Sequence Of Tone Bursts Research Articles

Top-down and bottom-up expectations in the prefrontal and auditory cortices

Auditory perceptual decision-making is modulated by interactions between bottom-up (sensory-driven) and top-down (expectation-driven) processes. Despite the importance of these interactions, little is known about their underlying neural mechanisms. We investigated these mechanisms by recording neural activity in the auditory and prefrontal cortices of rhesus monkeys while they performed a challenging auditory decision-making task. The monkeys decided whether the last (“test tone”) in a sequence of tone bursts, embedded in broadband noise, was low or high frequency. Task difficulty was titrated by varying the sound level of the test tone relative to the noisy background. Bottom-up expectations were manipulated by presenting three identical low- or high-frequency tone bursts (“pre-tones”), establishing sequence regularity. Top-down processing was manipulated by presenting a visual cue that indicated the prior probability that the subsequent test-tone would be high or low frequency (“pre-cue”). The monkeys’ behavioral choices and response times were biased by both the pre-tones and the pre-cues, with stronger and more consistent effects by the pre-cues. Neural activity was modulated preferentially by the pre-tones in auditory cortex and by the pre-cues in prefrontal cortex. These findings imply functional segregation between bottom-up and top-down processing in the primate brain during auditory perceptual decision-making.

The Parallel Auditory Brainstem Response.

The frequency-specific tone-evoked auditory brainstem response (ABR) is an indispensable tool in both the audiology clinic and research laboratory. Most frequently, the toneburst ABR is used to estimate hearing thresholds in infants, toddlers, and other patients for whom behavioral testing is not feasible. Therefore, results of the ABR exam form the basis for decisions regarding interventions and hearing habilitation with implications extending far into the child’s future. Currently, responses are elicited by periodic sequences of toneburst stimuli presented serially to one ear at a time, which take a long time to measure multiple frequencies and intensities, and provide incomplete information if the infant wakes up early. Here, we describe a new method, the parallel ABR (pABR), which uses randomly timed toneburst stimuli to simultaneously acquire ABR waveforms to five frequencies in both ears. Here, we describe the pABR and quantify its effectiveness in addressing the greatest drawback of current methods: test duration. We show that in adults with normal hearing the pABR yields high-quality waveforms over a range of intensities, with similar morphology to the standard ABR in a fraction of the recording time. Furthermore, longer latencies and smaller amplitudes for low frequencies at a high intensity evoked by the pABR versus serial ABR suggest that responses may have better place specificity due to the masking provided by the other simultaneous toneburst sequences. Thus, the pABR has substantial potential for facilitating faster accumulation of more diagnostic information that is important for timely identification and treatment of hearing loss.

Neuronal phase consistency tracks dynamic changes in acoustic spectral regularity.

The brain parses the auditory environment into distinct sounds by identifying those acoustic features in the environment that have common relationships (e.g., spectral regularities) with one another and then grouping together the neuronal representations of these features. Although there is a large literature that tests how the brain tracks spectral regularities that are predictable, it is not known how the auditory system tracks spectral regularities that are not predictable and that change dynamically over time. Furthermore, the contribution of brain regions downstream of the auditory cortex to the coding of spectral regularity is unknown. Here, we addressed these two issues by recording electrocorticographic activity, while human patients listened to tone-burst sequences with dynamically varying spectral regularities, and identified potential neuronal mechanisms of the analysis of spectral regularities throughout the brain. We found that the degree of oscillatory stimulus phase consistency (PC) in multiple neuronal-frequency bands tracked spectral regularity. In particular, PC in the delta-frequency band seemed to be the best indicator of spectral regularity. We also found that these regularity representations existed in multiple regions throughout cortex. This widespread reliable modulation in PC - both in neuronal-frequency space and in cortical space - suggests that phase-based modulations may be a general mechanism for tracking regularity in the auditory system specifically and other sensory systems more generally. Our findings also support a general role for the delta-frequency band in processing the regularity of auditory stimuli.

The Contribution of Primary Auditory Cortex to Auditory Categorization in Behaving Monkeys.

The specific contribution of core auditory cortex to auditory perception –such as categorization– remains controversial. To identify a contribution of the primary auditory cortex (A1) to perception, we recorded A1 activity while monkeys reported whether a temporal sequence of tone bursts was heard as having a “small” or “large” frequency difference. We found that A1 had frequency-tuned responses that habituated, independent of frequency content, as this auditory sequence unfolded over time. We also found that A1 firing rate was modulated by the monkeys’ reports of “small” and “large” frequency differences; this modulation correlated with their behavioral performance. These findings are consistent with the hypothesis that A1 contributes to the processes underlying auditory categorization.

Improving acquisition time of the frequency-specific auditory brainstem response through simultaneous independently random toneburst sequences

The frequency-specific auditory brainstem response (ABR) is an objective electroencephalographic (EEG) method for estimating auditory thresholds when behavioral thresholds are not attainable, primarily in infants and toddlers. It is recorded by repeatedly presenting brief, band-limited tonebursts and averaging the scalp potential response. In a typical ABR evaluation, measurements are made at multiple intensities, at multiple frequencies, and in both ears, leading to a large combinatorial space and long test times. Here, we present a method of recording the responses at five frequencies in both ears simultaneously, along with preliminary data demonstrating its effectiveness. We created ten toneburst trains—five octave frequencies (500–8000 Hz) by two ears—for simultaneous presentation. Importantly, the toneburst timing for each train was dictated by an independent random process, rather than being periodic. Independent sequences allow separate computation of the ABR to each of the toneburst trains as the cross-correlation of its timing sequence and the EEG recording. Early results suggest substantial improvements in recording time, particularly at lower stimulus intensities. It also appears that cochlear spread of excitation—a problem at high intensities—is mitigated by our method. This improvement in place specificity is predicted by modeling of auditory nerve activity.

Temporal Integration of Auditory Information Is Invariant to Temporal Grouping Cues

Auditory perception depends on the temporal structure of incoming acoustic stimuli. Here, we examined whether a temporal manipulation that affects the perceptual grouping also affects the time dependence of decisions regarding those stimuli. We designed a novel discrimination task that required human listeners to decide whether a sequence of tone bursts was increasing or decreasing in frequency. We manipulated temporal perceptual-grouping cues by changing the time interval between the tone bursts, which led to listeners hearing the sequences as a single sound for short intervals or discrete sounds for longer intervals. Despite these strong perceptual differences, this manipulation did not affect the efficiency of how auditory information was integrated over time to form a decision. Instead, the grouping manipulation affected subjects' speed-accuracy trade-offs. These results indicate that the temporal dynamics of evidence accumulation for auditory perceptual decisions can be invariant to manipulations that affect the perceptual grouping of the evidence.

The effect of boundary proximity on the response of individual ultrasound contrast agent microbubbles

The effect of boundary proximity on ultrasound contrast agent microbubble emissions can play an important role in the context of both targeted microbubble imaging and contrast imaging of microvascular perfusion. In this study, individual microbubbles (n = 104) were insonicated as a function of distance from either a polystyrene membrane (OpticellTM) or a compliant agarose boundary up to offset distances of 1000 µm by use of an optical trapping setup. An ‘acoustic spectroscopy’ approach was employed, which entailed transmitting a sequence of tone bursts with centre frequencies ranging from 4 to 13.5 MHz to determine the frequency and amplitude of maximum radial response (fMR and AMR, respectively). For the OpticellTM case, microbubble response exhibited a distinctly oscillatory pattern with increasing offset distance, with an average maximal change in peak frequency and scattered pressure amplitude of 29.6% and 73.2%, respectively, as compared to their values adjacent to the boundary. For the agarose case, microbubbles exhibited an increase in fMR and a decrease in AMR with respect to their values in free space. Simulations indicate the oscillatory dependence on OpticellTM distance stems from wavelength-dependent interference phenomena. A recent analytical bubble-boundary model is in broad agreement with the relative AMR changes due to the more compliant agarose layer, however underestimates the change in relative fMR at the boundary.

High-frequency (20 to 40 MHz) acoustic response of liquid-filled nanocapsules

Liquid-core nanoparticles are promising candidates for targeted ultrasound-controlled therapy, but their acoustic detection remains challenging. High-frequency (20 to 40 MHz) tone burst sequences were implemented with a programmable ultrasound biomicroscope to characterize acoustic response from perfluorooctyl bromide-core nanoparticles with thick poly(lactide-coglycolide) (PLGA) shells. Radio-frequency signals were acquired from flowing solutions of nanoparticles with two different shell-thickness-to-particle-radius ratios, solid PLGA nanoparticles, and latex nanobeads (linear controls). Normalized fundamental (20 MHz) and second-harmonic power spectral density (PSD) increased with particle concentration and was highest for the thinnest shelled particles. The second- harmonic PSD was detectable from the nanoparticles for peak rarefactional pressures (PRP) from 0.97 to 2.01 MPa at 23 cycles and for tone bursts from 11 to 23 cycles at 2.01 MPa. Their second-harmonic¿to¿fundamental ratio increased as a function of PRP and number of cycles. Within the same PRP and cycle ranges, the second-harmonic¿to¿fundamental ratios from matched concentration solutions of latex nanobeads and solid PLGA nanoparticles was more weakly detectable but also increased with PRP and number of cycles. Nanoparticles were detectable under flow conditions in vitro using the contrast agent mode of a high-frequency commercial scanner. These results characterize linear acoustic response from the nanoparticles (20 to 40 MHz) and demonstrate potential for their highfrequency detection.

Nonlinear resonance behavior and linear shell estimates for Definity™ and MicroMarker™ assessed with acoustic microbubble spectroscopy

There is a growing interest in microbubble based ultrasound contrast imaging applications in the 5-15 MHz range. In this study, individual microbubbles were insonified at low pressures (≤ 25 kPa) using an "acoustic spectroscopy" approach which entailed transmitting a sequence of tone bursts with center frequencies ranging from 4 to 13.5 MHz. The fundamental (transmit) frequency radial excursion amplitude was calculated from the scattered signals to produce a resonance curve for each bubble. For diameters between 2.5 to 4 μm, 69% of Target-Ready MicroMarker™ (Bracco, Geneva; Visualsonics, Canada) exhibited asymmetric resonance, characterized by a skewing of the resonance curve and indicative of nonlinear behavior. For Definity™ (Lantheus Medical Imaging, N. Billerica, MA), these responses were observed for 8% of diameters between 1.7 to 3.1 μm. For the subset of bubbles exhibiting linear, symmetric resonance curves, resonant frequencies, shell elasticity, and viscosity values were estimated. Between 10 to 12 MHz, for example, Target-Ready MicroMarker between 2.7 to 3.3 μm in diameter was resonant, where Definity was resonant between 1.7 to 2.6 μm. From 4 to 13.5 MHz, Target-Ready MicroMarker is characterized by a stiffer shell (3 < χ(0) < 5) N/m than Definity (0.5 < χ(0) < 2.5) N/m, and distinct strain-softening and shear-thinning rheological behavior. For Definity, no clear strain or shear-rate dependence of the shell properties is evident.

Simultaneous Acquisition of 80 Hz ASSRs and ABRs From Quasi ASSRs for Threshold Estimation

Both 80 Hz auditory steady state responses (ASSRs) and tone burst auditory brainstem responses (ABRs) have been shown to provide reasonable estimates of the behavioral thresholds. Although ASSRs provide statistically objective estimates that can be easily automated by computers, they present no information for the neurophysiological interpretation of the results. ABRs, on the other hand, do not provide easily automated information and usually need expert interpretation of the recorded waveforms. A recently developed continuous loop averaging deconvolution algorithm offers an alternative solution by acquiring slightly jittered 80 Hz quasi auditory steady state responses (QASSRs), thus enabling the acquisition of both recordings simultaneously. The purpose of this study is to investigate a specially developed 80 Hz QASSR paradigm for simultaneous acquisition for both responses for threshold detection purposes. Sixteen ears from eight adults with normal hearing were tested. Amplitude modulated QASSRs were obtained using slightly jittered temporal sequences of tone bursts presented at a mean rate of 78.125 Hz. Four carrier frequencies (500, 1000, 2000, and 4000 Hz) at several stimulus intensity levels were monaurally presented and QASSRs to 128 sweeps blocks were recorded. The ABRs were extracted using the CLAD algorithm. Wave V was visually identified and analyzed in the time domain as in everyday clinical practice. In addition, statistically objective ƒMP computation method was used to automatically detect ABR threshold as well. The QASSRs were analyzed in the frequency domain and magnitudes, phase delays, and thresholds were obtained. Phasor (polar plot) diagrams were constructed. QASSR and ABR hearing thresholds were obtained and compared with behavioral thresholds. Study reveals that the QASSR method provides accurate objective estimation of the audiometric thresholds from extracted ASSRs and latency/amplitude information from extracted ABRs. The largest mean threshold difference for QASSR was within 5 dB for all carrier frequencies including 500 Hz. For auditory threshold estimation in adults with normal hearing, the Hotelling's T-Square test in four dimensions in the frequency domain was more accurate than the ƒMP or visual ABR threshold detection in the time domain. Simultaneously recorded ASSR and ABR from QASSRs provide accurate and effective method for frequency-specific hearing threshold estimation with neurophysiological information in adults with normal hearing. Further research is required for hearing-impaired adults, newborns, and infants.

Frequency-specific, location-nonspecific adaptation of interaural time difference sensitivity

Human listeners' sensitivity to interaural time differences (ITD) was assessed for 1000 Hz tone bursts (500 ms duration) preceded by trains of 500-ms “adapter” tone bursts (7 s total adapter duration, frequencies of 200, 665, 1000, or 1400 Hz) carrying random ITD, or by an equal-duration period of silence. Presentation of the adapter burst train reduced ITD sensitivity in a frequency-specific manner. The observed effect differs from previously described forms of location-specific psychophysical adaptation, as it was produced using a binaurally diffuse sequence of tone bursts (i.e., a location-nonspecific adapter stimulus). Results are discussed in the context of pre-binaural adaptation.

Contextual effects in the identification of nonspeech auditory patterns.

This study investigated the benefit of a priori cues in a masked nonspeech pattern identification experiment. Targets were narrowband sequences of tone bursts forming six easily identifiable frequency patterns selected randomly on each trial. The frequency band containing the target was randomized. Maskers were also narrowband sequences of tone bursts chosen randomly on every trial. Targets and maskers were presented monaurally in mutually exclusive frequency bands, producing large amounts of informational masking. Cuing the masker produced a significant improvement in performance, while holding the target frequency band constant provided no benefit. The cue providing the greatest benefit was a copy of the masker presented ipsilaterally before the target-plus-masker. The masker cue presented contralaterally, and a notched-noise cue produced smaller benefits. One possible mechanism underlying these findings is auditory "enhancement" in which the neural response to the target is increased relative to the masker by differential prior stimulation of the target and masker frequency regions. A second possible mechanism provides a benefit to performance by comparing the spectrotemporal correspondence of the cue and target-plus-masker and is effective for either ipsilateral or contralateral cue presentation. These effects improve identification performance by emphasizing spectral contrasts in sequences or streams of sounds.

The just audible tonality of short exponential and Gaussian pure tone bursts

This paper reports on listening tests performed to investigate the just audible tonality (JAT) of decaying pure tone bursts. Both exponential and Gaussian functions are used to shape the envelopes of the tone bursts and critical band center frequencies between 150 and 7000 Hz are studied. Loudness compensation is implemented to compensate for the reduced loudness of short tone bursts and attack functions are used for minimizing clicks. By using the method of limits, a sequence of tone bursts with increasing decay times and constant frequencies is presented to the listeners at 0.9 s intervals. The first burst in the sequence which is perceived as being tonal is indicated by the listeners. When that happens, the decay times of the tone bursts decrease and the listeners are asked to select the first tone burst with no audible tonality. The listeners are allowed to freely define tonality. No reference is given. For frequencies above 3.4 kHz, the results indicate that tonality is just audible for tone burst lengths of approximately 2.6-3.0 ms. For the lowest stimuli frequencies, the corresponding burst length is approximately 20-23 ms.

Influence of change in frequency on the movement of sound sources induced by interaural time differences

When a tone-burst train with a short inter-burst interval is lateralized to the left and is followed by another tone-burst train lateralized to the right, listeners report a smooth shift of tone bursts along the intracranial axis from left to right (known as auditory saltation). When a sequence of tone bursts with a changing interaural time difference is presented, listeners also report a smooth shift of tone bursts (simulated auditory motion). In this study, an investigation was carried out to determine whether the movement of sound sources, such as auditory saltation and simulated auditory motion, are influenced by changes in frequency between or across tone bursts. The results show that abrupt changes in frequency hamper the perceived smoothness of auditory saltation and simulated auditory motion. In contrast, gradual changes in frequency retain the smoothness of auditory saltation and simulated auditory motion. These results indicate that perceptual grouping based on frequency of tone bursts influences the smoothness of the movement of sound sources.

Asymmetrical retention functions for sequences of light flashes or tone bursts in the rat

In Experiment 1, rats were trained in a symbolic delayed matching-to-sample task to discriminate sample stimuli that consisted of sequences of magazine light flashes. The intertrial interval was illuminated by the houselight for Group Light, and it was dark for Group Dark. Retention functions exhibited a choose-many response bias when the delay interval was illuminated by the houselight in both groups, and no consistent response bias when the delay interval was dark. In Experiment 2, rats were trained to discriminate sample stimuli that consisted of sequences of tone bursts. During delay testing, a different tone (i.e., different frequency and location than the sample tone) was present or absent during the delay interval. The retention functions exhibited a significant choose-many bias when tone was present during the delay and a choose-few bias when tone was absent. Asymmetrical retention functions for tone burst and light flash sequences are due to the similarity between the stimulus conditions of the delay interval and the modality of the sequential event being discriminated. These results are consistent with an instructional ambiguity explanation of response biases in memory for number.

Memory for sequences of tone bursts in the rat: Reliance on temporal cues and evidence for an instructional ambiguity explanation of the choose-few effect

Two groups of rats were trained in a symbolic delayed matching-to-sample task with a 0-s delay to discriminate sample stimuli that consisted of sequences of tone bursts. For one group, sequences varied in number with total sequence duration controlled. For the other group, total sequence duration, sum of the tone durations, and sum of the gap durations were all controlled. The former group of rats acquired the discrimination, but the latter group of rats were not able to learn the discrimination with the additional temporal cues controlled. Retention functions for the group that acquired the discrimination exhibited a choose-many bias at the 1-s delay and a choose-few bias at the 8-s delay regardless of the similarity in the intertrial interval and delay interval illumination condition. The asymmetrical retention functions appeared to be due to instructional ambiguity which resulted from the similarity of the delay interval to temporal features of the tone burst sequence, such as the gap between tone bursts and the total duration of tone. In Experiment 2, diagnostic tests provided evidence that rats discriminated the sequences of tone bursts by timing and summing the duration of individual tone bursts rather than using an event switch to count tones. Like pigeons, rats use multiple temporal features rather than number to discriminate sequences of successive events.

Rapid acquisition of auditory brainstem responses with multiple frequency and intensity tone-bursts

Auditory brainstem response (ABR) thresholds, latency and amplitude functions were obtained in mice using stimuli presented singly and as a multiple stimulus sequence. All stimuli were tone-bursts at frequencies from 4 to 32 kHz. The multiple stimulus consisted of a sequence of 20 tone-bursts of four different frequencies at five intensities separated by 12 ms. A comparison of responses to stimuli presented singly and those obtained with the 20-stimulus train showed no significant difference in thresholds. Also, no differences were found in response latencies or amplitudes, indicating that the responses from multiple stimuli were not adapted or otherwise affected. The use of this 20-stimulus train can result in a significant time savings for data acquisition compared with single stimuli. These findings demonstrate the feasibility of the rapid acquisition of unadapted cochlear and brainstem responses at different frequencies using a sequence of tone-bursts at different frequencies and intensities.

Testing the response of personal noise exposure meters (noise dosimeters) to impulse-like signals using a laboratory reference noise dosimeter and a theoretical model (after ANSI S1.25-1978)

A laboratory reference noise dosimeter consisting of a measuring amplifier and instrument controller was assembled and characterized. A theoretical expression was obtained for the A-weighted, rms-detected output of a noise dosimeter assuming an input signal equal to that of a tone-burst sequence containing bursts comprised of an integral number of cycles of a sine wave. The output of the theoretical detector was numerically integrated to obtain percentage criterion exposure or time-weighted equivalent level. Equivalent levels were measured and calculated for each sequence in a set of tone-burst sequences with burst durations of 1 to 1000 cycles and crest factors of 4.8 to 30 dB. The agreement between equivalent levels obtained using the reference dosimeter and theoretical calculations was typically +0.1 dB. The results of these measurements and calculations were then used as a basis of comparison for testing the response of commercially available noise dosimeters to a subset of the tone-burst sequences. [Work supported by OSHA.]

Intermodal selective attention. I. Effects on event-related potentials to lateralized auditory and visual stimuli

The effects of intermodal selective attention on event-related brain potentials (ERPs) were examined in 2 experiments. In experiment 1, auditory ERPs were compared (1) when subjects responded to easy and difficult-to-detect target tones in sequences of tone bursts; and (2) when they ignored the same auditory sequences and played a demanding video game. In experiment 2, auditory ERPs to tone bursts and visual ERPs to vertical line gratings were compared as subjects responded to difficult-to-detect targets in one modality or the other. Attention to auditory stimuli resulted in biphasic enhancements in auditory ERPs, the Nd a (negative auditory difference wave, latency 120–160 msec) and the Pd a (positive auditory difference wave, latency 200–240 msec) waves. These had longer latencies and somewhat different scalp distributions than N1 and P2 components evoked by non-attended tones. The Nd a and Pd a could be contrasted with the monophasic processing negativities typically found in dichotic selective attention tasks. Nd a amplitudes were larger for difficult-to-detect targets (closely resembling standards) than for standards themselves, but no Nd as were recorded to highly deviant targets. Deviant auditory stimuli evoked mismatch negativities (MMNs) that persisted during visual attention. MMN amplitudes to difficult-to-detect deviants were enlarged with attention, but no change was found in MMN amplitudes to easy-to-detect deviants. In experiment 2 intermodal attention was associated with biphasic changes in visual ERPs over the posterior scalp: the occipital Pd v (100–130 msec), and contralateral-temporal Nd v (120–320 msec) deflections. Deviant visual stimuli also elicited mismatch negativity/N2b components, largest over the inferotemporal cortex contralateral to the stimulated visual field. Like the auditory MMN, the MMN increased in amplitude with attention, but it was also evident during attend auditory conditions. The results suggest that sustained, intermodal attention depends primarily in processing modulations in modality-specific cortex. We found no evidence of the participation of modality non-specific cortex. This excludes the possibility that intermodal attention depends on a single, supramodal attention system. The relatively long latency of intermodal effects suggests that they may depend on the reafferent (top down) modulation, and do not index “template matching” operations.

Spectral specificity in auditory detection: The effect of listening on hearing.

Many experimental data suggest that a listener who focuses attention on a specific spectral region (or regions) becomes more sensitive to sounds falling there than elsewhere. Most often, the subject's task has been to detect a pure tone in noise. For example, in a two-interval, forced-choice paradigm, scores were around 90% when the signal was at an expected target frequency (0.5, 1, 2, or 4kHz) and were near chance, 50%, when the signal was at an unexpected frequency more than a half critical band away. In other tests, subjects detected unexpected temporal patterns (repeated tone bursts) just as well as expected patterns, provided spectral frequencies were the same. It has also been shown that when listening to a sequence of tone bursts that rise (or fall) in frequency, subjects miss a burst at a frequency significantly different from the value it normally has in the sequence. Other data suggest similar spectral specificity in the discriminationof complex sounds, including speech. Just what mechanism improves performance remains unclear. Nevertheless, some measurements of evoked physiological responses leave open the possibility that spectral specificity is achieved by efferent input to the auditory periphery, perhaps even to the cochlea.