic fluctuation in speech.SIGNIFICANCE STATEMENT Speech perception is facilitated by regular prosodic fluctuations that temporally structure the auditory signal. Auditory speech processing involves the left motor cortex and associated δ oscillations. However, visual prosody (i.e., a speaker's body movements) complements auditory prosody, and it is unclear how the brain temporally analyses different prosodic features in multisensory speech perception. We combined an audiovisual asynchrony detection task with electroencephalographic (EEG) recordings to investigate how δ oscillations support the temporal analysis of multisensory speech. Results confirmed that asynchrony detection of visual and auditory prosodies leads to increased δ power in left motor cortex and correlates with performance. We conclude that δ oscillations are invoked in an effort to resolve denoted temporal asynchrony in multisensory speech perception.

Internal Mammary Lymph Node Biopsy during Microsurgical Breast Reconstruction: A Prospective Study.

BACKGROUND: Accurate assessment of regional lymph node basins is critical for oncological management of breast cancer. The internal mammary lymph node (IMLN) basin directly drains the medial pole of the breast, but biopsy is not commonly performed. While the axillary sentinel lymph node sample remains the standard of care, the majority of patients who have been found to have a positive IMLN biopsy have simultaneously had negative axillary sentinel lymph nodes. This study prospectively examines routine IMLN biopsy during microsurgical breast reconstruction. METHODS: An IRB-approved study of routine IMLN biopsies in 270 consecutive patients who underwent microsurgical breast reconstruction was performed from July 1, 2018, to June 1, 2021. Recorded data included unilateral or bilateral breast reconstruction, unilateral or bilateral IMLN sampling, patient demographics, disease stage, and pathologic findings of IMLN. RESULTS: The majority of patients, 240 of 270 patients (88.9%), had bilateral reconstruction. Overall, 5 out of 270 (1.9%) patients had positive IMLN; one of these patients had positive axillary sentinel lymph nodes. The IMLN biopsy results in two of the five patients affected the clinical course as they were upstaged and required chemoradiation. CONCLUSION: Direct visualization of the internal mammary lymph nodes during dissection of the recipient vessels for microsurgical breast reconstruction allows for convenient sampling, with minimal donor site morbidity and enhances the therapeutic management of patients in whom nodal involvement is present. As such, the authors recommend IMLN sampling.

Effects of face masks on acoustic analysis and speech perception: Implications for peri-pandemic protocols.

Wearing face masks (alongside physical distancing) provides some protection against infection from COVID-19. Face masks can also change how people communicate and subsequently affect speech signal quality. This study investigated how three common face mask types (N95, surgical, and cloth) affected acoustic analysis of speech and perceived intelligibility in healthy subjects. Acoustic measures of timing, frequency, perturbation, and power spectral density were measured. Speech intelligibility and word and sentence accuracy were also examined using the Assessment of Intelligibility of Dysarthric Speech. Mask type impacted the power distribution in frequencies above 3 kHz for the N95 mask, and above 5 kHz in surgical and cloth masks. Measures of timing and spectral tilt mainly differed with N95 mask use. Cepstral and harmonics to noise ratios remained unchanged across mask type. No differences were observed across conditions for word or sentence intelligibility measures; however, accuracy of word and sentence translations were affected by all masks. Data presented in this study show that face masks change the speech signal, but some specific acoustic features remain largely unaffected (e.g., measures of voice quality) irrespective of mask type. Outcomes have bearing on how future speech studies are run when personal protective equipment is worn.

Postoperative Upper Extremity Function in Implant and Autologous Breast Reconstruction.

BACKGROUND: After mastectomy and breast reconstruction, many patients experience upper extremity complications, such as pain, restriction in motion, and lymphedema. Despite an aesthetically satisfactory outcome, these occurrences can diminish a patient's postoperative quality of life. Several studies have investigated the causes and incidence of these complications. However, there is currently a paucity of data comparing postoperative upper extremity function according to reconstruction technique. METHODS: A review was performed of patients enrolled in a physical therapy (PT) program after mastectomy and immediate breast reconstruction. PT initial encounter evaluations were used to gather data on patients' postoperative upper extremity function. Hospital records were used to gather surgical and demographic data. For each patient, data were collected for each upper extremity that was ipsilateral to a reconstructed breast. Data were then compared between patients who underwent implant-based versus autologous deep inferior epigastric perforator flap reconstruction. RESULTS: A total of 72 patients were identified, including 39 autologous and 33 implant-based reconstruction cases. Proportions of patients who underwent sentinel lymph node biopsies and axillary lymph node dissections were similar between the two groups. The autologous-based reconstruction patients had significantly higher arm pain at rest (p = 0.004) and with activity (p = 0.031) compared with implant patients. Shoulder range of motion and manual muscle test results were similar between groups, with the exception of elbow flexion, which was weaker in implant patients (p = 0.030). Implant patients were also more likely to report "severe difficulty" or "inability" to perform activities of daily living (p = 0.022). Edema/swelling, axillary cording, and lymphedema girth measurements were similar between the two groups. CONCLUSION: Different techniques of breast reconstruction can result in different postoperative upper extremity complications. These data show specific areas where postoperative care and PT can be customized according to reconstruction type. Investigation is currently underway to determine the effect of PT on upper extremity function in these patients.

Whistling shares a common tongue with speech: bioacoustics from real-time MRI of the human vocal tract.

Most human communication is carried by modulations of the voice. However, a wide range of cultures has developed alternative forms of communication that make use of a whistled sound source. For example, whistling is used as a highly salient signal for capturing attention, and can have iconic cultural meanings such as the catcall, enact a formal code as in boatswain's calls or stand as a proxy for speech in whistled languages. We used real-time magnetic resonance imaging to examine the muscular control of whistling to describe a strong association between the shape of the tongue and the whistled frequency. This bioacoustic profile parallels the use of the tongue in vowel production. This is consistent with the role of whistled languages as proxies for spoken languages, in which one of the acoustical features of speech sounds is substituted with a frequency-modulated whistle. Furthermore, previous evidence that non-human apes may be capable of learning to whistle from humans suggests that these animals may have similar sensorimotor abilities to those that are used to support speech in humans.

The roles of musical expertise and sensory feedback in beat keeping and joint action.

Auditory feedback of actions provides additional information about the timing of one's own actions and those of others. However, little is known about how musicians and nonmusicians integrate auditory feedback from multiple sources to regulate their own timing or to (intentionally or unintentionally) coordinate with a partner. We examined how musical expertise modulates the role of auditory feedback in a two-person synchronization-continuation tapping task. Pairs of individuals were instructed to tap at a rate indicated by an initial metronome cue in all four auditory feedback conditions: no feedback, self-feedback (cannot hear their partner), other feedback (cannot hear themselves), or full feedback (both self and other). Participants within a pair were either both musically trained (musicians), both untrained (nonmusicians), or one musically trained and one untrained (mixed). Results demonstrated that all three pair types spontaneously synchronized with their partner when receiving other or full feedback. Moreover, all pair types were better at maintaining the metronome rate with self-feedback than with no feedback. Musician pairs better maintained the metronome rate when receiving other feedback than when receiving no feedback; in contrast, nonmusician pairs were worse when receiving other or full feedback compared to no feedback. Both members of mixed pairs maintained the metronome rate better in the other and full feedback conditions than in the no feedback condition, similar to musician pairs. Overall, nonmusicians benefited from musicians' expertise without negatively influencing musicians' ability to maintain the tapping rate. One implication is that nonmusicians may improve their beat-keeping abilities by performing tasks with musically skilled individuals.

The implicit learning of metrical and non-metrical rhythms in blind and sighted adults.

Forming temporal expectancies plays a crucial role in our survival as it allows us to identify the occurrence of temporal deviants that might signal potential dangers. The dynamic attending theory suggests that temporal expectancies are formed more readily for rhythms that imply a beat (i.e., metrical rhythms) compared to those that do not (i.e., nonmetrical rhythms). Moreover, metrical frameworks can be used to detect temporal deviants. Although several studies have demonstrated that congenital or early blindness correlates with modality-specific neural changes that reflect compensatory mechanisms, few have examined whether blind individuals show a learning advantage for auditory rhythms and whether learning can occur unintentionally and without awareness, that is, implicitly. We compared blind to sighted controls in their ability to implicitly learn metrical and nonmetrical auditory rhythms. We reasoned that the loss of sight in blindness might lead to improved sensitivity to rhythms and predicted that the blind learn rhythms more readily than the sighted. We further hypothesized that metrical rhythms are learned more readily than nonmetrical rhythms. Results partially confirmed our predictions; the blind group learned nonmetrical rhythms more readily than the sighted group but the blind group learned metrical rhythms less readily than the sighted group. Only the sighted group learned metrical rhythms more readily than nonmetrical rhythms. The blind group demonstrated awareness of the nonmetrical rhythms while learning was implicit for all other conditions. Findings suggest that improved deviant-sensitivity might have provided the blind group a learning advantage for nonmetrical rhythms. Future research could explore the plastic changes that affect deviance-detection and stimulus-specific adaptation in blindness.

The Schultz MIDI Benchmarking Toolbox for MIDI interfaces, percussion pads, and sound cards.

The Musical Instrument Digital Interface (MIDI) was readily adopted for auditory sensorimotor synchronization experiments. These experiments typically use MIDI percussion pads to collect responses, a MIDI-USB converter (or MIDI-PCI interface) to record responses on a PC and manipulate feedback, and an external MIDI sound module to generate auditory feedback. Previous studies have suggested that auditory feedback latencies can be introduced by these devices. The Schultz MIDI Benchmarking Toolbox (SMIDIBT) is an open-source, Arduino-based package designed to measure the point-to-point latencies incurred by several devices used in the generation of response-triggered auditory feedback. Experiment 1 showed that MIDI messages are sent and received within 1 ms (on average) in the absence of any external MIDI device. Latencies decreased when the baud rate increased above the MIDI protocol default (31,250 bps). Experiment 2 benchmarked the latencies introduced by different MIDI-USB and MIDI-PCI interfaces. MIDI-PCI was superior to MIDI-USB, primarily because MIDI-USB is subject to USB polling. Experiment 3 tested three MIDI percussion pads. Both the audio and MIDI message latencies were significantly greater than 1 ms for all devices, and there were significant differences between percussion pads and instrument patches. Experiment 4 benchmarked four MIDI sound modules. Audio latencies were significantly greater than 1 ms, and there were significant differences between sound modules and instrument patches. These experiments suggest that millisecond accuracy might not be achievable with MIDI devices. The SMIDIBT can be used to benchmark a range of MIDI devices, thus allowing researchers to make informed decisions when choosing testing materials and to arrive at an acceptable latency at their discretion.

Generic, phenomenological, on-the-fly renormalized repulsion model for self-limited organization of terminal supraparticle assemblies.

Self-limited, or terminal, supraparticles have long received great interest because of their abundance in biological systems (DNA bundles and virus capsids) and their potential use in a host of applications ranging from photonics and catalysis to encapsulation for drug delivery. Moreover, soft, uniform colloidal aggregates are a promising candidate for quasicrystal and other hierarchical assemblies. In this work, we present a generic coarse-grained model that captures the formation of self-limited assemblies observed in various soft-matter systems including nanoparticles, colloids, and polyelectrolytes. Using molecular dynamics simulations, we demonstrate that the assembly process is self-limited when the repulsion between the particles is renormalized to balance their attraction during aggregation. The uniform finite-sized aggregates are further shown to be thermodynamically stable and tunable with a single dimensionless parameter. We find large aggregates self-organize internally into a core-shell morphology and exhibit anomalous uniformity when the constituent nanoparticles have a polydisperse size distribution.

Minimally Invasive Approach for Resection of Masseteric Vascular Malformations.

OBJECTIVE: Vascular malformations (VMs) in the head and neck region often cause esthetic as well as functional problems for patients. Intramuscular VMs (IVM), such as those in the masseter, can cause severe facial asymmetry and typically are excised transcutaneously to facilitate wide exposure and safe dissection from the facial nerve. This requires extensive dissection, prolonged healing, and can lead to suboptimal facial scarring. METHODS: We describe the technique of resecting large IVMs of the masseter muscle in 3 patients using an entirely intraoral approach with continuous nerve monitoring and without visible facial scarring or secondary deformity. Preoperative injection of sclerotherapy was performed to reduce intra-operative bleeding and optimize resection. RESULTS: Successful excision was performed without complication in 3 patients to date. Total average operating room time was 120 minutes (range 95-145 minutes). Estimated blood loss was 213 mL (range 180-240 mL). The patients were discharged home either post-operative day (POD) 1 or 2, with 1 returning to work POD 4. Facial nerve function was normal postoperatively and no hematomas developed. Subjective masticatory function was equivalent to preoperative levels in all patients. CONCLUSIONS: Intraoral excision of VMs of the masseter muscle can be safely performed without added risk or complication. Continuous facial nerve monitoring allows minimally invasive approaches to be considered with less risk of iatrogenic facial nerve injury. We purport that this is a safe and effective method with substantially better esthetic outcomes compared with traditional transcutaneous approaches.

Actuation of shape-memory colloidal fibres of Janus ellipsoids.

Many natural micrometre-scale assemblies can be actuated to control their optical, transport and mechanical properties, yet such functionality is lacking in colloidal structures synthesized thus far. Here, we show with experiments and computer simulations that Janus ellipsoids can self-assemble into self-limiting one-dimensional fibres with shape-memory properties, and that the fibrillar assemblies can be actuated on application of an external alternating-current electric field. Actuation of the fibres occurs through a sliding mechanism that permits the rapid and reversible elongation and contraction of the Janus-ellipsoid chains by ~36% and that on long timescales leads to the generation of long, uniform self-assembled fibres. Colloidal-scale actuation might be useful in microrobotics and in applications of shape-memory materials.

Mutual coordination strengthens the sense of joint agency in cooperative joint action.

Philosophers have proposed that when people coordinate their actions with others they may experience a sense of joint agency, or shared control over actions and their effects. However, little empirical work has investigated the sense of joint agency. In the current study, pairs coordinated their actions to produce tone sequences and then rated their sense of joint agency on a scale ranging from shared to independent control. People felt more shared than independent control overall, confirming that people experience joint agency during joint action. Furthermore, people felt stronger joint agency when they (a) produced sequences that required mutual coordination compared to sequences in which only one partner had to coordinate with the other, (b) held the role of follower compared to leader, and (c) were better coordinated with their partner. Thus, the strength of joint agency is influenced by the degree to which people mutually coordinate with each other's actions.

Tap Arduino: An Arduino microcontroller for low-latency auditory feedback in sensorimotor synchronization experiments.

Timing abilities are often measured by having participants tap their finger along with a metronome and presenting tap-triggered auditory feedback. These experiments predominantly use electronic percussion pads combined with software (e.g., FTAP or Max/MSP) that records responses and delivers auditory feedback. However, these setups involve unknown latencies between tap onset and auditory feedback and can sometimes miss responses or record multiple, superfluous responses for a single tap. These issues may distort measurements of tapping performance or affect the performance of the individual. We present an alternative setup using an Arduino microcontroller that addresses these issues and delivers low-latency auditory feedback. We validated our setup by having participants (N = 6) tap on a force-sensitive resistor pad connected to the Arduino and on an electronic percussion pad with various levels of force and tempi. The Arduino delivered auditory feedback through a pulse-width modulation (PWM) pin connected to a headphone jack or a wave shield component. The Arduino's PWM (M = 0.6 ms, SD = 0.3) and wave shield (M = 2.6 ms, SD = 0.3) demonstrated significantly lower auditory feedback latencies than the percussion pad (M = 9.1 ms, SD = 2.0), FTAP (M = 14.6 ms, SD = 2.8), and Max/MSP (M = 15.8 ms, SD = 3.4). The PWM and wave shield latencies were also significantly less variable than those from FTAP and Max/MSP. The Arduino missed significantly fewer taps, and recorded fewer superfluous responses, than the percussion pad. The Arduino captured all responses, whereas at lower tapping forces, the percussion pad missed more taps. Regardless of tapping force, the Arduino outperformed the percussion pad. Overall, the Arduino is a high-precision, low-latency, portable, and affordable tool for auditory experiments.

Controlling Chirality of Entropic Crystals.

Colloidal crystal structures with complexity and diversity rivaling atomic and molecular crystals have been predicted and obtained for hard particles by entropy maximization. However, thus far homochiral colloidal crystals, which are candidates for photonic metamaterials, are absent. Using Monte Carlo simulations we show that chiral polyhedra exhibiting weak directional entropic forces self-assemble either an achiral crystal or a chiral crystal with limited control over the crystal handedness. Building blocks with stronger faceting exhibit higher selectivity and assemble a chiral crystal with handedness uniquely determined by the particle chirality. Tuning the strength of directional entropic forces by means of particle rounding or the use of depletants allows for reconfiguration between achiral and homochiral crystals. We rationalize our findings by quantifying the chirality strength of each particle, both from particle geometry and potential of mean force and torque diagrams.

Phase behavior of Janus colloids determined by sedimentation equilibrium.

We investigate the phase behavior of short-range interacting isotropic particles and single-patch Janus particles via simulations of sedimentation equilibrium, which allows for a rapid assessment of the equation of state and phase behavior directly from simulation. The methodology is tested against results by traditional methods and is found to yield good agreement for isotropic interactions. The method is then used to study single-patch Janus particles with different interaction strengths and patch sizes with particle area coverage greater than ∼0.63. Our results show an interplay between translational and orientational order. We observe a lamellar phase, a fluid phase and a rotator close-packed structure. The lamellar phase is shown to have a different range of stability than previously observed in simulation studies for systems of similar and longer-ranged interactions.

Chest wall, thymus, and heart vascularized composite allograft proof of concept cadaveric model for heart transplantation.

The use of vascularized composite allografts allows for the reconstruction of complex scenarios that previously have required multistaged operations. Heart transplantation often follows a series of previous operations leading to chest wall deformities and significant mediastinal adhesions that can limit the use of larger hearts, making it difficult to find a suitable donor. Further, research has shown that the use of vascularized bone marrow and vascularized thymus in transplantation potentially prolongs graft survival with decreased immunosuppression requirements. The authors propose using a vascularized composite allograft of the chest wall consisting of sternum and thymus in conjunction with the heart for cardiac transplantation to allow for more flexibility from the donor pool, maintain chest wall integrity and physiology, and potentially immunoregulate the concomitant solid organ transplant.

Synthesis, assembly, and image analysis of spheroidal patchy particles.

We report a method to synthesize and image Janus spheroid and "kayak" shaped patchy particles that combine both shape and interaction anisotropy. These particles are fabricated by sequentially combining evaporative deposition of chrome and gold with the uniaxial deformation of the colloidal particles into spheroids. We introduce combined reflection and fluorescence confocal microscopy to image each component of the patchy particle. Image analysis algorithms that resolve patch orientation from these image volumes are described and used to characterize self-assembly behavior. Assemblies of the Janus spheroid and kayak particles produced at different salt concentrations demonstrate the functional nature of the patch-to-patch interactions between the particles. Selective gold-to-gold patch bonding is observed at intermediate salt concentrations, while higher salt concentrations yield gel-like structures with nonselective patch-to-patch bonding. At intermediate salt concentrations, differences in the orientational order of the assemblies indicate that both the preferential gold-to-gold patch bonding and the particles' shape anisotropy influence the self-assembled structure.

A Cross-sectional Study of Perceptual and Acoustic Voice Characteristics in Healthy Aging.

PURPOSE: The human voice qualitatively changes across the lifespan. Although some of these vocal changes may be pathologic, other changes likely reflect natural physiological aging. Normative data for voice characteristics in healthy aging is limited and disparate studies have used a range of different acoustic features, some of which are implicated in pathologic voice changes. We examined the perceptual and acoustic features that predict healthy aging. METHOD: Participants (N = 150) aged between 50 and 92 years performed a sustained vowel task. Acoustic features were measured using the Multi-Dimensional Voice Program and the Analysis of Dysphonia in Speech and Voice. We used forward and backward variable elimination techniques based on the Bayesian information criterion and linear regression to assess which of these acoustic features predict age and perceptual features. Hearing thresholds were determined using pure-tone audiometry tests at frequencies 250 Hz, 500 Hz, 1000 Hz, 2000 Hz, and 4000 Hz. We further explored potential relationships between these acoustic features and clinical assessments of voice quality using the Consensus Auditory-Perceptual Evaluation of Voice. RESULTS: Chronological age was significantly predicted by greater voice turbulence, variability of cepstral fundamental frequency, low relative to high spectral energy, and cepstral intensity. When controlling for hearing loss, age was significantly predicted by amplitude perturbations and cepstral intensity. Clinical assessments of voice indicated perceptual characteristics of speech were predicted by different acoustic features. For example, breathiness was predicted by the soft phonation index, mean cepstral peak prominence, mean low-high spectral ratio, and mean cepstral intensity. CONCLUSIONS: Findings suggest that acoustic features that predict healthy aging are different than those previously reported for the pathologic voice. We propose a model of healthy and pathologic voice development in which voice characteristics are mediated by the inability to monitor vocal productions associated with age-related hearing loss. This normative data of healthy vocal aging may assist in separating voice pathologies from healthy aging.

Disease Delineation for Multiple Sclerosis, Friedreich Ataxia, and Healthy Controls Using Supervised Machine Learning on Speech Acoustics.

Neurodegenerative disease often affects speech. Speech acoustics can be used as objective clinical markers of pathology. Previous investigations of pathological speech have primarily compared controls with one specific condition and excluded comorbidities. We broaden the utility of speech markers by examining how multiple acoustic features can delineate diseases. We used supervised machine learning with gradient boosting (CatBoost) to delineate healthy speech from speech of people with multiple sclerosis or Friedreich ataxia. Participants performed a diadochokinetic task where they repeated alternating syllables. We subjected 74 spectral and temporal prosodic features from the speech recordings to machine learning. Results showed that Friedreich ataxia, multiple sclerosis and healthy controls were all identified with high accuracy (over 82%). Twenty-one acoustic features were strong markers of neurodegenerative diseases, falling under the categories of spectral qualia, spectral power, and speech rate. We demonstrated that speech markers can delineate neurodegenerative diseases and distinguish healthy speech from pathological speech with high accuracy. Findings emphasize the importance of examining speech outcomes when assessing indicators of neurodegenerative disease. We propose large-scale initiatives to broaden the scope for differentiating other neurological diseases and affective disorders.

Sensory gating functions of the auditory thalamus: Adaptation and modulations through noise-exposure and high-frequency stimulation in rats.

The medial geniculate body (MGB) of the thalamus is an obligatory relay for auditory processing. A breakdown of adaptive filtering and sensory gating at this level may lead to multiple auditory dysfunctions, while high-frequency stimulation (HFS) of the MGB might mitigate aberrant sensory gating. To further investigate the sensory gating functions of the MGB, this study (i) recorded electrophysiological evoked potentials in response to continuous auditory stimulation, and (ii) assessed the effect of MGB HFS on these responses in noise-exposed and control animals. Pure-tone sequences were presented to assess differential sensory gating functions associated with stimulus pitch, grouping (pairing), and temporal regularity. Evoked potentials were recorded from the MGB and acquired before and after HFS (100 Hz). All animals (unexposed and noise-exposed, pre- and post-HFS) showed gating for pitch and grouping. Unexposed animals also showed gating for temporal regularity not found in noise-exposed animals. Moreover, only noise-exposed animals showed restoration comparable to the typical EP amplitude suppression following MGB HFS. The current findings confirm adaptive thalamic sensory gating based on different sound characteristics and provide evidence that temporal regularity affects MGB auditory signaling.