Intertone Interval Research Articles

Time scale of adaptation at the tonal sequence processing in the awake mice auditory cortex neurons

The study was firstly carried out on stimulus-specific adaptation of neurons in the primary and anterior fields of the awake house mice auditory cortex to sound sequences of four 100-ms tonal signals, with frequency of tones corresponding to the neuronal characteristic frequency, and also with the inter-tone interval constant for one sequence and varying from 0 to 2000 ms in different sequences. The analysis of the data obtained showed the adaptation effect in the responses of all studied primary auditory cortex neurons, which was observed as the absence or significant decrease in activity evoked by the components of a series of tones following the 1st, at inter-stimulus intervals of 0–500 ms. A quantitative assessment of the adaptation effects as a function of inter-stimulus intervals within the tonal sequence, performed over whole population of studied neurons, showed that the individual time scales of adaptation of neurons varied significantly, which may be crucial for the formation of optimal time windows for the processing of grouping and separation of sound events, which are important both for perception of animal vocalizations and human speech.

Increasing the complexity of isolated musical chords benefits concurrent associative memory formation

The effects of background music on learning and memory are inconsistent, partially due to the intrinsic complexity and diversity of music, as well as variability in music perception and preference. By stripping down musical harmony to its building blocks, namely discrete chords, we explored their effects on memory formation of unfamiliar word-image associations. Chords, defined as two or more simultaneously played notes, differ in the number of tones and inter-tone intervals, yielding varying degrees of harmonic complexity, which translate into a continuum of consonance to dissonance percepts. In the current study, participants heard four different types of musical chords (major, minor, medium complex, and high complex chords) while they learned new word-image pairs of a foreign language. One day later, their memory for the word-image pairs was tested, along with a chord rating session, in which they were required to assess the musical chords in terms of perceived valence, tension, and the extent to which the chords grabbed their attention. We found that musical chords containing dissonant elements were associated with higher memory performance for the word-image pairs compared with consonant chords. Moreover, tension positively mediated the relationship between roughness (a key feature of complexity) and memory, while valence negatively mediated this relationship. The reported findings are discussed in light of the effects that basic musical features have on tension and attention, in turn affecting cognitive processes of associative learning.

Isoflurane effects on the N1 and other long-latency auditory evoked potentials in Wistar rats

Long-latency auditory evoked potentials (LLAEPs) may help further advances in understanding consciousness under general anesthesia and promote more objective means of assessing sedation depth than conventional clinical signs. Among the LLAEP components, the auditory N1 shows promise as a measure of sedation depth and a marker of consciousness, but findings are so far inconclusive. Research with animals can help elucidate the effects of various anesthetics on the N1 and other LLAEPs, but investigations of LLAEPs under anesthesia in animals is lacking. To address this deficit, we examined the P1, N1, P2, and N2, along with their corresponding peak-to-peak complexes, in 10 Wistar rats anesthetized with 1.5–2 % isoflurane in pure oxygen and again after recovery. While under anesthesia, subdermal needle electrodes were inserted and secured for electroencephalographic (EEG) recordings. LLAEPs were assessed during a 20-min, passive, two-tone (500 ms inter-tone interval) paradigm with randomized short (1 s) and long (5 s) inter-pair intervals (IPIs). Overall, while the LLAEP peaks under isoflurane were less defined, they were not eliminated. The peak-to-peak amplitudes, particularly the P1-N1, were significantly smaller under isoflurane than during post-recovery. Our preliminary findings indicate that isoflurane produces global suppression across LLAEP components, presumably reflecting impaired integration of top-down and bottom-up attention and sensory systems under profound sedation with isoflurane.

Closed-loop system to enhance slow-wave activity

Objective. Recent evidence reports cognitive, metabolic, and sleep restoration benefits resulting from the enhancement of sleep slow-waves using auditory stimulation. Our objective is to make this concept practical for consumer use by developing and validating an electroencephalogram (EEG) closed-loop system to deliver auditory stimulation during sleep to enhance slow-waves. Approach. The system automatically detects slow-wave sleep with 74% sensitivity and 97% specificity and optimally delivers stimulation in the form of 50 ms-long tones separated by a constant one-second inter-tone interval at a volume that is dynamically modulated such that louder tones are delivered when sleep is deeper. The system was tested in a study involving 28 participants (18F, 10M; 36.9 ± 7.3 years old; median age: 40 years old) who used the system for ten nights (five nights in a sham condition and five in a stimulation condition). Four nights in each condition were recorded at-home and the fifth one in-lab. Main results. The analysis in two age groups defined by the median age of participants in the study shows significant slow wave activity enhancement (+16.1%, p < 0.01) for the younger group and absence of effect on the older group. However, the older group received only a fraction (57%) of the stimulation compared to the younger group. Changes in sleep architecture and EEG properties due to aging have influenced the amount of stimulation. The analysis of the stimulation timing suggests an entrainment-like phenomenon where slow-waves align to the stimulation periodicity. In addition, enhancement of spindle power in the stimulation condition was found. Significance. We show evidence of the viability of delivering auditory stimulation during sleep, at home, to enhance slow wave activity. The system ensures the stimulation delivery to be at the right time during sleep without causing disturbance.

Behavioral evaluation of auditory stream segregation in rats

Perceptual organization of sound sequences into separate sound sources or streams is called auditory stream segregation. Neural substrates for this process in both the spectral and temporal domains remain to be elucidated. Despite abundant knowledge about their auditory physiology, behavioral evidence for auditory streaming in rodents is still limited. We provided behavioral evidence for auditory streaming in the go/no-go discrimination task, but not in the two-alternative choice task. In the go/no-go discrimination phase, rats were able to discriminate different rhythms corresponding to segregated or integrated tone sequences in both short inter-tone interval (ITI) and long ITI conditions. Nevertheless, performance was poorer in the long ITI group. In probe testing, which assessed the ability to discriminate one of the segregated tone sequences from ABA- tone sequences, the detection rate increased with the difference in frequency (ΔF) for short (100 ms), but not long (200 ms) ITIs. Our results indicate that auditory streaming in rats on both the spectral and temporal features in the ABA- tone paradigm is qualitatively analogous to that observed in human psychophysics studies. This suggests that rodents are a valuable model for investigating the neural substrates of auditory streaming.

P 102 Domain-specific effects of transcranial random noise stimulation (tRNS) on auditory feature processing

Theoretical background Decoding acoustic speech signals requires to parse the acoustic stream into linguistically meaningful units, and to extract stress and prosody. Accordingly, the temporal and spectral resolution of the auditory cortex is essential in successful speech processing ( Rosen, 1992 ). The reduced acuity in discriminating these features is considered as key factor in dyslexia ( Goswami, 2011 ) but is also a consequence of normal aging ( Walton, 2010 ). Transcranial random noise stimulation (tRNS), a non-invasive brain stimulation technique that applies weak currents at multiple frequencies, is assumed to modulate the excitability of neural assemblies and, in consequence, the reactivity of cortical structures. However, the effect of tRNS on the auditory system is yet unclear. The present study aimed to fill this gap by investigating the impact of tRNS on basic auditory feature processing. Considering the hemispheric specialization of the auditory system in analyzing theses features we hypothesized that a site-specific tRNS application leads to domain-specific changes in auditory features processing. In concrete, tRNS over the left auditory cortex (lAC) was hypothesized to affect the temporal domain while tRNS over the right auditory cortex (rAC) was assumed to modulate the spectral domain. Finally, we investigated whether tRNS over bilateral auditory cortex (bAC) leads to a modulation of both dimensions. Methods On four days 18 healthy, right-handed adults received 30 min. tRNS at an intensity of 1.5 mA either over the lAC, over the rAC, over bAC or sham stimulation while continuous EEG was recorded. The task consisted of the detection of a deviant tone in a sequence of three sine wave tones. While the duration of all tones and the pitch of the standard tones was kept stable, the inter-tone interval (temporal information) and the frequency in that the deviant tone differed from the standard tones (spectral information) was modulated. Results In result, we found that tRNS applied over the lAC and over bAC inferred with task performance. This effect was specifically modulated by the inter-tone interval between the tone triplets but not by the frequency of the deviant tone. On the electrophysiological level, this finding was paralleled by feature-specific brain response patterns in the alpha and the lower gamma band. Discussion Our findings demonstrate the functional relevance of the lAC in processing temporal features. Most importantly, we proved tRNS as a valid technique to modulate basic auditory perception. The current results stress the need for further investigations on the effect of tRNS in the auditory domain. Systematically assessing the most effective stimulation parameters provides the basis for the clinical application of tRNS in the context of speech and language disorders.

Auditory Event-Related Potentials in the Interictal Phase of Migraine Indicate Alterations in Automatic Attention.

Migraine has been characterized by interictal cortical hyperresponsivity. We compared event-related brain potentials (ERPs) to unattended tone pairs in migraineurs (interictal) versus non-headache controls, with particular interest in attention-related activity (i.e., the N1 component). Electroencephalograms were recorded from 11 interictal migraineurs and 14 headache-free controls while they watched a silent video. Pairs of 50-ms tones with 500-ms inter-tone intervals were presented with inter-pair intervals of 1 or 5s. P1, N1, P2, and N2 components were analyzed. N1 peak amplitudes were larger in migraineurs than in controls, especially after the 5-s inter-pair interval. However, there was no difference between groups in the attenuation of the N1 (i.e., no interaction). P2 peak amplitudes were larger in migraineurs, but only after the first tone in the pair. The three migraineurs without aura had larger N1s than the eight with aura. Our findings are consistent with interictal hyperresponsivity of cortical generators of these ERPs in migraineurs. However, areas that inhibit the responses with stimulus repetition do not seem to be affected.

Stimulus phase locking of cortical oscillation for perceptual organization

The phase of cortical oscillations contains rich information and is valuable for encoding sound stimuli. We tested whether and how spatial patterns of oscillatory phase locking within the auditory cortex better predicted perceptual organization than those of response amplitude. A high-density microelectrode array with 10 × 10 sites within 4 × 4 mm2 mapped LFPs at the 4th layer of auditory cortex in rats. First, in response to ABA-sequences with different inter-tone intervals and frequency differences, neurometric functions based on stimulus phase locking in the gamma band could better describe van Noorden’s perceptual boundary than the LFP amplitude. Second, when a random tone sequence was switched to a regular tone sequence, the gamma-band phase locking increased immediately after the transition from random to regular sequences. The amplitude of the tone-evoked response, on the other hand, increased with frequency separation with respect to the prior tone, irrespective of putative organization of auditory objects. These results suggest that the evoked-response amplitude encodes the local order of tones, while the phase locking better predicts the perceptual organization.

Strain dependent effects of conditioned fear in adult C57Bl/6 and Balb/C mice following postnatal exposure to chlorpyrifos: relation to expression of brain acetylcholinesterase mRNA.

Following reports of emotional psychopathology in children and adults exposed to organophosphates, the effects of postnatal chlorpyrifos (CPF) on fear-conditioning and depression-like behaviors were tested in adult mice. Concomitant changes in expression of mRNA for synaptic and soluble splice variants of acetylcholinesterase (AChE) were examined in mouse pups and adults of the Balb/C and C57Bl/6 (B6) strains, which differ in their behavioral and hormonal stress response. Mice were injected subcutaneously with 1 mg/kg CPF on postnatal days 4–10 and tested as adults for conditioned fear, sucrose preference, and forced swim. Acetylcholinesterase activity was assessed in the brains of pups on the first and last day of treatment. Expression of soluble and synaptic AChE mRNA was assessed in brains of treated pups and fear-conditioned adults using real-time PCR. Adult Balb/C mice exposed postnatally to CPF showed exacerbated fear-conditioning and impaired active avoidance. Adult B6 mice exposed postnatally to CPF showed a more specific fear response to tones and less freezing in the inter-tone intervals, in contrast to the vehicle-pretreated mice. Chlorpyrifos also attenuated sweet preference and enhanced climbing in the forced swim test. Chlorpyrifos-treated mice had increased expression of both synaptic and readthrough AChE transcripts in the hippocampus of Balb/C mice and decreased expression in the amygdala following fear-conditioning. In conclusion, postnatal CPF had long-term effects on fear and depression, as well as on expression of AChE mRNA. These changes may be related to alteration in the interaction between hippocampus and amygdala in regulating negative emotions.

The role of working memory in the temporal control of discrete and continuous movements.

Music performance requires precise control of limb movements in order to achieve temporal precision of performed tone onsets. Previous findings suggest that processes recruited for the temporal control of rhythmic body movements, such as those required in music performance, depend on the movement type (discrete vs. continuous) and the rate of the produced interonset intervals (sub-second vs. supra-second). Using a dual-task paradigm, the current study addressed these factors in the temporal control of cellists’ bowing movements. Cellists performed melodies in a synchronization-continuation timing task at a specified fast (intertone interval = 700 ms) or slow (intertone interval = 1,100 ms) tempo with either discrete (staccato) or continuous (legato) bowing movements. A secondary working memory task involved a concurrent digit-switch counting task. Analyses of the produced tone durations showed that the working memory load significantly impaired temporal regularity when the melodies were performed with discrete bowing movements at the slower tempo. In addition, discrete movements led to more errors on the working memory task. These findings suggest that continuous body movements provide temporal control information to performers under high cognitive load conditions.

Tapping to a slow tempo in the presence of simple and complex meters reveals experience-specific biases for processing music.

Musical meters vary considerably across cultures, yet relatively little is known about how culture-specific experience influences metrical processing. In Experiment 1, we compared American and Indian listeners' synchronous tapping to slow sequences. Inter-tone intervals contained silence or to-be-ignored rhythms that were designed to induce a simple meter (familiar to Americans and Indians) or a complex meter (familiar only to Indians). A subset of trials contained an abrupt switch from one rhythm to another to assess the disruptive effects of contradicting the initially implied meter. In the unfilled condition, both groups tapped earlier than the target and showed large tap-tone asynchronies (measured in relative phase). When inter-tone intervals were filled with simple-meter rhythms, American listeners tapped later than targets, but their asynchronies were smaller and declined more rapidly. Likewise, asynchronies rose sharply following a switch away from simple-meter but not from complex-meter rhythm. By contrast, Indian listeners performed similarly across all rhythm types, with asynchronies rapidly declining over the course of complex- and simple-meter trials. For these listeners, a switch from either simple or complex meter increased asynchronies. Experiment 2 tested American listeners but doubled the duration of the synchronization phase prior to (and after) the switch. Here, compared with simple meters, complex-meter rhythms elicited larger asynchronies that declined at a slower rate, however, asynchronies increased after the switch for all conditions. Our results provide evidence that ease of meter processing depends to a great extent on the amount of experience with specific meters.

Substructure of Functional Network for Auditory Stream Segregation in Auditory Cortex

SUMMARYPerceptual integration and segregation of alternating tone sequences differing in frequency (ABA‐ABA‐...) depend on the frequency differences (ΔFs) between the A and B tones and the intertone intervals (ITIs) between successive tones. In the auditory cortex, tonotopic separation, forward suppression, and multisecond habituation have been considered as possible neural mechanisms of this perceptual phenomenon. These mechanisms, however, cannot completely account for van Noorden's perceptual boundary and the temporally continuous perception of auditory streaming. Here we examined the temporal changes of the functional network properties in the auditory cortex in response to tone sequences with different ΔFs and ITIs. Specifically, we recorded LFPs using microelectrode arrays from anesthetized rats and constructed the functional network based on phase synchrony in gamma‐band oscillation. Consequently, the networks consisted of subnetworks highly correlated with the place code of frequency, that is, a tonotopic map, and the subnetwork selective to B tones lasted for a prolonged period at large ΔF. Such characteristic substructures of the functional network are a possible candidate for the neural basis of auditory stream segregation.

Stimulus Phase Locking of Cortical Oscillation for Auditory Stream Segregation in Rats

The phase of cortical oscillations contains rich information and is valuable for encoding sound stimuli. Here we hypothesized that oscillatory phase modulation, instead of amplitude modulation, is a neural correlate of auditory streaming. Our behavioral evaluation provided compelling evidences for the first time that rats are able to organize auditory stream. Local field potentials (LFPs) were investigated in the cortical layer IV or deeper in the primary auditory cortex of anesthetized rats. In response to ABA- sequences with different inter-tone intervals and frequency differences, neurometric functions were characterized with phase locking as well as the band-specific amplitude evoked by test tones. Our results demonstrated that under large frequency differences and short inter-tone intervals, the neurometric function based on stimulus phase locking in higher frequency bands, particularly the gamma band, could better describe van Noorden’s perceptual boundary than the LFP amplitude. Furthermore, the gamma-band neurometric function showed a build-up-like effect within around 3 seconds from sequence onset. These findings suggest that phase locking and amplitude have different roles in neural computation, and support our hypothesis that temporal modulation of cortical oscillations should be considered to be neurophysiological mechanisms of auditory streaming, in addition to forward suppression, tonotopic separation, and multi-second adaptation.

Amplitude and phase-locking adaptation of neural oscillation in the rat auditory cortex in response to tone sequence

Sensory adaptation allows stimulus sensitivity to be dynamically modulated according to stimulus statistics and plays pivotal roles in efficient neural computation. Here, it is hypothesized that in the auditory cortex, phase locking of local field potentials (LFPs) to test tones exhibits an adaptation property, i.e., phase-locking adaptation, which is distinct from the amplitude adaptation of oscillatory components. Series of alternating tone sequences were applied in which the inter-tone interval (ITI) and frequency difference (ΔF) between successive tones were varied. Then, adaptation was characterized by the temporal evolution of the band-specific amplitude and phase locking evoked by the test tones. Differences as well as similarities were revealed between amplitude and phase-locking adaptations. First, both amplitude and phase-locking adaptations were enhanced by short ITIs and small ΔFs. Second, the amplitude adaptation was more effective in a higher frequency band, while the phase-locking adaptation was more effective in a lower frequency band. Third, as with the adaptation of multiunit activities (MUAs), the amplitude adaptation occurred mainly within a second, while the phase-locking showed multi-second adaptation specifically in the gamma band for short ITI and small ΔF conditions. Fourth, the amplitude adaptation and phase-locking adaptation were co-modulated in a within-second time scale, while this co-modulation was not observed in a multi-second time scale. These findings suggest that the amplitude and phase-locking adaptations have different mechanisms and functions. The phase-locking adaptation is likely to play more crucial roles in encoding a temporal structure of stimulus than the amplitude adaptation.

Functional subnetwork structure in auditory cortex for stream segregation

Perceptual integration and segregation of alternating tone sequence differing in frequency (ABA-ABA-...) depend on the frequency differences (Delta-Fs) between A and B tones and the inter-tone intervals (ITIs) between successive tones. In the auditory cortex, tonotopic separation, forward suppression and multisecond habituation have been considered as possible neural correlates of this perceptual phenomenon. This model, however, cannot completely account for the van Noorden's perceptual boundary and the temporally continuous perception of auditory streaming. Here we examined the temporal changes of the functional network properties in auditory cortex to tone sequences with different Delta-Fs and ITIs. Specifically, we recorded local field potentials using microelectrode arrays from anesthetized and awake rats and constructed the functional network based on phase synchrony in gamma-band oscillation. As the results, the networks consisted of sub-networks highly correlated with tonotopy, and the sub-network selective to B tones lasted for a prolonged period at large Delta-F. Such characteristic substructures of functional network are a possible candidate of neural mechanisms of auditory stream segregation.

Substructure of Functional Network for Auditory Stream Segregation in Auditory Cortex

SUMMARY Perceptual integration and segregation of alternating tone sequences differing in frequency (ABA-ABA-...) depend on the frequency differences (ΔFs) between the A and B tones and the intertone intervals (ITIs) between successive tones. In the auditory cortex, tonotopic separation, forward suppression, and multisecond habituation have been considered as possible neural mechanisms of this perceptual phenomenon. These mechanisms, however, cannot completely account for van Noorden's perceptual boundary and the temporally continuous perception of auditory streaming. Here we examined the temporal changes of the functional network properties in the auditory cortex in response to tone sequences with different ΔFs and ITIs. Specifically, we recorded LFPs using microelectrode arrays from anesthetized rats and constructed the functional network based on phase synchrony in gamma-band oscillation. Consequently, the networks consisted of subnetworks highly correlated with the place code of frequency, that is, a tonotopic map, and the subnetwork selective to B tones lasted for a prolonged period at large ΔF. Such characteristic substructures of the functional network are a possible candidate for the neural basis of auditory stream segregation.

Intelligence and Information Processing

The relationship between mental ability (MA, Raven Progressive Matrices) and speed of information processing was examined by recording mismatch negativity (MMN) parameters from 41 women during passive listening to auditory standard and deviant stimuli with backward masking. The intertone interval (ITI) between the offset of the standard or deviant tone and the onset of the masking tone was varied between conditions (25, 50, or 150 ms). Three versions of a trail-making test (Zahlen-Verbindungs-Test, ZVT) were also presented to obtain a behavioral index of information processing speed. Multiple regression analysis showed that the more difficult versions of the ZVT and midline frontal MMN latency at 25-ms ITI were both significant predictors of MA. Across all ITI conditions, the higher ability (HA) group exhibited a shorter MMN latency than the lower ability (LA) group. Finally, the HA group also had a larger MMN amplitude than the LA group for the 25-ms ITI condition. These results indicate that low-level auditory discrimination, indexed by MMN, contributes to individual differences in fluid intelligence. In this regard, MMN provides a valuable tool for examining individual differences in intelligence in individuals who are not able to comply with psychometric testing.

The role of temporal regularity in auditory segregation

The idea that predictive modelling and extraction of regularities plays a pivotal role in auditory segregation has recently attracted considerable attention. The present study investigated the effect of one basic form of regularity, rhythmic regularity, on auditory stream segregation. We departed from the classic streaming paradigm and developed a new stimulus, Rand-AB, consisting of two, concurrently presented, temporally uncorrelated, tone sequences (with frequencies A and B). To evaluate segregation, we used an objective measure of the extent to which listeners are able to selectively attend to one of the sequences in the presence of the other. Performance was quantified on a difficult pattern detection task which involves detecting a rarely occurring pattern of amplitude modulation applied to three consecutive A or B tones. In all cases the attended sequence was temporally irregular (with a random inter-tone-interval (ITI) between 100 and 400 ms) and the regularity status of the competing sequence was set to one of four conditions: (1) random ITI between 100 and 400 ms (2) isochronous with ITI = 400 ms. (3) isochronous with ITI = 250 ms (equal to the mean rate of the attended sequence) (4) isochronous with ITI = 100 ms. For a frequency separation of 2 (but not 4) semi tones we observed improved performance in conditions (3) and (4) relative to (1), suggesting that stream segregation is facilitated when the distracter sequence is temporally regular, but that the effect of temporal regularity as a cue for segregation is limited to relatively fast rates and to situations where frequency separation is insufficient for segregation. These findings provide new evidence to support models of streaming that involve segregation based on the formation of predictive models.

Tone Language Fluency Impairs Pitch Discrimination

Here we present evidence that native speakers of a tone language, in which pitch contributes to word meaning, are impaired in the discrimination of falling pitches in tone sequences, as compared to speakers of a non-tone language. Both groups were presented with monotonic and isochronous sequences of five tones (i.e., constant pitch and intertone interval). They were required to detect when the fourth tone was displaced in pitch or time. While speakers of a tone language performed more poorly in the detection of downward pitch changes, they did not differ from non-tone language speakers in their perception of upward pitch changes or in their perception of subtle time changes. Moreover, this impairment cannot be attributed to poor musical abilities since the impairment remains unchanged when individual differences in musical pitch-based processing is taken into account. Thus, the impairment appears highly specific and may reflect the influence of statistical regularities of tone languages.

Neural correlates of auditory temporal-interval discrimination in cats

Auditory temporal cues are very important in the perception of speech; nevertheless, the neural correlates underlying even a simple temporal task, such as interval discrimination, remain unclear, mainly due to the lack of comparable data of psychophysical and electrophysiological experiments in the same species. To address this, we measured both behavioral and neural responses in cats. Cats’ ability to discriminate differences in sound intervals was tested by presenting two identical pure tone markers interrupted by intervals ranging from 10 to 320 ms duration. All three subjects could accurately discriminate tones of 80–320 ms interval from those of 10 ms interval (correct rate > 75%), but could not discriminate 20–40 ms interval from 10 ms interval. Neural responses to the same stimuli were recorded in the primary auditory cortex (A1) of three others awake cats. Consistent with previous studies, we found that the majority of A1 neurons showed a suppressed response to the second tone, and the amount of suppression generally increased with the decrease of intertone interval. Neurometric analysis revealed that neural responses could be used to discriminate the intertone interval, while discrimination performance was dependent on temporal precision to read the neural information. When spike activities were analyzed by 100 ms bin size, 80% of neurometric functions matched the cats’ psychometric function, suggesting a possible correlation between A1 activities and interval perception.