Frontal cortex activity during the production of diverse social communication calls in marmoset monkeys

Human frontal cortex plays a crucial role in speech production. However, it has remained unclear whether the frontal cortex of nonhuman primates is involved in the production of self-initiated vocalizations during natural vocal communication. Using a wireless multichannel neural recording technique, we observed in the premotor cortex neural activation and suppression both before and during self-initiated vocalizations when marmosets, a highly vocal New World primate species, engaged in vocal exchanges with conspecifics. A novel finding of the present study is the discovery of a subpopulation of premotor cortex neurons that was activated by vocal production, but not by orofacial movement. These observations provide clear evidence of the premotor cortex's involvement in vocal production in a New World primate species.

Cognitive neural prosthetics

The control of speech and vocal production involves the calculation of error between the intended vocal output and the resulting auditory feedback. Consistent with this model, recent evidence has demonstrated that the auditory cortex is suppressed immediately before and during vocal production, yet is still sensitive to differences between vocal output and altered auditory feedback. This suppression has been suggested to be the result of top-down signals containing information about the intended vocal output, potentially originating from motor or other frontal cortical areas. However, whether such frontal areas are the source of suppressive and predictive signaling to the auditory cortex during vocalization is unknown. Here, we simultaneously recorded neural activity from both the auditory and frontal cortices of marmoset monkeys while they produced self-initiated vocalizations. We found increases in neural activity in both brain areas preceding the onset of vocal production, notably changes in both multi-unit activity and local field potential theta-band power. Connectivity analysis using Granger causality demonstrated that frontal cortex sends directed signaling to the auditory cortex during this pre-vocal period. Importantly, this pre-vocal activity predicted both vocalization-induced suppression of the auditory cortex as well as the acoustics of subsequent vocalizations. These results suggest that frontal cortical areas communicate with the auditory cortex preceding vocal production, with frontal-auditory signals that may reflect the transmission of sensory prediction information. This interaction between frontal and auditory cortices may contribute to mechanisms that calculate errors between intended and actual vocal outputs during vocal communication.

Vocal communication in nonhuman primates receives considerable research attention, with many investigators arguing for similarities between this calling and speech in humans. Data from development and neural organization show a central role of affect in monkey and ape sounds, however, suggesting that their calls are homologous to spontaneous human emotional vocalizations while having little relation to spoken language. Based on this evidence, we propose two principles that can be useful in evaluating the many and disparate empirical findings that bear on the nature of vocal production in nonhuman and human primates. One principle distinguishes production-first from reception-first vocal development, referring to the markedly different role of auditory-motor experience in each case. The second highlights a phenomenon dubbed dual neural pathways, specifically that when a species with an existing vocal system evolves a new functionally distinct vocalization capability, it occurs through emergence of a second parallel neural pathway rather than through expansion of the extant circuitry. With these principles as a backdrop, we review evidence of acoustic modification of calling associated with background noise, conditioning effects, audience composition, and vocal convergence and divergence in nonhuman primates. Although each kind of evidence has been interpreted to show flexible cognitively mediated control over vocal production, we suggest that most are more consistent with affectively grounded mechanisms. The lone exception is production of simple, novel sounds in great apes, which is argued to reveal at least some degree of volitional vocal control. If also present in early hominins, the cortically based circuitry surmised to be associated with these rudimentary capabilities likely also provided the substrate for later emergence of the neural pathway allowing volitional production in modern humans.

Human language is largely a vocal behavior, but its evolutionary origins remain elusive. Although vocalizations are also the main way by which nonhuman primates communicate and interact socially, it has been difficult to demonstrate direct transitions from nonlinguistic primate vocal communication to human language. Nonhuman primates produce and perceive sounds by specialized anatomical and neural structures also present in humans. Compared to humans, however, nonhuman primates are severely limited in the control they have over vocal production, which restricts their ability to produce rapid sound combinations and limits vocal learning. But language is also a cognitive capacity, and there is good evidence that nonhuman primates understand others’ calls as given by specific individuals to specific events or as part of specific social interactions. In great apes, callers can take the past history with their audience into account by suppressing, exaggerating, and socially directing their calls in seemingly strategic ways. But there is no clear evidence that primates, apart from humans, perceive others as governed by complex mental states, especially knowledge, during acts of communication, nor is there evidence that they are motivated to seek common ground and actively inform their audience accordingly. There is also no clear indication that nonhuman primates use vocalizations for the sole purpose of social bonding. One hypothesis is that these differences in cognitive ability and social motivation may have prevented the evolution of flexible and combinatorial vocal communication in nonhuman primates.

If we accept the view that language first evolved from the conceptual structure of our pre-linguistic ancestors, several questions arise, including: What kind of structure? Concepts about what? Here we review research on the vocal communication and cognition of nonhuman primates, focusing on results that may be relevant to the earliest stages of language evolution. From these data we conclude, first, that nonhuman primates’ inability to represent the mental states of others makes their communication fundamentally different from human language. Second, while nonhuman primates’ production of vocalizations is highly constrained, their ability to extract complex information from sounds is not. Upon hearing vocalizations, listeners acquire information about their social companions that is referential, discretely coded, hierarchically structured, rule-governed, and propositional. We therefore suggest that, in the earliest stages of language evolution, communication had a formal structure that grew out of its speakers’ knowledge of social relations.

The physiological mechanisms and acoustic principles underlying sound production in primates are important for analyzing and synthesizing primate vocalizations, for determining the range of calls that are physically producible, and for understanding primate communication in the broader comparative context of what is known about communication in other vertebrates. In this paper we discuss what is known about vocal production in nonhuman primates, relying heavily on models from speech and musical acoustics. We first describe the role of the lungs and larynx in generating the sound source, and then discuss the effects of the supralaryngeal vocal tract in modifying this source. We conclude that more research is needed to resolve several important questions about the acoustics of primate calls, including the nature of the vocal tract's contribution to call production. Nonetheless, enough is known to explore the implications of call acoustics for the evolution of primate communication. In particular, we discuss how anatomy and physiology may provide constraints resulting in "honest" acoustic indicators of body size. © 1995 Wiley-Liss, Inc.

Cortical network switching: possible role of the lateral septum and cholinergic arousal.

In searching for the roots of human language, comparative researchers investigate whether precursors to language are already present in our closest relatives, the non-human primates. As the majority of studies into primates’ communication use a unimodal approach with focus on one signal type only, researchers investigate very different aspects depending on whether they are interested in vocal, gestural, or facial communication. Here, we focus on two signal types and discuss how meaning is created in the gestural (visual, tactile/auditory) as compared to the vocal modality in non-human primates, to highlight the different research foci across these modalities. First, we briefly describe the defining features of meaning in human language and introduce some debates concerning meaning in non-human communication. Second, with focus on these features, we summarize the current evidence for meaningful communication in gestural as compared to vocal communication and demonstrate that meaning is operationalized very differently by researchers in these two fields. As a result, it is currently not possible to generalize findings across these modalities. Rather than arguing for or against the occurrence of semantic communication in non-human primates, we aim at pointing to gaps of knowledge in studying meaning in our closest relatives, and these gaps might be closed.

Compared to humans, non-human primates have very little control over their vocal production. Nonetheless, some primates produce various call combinations, which may partially offset their lack of acoustic flexibility. A relevant example is male Campbell's monkeys (Cercopithecus campbelli), which give one call type ('Krak') to leopards, while the suffixed version of the same call stem ('Krak-oo') is given to unspecific danger. To test whether recipients attend to this suffixation pattern, we carried out a playback experiment in which we broadcast naturally and artificially modified suffixed and unsuffixed 'Krak' calls of male Campbell's monkeys to 42 wild groups of Diana monkeys (Cercopithecus diana diana). The two species form mixed-species groups and respond to each other's vocalizations. We analysed the vocal response of male and female Diana monkeys and overall found significantly stronger vocal responses to unsuffixed (leopard) than suffixed (unspecific danger) calls. Although the acoustic structure of the 'Krak' stem of the calls has some additional effects, subject responses were mainly determined by the presence or the absence of the suffix. This study indicates that suffixation is an evolved function in primate communication in contexts where adaptive responses are particularly important.

Hemodialysis (HD) is associated with cognitive impairment in patients with end-stage renal disease (ESRD). However, the neural mechanism of spatial working memory (SWM) impairment in HD-ESRD patients remains unclear. We investigated the abnormal alterations in SWM-associated brain activity patterns in HD-ESRD patients using blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) technique during n-back tasks. Twenty-two HD-ESRD patients and 22 well-matched controls underwent an fMRI scan while undergoing a three-load n-back tasks with different difficulty levels. Cognitive and mental states were assessed using a battery of neuropsychologic tests. The HD-ESRD patients exhibited worse memory abilities than controls. Compared with the control group, the HD-ESRD patient group showed lower accuracy and longer response time under the n-back tasks, especially in the 2-back task. The patterns of brain activation changed under different working memory loads in the HD-ESRD patients, showing decreased activity in the right medial frontal gyrus and inferior frontal gyrus under 0-back and 1-back task, while more decreased activation in the bilateral frontal cortex, parietal lobule, anterior/posterior cingulate cortex and insula cortex under 2-back task. With the increase of task difficulty, the activation degree of the frontal and parietal cortex decreased. More importantly, we found that lower activation in frontal cortex and parietal lobule was associated with worse cognitive function in the HD-ESRD patients. These results demonstrate that the abnormal brain activity patterns of frontal cortex and parietal lobule may reflect the neural mediation of SWM impairment.

Vocal communication is common in the animal kingdom. Researchers often examine vocal communication in nonhuman primates (primates) with the aim of identifying similarities and differences with human language and speech, in order to trace the evolutionary origins of our complex communication system. Primates can produce distinct calls in response to specific events, such as the discovery of a certain predator, and listeners seem to understand what these calls refer to. Although on the surface there are similarities between this type of communication and human referential words, the mental processes that underlie them may be very different. While in general the flexibility shown by primate receivers may demonstrate some commonalities with humans, there is much more controversy over whether there are similarities between the production of primate vocalizations and language. It is widely accepted that primates, unlike humans, lack the ability to generate new vocalizations. Although this means primates have a closed repertoire of calls that cannot be expanded, primates are capable of combining their existing calls to generate new messages. The degree of voluntary control and intentionality involved in the use of calls is also a matter of debate, with recent evidence on both a neural and behavioral level challenging traditional assumptions that primate vocalizations are used in an automatic, reflexive manner. More research is needed to examine the mental processes underlying communicative behavior in both the producer and the receiver. In the future adopting a more holistic, multimodal approach to studying primate communication is likely to challenge and ultimately improve our understanding of primate communication and the evolution of human language.

Endogenous thrombopoietin (TPO) stimulates platelet production in nonhuman primates dose-dependentbyinducing megakaryocyte development from early marrow hematopoietic progenitors and subsequent proliferation and endoreduplication. Recombinant human TPO, nonpegylated or pegylated recombinant human megakaryocyte growth and development factor produce log-linear responses in peak peripheral platelet counts (or peripheral platelet mass turnover), platelet TPO receptor density, and marrow megakaryocyte volume, ploidy, number and mass. Mpl ligand therapy sustains normal peripheral platelet concentrations following myelosuppressive chemotherapy in baboons and corrects peripheral platelet counts in HIV-infected chimpanzees with severe thrombocytopenia. Whereas Mpl ligands do not directly induce platelet aggregation in vitro, they enhance aggregatory responsiveness of platelets to physiologic agonists both in vitro and transiently ex vivo following treatment with Mpl ligands. However, platelet recruitment into forming thrombus is not augmented by these agents when evaluated in quantitative rabbit or baboon models of platelet-dependent thrombus formation, except for the direct effect of platelet concentration per se. These findings indicate that appropriate dosing of these agents prevents thrombocytopenia without increasing the risk of platelet-dependent thrombo-occlusive complications.

Communication is an inherently interactive process that weaves together the fabric of both human and nonhuman primate societies. To investigate the properties of the primate brain during active social signaling, we recorded the responses of frontal cortex neurons as freely moving marmosets engaged in conversational exchanges with a visually occluded virtual marmoset. We found that small changes in firing rate (∼1 Hz) occurred across a broadly distributed population of frontal cortex neurons when marmosets heard a conspecific vocalization, and that these changes corresponded to subjects' likelihood of producing or withholding a vocal reply. Although the contributions of individual neurons were relatively small, large populations of neurons were able to clearly distinguish between these social contexts. Most significantly, this social context-dependent change in firing rate was evident even before subjects heard the vocalization, indicating that the probability of a conversational exchange was determined by the state of the frontal cortex at the time a vocalization was heard, and not by a decision driven by acoustic characteristics of the vocalization. We found that changes in neural activity scaled with the length of the conversation, with greater changes in firing rate evident for longer conversations. These data reveal specific and important facets of this neural activity that constrain its possible roles in active social signaling, and we hypothesize that the close coupling between frontal cortex activity and this natural, active primate social-signaling behavior facilitates social-monitoring mechanisms critical to conversational exchanges.SIGNIFICANCE STATEMENT We provide evidence for a novel pattern of neural activity in the frontal cortex of freely moving, naturally behaving, marmoset monkeys that may facilitate natural primate conversations. We discovered small (∼1 Hz), but reliable, changes in neural activity that occurred before marmosets even heard a conspecific vocalization that, as a population, almost perfectly predicted whether subjects would produce a vocalization in response. The change in the state of the frontal cortex persisted throughout the conversation and its magnitude scaled linearly with the length of the interaction. We hypothesize that this social context-dependent change in frontal cortex activity is supported by several mechanisms, such as social arousal and attention, and facilitates social monitoring critical for vocal coordination characteristic of human and nonhuman primate conversations.

Effects of imipramine and sertraline on protein kinase activity in rat frontal cortex.