The Representation of Time Windows in Primate Auditory Cortex.

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

The distribution and nature of responses to broadband sounds associated with pitch in the macaque auditory cortex.

The organisation of pitch-perception mechanisms in the primate cortex is controversial, in that divergent results have been obtained, ranging from a single circumscribed 'pitch centre' to systems widely distributed across auditory cortex. Possible reasons for such discrepancies include different species, recording techniques, pitch stimuli, sampling of auditory fields, and the neural metrics recorded. In the present study, we sought to bridge some of these divisions by examining activity related to pitch in both neurons and neuronal ensembles within the auditory cortex of the rhesus macaque, a primate species with similar pitch perception and auditory cortical organisation to humans. We demonstrate similar responses, in primary and non-primary auditory cortex, to two different types of broadband pitch above the macaque lower limit in both neurons and local field potential (LFP) gamma oscillations. The majority of broadband pitch responses in neurons and LFP sites did not show equivalent tuning for sine tones.

Auditory motion-specific mechanisms in the primate brain.

This work examined the mechanisms underlying auditory motion processing in the auditory cortex of awake monkeys using functional magnetic resonance imaging (fMRI). We tested to what extent auditory motion analysis can be explained by the linear combination of static spatial mechanisms, spectrotemporal processes, and their interaction. We found that the posterior auditory cortex, including A1 and the surrounding caudal belt and parabelt, is involved in auditory motion analysis. Static spatial and spectrotemporal processes were able to fully explain motion-induced activation in most parts of the auditory cortex, including A1, but not in circumscribed regions of the posterior belt and parabelt cortex. We show that in these regions motion-specific processes contribute to the activation, providing the first demonstration that auditory motion is not simply deduced from changes in static spatial location. These results demonstrate that parallel mechanisms for motion and static spatial analysis coexist within the auditory dorsal stream.

The topography of frequency and time representation in primate auditory cortices.

Natural sounds can be characterised by their spectral content and temporal modulation, but how the brain is organized to analyse these two critical sound dimensions remains uncertain. Using functional magnetic resonance imaging, we demonstrate a topographical representation of amplitude modulation rate in the auditory cortex of awake macaques. The representation of this temporal dimension is organized in approximately concentric bands of equal rates across the superior temporal plane in both hemispheres, progressing from high rates in the posterior core to low rates in the anterior core and lateral belt cortex. In A1 the resulting gradient of modulation rate runs approximately perpendicular to the axis of the tonotopic gradient, suggesting an orthogonal organisation of spectral and temporal sound dimensions. In auditory belt areas this relationship is more complex. The data suggest a continuous representation of modulation rate across several physiological areas, in contradistinction to a separate representation of frequency within each area.

A perceptual pitch boundary in a non-human primate.

Pitch is an auditory percept critical to the perception of music and speech, and for these harmonic sounds, pitch is closely related to the repetition rate of the acoustic wave. This paper reports a test of the assumption that non-human primates and especially rhesus monkeys perceive the pitch of these harmonic sounds much as humans do. A new procedure was developed to train macaques to discriminate the pitch of harmonic sounds and thereby demonstrate that the lower limit for pitch perception in macaques is close to 30 Hz, as it is in humans. Moreover, when the phases of successive harmonics are alternated to cause a pseudo-doubling of the repetition rate, the lower pitch boundary in macaques decreases substantially, as it does in humans. The results suggest that both species use neural firing times to discriminate pitch, at least for sounds with relatively low repetition rates.

Merging functional and structural properties of the monkey auditory cortex.

Recent neuroimaging studies in primates aim to define the functional properties of auditory cortical areas, especially areas beyond A1, in order to further our understanding of the auditory cortical organization. Precise mapping of functional magnetic resonance imaging (fMRI) results and interpretation of their localizations among all the small auditory subfields remains challenging. To facilitate this mapping, we combined here information from cortical folding, micro-anatomy, surface-based atlas and tonotopic mapping. We used for the first time, phase-encoded fMRI design for mapping the monkey tonotopic organization. From posterior to anterior, we found a high-low-high progression of frequency preference on the superior temporal plane. We show a faithful representation of the fMRI results on a locally flattened surface of the superior temporal plane. In a tentative scheme to delineate core versus belt regions which share similar tonotopic organizations we used the ratio of T1-weighted and T2-weighted MR images as a measure of cortical myelination. Our results, presented along a co-registered surface-based atlas, can be interpreted in terms of a current model of the monkey auditory cortex.

A unified framework for the organization of the primate auditory cortex.

In non-human primates a scheme for the organization of the auditory cortex is frequently used to localize auditory processes. The scheme allows a common basis for comparison of functional organization across non-human primate species. However, although a body of functional and structural data in non-human primates supports an accepted scheme of nearly a dozen neighboring functional areas, can this scheme be directly applied to humans? Attempts to expand the scheme of auditory cortical fields in humans have been severely hampered by a recent controversy about the organization of tonotopic maps in humans, centered on two different models with radically different organization. We point out observations that reconcile the previous models and suggest a distinct model in which the human cortical organization is much more like that of other primates. This unified framework allows a more robust and detailed comparison of auditory cortex organization across primate species including humans.

Long-term exposure to music enhances the sensitivity of the auditory system in children.

This event-related brain potential study aims to contribute to the present debate regarding the effect of musical training on the maturation of the human auditory nervous system. To address this issue, we recorded the mismatch negativity (MMN) evoked by violin and pure sine-wave tones in a group of 7.5- to 12-year-old children who had either several years of musical experience with Suzuki violin lessons, or no musical training. The strength of the MMN responses to violin tones evident in the Suzuki students clearly surpassed responses in controls; the reverse pattern was observed for sine-wave tones. Suzuki students showed significantly shorter MMN latencies to violin tones than to pure tones; the MMN latency did not differ significantly between pure tones and violin sounds in the control group. Thus, our data provide general evidence of how and to what extent extensive musical experience affects the maturation of human auditory function at multiple levels, namely, accuracy and speed of auditory discrimination processing. Our findings add to the present understanding of neuroplastic organization and function of the mammalian nervous system. Furthermore, behavioural recordings obtained from the participating children provide corroborating evidence for a relationship between the duration and intensity of training, the specific sensitivity to instrumental timbre, and pitch recognition abilities.

Orthogonal representation of sound dimensions in the primate midbrain.

Natural sounds are characterized by their spectral content and the modulation of energy over time. Using functional magnetic resonance imaging in awake macaques, we observed topographical representations of these spectral and temporal dimensions in a single structure, the inferior colliculus, the principal auditory nucleus in the midbrain. These representations are organized as a map with two approximately perpendicular axes: one representing increasing temporal rate and the other increasing spectral frequency.

Characterisation of the BOLD response time course at different levels of the auditory pathway in non-human primates.

Non-human-primate fMRI is becoming increasingly recognised as the missing link between the widely applied methods of human imaging and intracortical animal electrophysiology. A crucial requirement for the optimal application of this method is the precise knowledge of the time course of the Blood Oxygenation Level Dependent (BOLD) signal. We mapped the BOLD signal time course in the inferior colliculus (IC), medial geniculate body (MGB) and in tonotopically defined fields in the auditory cortex of two macaques. The results show little differences in the BOLD-signal time courses within the auditory pathway. However, we observed systematic differences in the magnitude of the change in the BOLD signal with significantly stronger signal changes in field A1 of the auditory cortex compared to field R. The measured time course of the signal was in good agreement with similar studies in human auditory cortex but showed considerable differences to data reported from macaque visual cortex. Consistent with the studies in humans we measured a peak in the BOLD response around 4 s after the onset of 2-s broadband noise stimuli while previous studies recorded from the primary visual cortex of the same species reported the earliest peaks to short visual stimuli several seconds later. The comparison of our results with previous studies does not support differences in haemodynamic responses within the auditory system between human and non-human primates. Furthermore, the data will aid optimal design of future auditory fMRI studies in non-human primates.

In vitro myogenic differentiation of human bone marrow-derived mesenchymal stem cells as a potential treatment for urethral sphincter muscle repair.

To explore a new treatment strategy for urinary incontinence, human bone marrow mesenchymal stem cells (MSC) of the first in vitro passage were exposed to 5-azacytidine (AZA) to induce myogenic differentiation, and cultured for a total of six passages. Expression of stem cell surface antigens and intracellular alpha-actin was examined by flow cytometry at the end of each passage and compared to that of native MSC (not exposed to AZA) cultured in parallel. To analyze differentiation into striated muscle, expression of the transcription factor MyoD1 and myosin heavy chain (MyHC) was examined by RT-PCR. Both native and AZA-exposed MSC of all passages were negative for the progenitor/endothelial antigen CD34, leukocytic CD45, and endothelial/monocytic CD31. In contrast, the MSC markers CD73, CD90, CD105, and intracellular actin were detected in both groups of MSC throughout the culture period. After an initial increase, the expression level of MSC antigens decreased over time particularly in AZA-exposed MSC. Expression of smooth muscle alpha-actin also declined, but was greater in AZA-exposed MSC throughout the culture period. Varying percentages of MSC cultures expressed MyoD1 and MyHC mRNA. In late passages, AZA-exposed MSC tended to be more frequently positive than native MSC. In pilot experiments, transplantation of MSC into the bladder neck tissue of athymic rats was feasible; long-term analyses are pending. We conclude that independent of AZA exposure, MSC express smooth and striated muscle antigens. Treatment with AZA slightly increases myogenic differentiation, but may not be necessary in future studies of MSC as a treatment modality for urinary incontinence.

Enhancement of auditory-evoked potentials in musicians reflects an influence of expertise but not selective attention.

Instrumental tones and, in some instances, simple sine-wave tones were shown to evoke stronger auditory-evoked responses in musicians compared to nonmusicians. This effect was taken as an example for plasticity in the auditory cortex elicited by training. To date, however, it is unknown whether an enlarged cortical representation for (instrumental) tones or increased neuronal activity provoked by focused attention in musicians accounts for the reported difference. In an attempt to systematically investigate the influence of attention on the processing of simple sine wave and instrumental tones, we compared auditory-evoked potentials recorded from musicians and nonmusicians. During the electroencephalogram recording, the participants were involved in tasks requiring selective attention to specific sound features such as pitch or timbre. Our results demonstrate that the effect of selective attention on the auditory event-related potential (AEP) has a different time course and shows a different topography than the reproduced effect of music expertise at the N1 component or the previously demonstrated effect at the P2 component. N1 peak potentials were unaffected by attention modulation. These results indicate that the effect of music expertise, which was traced by current density mapping to the auditory cortex, is not primarily caused by selective attention, and it supports the view that increased AEPs on tones in musicians reflect an enlarged neuronal representation for specific sound features of these tones. However, independent from the N1-P2 complex, attention evoked an Nd-like negative component in musicians but not in nonmusicians, which suggests that plasticity also affects top-down processes.

Short-term plasticity in the auditory system: differential neural responses to perception and imagery of speech and music.

PURPOSE: In this EEG study we sought to examine the neuronal underpinnings of short-term plasticity as a top-down guided auditory learning process. We hypothesized, that (i) auditory imagery should elicit proper auditory evoked effects (N1/P2 complex) and a late positive component (LPC). Generally, based on recent human brain mapping studies we expected (ii) to observe the involvement of different temporal and parietal lobe areas in imagery and in perception of acoustic stimuli. Furthermore we predicted (iii) that temporal regions show an asymmetric trend due to the different specialization of the temporal lobes in processing speech and non-speech sounds. Finally we sought evidence supporting the notion that short-term training is sufficient to drive top-down activity in brain regions that are not normally recruited by sensory induced bottom up processing. METHODS: 18 non-musicians partook in a 30 channels based EEG session that investigated spatio-temporal dynamics of auditory imagery of "consonant-vowel" (CV) syllables and piano triads. To control for conditioning effects, we split the volunteers in two matched groups comprising the same conditions (visual, auditory or bimodal stimulation) presented in a slightly different serial order. Furthermore the study presents electromagnetic source localization (LORETA) of perception and imagery of CV- and piano stimuli. RESULTS: Our results imply that auditory imagery elicited similar electrophysiological effects at an early stage (N1/P2) as auditory stimulation. However, we found an additional LPC following the N1/P2 for auditory imagery only. Source estimation evinced bilateral engagement of anterior temporal cortex, which was generally stronger for imagery of music relative to imagery of speech. While we did not observe lateralized activity for the imagery of syllables we noted significantly increased rightward activation over the anterior supratemporal plane for musical imagery. CONCLUSION: Thus, we conclude that short-term top-down training based auditory imagery of music and speech prompts involvement of distinct neural circuits residing in the perisylvian cortex.

Comparison of "silent" clustered and sparse temporal fMRI acquisitions in tonal and speech perception tasks.

In the functional imaging of auditory cortical functions, long silent periods between the data acquisitions prevent interferences between scanner noise and the auditory stimulus processing. Recent fMRI studies have shown that sparse temporal acquisition designs are advantageous over continuous scanning protocols on physiological, perceptual, and cognitive levels. Sparse temporal acquisition schemes (STA) which use a single volume acquisition after each trial imply the advantage of auditory stimulation devoid of ambient scanner noise but have the drawback of a reduced statistical power. To alleviate this effect, STA schemes have been extended to clustered-sparse temporal acquisition (CTA) designs which record several subsequent BOLD contrast images in rapid succession. In the present study, we collected data from 13 healthy volunteers performing a speech and a tonal discrimination task using both a CTA and STA scheme to carry out a systematic evaluation of these acquisition protocols. By statistical modeling of the fMRI data sets, we revealed stronger effect sizes for the STA protocol regardless of the task, reflecting the better signal-to-noise-ratio of MR images acquired with this scheme. In contrast, we demonstrate higher statistical power for the use of a CTA protocol. Accordingly, in the context of standard fMRI analysis, the CTA protocol clearly outperformed the STA scheme at the level of single-subject analysis and fixed-effects group analysis. Our results clearly suggest that it is advantageous to acquire several sample points per trial if one wants to use the benefit of "silent" fMRI. Furthermore, our data demonstrate the feasibility of the clustered acquisition of subsequent imaging volumes along the T1-decay.

A network for audio-motor coordination in skilled pianists and non-musicians.

Playing a musical instrument requires efficient auditory and motor processing. Fast feed forward and feedback connections that link the acoustic target to the corresponding motor programs need to be established during years of practice. The aim of our study is to provide a detailed description of cortical structures that participate in this audio-motor coordination network in professional pianists and non-musicians. In order to map these interacting areas using functional magnetic resonance imaging (fMRI), we considered cortical areas that are concurrently activated during silent piano performance and motionless listening to piano sound. Furthermore we investigated to what extent interactions between the auditory and the motor modality happen involuntarily. We observed a network of predominantly secondary and higher order areas belonging to the auditory and motor modality. The extent of activity was clearly increased by imagination of the absent modality. However, this network did neither comprise primary auditory nor primary motor areas in any condition. Activity in the lateral dorsal premotor cortex (PMd) and the pre-supplementary motor cortex (preSMA) was significantly increased for pianists. Our data imply an intermodal transformation network of auditory and motor areas which is subject to a certain degree of plasticity by means of intensive training.

How the brain laughs. Comparative evidence from behavioral, electrophysiological and neuroimaging studies in human and monkey.

Laughter is an affective nonspeech vocalization that is not reserved to humans, but can also be observed in other mammalians, in particular monkeys and great apes. This observation makes laughter an interesting subject for brain research as it allows us to learn more about parallels and differences of human and animal communication by studying the neural underpinnings of expressive and perceptive laughter. In the first part of this review we will briefly sketch the acoustic structure of a bout of laughter and relate this to the differential anatomy of the larynx and the vocal tract in human and monkey. The subsequent part of the article introduces the present knowledge on behavioral and brain mechanisms of "laughter-like responses" and other affective vocalizations in monkeys and apes, before we describe the scant evidence on the cerebral organization of laughter provided by neuroimaging studies. Our review indicates that a densely intertwined network of auditory and (pre-) motor functions subserves perceptive and expressive aspects of human laughter. Even though there is a tendency in the present literature to suggest a rightward asymmetry of the cortical representation of laughter, there is no doubt that left cortical areas are also involved. In addition, subcortical areas, namely the amygdala, have also been identified as part of this network. Furthermore, we can conclude from our overview that research on the brain mechanisms of affective vocalizations in monkeys and great apes report the recruitment of similar cortical and subcortical areas similar to those attributed to laughter in humans. Therefore, we propose the existence of equivalent brain representations of emotional tone in human and great apes. This reasoning receives support from neuroethological models that describe laughter as a primal behavioral tool used by individuals - be they human or ape - to prompt other individuals of a peer group and to create a mirthful context for social interaction and communication.

Hemodynamic responses in human multisensory and auditory association cortex to purely visual stimulation.

BACKGROUND: Recent findings of a tight coupling between visual and auditory association cortices during multisensory perception in monkeys and humans raise the question whether consistent paired presentation of simple visual and auditory stimuli prompts conditioned responses in unimodal auditory regions or multimodal association cortex once visual stimuli are presented in isolation in a post-conditioning run. To address this issue fifteen healthy participants partook in a "silent" sparse temporal event-related fMRI study. In the first (visual control) habituation phase they were presented with briefly red flashing visual stimuli. In the second (auditory control) habituation phase they heard brief telephone ringing. In the third (conditioning) phase we coincidently presented the visual stimulus (CS) paired with the auditory stimulus (UCS). In the fourth phase participants either viewed flashes paired with the auditory stimulus (maintenance, CS-) or viewed the visual stimulus in isolation (extinction, CS+) according to a 5:10 partial reinforcement schedule. The participants had no other task than attending to the stimuli and indicating the end of each trial by pressing a button. RESULTS: During unpaired visual presentations (preceding and following the paired presentation) we observed significant brain responses beyond primary visual cortex in the bilateral posterior auditory association cortex (planum temporale, planum parietale) and in the right superior temporal sulcus whereas the primary auditory regions were not involved. By contrast, the activity in auditory core regions was markedly larger when participants were presented with auditory stimuli. CONCLUSION: These results demonstrate involvement of multisensory and auditory association areas in perception of unimodal visual stimulation which may reflect the instantaneous forming of multisensory associations and cannot be attributed to sensation of an auditory event. More importantly, we are able to show that brain responses in multisensory cortices do not necessarily emerge from associative learning but even occur spontaneously to simple visual stimulation.

Electrical brain imaging reveals spatio-temporal dynamics of timbre perception in humans.

Timbre is a major attribute of sound perception and a key feature for the identification of sound quality. Here, we present event-related brain potentials (ERPs) obtained from sixteen healthy individuals while they discriminated complex instrumental tones (piano, trumpet, and violin) or simple sine wave tones that lack the principal features of timbre. Data analysis yielded enhanced N1 and P2 responses to instrumental tones relative to sine wave tones. Furthermore, we applied an electrical brain imaging approach using low-resolution electromagnetic tomography (LORETA) to estimate the neural sources of N1/P2 responses. Separate significance tests of instrumental vs. sine wave tones for N1 and P2 revealed distinct regions as principally governing timbre perception. In an initial stage (N1), timbre perception recruits left and right (peri-)auditory fields with an activity maximum over the right posterior Sylvian fissure (SF) and the posterior cingulate (PCC) territory. In the subsequent stage (P2), we uncovered enhanced activity in the vicinity of the entire cingulate gyrus. The involvement of extra-auditory areas in timbre perception may imply the presence of a highly associative processing level which might be generally related to musical sensations and integrates widespread medial areas of the human cortex. In summary, our results demonstrate spatio-temporally distinct stages in timbre perception which not only involve bilateral parts of the peri-auditory cortex but also medially situated regions of the human brain associated with emotional and auditory imagery functions.

Neural control of playing a reversed piano: empirical evidence for an unusual cortical organization of musical functions.

Using functional magnetic imaging techniques and neuropsychological tests, we studied a young male musician (C.S.) who performs at a professional level both on a regular piano keyboard and on a reverse keyboard (reversed right to left). The participant was left-handed, had left dominance for language but, remarkably, right dominance for the control of piano playing on both keyboards. With respect to music perception, C.S. showed left-sided activation dominance within the left superior temporal sulcus, which is normally associated with higher order auditory processing and right-sided activations in the secondary sensory cortex extending into the supramarginal gyrus. We suggest that C.S.'s pattern of functional asymmetry, characterized by audio-motor control using a right-sided network, could be a factor in his exceptional piano-playing ability on both the standard and reversed keyboard.

A network for sensory-motor integration: what happens in the auditory cortex during piano playing without acoustic feedback?

Playing a musical instrument requires efficient auditory as well as motor processing. We provide evidence for the existence of a neuronal network of secondary and higher-order areas belonging to the auditory and motor modality that is important in the integration of auditory and motor domains.