Prefrontal neurons predict choices during an auditory same-different task

The detection of stimuli is critical for an animal's survival [1]. However, it is not adaptive for an animal to respond automatically to every stimulus that is present in the environment [2-5]. Given that the prefrontal cortex (PFC) plays a key role in executive function [6-8], we hypothesized that PFC activity should be involved in context-dependent responses to uncommon stimuli. As a test of this hypothesis, monkeys participated in a same-different task, a variant of an oddball task [2]. During this task, a monkey heard multiple presentations of a "reference" stimulus that were followed by a "test" stimulus and reported whether these stimuli were the same or different. While they participated in this task, we recorded from neurons in the ventrolateral prefrontal cortex (vPFC; a cortical area involved in aspects of nonspatial auditory processing [9, 10]). We found that vPFC activity was correlated with the monkeys' choices. This finding demonstrates a direct link between single neurons and behavioral choices in the PFC on a nonspatial auditory task.     

Food for song: expression of c-Fos and ZENK in the zebra finch song nuclei during food aversion learning

Background

Specialized neural pathways, the song system, are required for acquiring, producing, and perceiving learned avian vocalizations. Birds that do not learn to produce their vocalizations lack telencephalic song system components. It is not known whether the song system forebrain regions are exclusively evolved for song or whether they also process information not related to song that might reflect their ‘evolutionary history’.

Methodology/Principal Findings

To address this question we monitored the induction of two immediate-early genes (IEGs) c-Fos and ZENK in various regions of the song system in zebra finches (Taeniopygia guttata) in response to an aversive food learning paradigm; this involves the association of a food item with a noxious stimulus that affects the oropharyngeal-esophageal cavity and tongue, causing subsequent avoidance of that food item. The motor response results in beak and head movements but not vocalizations. IEGs have been extensively used to map neuro-molecular correlates of song motor production and auditory processing. As previously reported, neurons in two pallial vocal motor regions, HVC and RA, expressed IEGs after singing. Surprisingly, c-Fos was induced equivalently also after food aversion learning in the absence of singing. The density of c-Fos positive neurons was significantly higher than that of birds in control conditions. This was not the case in two other pallial song nuclei important for vocal plasticity, LMAN and Area X, although singing did induce IEGs in these structures, as reported previously.

Conclusions/Significance

Our results are consistent with the possibility that some of the song nuclei may participate in non-vocal learning and the populations of neurons involved in the two tasks show partial overlap. These findings underscore the previously advanced notion that the specialized forebrain pre-motor nuclei controlling song evolved from circuits involved in behaviors related to feeding.     

Comparison of Neural Responses to Cat Meows and Human Vowels in the Anterior and Posterior Auditory Field of Awake Cats

For humans and animals, the ability to discriminate speech and conspecific vocalizations is an important physiological assignment of the auditory system. To reveal the underlying neural mechanism, many electrophysiological studies have investigated the neural responses of the auditory cortex to conspecific vocalizations in monkeys. The data suggest that vocalizations may be hierarchically processed along an anterior/ventral stream from the primary auditory cortex (A1) to the ventral prefrontal cortex. To date, the organization of vocalization processing has not been well investigated in the auditory cortex of other mammals. In this study, we examined the spike activities of single neurons in two early auditory cortical regions with different anteroposterior locations: anterior auditory field (AAF) and posterior auditory field (PAF) in awake cats, as the animals were passively listening to forward and backward conspecific calls (meows) and human vowels. We found that the neural response patterns in PAF were more complex and had longer latency than those in AAF. The selectivity for different vocalizations based on the mean firing rate was low in both AAF and PAF, and not significantly different between them; however, more vocalization information was transmitted when the temporal response profiles were considered, and the maximum transmitted information by PAF neurons was higher than that by AAF neurons. Discrimination accuracy based on the activities of an ensemble of PAF neurons was also better than that of AAF neurons. Our results suggest that AAF and PAF are similar with regard to which vocalizations they represent but differ in the way they represent these vocalizations, and there may be a complex processing stream between them.     

Food-associated calls in rhesus macaques (Macaca mulatta): I. Socioecological factors

Upon discovering food, free-living rhesus macaques (Macaca mulatta)on the island of Cayo Santiago, Puerto Rico, produce a complexof vocal signals consisting of five acoustically distinguishablecalls. This report examines the socioecological factors elicitingcall production and the information protentially conveyed toothers. The primary contexts for three vocalizations ("warbles," "harmonicarches, " and "chirps") are encounters with rareand highly preferred foods (e.g., coconut). Two other vocalizations("coos" and "grunts") are produced both in food (primarily provisionedchow) and in nonfood contexts, such as during mother-infantseparation and grooming interactions. Grunts given upon encounteringfood are acoustically distinct from those given in nonfood contexts.In contrast, coos associated with food are statistically indistinguishablefrom coos given in other contexts. When conspecitics hear thesefood-associated calls, they typically approach the caller. Coosare less likely to lead to approach than other food-associatedcalls, Results from all-day follows on adult males and adultfemales reveal that changes in hunger level influence call ratebut not call type; the different call types are produced throughoutthe day. We infer that the structure of food-associated callsprovides information about the quality of the food discovered,whereas call rate conveys information about the relative hungerlevel of the caller. In this population, adult males give fewerfood-associated calls than adult females. In addition, femaleswithin large matrilines call more than females within smallermatrilines, and males who are resident in a group are more vocalthan peripheral males.     

Rhesus Monkeys' Valuation of Vocalizations during a Free-Choice Task

Adaptive behavior requires that animals integrate current and past information with their decision-making. One important type of information is auditory-communication signals (i.e., species-specific vocalizations). Here, we tested how rhesus monkeys incorporate the opportunity to listen to different species-specific vocalizations into their decision-making processes. In particular, we tested how monkeys value these vocalizations relative to the opportunity to get a juice reward. To test this hypothesis, monkeys chose one of two targets to get a varying juice reward; at one of those targets, in addition to the juice reward, a vocalization was presented. By titrating the juice amounts at the two targets, we quantified the relationship between the monkeys'' juice choices relative to the opportunity to listen to a vocalization. We found that, rhesus were not willing to give up a large juice reward to listen to vocalizations indicating that, relative to a juice reward, listening to vocalizations has a low value.     

Rhesus monkey (Macaca mulatta) screams: Representational signalling in the recruitment of agonistic aid

Free-ranging rhesus monkeys on Cayo Santiago (Puerto Rico) give five acoustically distinct scream vocalizations during agonistic encounters. These calls are thought to be an important mechanism in the recruitment of support from allies against opponents. Alliance formation during agonistic encounters is known to vary with the dominance rank and matrilineal relatedness of opponents, as well as with the severity of aggression. In contrast to previous interpretations of screams as graded signals reflecting the level of arousal of the caller, we found these calls to be much more discrete, with each of the five acoustic types significantly associated with a particular class of opponent and level of physical aggression. We performed a series of field experiments in which tape-recorded screams of immature rhesus monkeys were played to their mothers in the absence of any other information. The results suggest that the information necessary for differential responses is conveyed by the scream vocalizations themselves. We conclude that screams are representational signals that refer to external objects and events and function in the system of agonistic alliance formation.     

Light Evokes Melanopsin-Dependent Vocalization and Neural Activation Associated with Aversive Experience in Neonatal Mice

Melanopsin-expressing intrinsically photosensitive retinal ganglion cells (ipRGCs) are the only functional photoreceptive cells in the eye of newborn mice. Through postnatal day 9, in the absence of functional rods and cones, these ipRGCs mediate a robust avoidance behavior to a light source, termed negative phototaxis. To determine whether this behavior is associated with an aversive experience in neonatal mice, we characterized light-induced vocalizations and patterns of neuronal activation in regions of the brain involved in the processing of aversive and painful stimuli. Light evoked distinct melanopsin-dependent ultrasonic vocalizations identical to those emitted under stressful conditions, such as isolation from the litter. In contrast, light did not evoke the broad-spectrum calls elicited by acute mechanical pain. Using markers of neuronal activation, we found that light induced the immediate-early gene product Fos in the posterior thalamus, a brain region associated with the enhancement of responses to mechanical stimulation of the dura by light, and thought to be the basis for migrainous photophobia. Additionally, light induced the phosphorylation of extracellular-related kinase (pERK) in neurons of the central amygdala, an intracellular signal associated with the processing of the aversive aspects of pain. However, light did not activate Fos expression in the spinal trigeminal nucleus caudalis, the primary receptive field for painful stimulation to the head. We conclude that these light-evoked vocalizations and the distinct pattern of brain activation in neonatal mice are consistent with a melanopsin-dependent neural pathway involved in processing light as an aversive but not acutely painful stimulus.     

Reduced Inhibition of Return to Food Images in Obese Individuals

Previous research has shown that obese individuals may be biased towards attending to food over non-food information, and this bias may contribute to the development and/or maintenance of obesity. The present study sought to extend our understanding of maladaptive attentional processing in this population by investigating whether obese individuals have difficulty in disengaging attention from food compared with non-food images, relative to normal-weight controls. To address this question, we measured inhibition of return (IOR) in an attentional cueing task. The participants were 29 obese and 35 normal-weight satiated females without eating disorders. The obese group displayed less IOR to food images than the normal-weight group, while there was no difference in IOR between the groups for non-food images. This suggests that obese females have greater difficulty disengaging attention from food than normal-weight females. Our findings provide a new focus for studies investigating maintenance factors in obesity and are discussed in relation to a theory of incentive-sensitisation.     

Human cerebral response to animal affective vocalizations

It is presently unknown whether our response to affective vocalizations is specific to those generated by humans or more universal, triggered by emotionally matched vocalizations generated by other species. Here, we used functional magnetic resonance imaging in normal participants to measure cerebral activity during auditory stimulation with affectively valenced animal vocalizations, some familiar (cats) and others not (rhesus monkeys). Positively versus negatively valenced vocalizations from cats and monkeys elicited different cerebral responses despite the participants' inability to differentiate the valence of these animal vocalizations by overt behavioural responses. Moreover, the comparison with human non-speech affective vocalizations revealed a common response to the valence in orbitofrontal cortex, a key component on the limbic system. These findings suggest that the neural mechanisms involved in processing human affective vocalizations may be recruited by heterospecific affective vocalizations at an unconscious level, supporting claims of shared emotional systems across species.     

Visual categorization of natural and abstract items in forest monkeys and humans

A preference for novelty paradigm was used to investigate whether mangabeys (Lophocebus albigena), an arboreal non-human primate species, were able to discriminate and to categorize different visual stimuli belonging to natural (food items) and abstract (non-food items) categories. In a comparative perspective human subjects were tested with the same procedure and the same stimuli. Two out of four mangabeys and three out of the four humans showed significant preference for novelty when comparing food versus non-food items. Hence they discriminated between these two sets of items. The two mangabeys and one non-adult human subject sorted the food items in one category, showing no preference for novelty when comparing known and unknown food-items and different views of the same food items. In contrast the two adult human subjects who showed preference for novelty in the between-category, did not show preference for novelty when comparing known and unknown food-items but did show such a preference when comparing different views of the same food items. Compared to human performances, the results suggest that mangabeys are able to form at least a perceptual category of natural, ecologically relevant stimuli.     

Sources of Acoustic Variation in Rhesus Macaque (Macaca mulatta))Vocalizations

All species in the genus Macaca produce a set of harmonically rich vocalizations known as “coos”. Extensive acoustic variation occurs within this call type, a large proportion of which is thought to be associated with different social contexts such as mother-infant separation and the discovery of food. Prior studies of these calls have not taken into account the potential contributions of individual differences and changes in emotional or motivational state. To understand the function of a call and the perceptual salience of different acoustic features, however, it is important to determine the different sources of acoustic variation. I present data on the rhesus macaques' (M. mulatta) coo vocalization and attempt to establish some of the causes of acoustic variation. A large proportion of the variation observed was due to differences between individuals and to putative changes in arousal, not to differences in social context. Specifically, results from a discriminant-function analysis indicated that coo exemplars were accurately assigned to the appropriate individual, but vocal “signatures” were more variable in some contexts than in others. Moreover, vocal signatures may not always be reliable cues to caller identity because closely related individuals sound alike. Rhesus macaque coos evidently provide sufficient acoustic information for individual recognition and possibly kin recognition, but are unlikely to provide sufficient information about an external referent.     

Developmental experience alters information coding in auditory midbrain and forebrain neurons

In songbirds, species identity and developmental experience shape vocal behavior and behavioral responses to vocalizations. The interaction of species identity and developmental experience may also shape the coding properties of sensory neurons. We tested whether responses of auditory midbrain and forebrain neurons to songs differed between species and between groups of conspecific birds with different developmental exposure to song. We also compared responses of individual neurons to conspecific and heterospecific songs. Zebra and Bengalese finches that were raised and tutored by conspecific birds, and zebra finches that were cross‐tutored by Bengalese finches were studied. Single‐unit responses to zebra and Bengalese finch songs were recorded and analyzed by calculating mutual information (MI), response reliability, mean spike rate, fluctuations in time‐varying spike rate, distributions of time‐varying spike rates, and neural discrimination of individual songs. MI quantifies a response's capacity to encode information about a stimulus. In midbrain and forebrain neurons, MI was significantly higher in normal zebra finch neurons than in Bengalese finch and cross‐tutored zebra finch neurons, but not between Bengalese finch and cross‐tutored zebra finch neurons. Information rate differences were largely due to spike rate differences. MI did not differ between responses to conspecific and heterospecific songs. Therefore, neurons from normal zebra finches encoded more information about songs than did neurons from other birds, but conspecific and heterospecific songs were encoded equally. Neural discrimination of songs and MI were highly correlated. Results demonstrate that developmental exposure to vocalizations shapes the information coding properties of songbird auditory neurons. © 2009 Wiley Periodicals, Inc. Develop Neurobiol 70: 235–252, 2010.     

Food Transfer and Development of Feeding Behavior and Food-Associated Vocalizations in Cotton-Top Tamarins

Food transfer between adults and infants is common in many marmoset and tamarin monkeys, and is often accompanied by vocalizations. We hypothesized that vocalizations by adults in a food transfer context creates an opportunity for infants to learn not only what foods are appropriate but what vocalizations are appropriate in feeding contexts. We studied the development of feeding behavior and food-associated vocalizations in 10 infant cotton-top tamarins through the first 20 wks of life. Infants obtained solid food through transfers from older group members, primarily the adult male, beginning at weeks 5–6. Both adults and infants vocalized during food transfers with adults, producing rapid sequences of the call types adults normally give when feeding. Infants were usually successful in obtaining food primarily when the adult was vocalizing. The sooner infants were active participants in food transfers, the sooner they began to feed independently. In the early weeks, infants produced a large number of vocal types during food transfers, but with increasing age there was a steady increase in the number of adult-form food calls and a reduction in other, non-food-associated calls. Infants that fed independently at an early age produced fewer non-food-associated calls by the last month of observation. Infants called at higher rates to their most preferred food. Food transfers accompanied by vocalizations may provide an opportunity for infants to learn about appropriate foods as well as the vocalizations that accompany feeding in adults, and may represent a form of 'coaching' or information donation by adults.     

Gender and weight shape brain dynamics during food viewing

Hemodynamic imaging results have associated both gender and body weight to variation in brain responses to food-related information. However, the spatio-temporal brain dynamics of gender-related and weight-wise modulations in food discrimination still remain to be elucidated. We analyzed visual evoked potentials (VEPs) while normal-weighted men (n = 12) and women (n = 12) categorized photographs of energy-dense foods and non-food kitchen utensils. VEP analyses showed that food categorization is influenced by gender as early as 170 ms after image onset. Moreover, the female VEP pattern to food categorization co-varied with participants' body weight. Estimations of the neural generator activity over the time interval of VEP modulations (i.e. by means of a distributed linear inverse solution [LAURA]) revealed alterations in prefrontal and temporo-parietal source activity as a function of image category and participants' gender. However, only neural source activity for female responses during food viewing was negatively correlated with body-mass index (BMI) over the respective time interval. Women showed decreased neural source activity particularly in ventral prefrontal brain regions when viewing food, but not non-food objects, while no such associations were apparent in male responses to food and non-food viewing. Our study thus indicates that gender influences are already apparent during initial stages of food-related object categorization, with small variations in body weight modulating electrophysiological responses especially in women and in brain areas implicated in food reward valuation and intake control. These findings extend recent reports on prefrontal reward and control circuit responsiveness to food cues and the potential role of this reactivity pattern in the susceptibility to weight gain.     

Voice processing in human and non-human primates

Humans share with non-human primates a number of voice perception abilities of crucial importance in social interactions, such as the ability to identify a conspecific individual from its vocalizations. Speech perception is likely to have evolved in our ancestors on the basis of pre-existing neural mechanisms involved in extracting behaviourally relevant information from conspecific vocalizations (CVs). Studying the neural bases of voice perception in primates thus not only has the potential to shed light on cerebral mechanisms that may be--unlike those involved in speech perception--directly homologous between species, but also has direct implications for our understanding of how speech appeared in humans. In this comparative review, we focus on behavioural and neurobiological evidence relative to two issues central to voice perception in human and non-human primates: (i) are CVs 'special', i.e. are they analysed using dedicated cerebral mechanisms not used for other sound categories, and (ii) to what extent and using what neural mechanisms do primates identify conspecific individuals from their vocalizations?     

Social and nonsocial content differentially modulates visual attention and autonomic arousal in Rhesus macaques

The sophisticated analysis of gestures and vocalizations, including assessment of their emotional valence, helps group-living primates efficiently navigate their social environment. Deficits in social information processing and emotion regulation are important components of many human psychiatric illnesses, such as autism, schizophrenia and social anxiety disorder. Analyzing the neurobiology of social information processing and emotion regulation requires a multidisciplinary approach that benefits from comparative studies of humans and animal models. However, many questions remain regarding the relationship between visual attention and arousal while processing social stimuli. Using noninvasive infrared eye-tracking methods, we measured the visual social attention and physiological arousal (pupil diameter) of adult male rhesus monkeys (Macaca mulatta) as they watched social and nonsocial videos. We found that social videos, as compared to nonsocial videos, captured more visual attention, especially if the social signals depicted in the videos were directed towards the subject. Subject-directed social cues and nonsocial nature documentary footage, compared to videos showing conspecifics engaging in naturalistic social interactions, generated larger pupil diameters (indicating heightened sympathetic arousal). These findings indicate that rhesus monkeys will actively engage in watching videos of various kinds. Moreover, infrared eye tracking technology provides a mechanism for sensitively gauging the social interest of presented stimuli. Adult male rhesus monkeys' visual attention and physiological arousal do not always trend in the same direction, and are likely influenced by the content and novelty of a particular visual stimulus. This experiment creates a strong foundation for future experiments that will examine the neural network responsible for social information processing in nonhuman primates. Such studies may provide valuable information relevant to interpreting the neural deficits underlying human psychiatric illnesses such as autism, schizophrenia and social anxiety disorder.     

Serotonin modulates responses to species-specific vocalizations in the inferior colliculus

Neuromodulators such as serotonin are capable of altering the neural processing of stimuli across many sensory modalities. In the inferior colliculus, a major midbrain auditory gateway, serotonin alters the way that individual neurons respond to simple tone bursts and linear frequency modulated sweeps. The effects of serotonin are complex, and vary among neurons. How serotonin transforms the responses to spectrotemporally complex sounds of the type normally heard in natural settings has been poorly examined. To explore this issue further, the effects of iontophoretically applied serotonin on the responses of individual inferior colliculus neurons to a variety of recorded species-specific vocalizations were examined. These experiments were performed in the Mexican free-tailed bat, a species that uses a rich repertoire of vocalizations for the purposes of communication as well as echolocation. Serotonin frequently changed the number of recorded calls that were capable of evoking a response from individual neurons, sometimes increasing (15% of serotonin-responsive neurons), but usually decreasing (62% of serotonin-responsive neurons), this number. A functional consequence of these serotonin-evoked changes would be to change the population response to species-specific vocalizations.     

Noradrenergic control of gene expression and long-term neuronal adaptation evoked by learned vocalizations in songbirds

Norepinephrine (NE) is thought to play important roles in the consolidation and retrieval of long-term memories, but its role in the processing and memorization of complex acoustic signals used for vocal communication has yet to be determined. We have used a combination of gene expression analysis, electrophysiological recordings and pharmacological manipulations in zebra finches to examine the role of noradrenergic transmission in the brain's response to birdsong, a learned vocal behavior that shares important features with human speech. We show that noradrenergic transmission is required for both the expression of activity-dependent genes and the long-term maintenance of stimulus-specific electrophysiological adaptation that are induced in central auditory neurons by stimulation with birdsong. Specifically, we show that the caudomedial nidopallium (NCM), an area directly involved in the auditory processing and memorization of birdsong, receives strong noradrenergic innervation. Song-responsive neurons in this area express α-adrenergic receptors and are in close proximity to noradrenergic terminals. We further show that local α-adrenergic antagonism interferes with song-induced gene expression, without affecting spontaneous or evoked electrophysiological activity, thus dissociating the molecular and electrophysiological responses to song. Moreover, α-adrenergic antagonism disrupts the maintenance but not the acquisition of the adapted physiological state. We suggest that the noradrenergic system regulates long-term changes in song-responsive neurons by modulating the gene expression response that is associated with the electrophysiological activation triggered by song. We also suggest that this mechanism may be an important contributor to long-term auditory memories of learned vocalizations.     

Detection of an activating c-kit mutation by real-time PCR in patients with anaphylaxis

A well-characterised gain-of-function point mutation within exon 17 of the c-kit proto-oncogene known as Asp816Val is present in patients with mastocytosis. Activation of mast cells through this receptor primes them for IgE-dependent activation, and patients with mastocytosis are at increased risk of anaphylaxis. We hypothesised that the Asp816Val mutation is associated with a history of anaphylaxis in the general population. A mismatch amplification real-time PCR assay was developed and validated to test for the Asp816Val mutation. Subjects were recruited to four subject groups: normal non-atopics, atopics without anaphylaxis, food-induced anaphylactics and non-food anaphylactics. Blood samples collected from forty subjects were tested for the presence of Asp816Val. Thirteen subjects were found to carry the mutation; normals (2/9), atopics (2/10), food anaphylactics (5/11) and non-food anaphylactics (4/10). Statistical analysis of the data determined that there was no significant difference between the numbers of subjects found to carry the Asp816Val mutation in each of the groups although a trend towards an increased occurrence in anaphylactics was observed. In summary, the hypothesis that the presence of the Asp816Val mutation is linked to the occurrence of anaphylaxis was not supported, but interestingly, we have shown for the first time Asp816Val may occur more frequently than previously reported within the general population.     

Conspecific discrimination in an object-choice task in African grey parrots (Psittacus erithacus)

Living in social groups presents the opportunity to use information provided by other individuals. Several animal species emit specific vocalizations when they find food. Here, we investigate whether African grey parrots (Psittacus erithacus) use vocal and non-vocal information provided by a conspecific in order to find a hidden food source. One subject was attracted by the presence or the vocalizations of a subordinate conspecific, but not of a dominant, which brings us to hypothesize that parrots could be capable of individual vocal discrimination.