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The perception of pitch is a fundamental percept, which is mediated by the auditory system, requiring the abstraction of stimulus properties related to the spectro-temporal structure of sound. Despite its importance, there is still debate as to the precise areas responsible for its encoding, which may be due to species differences or differences in the recording measures and choices of stimuli used in previous studies. Moreover, it was unknown whether the human brain contains pitch neurons and how distributed such neurons might be. Here, we present the first study to measure multiunit neural activity in response to pitch stimuli in the auditory cortex of intracranially implanted humans. The stimulus sets were regular-interval noise with a pitch strength that is related to the temporal regularity and a pitch value determined by the repetition rate and harmonic complexes. Specifically, we demonstrate reliable responses to these different pitch-inducing paradigms that are distributed throughout Heschl’s gyrus, rather than being localized to a particular region, and this finding was evident regardless of the stimulus presented. These data provide a bridge across animal and human studies and aid our understanding of the processing of a critical percept associated with acoustic stimuli.

Ethical frameworks are the foundation for any research with humans or nonhuman animals. Human research is guided by overarching international ethical principles, such as those defined in the Helsinki Declaration by the World Medical Association. However, for nonhuman animal research, because there are several sets of ethical principles and national frameworks, it is commonly thought that there is substantial variability in animal research approaches internationally and a lack of an animal research 'Helsinki Declaration', or the basis for one. We first overview several prominent sets of ethical principles, including the 3Rs, 3Ss, 3Vs, 4Fs and 6Ps. Then using the 3Rs principles, originally proposed by Russell & Burch, we critically assess them, asking if they can be Replaced, Reduced or Refined. We find that the 3Rs principles have survived several replacement challenges, and the different sets of principles (3Ss, 3Vs, 4Fs and 6Ps) are complementary, a natural refinement of the 3Rs and are ripe for integration into a unified set of principles, as proposed here. We also overview international frameworks and documents, many of which incorporate the 3Rs, including the Basel Declaration on animal research. Finally, we propose that the available animal research guidance documents across countries can be consolidated, to provide a similar structure as seen in the Helsinki Declaration, potentially as part of an amended Basel Declaration on animal research. In summary, we observe substantially greater agreement on and the possibility for unification of the sets of ethical principles and documents that can guide animal research internationally.

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

Mapping the causal effects of one brain region on another (effective connectivity) is a challenging problem in neuroscience, since it requires invasive direct manipulation of brain function, together with whole-brain measurement of the effects produced. Here we establish a unique resource and present data from 26 human patients who underwent electrical stimulation during functional magnetic resonance imaging (es-fMRI). The patients had medically refractory epilepsy requiring surgically implanted intracranial electrodes in cortical and subcortical locations. One or multiple contacts on these electrodes were stimulated while simultaneously recording BOLD-fMRI activity in a block design. Multiple runs exist for patients with different stimulation sites. We describe the resource, data collection process, preprocessing using the fMRIPrep analysis pipeline and management of artifacts, and provide end-user analyses to visualize distal brain activation produced by site-specific electrical stimulation. The data are organized according to the brain imaging data structure (BIDS) specification, and are available for analysis or future dataset contributions on openneuro.org including both raw and preprocessed data.

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.

Empirical advances have been made in understanding how human language, in its combinatorial complexity and unbounded expressivity, may have evolved from the communication systems present in our evolutionary ancestors. However, a number of cognitive processes and neurobiological mechanisms that support language may not have evolved specifically for communication, but rather from abilities that support perception and cognition more generally. We review recent evidence from comparative behavioural and neurobiological studies on structured sequence learning in human and nonhuman primates. These studies support the notion that certain sequence learning abilities are evolutionarily conserved and engage corresponding inferior frontal brain regions across the species, regions also involved in processing language in humans. Alongside the cross-species similarities is evidence for human specialisations, illuminating the likely evolutionary pathways towards language in modern humans. We argue that cognitive abilities that were in place for animals to learn combinatorial relationships in the sensory world were available and co-opted for language in humans.

Natural environments elicit both phase-locked and non-phase-locked neural responses to the stimulus in the brain. The interpretation of the BOLD signal to date has been based on an association of the non-phase-locked power of high-frequency local field potentials (LFPs), or the related spiking activity in single neurons or groups of neurons. Previous studies have not examined the prediction of the BOLD signal by phase-locked responses. We examined the relationship between the BOLD response and LFPs in the same nine human subjects from multiple corresponding points in the auditory cortex, using amplitude modulated pure tone stimuli of a duration to allow an analysis of phase locking of the sustained time period without contamination from the onset response. The results demonstrate that both phase locking at the modulation frequency and its harmonics, and the oscillatory power in gamma/high-gamma bands are required to predict the BOLD response. Biophysical models of BOLD signal generation in auditory cortex therefore require revision and the incorporation of both phase locking to rhythmic sensory stimuli and power changes in the ensemble neural activity.

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

Background: Understanding brain function requires knowledge of how one brain region causally influences another. This information is difficult to obtain directly in the human brain, and is instead typically inferred from resting-state fMRI. New method: Here, we demonstrate the safety and scientific promise of a novel and complementary approach: concurrent electrical stimulation and fMRI (es-fMRI) at 3 T in awake neurosurgical patients with implanted depth electrodes. Results: We document the results of safety testing, actual experimental setup, and stimulation parameters, that safely and reliably evoke activation in distal structures through stimulation of amygdala, cingulate, or prefrontal cortex. We compare connectivity inferred from the evoked patterns of activation with that estimated from standard resting-state fMRI in the same patients: while connectivity patterns obtained with each approach are correlated, each method produces unique results. Response patterns were stable over the course of 11 min of es-fMRI runs. Comparison with existing method: es-fMRI in awake humans yields unique information about effective connectivity, complementing resting-state fMRI. Although our stimulations were below the level of inducing any apparent behavioral or perceptual effects, a next step would be to use es-fMRI to modulate task performances. This would reveal the acute network-level changes induced by the stimulation that mediate the behavioral and cognitive effects seen with brain stimulation. Conclusions: es-fMRI provides a novel and safe approach for mapping effective connectivity in the human brain in a clinical setting, and will inform treatments for psychiatric and neurodegenerative disorders that use deep brain stimulation.

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.

Sensation in natural environments requires the analysis of time-varying signals. While previous work has uncovered how a signal's temporal rate is represented by neurons in sensory cortex, in this issue of Neuron, new evidence from Gao et al. (2016) provides insights on the underlying mechanisms.

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 interactions of many social animals critically depend on identifying other individuals to approach or avoid. Recognizing specific individuals requires extracting and integrating cross-sensory indexical cues from richly informative communication signals such as voice and face content. Knowledge on how the brain processes faces and voices as unisensory or multisensory signals has grown; neurobiological insights are now available not only from human neuroimaging data but also from comparative neuroimaging studies in nonhuman animals, which together identify the correspondences that can be made between brain processes in humans and other species. These advances have also had the added benefit of establishing animal models in which neuronal processes and pathways are interrogated at finer neurobiological scales than possible in humans. This chapter overviews the latest insights on neuronal representations of voice and face content, including information on sensory convergence sites and pathways that combine multisensory signals in the primate temporal lobe. The information synthesized here leads to a conceptual model whereby the sensory integration of voice and face content depends on temporal lobe convergence sites, which are a midway processing stage and a conduit between audiovisual sensory-processing streams and the frontal cortex.

The social interactions of many animals critically depend on identifying other individuals to interact with or avoid. Recognizing specific individuals by voice requires extracting auditory indexical cues in communication signals, such as the voice-identity related content in vocalizations. Moreover, recognizing individuals can be facilitated by combining different forms of sensory inputs, such as when a vocalization is heard while the corresponding facial expression is seen. Our understanding of the neuronal substrates involved in processing voice content in communication sounds has been steadily increasing: neurobiological insights are now available not only from human neuroimaging studies but also from comparative neuroimaging data in non-human animals, which together identify the cross-species correspondences that can be made between voice-sensitive brain regions. The insights obtained using brain functional imaging have also had the added benefit of establishing certain animals as model systems in which neuronal processes and pathways can be interrogated at finer neurobiological scales than is possible in humans. The use of bridging neuroimaging techniques in humans and other animals allows the neuronal-level insights obtained in animal models to better translate to and inform the understanding of homologous processes in the human brain. This chapter provides an overview of these developments, summarizing knowledge on the functional characteristics of voice-sensitive neurons and on cortical pathways that integrate auditory voice with visual face input. It highlights how some of the gaps in our understanding have begun to close and identifies empirical challenges that remain on the horizon.

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.

Patients with non-fluent aphasias display impairments of expressive and receptive grammar. This has been attributed to deficits in processing configurational and hierarchical sequencing relationships. This hypothesis had not been formally tested. It was also controversial whether impairments are specific to language, or reflect domain general deficits in processing structured auditory sequences. Here we used an artificial grammar learning paradigm to compare the abilities of controls to participants with agrammatic aphasia of two different aetiologies: stroke and frontotemporal dementia. Ten patients with non-fluent variant primary progressive aphasia (nfvPPA), 12 with non-fluent aphasia due to stroke, and 11 controls implicitly learned a novel mixed-complexity artificial grammar designed to assess processing of increasingly complex sequencing relationships. We compared response profiles for otherwise identical sequences of speech tokens (nonsense words) and tone sweeps. In all three groups the ability to detect grammatical violations varied with sequence complexity, with performance improving over time and being better for adjacent than non-adjacent relationships. Patients performed less well than controls overall, and this was related more strongly to aphasia severity than to aetiology. All groups improved with practice and performed well at a control task of detecting oddball nonwords. Crucially, group differences did not interact with sequence complexity, demonstrating that aphasic patients were not disproportionately impaired on complex structures. Hierarchical cluster analysis revealed that response patterns were very similar across all three groups, but very different between the nonsense word and tone tasks, despite identical artificial grammar structures. Overall, we demonstrate that agrammatic aphasics of two different aetiologies are not disproportionately impaired on complex sequencing relationships, and that the learning of phonological and non-linguistic sequences occurs independently. The similarity of profiles of discriminatory abilities and rule learning across groups suggests that insights from previous studies of implicit sequence learning in vascular aphasia are likely to prove applicable in nfvPPA., Graphical abstract fx1, Highlights • Patients with Broca's aphasia and nfvPPA show implicit artificial grammar learning. • Both groups displayed global deficits compared to controls but improved with practice. • Neither group was disproportionately impaired on more complex ordering relationships. • Learning did not transfer between otherwise identical speech and tone-based grammars. • Separate linguistic and non-linguistic sequence processing was maintained in aphasia.

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.

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.

We localized numerous fields in the auditory cortex of the macaque monkey and studied which regions are specialized for processing the communication sounds of the species. First, we used high resolution fMRI at 4.7 and 7 Tesla to functionally map the auditory cortex of behaving and of anesthetized monkeys. The identified fields included regions already well described by anatomical and neurophysiological techniques as well as those whose anatomical parcellation remained without functional support. To localize fields, we varied the frequency content of tonal or band-passed-noise sounds, and obtained spatially specific activity patterns throughout much of auditory cortex. We then statistically tested the frequency-selective gradients within these regions of auditory cortex and the results suggest that 11 fields contain neurons tuned for the frequency of sounds. The obtained maps provide functional support for a model according to which three fields in primary auditory cortex (the auditory ‘core’) are surrounded by eight neighboring ‘belt’ fields in non-primary auditory cortex. Following this non-invasive mapping, we examined which of the localized fields, if any, were specialized for processing the communication sounds of these species in relation to other sounds. Natural sounds were presented as stimulation, including the vocalizations of conspecifics, of other animals, and other natural sounds. Control stimuli were also used. The vocalizations of conspecifics generally elicited greater responses throughout auditory cortex than did the other sounds. The strongest specificity for these vocalizations seemed to be in the anterior fields of auditory cortex, but also extended anteriorly outside of the auditory core and belt fields that were localized with tone and noise stimuli. The data suggest a specialization for the processing of species-specific vocalizations in the anterior portions of auditory cortex, including the poorly understood fields of the auditory parabelt. These fMRI data reflect ethological influences on brain organization and can help us to delineate neural networks in the nonhuman primate that are expected to have an evolutionary relationship to speech processing areas in the human brain.

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.

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.

Despite dyslexia affecting a large number of people, the mechanisms underlying the disorder remain undetermined. There are numerous theories about the origins of dyslexia. Many of these relate dyslexia to low-level, sensory temporal processing deficits. Another group of theories attributes dyslexia to language-specific impairments. Here, we show that dyslexics perform worse than controls on an auditory perceptual grouping task. The results show differences in performance between the groups that depend on sound frequency and not solely on parameters related to temporal processing. Performance on this task suggests that dyslexics' deficits may result from impaired attentional control mechanisms. Such deficits are neither modality nor language-specific and may help to reconcile differences between theories of dyslexia.

SummaryVoices or faces that fall outside of the norm are the memorable ones. Recent human neuroimaging work, however, indicates that the average voice holds considerable currency for neuronal coding. The study also forges a bridge with the face recognition literature.

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.

The fields of primate neuroscience and ethology are star-crossed lovers, suggest Michael Platt and Asif Ghazanfar in Primate Neuroethology. But is this just a fleeting courtship, primed to fizzle after the novelty of it has worn off? Not if the contributors to this thorough and well-conceived volume have anything to say about it. After all, the goal of ethology is not only to uncover the adaptive value and evolutionary history of behavior, but also to determine the mechanisms responsible for behavior.

As you might experience it while reading this sentence, silent reading often involves an imagery speech component: we can hear our own “inner voice” pronouncing words mentally. Recent functional magnetic resonance imaging studies have associated that component with increased metabolic activity in the auditory cortex, including voice-selective areas. It remains to be determined, however, whether this activation arises automatically from early bottom-up visual inputs or whether it depends on late top-down control processes modulated by task demands. To answer this question, we collaborated with four epileptic human patients recorded with intracranial electrodes in the auditory cortex for therapeutic purposes, and measured high-frequency (50–150 Hz) “gamma” activity as a proxy of population level spiking activity. Temporal voice-selective areas (TVAs) were identified with an auditory localizer task and monitored as participants viewed words flashed on screen. We compared neural responses depending on whether words were attended or ignored and found a significant increase of neural activity in response to words, strongly enhanced by attention. In one of the patients, we could record that response at 800 ms in TVAs, but also at 700 ms in the primary auditory cortex and at 300 ms in the ventral occipital temporal cortex. Furthermore, single-trial analysis revealed a considerable jitter between activation peaks in visual and auditory cortices. Altogether, our results demonstrate that the multimodal mental experience of reading is in fact a heterogeneous complex of asynchronous neural responses, and that auditory and visual modalities often process distinct temporal frames of our environment at the same time.

Vocal learners such as humans and songbirds can learn to produce elaborate patterns of structurally organized vocalizations, whereas many other vertebrates such as non-human primates and most other bird groups either cannot or do so to a very limited degree. To explain the similarities among humans and vocal-learning birds and the differences with other species, various theories have been proposed. One set of theories are motor theories, which underscore the role of the motor system as an evolutionary substrate for vocal production learning. For instance, the motor theory of speech and song perception proposes enhanced auditory perceptual learning of speech in humans and song in birds, which suggests a considerable level of neurobiological specialization. Another, a motor theory of vocal learning origin, proposes that the brain pathways that control the learning and production of song and speech were derived from adjacent motor brain pathways. Another set of theories are cognitive theories, which address the interface between cognition and the auditory-vocal domains to support language learning in humans. Here we critically review the behavioral and neurobiological evidence for parallels and differences between the so-called vocal learners and vocal non-learners in the context of motor and cognitive theories. In doing so, we note that behaviorally vocal-production learning abilities are more distributed than categorical, as are the auditory-learning abilities of animals. We propose testable hypotheses on the extent of the specializations and cross-species correspondences suggested by motor and cognitive theories. We believe that determining how spoken language evolved is likely to become clearer with concerted efforts in testing comparative data from many non-human animal species.

In this review, we discuss some of the results of early multisensory influences on auditory processing, and provide evidence that sensory integration occurs distributed and across several processing stages. In particular, we discuss some of the methodological aspects relevant for studies seeking to localize and characterize multisensory influences, and emphasize some of the recent results pertaining to speech and voice integration.

Fitch proposes an appealing hypothesis that humans are dendrophiles, who constantly build mental trees supported by analogous hierarchical brain processes [1]. Moreover, it is argued that, by comparison, nonhuman animals build flat or more compact behaviorally-relevant structures. Should we thus expect less impressive hierarchical brain processes in other animals? Not necessarily. Neuroscientific evidence is showing that the brains of humans and many animals are dendrophiles. The well-established notion of hierarchical brain processing was informed by human and nonhuman animal work [2,3]. Moreover, the form of processing is not just serial or parallel, because human, monkey and rodent brains have both local ‘small world’ connectivity patterns, as well as hubs that interconnect different ‘worlds’ [4]. Also, dendrograms as neuronal representations are prominent in a range of species: dendrograms can well describe monkey ventral frontal cortex neurons responding to vocalization sounds [5], and rodent hippocampal neurons can create multi-layered dendritic structures to encode several features associated with a memory [6]. In neither case is there any suggestion that different vocalizations or memory features are hierarchically organized by the animals for behavior. Also, hierarchically nested brain oscillations responding to speech are evident in humans [7], which is complemented by computational models of speech parsing [8]. Yet, nested oscillations are also evident in monkeys listening to natural sounds [9] and violations to a non-hierarchical artificial grammar that monkeys can learn appears to modulate nested oscillations in auditory cortex [10]. Much less clear, as Fitch suggests [1], is how to access the mental structures that humans and other animals sculpt. He suggests testing alternative hypotheses on the computations being conducted. For example, if one is evaluating strings generated by an AnBn grammar, different individuals might glean different structures depending on the mechanisms used, such as: (1) ‘push-down-stack’, where associations are computed and allocated to memory; or, (2) ‘count-and-compare’, where multiple counters keep track of the number of As and Bs (in the case of n = 3, 3 As and 3 Bs) and a comparison function evaluates whether they are equal. In the case of a ‘push-down-stack’, one might envision the human inferior frontal cortex associating different forms of input and holding the associations in memory. But it is unclear how this would differ or be informed by insights on hierarchically organized cognition in studies of neurons from monkey frontal cortex [11], or those on hierarchically organized memories in rodent fronto-hippocampal networks [6]. In the case of ‘count-and-compare’, this could be informed by numerosity encoding in monkey frontal neurons [12]. The danger, however, which Fitch does not appear to condone, is overlooking the insights that we can gain from nonhuman animals if most are viewed as having, at least by human standards, unsophisticated mental structures. I agree that a priority is for hypotheses to be better developed and tested on the computations subserving different behaviorally-relevant structures, which even in humans has remained largely theoretical. Each computational hypothesis supported or refuted clarifies the types of structures being built by an individual or their species. Neurobiological evidence can provide mechanistic insights. However, it is incorrect to assume that hierarchical neural processes subserve only hierarchical representations of the forms that humans uniquely can build. After all, it is already abundantly clear that the brains of most animals like building elaborate structures.

Recent studies have made considerable progress in understanding how our brain combines the information from different sensory modalities and much evidence about the cortical regions involved has been provided by functional magnetic resonance imaging. Imaging studies have, for example, shown that cross-modal influences occur already at early stages of auditory cortex. However, given our still limited understanding of the functional organization of human auditory cortex, these results are often to interpret with respect to the exact localization of cross-modal influences. Here we discuss a localization technique, which provides a functional map of individual fields in the auditory cortex of individual subjects. Using high-resolution imaging techniques in an animal model with known organization of auditory cortex, we proved the feasibility of this functional mapping technique and demonstrated its use in localizing cross-modal influences to individual auditory fields. Our results show that cross-modal influences already occur in secondary auditory cortices and increase along the auditory processing hierarchy. While these results provide good evidence that auditory processing can be affected by non-acoustic stimuli very early on, we also discuss the interpretability of these findings with regard to the underlying neuronal activity, which is considerable hampered by the still unknown neural basis of the fMRI signal.