A population of neurons selective for human voice in the monkey brain.

Many animals can extract useful information from the vocalizations of other species. Neuroimaging studies have evidenced areas sensitive to conspecific vocalizations in the cerebral cortex of primates, but how these areas process heterospecific vocalizations remains unclear. Using fMRI-guided electrophysiology, we recorded the spiking activity of individual neurons in the anterior temporal voice patches of two macaques while they listened to complex sounds including vocalizations from several species. In addition to cells selective for conspecific macaque vocalizations, we identified an unsuspected subpopulation of neurons with strong selectivity for human voice, not merely explained by spectral or temporal structure of the sounds. The auditory representational geometry implemented by these neurons was strongly related to that measured in the human voice areas with neuroimaging and only weakly to low-level acoustical structure. These findings provide new insights into the neural mechanisms involved in auditory expertise and the evolution of communication systems in primates.

The path of voices in our brain.

Categorising voices is crucial for auditory-based social interactions. A recent study by Rupp and colleagues in PLOS Biology capitalises on human intracranial recordings to describe the spatiotemporal pattern of neural activity leading to voice-selective responses in associative auditory cortex.

Anatomo-functional correspondence in the voice-selective regions of human prefrontal cortex.

Group level analyses of functional regions involved in voice perception show evidence of 3 sets of bilateral voice-sensitive activations in the human prefrontal cortex, named the anterior, middle and posterior Frontal Voice Areas (FVAs). However, the relationship with the underlying sulcal anatomy, highly variable in this region, is still unknown. We examined the inter-individual variability of the FVAs in conjunction with the sulcal anatomy. To do so, anatomical and functional MRI scans from 74 subjects were analyzed to generate individual contrast maps of the FVAs and relate them to each subject's manually labeled prefrontal sulci. We report two major results. First, the frontal activations for the voice are significantly associated with the sulcal anatomy. Second, this correspondence with the sulcal anatomy at the individual level is a better predictor than coordinates in the MNI space. These findings offer new perspectives for the understanding of anatomical-functional correspondences in this complex cortical region. They also shed light on the importance of considering individual-specific variations in subject's anatomy.

Flexizyme-aminoacylated shortened tRNAs demonstrate that only the aminoacylated acceptor arms of the two tRNA substrates are required for cyclodipeptide synthase activity.

Cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs (AA-tRNAs) to catalyse cyclodipeptide formation in a ping-pong mechanism. Despite intense studies of these enzymes in past years, the tRNA regions of the two substrates required for CDPS activity are poorly documented, mainly because of two limitations. First, previously studied CDPSs use two identical AA-tRNAs to produce homocyclodipeptides, thus preventing the discriminative study of the binding of the two substrates. Second, the range of tRNA analogues that can be aminoacylated by aminoacyl-tRNA synthetases is limited. To overcome the limitations, we studied a new model CDPS that uses two different AA-tRNAs to produce an heterocyclodipeptide. We also developed a production pipeline for the production of purified shortened AA-tRNA analogues (AA-minitRNAs). This method combines the use of flexizymes to aminoacylate a diversity of minitRNAs and their subsequent purifications by anion-exchange chromatography. Finally, we were able to show that aminoacylated molecules mimicking the entire acceptor arms of tRNAs were as effective a substrate as entire AA-tRNAs, thereby demonstrating that the acceptor arms of the two substrates are the only parts of the tRNAs required for CDPS activity. The method developed in this study should greatly facilitate future investigations of the specificity of CDPSs and of other AA-tRNAs-utilizing enzymes.

Categorization of vocal and nonvocal stimuli in Guinea baboons (Papio papio).

Categorization of vocal sounds apart from other sounds is one of the key abilities in human voice processing, but whether this ability is present in other animals, particularly nonhuman primates, remains unclear. In the present study, 25 socially housed Guinea baboons (Papio papio) were tested on a vocal/nonvocal categorization task using Go/Nogo paradigm implemented on freely accessible automated learning devices. Three individuals from the group successfully learned to sort Grunt vocalizations from nonvocal sounds, and they generalized to new stimuli from the two categories, indicating that some baboons have the ability to develop open-ended categories in the auditory domain. Contrary to our hypothesis based on the human literature, these monkeys learned the nonvocal category faster than the Grunt category. Moreover, they failed to generalize their classification to new classes of conspecific vocalizations (wahoo, bark, yak, and copulation calls), and they categorized human vocalizations in the nonvocal category, suggesting that they had failed to represent the task as a vocal versus nonvocal categorization problem. Thus, our results do not confirm the existence of a separate perceptual category for conspecific vocalizations in baboons. Interestingly, the three successful baboons are the youngest of the group, with less training in visual tasks, which supports previous reports of age and learning history as crucial factors in auditory laboratory experiments.

Common functional localizers to enhance NHP & cross-species neuroscience imaging research.

Functional localizers are invaluable as they can help define regions of interest, provide cross-study comparisons, and most importantly, allow for the aggregation and meta-analyses of data across studies and laboratories. To achieve these goals within the non-human primate (NHP) imaging community, there is a pressing need for the use of standardized and validated localizers that can be readily implemented across different groups. The goal of this paper is to provide an overview of the value of localizer protocols to imaging research and we describe a number of commonly used or novel localizers within NHPs, and keys to implement them across studies. As has been shown with the aggregation of resting-state imaging data in the original PRIME-DE submissions, we believe that the field is ready to apply the same initiative for task-based functional localizers in NHP imaging. By coming together to collect large datasets across research group, implementing the same functional localizers, and sharing the localizers and data via PRIME-DE, it is now possible to fully test their robustness, selectivity and specificity. To do this, we reviewed a number of common localizers and we created a repository of well-established localizer that are easily accessible and implemented through the PRIME-RE platform.

Cracking the social code of speech prosody using reverse correlation.

Human listeners excel at forming high-level social representations about each other, even from the briefest of utterances. In particular, pitch is widely recognized as the auditory dimension that conveys most of the information about a speaker's traits, emotional states, and attitudes. While past research has primarily looked at the influence of mean pitch, almost nothing is known about how intonation patterns, i.e., finely tuned pitch trajectories around the mean, may determine social judgments in speech. Here, we introduce an experimental paradigm that combines state-of-the-art voice transformation algorithms with psychophysical reverse correlation and show that two of the most important dimensions of social judgments, a speaker's perceived dominance and trustworthiness, are driven by robust and distinguishing pitch trajectories in short utterances like the word "Hello," which remained remarkably stable whether male or female listeners judged male or female speakers. These findings reveal a unique communicative adaptation that enables listeners to infer social traits regardless of speakers' physical characteristics, such as sex and mean pitch. By characterizing how any given individual's mental representations may differ from this generic code, the method introduced here opens avenues to explore dysprosody and social-cognitive deficits in disorders like autism spectrum and schizophrenia. In addition, once derived experimentally, these prototypes can be applied to novel utterances, thus providing a principled way to modulate personality impressions in arbitrary speech signals.

Neural oscillations in human auditory cortex revealed by fast fMRI during auditory perception.

Previous work pointed to the neural and functional significance of infraslow neural oscillations below 1 â€‹Hz that can be detected and precisely located with fast functional magnetic resonance imaging (fMRI). While previous work demonstrated this significance for brain dynamics during very low-level sensory stimulation, we here provide the first evidence for the detectability and functional significance of infraslow oscillatory blood oxygenation level-dependent (BOLD) responses to auditory stimulation by the sociobiological relevant and more complex category of voices. Previous work pointed to a specific area of the mammalian auditory cortex (AC) that is sensitive to vocal signals as quantified by activation levels. Here we show, by using fast fMRI, that the human voice-sensitive AC prioritizes vocal signals not only in terms of activity level but also in terms of specific infraslow BOLD oscillations. We found unique sustained and transient oscillatory BOLD patterns in the AC for vocal signals. For transient oscillatory patterns, vocal signals showed faster peak oscillatory responses across all AC regions. Furthermore, we identified an exclusive sustained oscillatory component for vocal signals in the primary AC. Fast fMRI thus demonstrates the significance and richness of infraslow BOLD oscillations for neurocognitive mechanisms in social cognition as demonstrated here for the sociobiological relevance of voice processing.

Cyclodipeptide synthases: a promising biotechnological tool for the synthesis of diverse 2,5-diketopiperazines.

Covering: Up to mid-2019 Cyclodipeptide synthases (CDPSs) catalyse the formation of cyclodipeptides using aminoacylated-tRNA as substrates. The recent characterization of large sets of CDPSs has revealed that they can produce highly diverse products, and therefore have great potential for use in the production of different 2,5-diketopiperazines (2,5-DKPs). Sequence similarity networks (SSNs) are presented as a new, efficient way of classifying CDPSs by specificity and identifying new CDPS likely to display novel specificities. Several strategies for further increasing the diversity accessible with these enzymes are discussed here, including the incorporation of non-canonical amino acids by CDPSs and use of the remarkable diversity of 2,5-DKP-tailoring enzymes discovered in recent years.

In vivo characterization of the activities of novel cyclodipeptide oxidases: new tools for increasing chemical diversity of bioproduced 2,5-diketopiperazines in Escherichia coli.

BACKGROUND: Cyclodipeptide oxidases (CDOs) are enzymes involved in the biosynthesis of 2,5-diketopiperazines, a class of naturally occurring compounds with a large range of pharmaceutical activities. CDOs belong to cyclodipeptide synthase (CDPS)-dependent pathways, in which they play an early role in the chemical diversification of cyclodipeptides by introducing Cα-Cß dehydrogenations. Although the activities of more than 100 CDPSs have been determined, the activities of only a few CDOs have been characterized. Furthermore, the assessment of the CDO activities on chemically-synthesized cyclodipeptides has shown these enzymes to be relatively promiscuous, making them interesting tools for cyclodipeptide chemical diversification. The purpose of this study is to provide the first completely microbial toolkit for the efficient bioproduction of a variety of dehydrogenated 2,5-diketopiperazines. RESULTS: We mined genomes for CDOs encoded in biosynthetic gene clusters of CDPS-dependent pathways and selected several for characterization. We co-expressed each with their associated CDPS in the pathway using Escherichia coli as a chassis and showed that the cyclodipeptides and the dehydrogenated derivatives were produced in the culture supernatants. We determined the biological activities of the six novel CDOs by solving the chemical structures of the biologically produced dehydrogenated cyclodipeptides. Then, we assessed the six novel CDOs plus two previously characterized CDOs in combinatorial engineering experiments in E. coli. We co-expressed each of the eight CDOs with each of 18 CDPSs selected for the diversity of cyclodipeptides they synthesize. We detected more than 50 dehydrogenated cyclodipeptides and determined the best CDPS/CDO combinations to optimize the production of 23. CONCLUSIONS: Our study establishes the usefulness of CDPS and CDO for the bioproduction of dehydrogenated cyclodipeptides. It constitutes the first step toward the bioproduction of more complex and diverse 2,5-diketopiperazines.

Aminoacyl-tRNA-Utilizing Enzymes in Natural Product Biosynthesis.

Aminoacyl-tRNAs were long thought to be involved solely in ribosome-dependent protein synthesis and essential primary metabolism processes, such as targeted protein degradation and peptidoglycan synthesis. About 10 years ago, an aminoacyl-tRNA-dependent enzyme involved in the biosynthesis of the antibiotic valanimycin was discovered in a Streptomyces strain. Far from being an isolated case, this discovery has been followed by the description of an increasing number of aminoacyl-tRNA-dependent enzymes involved in secondary metabolism. This review describes the three groups of aminoacyl-tRNA-dependent enzymes involved in the synthesis of natural products. Each group is characterized by a particular chemical reaction, and its members are predicted to share a specific fold. The three groups are cyclodipeptide synthases involved in diketopiperazine synthesis, LanB-like dehydratases involved in the posttranslational modification of ribosomal peptides, and transferases from various biosynthesis pathways.

Structural basis for partition of the cyclodipeptide synthases into two subfamilies.

Cyclodipeptide synthases (CDPSs) use two aminoacyl-tRNAs to catalyze the formation of two peptide bonds leading to cyclodipeptides that can be further used for the synthesis of diketopiperazines. It was shown that CDPSs fall into two subfamilies, NYH and XYP, characterized by the presence of specific sequence signatures. However, current understanding of CDPSs only comes from studies of enzymes from the NYH subfamily. The present study reveals the crystal structures of three CDPSs from the XYP subfamily. Comparison of the XYP and NYH enzymes shows that the two subfamilies mainly differ in the first half of their Rossmann fold. This gives a structural basis for the partition of CDPSs into two subfamilies. Despite these differences, the catalytic residues adopt similar positioning regardless of the subfamily suggesting that the XYP and NYH motifs correspond to two structural solutions to facilitate the reactivity of the catalytic serine residue.

Functional connectivity within the voice perception network and its behavioural relevance.

Recognizing who is speaking is a cognitive ability characterized by considerable individual differences, which could relate to the inter-individual variability observed in voice-elicited BOLD activity. Since voice perception is sustained by a complex brain network involving temporal voice areas (TVAs) and, even if less consistently, extra-temporal regions such as frontal cortices, functional connectivity (FC) during an fMRI voice localizer (passive listening of voices vs non-voices) has been computed within twelve temporal and frontal voice-sensitive regions ("voice patches") individually defined for each subject (N = 90) to account for inter-individual variability. Results revealed that voice patches were positively co-activated during voice listening and that they were characterized by different FC pattern depending on the location (anterior/posterior) and the hemisphere. Importantly, FC between right frontal and temporal voice patches was behaviorally relevant: FC significantly increased with voice recognition abilities as measured in a voice recognition test performed outside the scanner. Hence, this study highlights the importance of frontal regions in voice perception and it supports the idea that looking at FC between stimulus-specific and higher-order frontal regions can help understanding individual differences in processing social stimuli such as voices.

Incorporation of Non-canonical Amino Acids into 2,5-Diketopiperazines by Cyclodipeptide Synthases.

The manipulation of natural product biosynthetic pathways is a powerful means of expanding the chemical diversity of bioactive molecules. 2,5-diketopiperazines (2,5-DKPs) have been widely developed by medicinal chemists, but their biological production is yet to be exploited. We introduce an in vivo method for incorporating non-canonical amino acids (ncAAs) into 2,5-DKPs using cyclodipeptide synthases (CDPSs), the enzymes responsible for scaffold assembly in many 2,5-DKP biosynthetic pathways. CDPSs use aminoacyl-tRNAs as substrates. We exploited the natural ability of aminoacyl-tRNA synthetases to load ncAAs onto tRNAs. We found 26 ncAAs to be usable as substrates by CDPSs, leading to the enzymatic production of approximately 200 non-canonical cyclodipeptides. CDPSs constitute an efficient enzymatic tool for the synthesis of highly diverse 2,5-DKPs. Such diversity could be further expanded, for example, by using various cyclodipeptide-tailoring enzymes found in 2,5-DKP biosynthetic pathways.

Automaticity of phonological and semantic processing during visual word recognition.

Reading involves activation of phonological and semantic knowledge. Yet, the automaticity of the activation of these representations remains subject to debate. The present study addressed this issue by examining how different brain areas involved in language processing responded to a manipulation of bottom-up (level of visibility) and top-down information (task demands) applied to written words. The analyses showed that the same brain areas were activated in response to written words whether the task was symbol detection, rime detection, or semantic judgment. This network included posterior, temporal and prefrontal regions, which clearly suggests the involvement of orthographic, semantic and phonological/articulatory processing in all tasks. However, we also found interactions between task and stimulus visibility, which reflected the fact that the strength of the neural responses to written words in several high-level language areas varied across tasks. Together, our findings suggest that the involvement of phonological and semantic processing in reading is supported by two complementary mechanisms. First, an automatic mechanism that results from a task-independent spread of activation throughout a network in which orthography is linked to phonology and semantics. Second, a mechanism that further fine-tunes the sensitivity of high-level language areas to the sensory input in a task-dependent manner.

Analysis of 51 cyclodipeptide synthases reveals the basis for substrate specificity.

Cyclodipeptide synthases (CDPSs) constitute a family of peptide bond-forming enzymes that use aminoacyl-tRNAs for the synthesis of cyclodipeptides. Here, we describe the activity of 41 new CDPSs. We also show that CDPSs can be classified into two main phylogenetically distinct subfamilies characterized by specific functional subsequence signatures, named NYH and XYP. All 11 previously characterized CDPSs belong to the NYH subfamily, suggesting that further special features may be yet to be discovered in the other subfamily. CDPSs synthesize a large diversity of cyclodipeptides made up of 17 proteinogenic amino acids. The identification of several CDPSs having the same specificity led us to determine specificity sequence motifs that, in combination with the phylogenetic distribution of CDPSs, provide a first step toward being able to predict the cyclodipeptides synthesized by newly discovered CDPSs. The determination of the activity of ten more CDPSs with predicted functions constitutes a first experimental validation of this predictive approach.

A language-familiarity effect for speaker discrimination without comprehension.

The influence of language familiarity upon speaker identification is well established, to such an extent that it has been argued that "Human voice recognition depends on language ability" [Perrachione TK, Del Tufo SN, Gabrieli JDE (2011) Science 333(6042):595]. However, 7-mo-old infants discriminate speakers of their mother tongue better than they do foreign speakers [Johnson EK, Westrek E, Nazzi T, Cutler A (2011) Dev Sci 14(5):1002-1011] despite their limited speech comprehension abilities, suggesting that speaker discrimination may rely on familiarity with the sound structure of one's native language rather than the ability to comprehend speech. To test this hypothesis, we asked Chinese and English adult participants to rate speaker dissimilarity in pairs of sentences in English or Mandarin that were first time-reversed to render them unintelligible. Even in these conditions a language-familiarity effect was observed: Both Chinese and English listeners rated pairs of native-language speakers as more dissimilar than foreign-language speakers, despite their inability to understand the material. Our data indicate that the language familiarity effect is not based on comprehension but rather on familiarity with the phonology of one's native language. This effect may stem from a mechanism analogous to the "other-race" effect in face recognition.

The Glasgow Voice Memory Test: Assessing the ability to memorize and recognize unfamiliar voices.

One thousand one hundred and twenty subjects as well as a developmental phonagnosic subject (KH) along with age-matched controls performed the Glasgow Voice Memory Test, which assesses the ability to encode and immediately recognize, through an old/new judgment, both unfamiliar voices (delivered as vowels, making language requirements minimal) and bell sounds. The inclusion of non-vocal stimuli allows the detection of significant dissociations between the two categories (vocal vs. non-vocal stimuli). The distributions of accuracy and sensitivity scores (d') reflected a wide range of individual differences in voice recognition performance in the population. As expected, KH showed a dissociation between the recognition of voices and bell sounds, her performance being significantly poorer than matched controls for voices but not for bells. By providing normative data of a large sample and by testing a developmental phonagnosic subject, we demonstrated that the Glasgow Voice Memory Test, available online and accessible from all over the world, can be a valid screening tool (~5 min) for a preliminary detection of potential cases of phonagnosia and of "super recognizers" for voices.

Speech rhythms and multiplexed oscillatory sensory coding in the human brain.

Cortical oscillations are likely candidates for segmentation and coding of continuous speech. Here, we monitored continuous speech processing with magnetoencephalography (MEG) to unravel the principles of speech segmentation and coding. We demonstrate that speech entrains the phase of low-frequency (delta, theta) and the amplitude of high-frequency (gamma) oscillations in the auditory cortex. Phase entrainment is stronger in the right and amplitude entrainment is stronger in the left auditory cortex. Furthermore, edges in the speech envelope phase reset auditory cortex oscillations thereby enhancing their entrainment to speech. This mechanism adapts to the changing physical features of the speech envelope and enables efficient, stimulus-specific speech sampling. Finally, we show that within the auditory cortex, coupling between delta, theta, and gamma oscillations increases following speech edges. Importantly, all couplings (i.e., brain-speech and also within the cortex) attenuate for backward-presented speech, suggesting top-down control. We conclude that segmentation and coding of speech relies on a nested hierarchy of entrained cortical oscillations.

A Neural Marker for Social Bias Toward In-group Accents.

Accents provide information about the speaker's geographical, socio-economic, and ethnic background. Research in applied psychology and sociolinguistics suggests that we generally prefer our own accent to other varieties of our native language and attribute more positive traits to it. Despite the widespread influence of accents on social interactions, educational and work settings the neural underpinnings of this social bias toward our own accent and, what may drive this bias, are unexplored. We measured brain activity while participants from two different geographical backgrounds listened passively to 3 English accent types embedded in an adaptation design. Cerebral activity in several regions, including bilateral amygdalae, revealed a significant interaction between the participants' own accent and the accent they listened to: while repetition of own accents elicited an enhanced neural response, repetition of the other group's accent resulted in reduced responses classically associated with adaptation. Our findings suggest that increased social relevance of, or greater emotional sensitivity to in-group accents, may underlie the own-accent bias. Our results provide a neural marker for the bias associated with accents, and show, for the first time, that the neural response to speech is partly shaped by the geographical background of the listener.