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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.

Information from Magnetic Resonance Imaging (MRI) is useful for diagnosis and treatment management of human neurological patients. MRI monitoring might also prove useful for non-human animals involved in neuroscience research provided that MRI is available and feasible and that there are no MRI contra-indications precluding scanning. However, MRI monitoring is not established in macaques and a resource is urgently needed that could grow with scientific community contributions. Here we show the utility and potential benefits of MRI-based monitoring in a few diverse cases with macaque monkeys. We also establish a PRIMatE MRI Monitoring (PRIME-MRM) resource within the PRIMatE Data Exchange (PRIME-DE) and quantitatively compare the cases to normative information drawn from MRI data from typical macaques in PRIME-DE. In the cases, the monkeys presented with no or mild/moderate clinical signs, were well otherwise and MRI scanning did not present a significant increase in welfare impact. Therefore, they were identified as suitable candidates for clinical investigation, MRI-based monitoring and treatment. For each case, we show MRI quantification of internal controls in relation to treatment steps and comparisons with normative data in typical monkeys drawn from PRIME-DE. We found that MRI assists in precise and early diagnosis of cerebral events and can be useful for visualising, treating and quantifying treatment response. The scientific community could now grow the PRIME-MRM resource with other cases and larger samples to further assess and increase the evidence base on the benefits of MRI monitoring of primates, complementing the animals' clinical monitoring and treatment regime.

Highlights • A non-human primate protective head cap that promotes wound healing after cranial implants. • Use of the head cap reduced wound dehiscence and the need to re-suture surgical wounds. • The head cap is easily adjustable to cover most primate cranial implants. • The head cap facilitates primate cranial implant wound management in neuroscience., Background Neuroscience studies with macaque monkeys may require cranial implants to stabilize the head or gain access to the brain for scientific purposes. Wound management that promotes healing after the cranial implant surgery in non-human primates can be difficult as it is not necessarily possible to cover the wound margins. New method Here, we developed an easily modifiable head cap that protects the sutured skin margins after cranial implant surgery and contributes to wound healing. The protective head cap was developed in response to monkeys picking at sutured skin margins around an implant, complicating healing. The user-friendly protective cap, made from Klarity- R™ Sheet (3.2 mm thick with 36 % or 42 % perforation) is affixed to the implant post-surgically. Once secured and while the monkey is still anesthetized, the plastic sheeting is molded around the implant. The protective head cap restricts the monkey’s finger access to its’ wound margins while allowing air to circulate to promote wound healing. Results and comparison with existing methods Across two UK primate facilities, the protective head cap promoted wound healing. In monkeys that did not wear the head cap, re-suturing was necessary in ∼30 % of cases. In contrast, none of the monkeys that wore the head cap required re-suturing. The monkeys wearing the head cap also had reduced numbers of days of prescribed antibiotics and analgesia. Conclusion This bespoken, easily adaptable, protective head cap supports postoperative wound healing, and enhances the welfare of monkeys involved in neuroscience research.

Brain perturbation studies allow detailed causal inferences of behavioral and neural processes. Because the combination of brain perturbation methods and neural measurement techniques is inherently challenging, research in humans has predominantly focused on non-invasive, indirect brain perturbations, or neurological lesion studies. Non-human primates have been indispensable as a neurobiological system that is highly similar to humans while simultaneously being more experimentally tractable, allowing visualization of the functional and structural impact of systematic brain perturbation. This review considers the state of the art in non-human primate brain perturbation with a focus on approaches that can be combined with neuroimaging. We consider both non-reversible (lesions) and reversible or temporary perturbations such as electrical, pharmacological, optical, optogenetic, chemogenetic, pathway-selective, and ultrasound based interference methods. Method-specific considerations from the research and development community are offered to facilitate research in this field and support further innovations. We conclude by identifying novel avenues for further research and innovation and by highlighting the clinical translational potential of the methods. ispartof: NEUROIMAGE vol:235 ispartof: location:United States status: published

Summary Human brain pathways supporting language and declarative memory are thought to have differentiated substantially during evolution. However, cross-species comparisons are missing on site-specific effective connectivity between regions important for cognition. We harnessed functional imaging to visualize the effects of direct electrical brain stimulation in macaque monkeys and human neurosurgery patients. We discovered comparable effective connectivity between caudal auditory cortex and both ventro-lateral prefrontal cortex (VLPFC, including area 44) and parahippocampal cortex in both species. Human-specific differences were clearest in the form of stronger hemispheric lateralization effects. In humans, electrical tractography revealed remarkably rapid evoked potentials in VLPFC following auditory cortex stimulation and speech sounds drove VLPFC, consistent with prior evidence in monkeys of direct auditory cortex projections to homologous vocalization-responsive regions. The results identify a common effective connectivity signature in human and nonhuman primates, which from auditory cortex appears equally direct to VLPFC and indirect to the hippocampus. Video Abstract, Graphical Abstract, Highlights • Privileged human auditory to ventral prefrontal connectivity, paralleled in monkeys • Common auditory to parahippocampal effective connectivity in both species • Stronger lateralization of connectivity effects in humans than in monkeys • Human fronto-temporal network rooted in conserved organizational principle, Interconnectivity between brain regions crucial for language and declarative memory is thought to have substantially evolutionarily differentiated in humans. Rocchi, Oya and colleagues visualize site-specific brain connectivity in monkeys and human neurosurgery patients. They discover a common neural organizational principle that bridges gaps between primates as neurobiological models and human patients.

Human languages all have a grammar, that is, rules that determine how symbols in a language can be combined to create complex meaningful expressions. Despite decades of research, the evolutionary, developmental, cognitive, and computational bases of grammatical abilities are still not fully understood. “Artificial Grammar Learning” (AGL) studies provide important insights into how rules and structured sequences are learned, the relevance of these processes to language in humans, and whether the cognitive systems involved are shared with other animals. AGL tasks can be used to study how human adults, infants, animals, or machines learn artificial grammars of various sorts, consisting of rules defined typically over syllables, sounds, or visual items. In this introduction, we distill some lessons from the nine other papers in this special issue, which review the advances made from this growing body of literature. We provide a critical synthesis, identify the questions that remain open, and recognize the challenges that lie ahead. A key observation across the disciplines is that the limits of human, animal, and machine capabilities have yet to be found. Thus, this interdisciplinary area of research firmly rooted in the cognitive sciences has unearthed exciting new questions and venues for research, along the way fostering impactful collaborations between traditionally disconnected disciplines that are breaking scientific ground.

Contains fulltext : 217200.pdf (Publisher’s version ) (Closed access) Nonhuman primate neuroimaging is on the cusp of a transformation, much in the same way its human counterpart was in 2010, when the Human Connectome Project was launched to accelerate progress. Inspired by an open data-sharing initiative, the global community recently met and, in this article, breaks through obstacles to define its ambitions. 4 p.

The human arcuate fasciculus pathway is crucial for language, interconnecting the posterior temporal and inferior frontal areas. Whether a monkey homolog exists is controversial and the nature of human-specific specialization unclear. Using monkey, ape and human auditory functional fields and diffusion-weighted MRI, we identified homologous pathways originating from the auditory cortex. This discovery establishes a primate auditory prototype for the arcuate fasciculus, reveals an earlier phylogenetic origin and illuminates its remarkable transformation.

Understanding how the brain forms representations of structured information distributed in time is a challenging endeavour for the neuroscientific community, requiring computationally and neurobiologically informed approaches. The neural mechanisms for segmenting continuous streams of sensory input and establishing representations of dependencies remain largely unknown, as do the transformations and computations occurring between the brain regions involved in these aspects of sequence processing. We propose a blueprint for a neurobiologically informed and informing computational model of sequence processing (entitled: Vector-symbolic Sequencing of Binding INstantiating Dependencies, or VS-BIND). This model is designed to support the transformation of serially ordered elements in sensory sequences into structured representations of bound dependencies, readily operates on multiple timescales, and encodes or decodes sequences with respect to chunked items wherever dependencies occur in time. The model integrates established vector symbolic additive and conjunctive binding operators with neurobiologically plausible oscillatory dynamics, and is compatible with modern spiking neural network simulation methods. We show that the model is capable of simulating previous findings from structured sequence processing tasks that engage fronto-temporal regions, specifying mechanistic roles for regions such as prefrontal areas 44/45 and the frontal operculum during interactions with sensory representations in temporal cortex. Finally, we are able to make predictions based on the configuration of the model alone that underscore the importance of serial position information, which requires input from time-sensitive cells, known to reside in the hippocampus and dorsolateral prefrontal cortex.This article is part of the theme issue ‘Towards mechanistic models of meaning composition’.

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. ispartof: NEUROIMAGE vol:237 ispartof: location:United States status: published

In natural settings, the prospect of reward often influences the focus of our attention, but how cognitive and motivational systems influence sensory cortex is not well understood. Also, challenges in training nonhuman animals on cognitive tasks complicate cross-species comparisons and interpreting results on the neurobiological bases of cognition. Incentivized attention tasks could expedite training and evaluate the impact of attention on sensory cortex. Here we develop an Incentivized Attention Paradigm (IAP) and use it to show that macaque monkeys readily learn to use auditory or visual reward cues, drastically influencing their performance within a simple auditory task. Next, this paradigm was used with functional neuroimaging to measure activation modulation in the monkey auditory cortex. The results show modulation of extensive auditory cortical regions throughout primary and non-primary regions, which although a hallmark of attentional modulation in human auditory cortex, has not been studied or observed as broadly in prior data from nonhuman animals. Psycho-physiological interactions were identified between the observed auditory cortex effects and regions including basal forebrain sites along acetylcholinergic and dopaminergic pathways. The findings reveal the impact and regional interactions in the primate brain during an incentivized attention engaging auditory task.

Summary Non-human primate neuroimaging is a rapidly growing area of research that promises to transform and scale translational and cross-species comparative neuroscience. Unfortunately, the technological and methodological advances of the past two decades have outpaced the accrual of data, which is particularly challenging given the relatively few centers that have the necessary facilities and capabilities. The PRIMatE Data Exchange (PRIME-DE) addresses this challenge by aggregating independently acquired non-human primate magnetic resonance imaging (MRI) datasets and openly sharing them via the International Neuroimaging Data-sharing Initiative (INDI). Here, we present the rationale, design, and procedures for the PRIME-DE consortium, as well as the initial release, consisting of 25 independent data collections aggregated across 22 sites (total = 217 non-human primates). We also outline the unique pitfalls and challenges that should be considered in the analysis of non-human primate MRI datasets, including providing automated quality assessment of the contributed datasets., Highlights • Openly shared, large non-human primate neuroimaging data resource • Multiple imaging modalities contributed from investigators around the world • Quality assessments of the dataset • Discussed pitfalls and challenges in analyzing the non-human primate MRI data, The PRIMatE Data Exchange (PRIME-DE) consortium is an open science resource for the neuroimaging community aiming to facilitate efforts to map the non-human primate connectome. It aggregates and shares anatomical, functional, and diffusion MRI datasets from laboratories throughout the world.

Optogenetics has revolutionized neuroscience in small laboratory animals, but its effect on animal models more closely related to humans, such as non-human primates (NHPs), has been mixed. To make evidence-based decisions in primate optogenetics, the scientific community would benefit from a centralized database listing all attempts, successful and unsuccessful, of using optogenetics in the primate brain. We contacted members of the community to ask for their contributions to an open science initiative. As of this writing, 45 laboratories around the world contributed more than 1,000 injection experiments, including precise details regarding their methods and outcomes. Of those entries, more than half had not been published. The resource is free for everyone to consult and contribute to on the Open Science Framework website. Here we review some of the insights from this initial release of the database and discuss methodological considerations to improve the success of optogenetic experiments in NHPs. ispartof: NEURON vol:108 issue:6 ispartof: location:United States status: published

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.

Language flexibly supports the human ability to communicate using different sensory modalities, such as writing and reading in the visual modality and speaking and listening in the auditory domain. Although it has been argued that nonhuman primate communication abilities are inherently multisensory, direct behavioural comparisons between human and nonhuman primates are scant. Artificial grammar learning (AGL) tasks and statistical learning experiments can be used to emulate ordering relationships between words in a sentence. However, previous comparative work using such paradigms has primarily investigated sequence learning within a single sensory modality. We used an AGL paradigm to evaluate how humans and macaque monkeys learn and respond to identically structured sequences of either auditory or visual stimuli. In the auditory and visual experiments, we found that both species were sensitive to the ordering relationships between elements in the sequences. Moreover, the humans and monkeys produced largely similar response patterns to the visual and auditory sequences, indicating that the sequences are processed in comparable ways across the sensory modalities. These results provide evidence that human sequence processing abilities stem from an evolutionarily conserved capacity that appears to operate comparably across the sensory modalities in both human and nonhuman primates. The findings set the stage for future neurobiological studies to investigate the multisensory nature of these sequencing operations in nonhuman primates and how they compare to related processes in humans.

There is considerable interest in understanding the ontogeny and phylogeny of the human language system, yet, neurobiological work at the interface of both fields is absent. Syntactic processes in language build on sensory processing and sequencing capabilities on the side of the receiver. While we better understand language-related ontogenetic changes in the human brain, it remains a mystery how neurobiological processes at specific human development stages compare with those in phylogenetically closely related species. To address this knowledge gap, we measured EEG event-related potentials (ERPs) in two macaque monkeys using a paradigm developed to evaluate human infant and adult brain potentials associated with the processing of non-adjacent ordering relationships in sequences of syllable triplets. Frequent standard triplet sequences were interspersed with infrequent voice pitch or non-adjacent rule deviants. Monkey ERPs show early pitch and rule deviant mismatch responses that are strikingly similar to those previously reported in human infants. This stands in contrast to adults’ later ERP responses for rule deviants. The results reveal how non-adjacent sequence ordering relationships are processed in the primate brain and provide evidence for evolutionarily conserved neurophysiological effects, some of which are remarkably like those seen at an early human developmental stage.

Artificial grammars (AG) are designed to emulate aspects of the structure of language, and AG learning (AGL) paradigms can be used to study the extent of nonhuman animals' structure-learning capabilities. However, different AG structures have been used with nonhuman animals and are difficult to compare across studies and species. We developed a simple quantitative parameter space, which we used to summarize previous nonhuman animal AGL results. This was used to highlight an under-studied AG with a forward-branching structure, designed to model certain aspects of the nondeterministic nature of word transitions in natural language and animal song. We tested whether two monkey species could learn aspects of this auditory AG. After habituating the monkeys to the AG, analysis of video recordings showed that common marmosets (New World monkeys) differentiated between well formed, correct testing sequences and those violating the AG structure based primarily on simple learning strategies. By comparison, Rhesus macaques (Old World monkeys) showed evidence for deeper levels of AGL. A novel eye-tracking approach confirmed this result in the macaques and demonstrated evidence for more complex AGL. This study provides evidence for a previously unknown level of AGL complexity in Old World monkeys that seems less evident in New World monkeys, which are more distant evolutionary relatives to humans. The findings allow for the development of both marmosets and macaques as neurobiological model systems to study different aspects of AGL at the neuronal level.

Songbirds have become impressive neurobiological models for aspects of human verbal communication because they learn to sequence their song elements, analogous, in some ways, to how humans learn to produce spoken sequences with syntactic structure. However, mammals such as non-human primates are considered to be at best limited-vocal learners and not able to sequence their vocalizations, although some of these animals can learn certain ‘artificial grammar’ sequences. Thus, conceptual issues have slowed the progress in exploring potential neurobiological homologues to language-related processes in species that are taxonomically closely related to humans. We consider some of the conceptual issues impeding a pursuit of, as we define them, ‘proto-syntactic’ capabilities and their neuronal substrates in non-human animals. We also discuss ways to better bridge comparative behavioural and neurobiological data between humans and other animals. Finally, we propose guiding neurobiological hypotheses with which we aim to facilitate the future testing of the level of correspondence between the human brain network for syntactic-learning and related neurobiological networks present in other primates. Insights from the study of non-human primates and other mammals are likely to complement those being obtained in birds to further our knowledge of the human language-related network at the cellular level.

Auditory cortex (AC) contains several primary-like, or "core," fields, which receive thalamic input and project to non-primary "belt" fields. In humans, the organization and layout of core and belt auditory fields are still poorly understood, and most auditory neuroimaging studies rely on macroanatomical criteria, rather than functional localization of distinct fields. A myeloarchitectonic method has been suggested recently for distinguishing between core and belt fields in humans (Dick F, Tierney AT, Lutti A, Josephs O, Sereno MI, Weiskopf N. 2012. In vivo functional and myeloarchitectonic mapping of human primary auditory areas. J Neurosci. 32:16095-16105). We propose a marker for core AC based directly on functional magnetic resonance imaging (fMRI) data and pattern classification. We show that a portion of AC in Heschl's gyrus classifies sound frequency more accurately than other regions in AC. Using fMRI data from macaques, we validate that the region where frequency classification performance is significantly above chance overlaps core auditory fields, predominantly A1. Within this region, we measure tonotopic gradients and estimate the locations of the human homologues of the core auditory subfields A1 and R. Our results provide a functional rather than anatomical localizer for core AC. We posit that inter-individual variability in the layout of core AC might explain disagreements between results from previous neuroimaging and cytological studies. peerReviewed

Considerable knowledge is available on the neural substrates for speech and language from brain-imaging studies in humans, but until recently there was a lack of data for comparison from other animal species on the evolutionarily conserved brain regions that process species-specific communication signals. To obtain new insights into the relationship of the substrates for communication in primates, we compared the results from several neuroimaging studies in humans with those that have recently been obtained from macaque monkeys and chimpanzees. The recent work in humans challenges the longstanding notion of highly localized speech areas. As a result, the brain regions that have been identified in humans for speech and nonlinguistic voice processing show a striking general correspondence to how the brains of other primates analyze species-specific vocalizations or information in the voice, such as voice identity. The comparative neuroimaging work has begun to clarify evolutionary relationships in brain function, supporting the notion that the brain regions that process communication signals in the human brain arose from a precursor network of regions that is present in nonhuman primates and is used for processing species-specific vocalizations. We conclude by considering how the stage now seems to be set for comparative neurobiology to characterize the ancestral state of the network that evolved in humans to support language.

Auditory perceptual 'restoration' occurs when the auditory system restores an occluded or masked sound of interest. Behavioral work on auditory restoration in humans began over 50 years ago using it to model a noisy environmental scene with competing sounds. It has become clear that not only humans experience auditory restoration: restoration has been broadly conserved in many species. Behavioral studies in humans and animals provide a necessary foundation to link the insights being obtained from human EEG and fMRI to those from animal neurophysiology. The aggregate of data resulting from multiple approaches across species has begun to clarify the neuronal bases of auditory restoration. Different types of neural responses supporting restoration have been found, supportive of multiple mechanisms working within a species. Yet a general principle has emerged that responses correlated with restoration mimic the response that would have been given to the uninterrupted sound of interest. Using the same technology to study different species will help us to better harness animal models of 'auditory scene analysis' to clarify the conserved neural mechanisms shaping the perceptual organization of sound and to advance strategies to improve hearing in natural environmental settings.

Summary When interfering objects occlude a scene, the visual system restores the occluded information. Similarly, when a sound of interest (a "foreground" sound) is interrupted (occluded) by loud noise, the auditory system restores the occluded information. This process, called auditory induction, can be exploited to create a continuity illusion. When a segment of a foreground sound is deleted and loud noise fills the missing portion, listeners incorrectly report hearing the foreground continuing through the noise. Here we reveal the neurophysiological underpinnings of illusory continuity in single-neuron responses from awake macaque monkeys' primary auditory cortex (A1). A1 neurons represented the missing segment of occluded tonal foregrounds by responding to discontinuous foregrounds interrupted by intense noise as if they were responding to the complete foregrounds. By comparison, simulated peripheral responses represented only the noise and not the occluded foreground. The results reveal that many A1 single-neuron responses closely follow the illusory percept.

An evolutionary account of human language as a neurobiological system must distinguish between human-unique neurocognitive processes supporting language and evolutionarily conserved, domain-general processes that can be traced back to our primate ancestors. Neuroimaging studies across species may determine whether candidate neural processes are supported by homologous, functionally conserved brain areas or by different neurobiological substrates. Here we use functional magnetic resonance imaging in Rhesus macaques and humans to examine the brain regions involved in processing the ordering relationships between auditory nonsense words in rule-based sequences. We find that key regions in the human ventral frontal and opercular cortex have functional counterparts in the monkey brain. These regions are also known to be associated with initial stages of human syntactic processing. This study raises the possibility that certain ventral frontal neural systems, which play a significant role in language function in modern humans, originally evolved to support domain-general abilities involved in sequence processing., This study uses functional magnetic resonance imaging in humans and monkeys to show similar ventral frontal and opercular cortical responses when processing sequences of auditory nonsense words. The study indicates that this frontal region is involved in evaluating the order of incoming sounds in a sequence, a process that may be conserved in primates.

Social animals can identify conspecifics by many forms of sensory input. However, whether the neuronal computations that support this ability to identify individuals rely on modality-independent convergence or involve ongoing synergistic interactions along the multiple sensory streams remains controversial. Direct neuronal measurements at relevant brain sites could address such questions, but this requires better bridging the work in humans and animal models. Here, we overview recent studies in nonhuman primates on voice and face identity-sensitive pathways and evaluate the correspondences to relevant findings in humans. This synthesis provides insights into converging sensory streams in the primate anterior temporal lobe (ATL) for identity processing. Furthermore, we advance a model and suggest how alternative neuronal mechanisms could be tested., Trends Our ability to identify unique entities, such as specific individuals, appears to depend on sensory convergence in the anterior temporal lobe. However, the neural mechanisms of sensory convergence in the anterior temporal lobe are unclear. Alternative accounts remain equivocal but could be tested by better bridging the findings in humans and animal models. Recent work in monkeys on face- and voice-identity processes is helping to close epistemic gaps between studies in humans and animal models. We synthesize recent knowledge on the convergence of auditory and visual identity-related processes in the anterior temporal lobe. This synthesis culminates in a model and insights into converging sensory streams in the primate brain, and is used to suggest how the neuronal mechanisms for identifying individuals could be tested.

Our nervous system is confronted with a barrage of sensory stimuli, but neural resources are limited and not all stimuli can be processed to the same extent. Mechanisms exist to bias attention towards the particularly salient events thereby providing a weighted representation of our environment [1]. Our understanding of these mechanisms is still limited, but theoretical models can replicate such a weighting of sensory inputs and provide a basis for understanding the underlying principles [2, 3]. Here we describe such a model for the auditory system amp;amp;amp;amp;amp;amp;8211; an auditory saliency map. We experimentally validate the model on natural acoustical scenarios demonstrating that it reproduces human judgments of auditory saliency and predicts the detectability of salient sounds embedded in noisy backgrounds. In addition, it also predicts the natural orienting behavior of naïve macaque monkeys to the same salient stimuli. The structure of the suggested model is identical to that of succ essf ully use d vi sual saliency maps. Hence we conclude that saliency is determined either by implementing similar mechanisms in different unisensory pathways, or by the same mechanism in multisensory areas. In any case, our results demonstrate that different primate sensory systems rely on common principles for extracting relevant sensory events.

To form a coherent percept of the environment, our brain combines information from different senses. Such multisensory integration occurs in higher association cortices; but supposedly it also occurs in early sensory areas. Confirming the latter hypothesis, we unequivocally demonstrate supra-additive integration of touch and sound stimulation at the second stage of the auditory cortex. Using high-resolution fMRI of the macaque monkey, we quantified the integration of auditory broad-band noise and tactile stimulation of hand and foot in anaesthetized animals. Integration was found posterior to and along the lateral side of the primary auditory cortex in the caudal auditory belt. Integration was stronger for temporally coincident stimuli and obeyed the principle of inverse effectiveness: greater enhancement for less effective stimuli. These findings demonstrates that multisensory integration occurs early and close to primary sensory areas, and amp;amp;amp;amp;8211; as it occurs in anaesthet ized ani mals //! --MFG_und--//amp;8211; suggests that this integration is mediated by pre-attentive bottom-up mechanisms.

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., Author summary Motion is a fundamental dimension of acoustic and visual stimuli that is critical for animals to interact with their environment. Yet, surprisingly, we still do not understand the basic mechanisms in the brain that underlie perception of auditory motion. For the last 30 y, this research field has been hampered by unsuccessful attempts to answer a simple but fundamental question: is auditory motion perception deduced from processing individual static sounds, or are there mechanisms in the auditory domain dedicated to detecting motion? Here we report the discovery of specific motion detectors located in the auditory cortex of primates. We demonstrate that these auditory motion detectors are close to the well-known visual motion detectors. Both types of detectors are likely to be crucial for the planning of limb and eye movement. This study addresses a fundamental issue in neuroscience and sheds new light on the brain mechanisms underlying the essential aspects of our ability to navigate the world.

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.

Highlights • First combined EEG and Artificial Grammar (AG) learning study in nonhuman animals. • Early and late frontal potentials modulated in response to violations of the AG sequencing relationships in the primate brain. • Informative similarities and differences are noted in relation to reported human EEG potentials associated with AG learning., Electroencephalography (EEG) has identified human brain potentials elicited by Artificial Grammar (AG) learning paradigms, which present participants with rule-based sequences of stimuli. Nonhuman animals are sensitive to certain AGs; therefore, evaluating which EEG Event Related Potentials (ERPs) are associated with AG learning in nonhuman animals could identify evolutionarily conserved processes. We recorded EEG potentials during an auditory AG learning experiment in two Rhesus macaques. The animals were first exposed to sequences of nonsense words generated by the AG. Then surface-based ERPs were recorded in response to sequences that were ‘consistent’ with the AG and ‘violation’ sequences containing illegal transitions. The AG violations strongly modulated an early component, potentially homologous to the Mismatch Negativity (mMMN), a P200 and a late frontal positivity (P500). The macaque P500 is similar in polarity and time of occurrence to a late EEG positivity reported in human AG learning studies but might differ in functional role.

Recent studies suggest that multisensory integration does not only occur in higher association cortices but also at early stages of auditory processing, possibly in primary or secondary auditory cortex. Support for such early multisensory influences comes from functional magnetic resonance imaging experiments in humans and monkeys. However we argue that the current understanding of neurovascular coupling and of the neuronal basis underlying the imaging signal does not permit the direct extrapolation from imaging data to properties of neurons in the same region. While imaging can guide subsequent electrophysiological studies, only these can determine whether and how neurons in auditory cortices combine information from multiple modalities. Indeed, electrophysiological studies only partly confirm the findings from imaging studies. While recordings of field potentials reveal strong influences of visual or somatosensory stimulation on synaptic activity even in primary auditory cortex, single unit studies find only a small minority of neurons as being influenced by non-acoustic stimuli. We propose the analysis of the information coding properties of individual neurons as one way to quantitatively determine whether the representation of our acoustic environment in (primary) auditory cortex indeed benefits from multisensory input.

Modern lesion and imaging work in humans has been clarifying which brain regions are involved in the processing of speech and language. Concurrently, some of this work has aimed to bridge the gap to the seemingly incompatible evidence for multiple brain-processing pathways that first accumulated in nonhuman primates. For instance, the idea of a posterior temporal-parietal “Wernicke’s” territory, which is thought to be instrumental for speech comprehension, conflicts with this region of the brain belonging to a spatial “where” pathway. At the same time a posterior speech-comprehension region ignores the anterior temporal lobe and its “what” pathway for evaluating the complex features of sensory input. Recent language models confirm that the posterior or dorsal stream has an important role in human communication, by a reconceptualization of the “where” into a “how-to” pathway with a connection to the motor system for speech comprehension. Others have tried to directly implicate the “what” pathway for speech comprehension, relying on the growing evidence in humans for anterior-temporal involvement in speech and voice processing. Coming full circle, we find that the recent imaging of vocalization and voice preferring regions in nonhuman primates allows us to make direct links to the human imaging data involving the anterior-temporal regions. The authors describe how comparison of the structure and function of the vocal communication system of humans and other animals is clarifying evolutionary relationships and the extent to which different species can model human brain function.

Our brain integrates the information provided by the different sensory modalities into a coherent percept, and recent studies suggest that this process is not restricted to higher association areas. Here we evaluate the hypothesis that auditory cortical fields are involved in cross-modal processing by probing individual neurons for audiovisual interactions. We find that visual stimuli modulate auditory processing both at the level of field potentials and single-unit activity and already in primary and secondary auditory fields. These interactions strongly depend on a stimulus' efficacy in driving the neurons but occur independently of stimulus category and for naturalistic as well as artificial stimuli. In addition, interactions are sensitive to the relative timing of audiovisual stimuli and are strongest when visual stimuli lead by 20-80 msec. Exploring the underlying mechanisms, we find that enhancement correlates with the resetting of slow (approximately 10 Hz) oscillations to a phase angle of optimal excitability. These results demonstrate that visual stimuli can modulate the firing of neurons in auditory cortex in a manner that depends on stimulus efficacy and timing. These neurons thus meet the criteria for sensory integration and provide the auditory modality with multisensory contextual information about co-occurring environmental events.

For vocal animals, recognizing species-specific vocalizations is important for survival and social interactions. In humans, a voice region has been identified that is sensitive to human voices and vocalizations. As this region also strongly responds to speech, it is unclear whether it is tightly associated with linguistic processing and is thus unique to humans. Using functional magnetic resonance imaging of macaque monkeys (Old World primates, Macaca mulatta) we discovered a high-level auditory region that prefers species-specific vocalizations over other vocalizations and sounds. This region not only showed sensitivity to the amp;amp;lsquo;voiceamp;amp;lsquo; of the species, but also to the vocal identify of conspecific individuals. The monkey voice region is located on the superior-temporal plane and belongs to an anterior auditory what pathway. These results establish functional relationships with the human voice region and support the notion tha t, for different primate species, the anterior temporal regions of the brain are adapted for recognizing communication signals from conspecifics.

The capability to systematically morph between different types of animal vocalizations will give us insights into how the features of vocal sounds are perceived by listening individuals. Following behavioral study, neurophysiological recordings in nonhuman animals, could reveal how neurons support the perception of communication signals. Signal processing algorithms are now available for creating sophisticated morphs between complex sounds, like human speech. However, most morphing approaches have been applied to harmonic sounds whose frequency components can be readily identified. We show that auditory morphing can be more generally applied by describing a procedure for using the STRAIGHT signal processing package to gradually morph between: (1) vocalizations from different macaque monkeys, (2) acoustically dissimilar types of monkey vocalizations, such as a ‘coo’ and a ‘grunt’, and (3) monkey and human vocalizations. We then evaluated the quality of the morphs and obtained classification curves from human listeners who seemed to categorize the monkey vocalizations much like the ones produced by humans. The outlined procedures prepare macaque-monkey vocalizations for neuroethological study and the approach establishes basic principles that will assist in creating suitable morphs of other natural sounds and animal vocalizations.

Neurons in auditory cortex are selective for the frequency content of acoustical stimuli. Classically, this response selectivity is studied at the single-neuron level. However, current research often employs functional imaging techniques to investigate the organization of auditory cortex. The signals underlying the imaging data arise from neural mass action and reflect the properties of populations of neurons. For example, the signal used for functional magnetic resonance imaging (fMRI-BOLD) was shown to correlate with the oscillatory activity quantified by local field potentials (LFPs). This raises the questions of how the frequency selectivity in neuronal population signals compares with the tuning of spiking responses. To address this, we quantified tuning properties of auditory-evoked potentials (AEP), different frequency bands of the LFP, analog multi-unit (AMUA), and spike-sorted single- and multiunit activity in auditory cortex. The AMUA showed a close correspondence in frequency tuning to the spike-sorted activity. In contrast, for the LFP, we found a clear dissociation of high- and low-frequency bands: there was a gradual increase of tuning-curve similarity, tuning specificity, and information about the stimulus with increasing LFP frequency. Although properties of the high-frequency LFP matched those of spiking activity, the lower-frequency bands differed considerably as did the AEP. These results demonstrate that electrophysiological population responses exhibit varying degrees of frequency tuning and suggest that those functional imaging methods that are related to high-frequency oscillatory activity should well reflect the neuronal processing of sound frequency.

Merging the information from different senses is essential for successful interaction with real-life situations. Indeed, sensory integration can reduce perceptual ambiguity, speed reactions, or change the qualitative sensory experience. It is widely held that integration occurs at later processing stages and mostly in higher association cortices; however, recent studies suggest that sensory convergence can occur in primary sensory cortex. A good model for early convergence proved to be the auditory cortex, which can be modulated by visual and tactile stimulation; however, given the large number and small size of auditory fields, neither human imaging nor microelectrode recordings have systematically identified which fields are susceptible to multisensory influences. To reconcile findings from human imaging with anatomical knowledge from nonhuman primates, we exploited high-resolution imaging (functional magnetic resonance imaging) of the macaque monkey to study the modulation of auditory processing by visual stimulation. Using a functional parcellation of auditory cortex, we localized modulations to individual fields. Our results demonstrate that both primary (core) and nonprimary (belt) auditory fields can be activated by the mere presentation of visual scenes. Audiovisual convergence was restricted to caudal fields [prominently the core field (primary auditory cortex) and belt fields (caudomedial field, caudolateral field, and mediomedial field)] and continued in the auditory parabelt and the superior temporal sulcus. The same fields exhibited enhancement of auditory activation by visual stimulation and showed stronger enhancement for less effective stimuli, two characteristics of sensory integration. Together, these findings reveal multisensory modulation of auditory processing prominently in caudal fields but also at the lowest stages of auditory cortical processing.

Despite the extensive physiological work performed on auditory cortex, our understanding of the basic functional properties of auditory cortical neurons is incomplete. For example, it remains unclear what stimulus features are most important for these cells. Determining these features is challenging given the considerable size of the relevant stimulus parameter space as well as the unpredictable nature of many neurons' responses to complex stimuli due to nonlinear integration across frequency. Here we used an adaptive stimulus optimization technique to obtain the preferred spectral input for neurons in macaque primary auditory cortex (AI). This method uses a neuron's response to progressively modify the frequency composition of a stimulus to determine the preferred spectrum. This technique has the advantage of being able to incorporate nonlinear stimulus interactions into a “best estimate” of a neuron's preferred spectrum. The resulting spectra displayed a consistent, relatively simple circumscribed form that was similar across scale and frequency in which excitation and inhibition appeared about equally prominent. In most cases, this structure could be described using two simple models, the Gabor and difference of Gaussians functions. The findings indicate that AI neurons are well suited for extracting important scale-invariant features in sound spectra and suggest that they are designed to efficiently represent natural sounds.

Anatomical studies propose that the primate auditory cortex contains more fields than have actually been functionally confirmed or described. Spatially resolved functional magnetic resonance imaging (fMRI) with carefully designed acoustical stimulation could be ideally suited to extend our understanding of the processing within these fields. However, after numerous experiments in humans, many auditory fields remain poorly characterized. Imaging the macaque monkey is of particular interest as these species have a richer set of anatomical and neurophysiological data to clarify the source of the imaged activity. We functionally mapped the auditory cortex of behaving and of anesthetized macaque monkeys with high resolution fMRI. By optimizing our imaging and stimulation procedures, we obtained robust activity throughout auditory cortex using tonal and band-passed noise sounds. Then, by varying the frequency content of the sounds, spatially specific activity patterns were observed over this region. As a result, the activity patterns could be assigned to many auditory cortical fields, including those whose functional properties were previously undescribed. The results provide an extensive functional tessellation of the macaque auditory cortex and suggest that 11 fields contain neurons tuned for the frequency of sounds. This study provides functional support for a model where three fields in primary auditory cortex are surrounded by eight neighboring “belt” fields in non-primary auditory cortex. The findings can now guide neurophysiological recordings in the monkey to expand our understanding of the processing within these fields. Additionally, this work will improve fMRI investigations of the human auditory cortex., High-resolution fMRI reveals a detailed functional description of auditory cortical fields in the macaque monkey.