The mosaic structure of the mammalian cognitive map.

The cognitive map, proposed by Tolman in the 1940s, is a hypothetical internal representation of space constructed by the brain to enable an animal to undertake flexible spatial behaviors such as navigation. The subsequent discovery of place cells in the hippocampus of rats suggested that such a map-like representation does exist, and also provided a tool with which to explore its properties. Single-neuron studies in rodents conducted in small singular spaces have suggested that the map is founded on a metric framework, preserving distances and directions in an abstract representational format. An open question is whether this metric structure pertains over extended, often complexly structured real-world space. The data reviewed here suggest that this is not the case. The emerging picture is that instead of being a single, unified construct, the map is a mosaic of fragments that are heterogeneous, variably metric, multiply scaled, and sometimes laid on top of each other. Important organizing factors within and between fragments include boundaries, context, compass direction, and gravity. The map functions not to provide a comprehensive and precise rendering of the environment but rather to support adaptive behavior, tailored to the species and situation.

Performance on inhibitory tasks does not relate to handedness in several small groups of Callitrichids.

Brain lateralization, a trait ubiquitous in vertebrates and invertebrates, refers to structural differences between the left and right sides of the brain or to the left and right sides controlling different functions or processing information in different ways. Many studies have looked into the advantages of lateralized brains and discovered that cerebral lateralization confers a fitness advantage. Enhancing cognitive ability has been proposed as one of the potential benefits of the lateralized brain, however, this has not been widely validated. In this study, we investigated the handedness of 34 subjects from four groups of Callitrichids, as well as their performance in two inhibitory control tasks (the revised A-not-B task and the cylinder task). The subjects had strong individual hand preferences, and only a few zoo-born individuals were ambidextrous. Sex and generation influence the strength of hand preference. In the cylinder task, the subjects showed differences between groups, and the performance of the second-generation was better than that of the first-generation. We found that neither the strength of hand preferences (ABS-HI) or direction of hand preferences (HI) was linked with success on the two inhibitory tasks. That is, we were unable to support the enhanced cognitive function hypothesis. We believe that individual ontogeny and the type of cognitive task have an impact on the support of this hypothesis. The advantages of lateralized brain may be reflected in tests that require multiple cognitive abilities.

A search pattern for the engram.

Roy and colleagues (Nature Communications, 13.1, 1-16, 2022) examined neuronal ensembles associated with contextual fear conditioning memory across multiple brain regions, referred to as a unified engram complex. Their four-step approach incorporating brain-wide mapping of activated neurons, engram indexing, and optogenetic and chemogenetic manipulations could offer a novel, holistic approach to implement in our continued search for the engram.

Dog-human social relationship: representation of human face familiarity and emotions in the dog brain.

This study investigated the behavioral and neural indices of detecting facial familiarity and facial emotions in human faces by dogs. Awake canine fMRI was used to evaluate dogs' neural response to pictures and videos of familiar and unfamiliar human faces, which contained positive, neutral, and negative emotional expressions. The dog-human relationship was behaviorally characterized out-of-scanner using an unsolvable task. The caudate, hippocampus, and amygdala, mainly implicated in reward, familiarity and emotion processing, respectively, were activated in dogs when viewing familiar and emotionally salient human faces. Further, the magnitude of activation in these regions correlated with the duration for which dogs showed human-oriented behavior towards a familiar (as opposed to unfamiliar) person in the unsolvable task. These findings provide a bio-behavioral basis for the underlying markers and functions of human-dog interaction as they relate to familiarity and emotion in human faces.

Chimpanzee brain morphometry utilizing standardized MRI preprocessing and macroanatomical annotations.

Chimpanzees are among the closest living relatives to humans and, as such, provide a crucial comparative model for investigating primate brain evolution. In recent years, human brain mapping has strongly benefited from enhanced computational models and image processing pipelines that could also improve data analyses in animals by using species-specific templates. In this study, we use structural MRI data from the National Chimpanzee Brain Resource (NCBR) to develop the chimpanzee brain reference template Juna.Chimp for spatial registration and the macro-anatomical brain parcellation Davi130 for standardized whole-brain analysis. Additionally, we introduce a ready-to-use image processing pipeline built upon the CAT12 toolbox in SPM12, implementing a standard human image preprocessing framework in chimpanzees. Applying this approach to data from 194 subjects, we find strong evidence for human-like age-related gray matter atrophy in multiple regions of the chimpanzee brain, as well as, a general rightward asymmetry in brain regions.

Multilevel fMRI adaptation for spoken word processing in the awake dog brain.

Human brains process lexical meaning separately from emotional prosody of speech at higher levels of the processing hierarchy. Recently we demonstrated that dog brains can also dissociate lexical and emotional prosodic information in human spoken words. To better understand the neural dynamics of lexical processing in the dog brain, here we used an event-related design, optimized for fMRI adaptation analyses on multiple time scales. We investigated repetition effects in dogs' neural (BOLD) responses to lexically marked (praise) words and to lexically unmarked (neutral) words, in praising and neutral prosody. We identified temporally and anatomically distinct adaptation patterns. In a subcortical auditory region, we found both short- and long-term fMRI adaptation for emotional prosody, but not for lexical markedness. In multiple cortical auditory regions, we found long-term fMRI adaptation for lexically marked compared to unmarked words. This lexical adaptation showed right-hemisphere bias and was age-modulated in a near-primary auditory region and was independent of prosody in a secondary auditory region. Word representations in dogs' auditory cortex thus contain more than just the emotional prosody they are typically associated with. These findings demonstrate multilevel fMRI adaptation effects in the dog brain and are consistent with a hierarchical account of spoken word processing.

Cross-species cortical alignment identifies different types of anatomical reorganization in the primate temporal lobe.

Evolutionary adaptations of temporo-parietal cortex are considered to be a critical specialization of the human brain. Cortical adaptations, however, can affect different aspects of brain architecture, including local expansion of the cortical sheet or changes in connectivity between cortical areas. We distinguish different types of changes in brain architecture using a computational neuroanatomy approach. We investigate the extent to which between-species alignment, based on cortical myelin, can predict changes in connectivity patterns across macaque, chimpanzee, and human. We show that expansion and relocation of brain areas can predict terminations of several white matter tracts in temporo-parietal cortex, including the middle and superior longitudinal fasciculus, but not the arcuate fasciculus. This demonstrates that the arcuate fasciculus underwent additional evolutionary modifications affecting the temporal lobe connectivity pattern. This approach can flexibly be extended to include other features of cortical organization and other species, allowing direct tests of comparative hypotheses of brain organization.

How did language evolve? Since the human lineage diverged from that of the other great apes millions of years ago, changes in the brain have given rise to behaviors that are unique to humans, such as language. Some of these changes involved alterations in the size and relative positions of brain areas, while others required changes in the connections between those regions. But did these changes occur independently, or can the changes observed in one actually explain the changes we see in the other? One way to answer this question is to use neuroimaging to compare the brains of related species, using different techniques to examine different aspects of brain structure. Imaging a fatty substance called myelin, for example, can produce maps showing the size and position of brain areas. Measuring how easily water molecules diffuse through brain tissue, by contrast, provides information about connections between areas. Eichert et al. performed both types of imaging in macaques and healthy human volunteers, and compared the results to existing data from chimpanzees. Computer simulations were used to manipulate the myelin-based images so that equivalent brain areas in each species occupied the same positions. In most cases, the distortions ­ or 'warping' ­ needed to superimpose brain regions on top of one another also predicted the differences between species in the connections between those regions. This suggests that movement of brain regions over the course of evolution explain the differences previously observed in brain connectivity. But there was one notable exception, namely a bundle of fibers with a key role in language called the arcuate fasciculus. This structure follows a slightly different route through the brain in humans compared to chimpanzees and macaques. Eichert et al. show that this difference cannot be explained solely by changes in the positions of brain regions. Instead, the arcuate fasciculus underwent additional changes in its course, which may have contributed to the evolution of language. The framework developed by Eichert et al. can be used to study evolution in many different species. Interspecies comparisons can provide clues to how brain structure and activity relate to each other and to behavior, and this knowledge could ultimately help to understand and treat brain disorders.

Higher neuron densities in the cerebral cortex and larger cerebellums may limit dive times of delphinids compared to deep-diving toothed whales.

Since the work of Tower in the 1950s, we have come to expect lower neuron density in the cerebral cortex of larger brains. We studied dolphin brains varying from 783 to 6215g. As expected, average neuron density in four areas of cortex decreased from the smallest to the largest brain. Despite having a lower neuron density than smaller dolphins, the killer whale has more gray matter and more cortical neurons than any mammal, including humans. To begin a study of non-dolphin toothed whales, we measured a 596g brain of a pygmy sperm whale and a 2004g brain of a Cuvier's beaked whale. We compared neuron density of Nissl stained cortex of these two brains with those of the dolphins. Non-dolphin brains had lower neuron densities compared to all of the dolphins, even the 6215g brain. The beaked whale and pygmy sperm whale we studied dive deeper and for much longer periods than the dolphins. For example, the beaked whale may dive for more than an hour, and the pygmy sperm whale more than a half hour. In contrast, the dolphins we studied limit dives to five or 10 minutes. Brain metabolism may be one feature limiting dolphin dives. The brain consumes an oversized share of oxygen available to the body. The most oxygen is used by the cortex and cerebellar gray matter. The dolphins have larger brains, larger cerebellums, and greater numbers of cortex neurons than would be expected given their body size. Smaller brains, smaller cerebellums and fewer cortical neurons potentially allow the beaked whale and pygmy sperm whale to dive longer and deeper than the dolphins. Although more gray matter, more neurons, and a larger cerebellum may limit dolphins to shorter, shallower dives, these features must give them some advantage. For example, they may be able to catch more elusive individual high-calorie prey in the upper ocean.

The physiological experiments of Constantin von Economo on the central pathways of mastication and deglutition.

The first study of Constantin von Economo on the mammalian brain was published in 1902. Experiments were carried out in rabbits at the Physiological Institute headed by Siegmund von Exner-Ewarten in Vienna to investigate the central pathways of chewing and swallowing. After placing cortical lesions, Economo applied cortical and subcortical electrical stimulation to obtain masticatory movements, and tracked degenerated fibers by means of the Marchi method. He traced fibers through the internal capsule, ventral nucleus of the thalamus, subthalamic nucleus, substantia nigra and its connections with the motor nucleus of the trigeminal nerve, and nucleus solitarius. He suggested that the substantia nigra is responsible for coordinating alimentation movements, with the involvement of cranial nerves V, VII, IX and X as well. We discuss these findings in a historical and a modern perspective, including the concept of a central pattern generator in the pontine reticular formation and its interaction with the nucleus solitarius. Today we understand that mastication is a voluntary action controlled by motor cortical areas, by motoneurons of the trigeminal, and by a neural pattern generator in the pons. On the other hand, deglutition comprises 'reflex swallowing' triggered by sensory fibers of cranial nerves V, IX and X, and 'voluntary swallowing' which may be controlled by both cortical fields and subcortical areas, such as the internal capsule, the hypothalamus and the mesencephalic reticular formation.

Pig Brains Have Homologous Resting-State Networks with Human Brains.

Many neurological and psychiatric diseases in humans are caused by disruptions to large-scale functional properties of the brain, including functional connectivity. There has been growing interest in discovering the functional organization of brain networks in larger animal models. As a result, the use of translational pig models in neuroscience has significantly increased in the past decades. The gyrencephalic pig brain resembles the human brain more in anatomy, growth, and development than the brains of commonly used small laboratory animals such as rodents. In this work, resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) data were acquired from a group of pigs (n = 12). rs-fMRI data were analyzed for resting-state networks (RSNs) by using independent component analysis and sparse dictionary learning. Six RSNs (executive control, cerebellar, sensorimotor, visual, auditory, and default mode) were detected that resemble their counterparts in human brains, as measured by Pearson spatial correlations and mean ratios. Supporting evidence of the validity of these RSNs was provided through the evaluation and quantification of structural connectivity measures (mean diffusivity, fractional anisotropy, fiber length, and fiber density) estimated from the DTI data. This study shows that as a translational, large animal model, pigs demonstrate great potential for mapping connectome-scale functional connectivity in experimental modeling of human brain disorders.

Site-specific effects of aromatase inhibition on the activation of male sexual behavior in male Japanese quail (Coturnix japonica).

Aromatization within the medial preoptic nucleus (POM) is essential for the expression of male copulatory behavior in Japanese quail. However, several nuclei within the social behavior network (SBN) also express aromatase. Whether aromatase in these loci participates in the behavioral activation is not known. Castrated male Japanese quail were implanted with 2 subcutaneous Silastic capsules filled with crystalline testosterone and with bilateral stereotaxic implants filled with the aromatase inhibitor Vorozole targeting the POM, the bed nucleus of the stria terminalis (BST) or the ventromedial nucleus of the hypothalamus (VMN). Control animals were implanted with testosterone and empty bilateral stereotaxic implants. Starting 2 days after the surgery, subjects were tested for the expression of consummatory sexual behavior (CSB) every other day for a total of 10 tests. They were also tested once for appetitive sexual behavior (ASB) as measured by the rhythmic cloacal sphincter movements displayed in response to the visual presentation of a female. CSB was drastically reduced when the Vorozole implants were localized in the POM, but not in the BST nor in the VMN. Birds with implants in the BST took longer to show CSB in the first 6 tests than controls, suggesting a role of the BST in the acquisition of the full copulatory ability. ASB was not significantly affected by aromatase blockade in any region. These data confirm the key role played by the POM in the control of male sexual behavior and suggest a minor role for aromatization in the BST or VMN.

Neural coding of intended and executed grasp force in macaque areas AIP, F5, and M1.

Considerable progress has been made over the last decades in characterizing the neural coding of hand shape, but grasp force has been largely ignored. We trained two macaque monkeys (Macaca mulatta) on a delayed grasping task where grip type and grip force were instructed. Neural population activity was recorded from areas relevant for grasp planning and execution: the anterior intraparietal area (AIP), F5 of the ventral premotor cortex, and the hand area of the primary motor cortex (M1). Grasp force was strongly encoded by neural populations of all three areas, thereby demonstrating for the first time the coding of grasp force in single- and multi-units of AIP. Neural coding of intended grasp force was most strongly represented in area F5. In addition to tuning analysis, a dimensionality reduction method revealed low-dimensional responses to grip type and grip force. Additionally, this method revealed a high correlation between latent variables of the neural population representing grasp force and the corresponding latent variables of electromyographic forearm muscle activity. Our results therefore suggest an important role of the cortical areas AIP, F5, and M1 in coding grasp force during movement execution as well as of F5 for coding intended grasp force.

Regional variations in stiffness in live mouse brain tissue determined by depth-controlled indentation mapping.

The mechanical properties of brain tissue play a pivotal role in neurodevelopment and neurological disorders. Yet, at present, there is no consensus on how the different structural parts of the tissue contribute to its stiffness variations. Here, we have gathered depth-controlled indentation viscoelasticity maps of the hippocampus of acute horizontal live mouse brain slices. Our results confirm the highly viscoelestic nature of brain tissue. We further show that the mechanical properties are non-uniform and at least related to differences in morphological composition. Interestingly, areas with higher nuclear density appear to be softer than areas with lower nuclear density.

Efficient Blood-Brain Barrier Opening in Primates with Neuronavigation-Guided Ultrasound and Real-Time Acoustic Mapping.

Brain diseases including neurological disorders and tumors remain under treated due to the challenge to access the brain, and blood-brain barrier (BBB) restricting drug delivery which, also profoundly limits the development of pharmacological treatment. Focused ultrasound (FUS) with microbubbles is the sole method to open the BBB noninvasively, locally, and transiently and facilitate drug delivery, while translation to the clinic is challenging due to long procedure, targeting limitations, or invasiveness of current systems. In order to provide rapid, flexible yet precise applications, we have designed a noninvasive FUS and monitoring system with the protocol tested in monkeys (from in silico preplanning and simulation, real-time targeting and acoustic mapping, to post-treatment assessment). With a short procedure (30 min) similar to current clinical imaging duration or radiation therapy, the achieved targeting (both cerebral cortex and subcortical structures) and monitoring accuracy was close to the predicted 2-mm lower limit. This system would enable rapid clinical transcranial FUS applications outside of the MRI system without a stereotactic frame, thereby benefiting patients especially in the elderly population.

Rapid changes in auditory processing in songbirds following acute aromatase inhibition as assessed by fMRI.

Contribution to Special Issue on Fast effects of steroids. This review introduces functional MRI (fMRI) as an outstanding tool to assess rapid effects of sex steroids on auditory processing in seasonal songbirds. We emphasize specific advantages of this method as compared to other more conventional and invasive methods used for this purpose and summarize an exemplary auditory fMRI study performed on male starlings exposed to different types of starling song before and immediately after the inhibition of aromatase activity by an i.p. injection of Vorozole™. We describe how most challenges that relate to the necessity to anesthetize subjects and minimize image- and sound-artifacts can be overcome in order to obtain a voxel-based 3D-representation of changes in auditory brain activity to various sound stimuli before and immediately after a pharmacologically-induced depletion of endogenous estrogens. Analysis of the fMRI data by assumption-free statistical methods identified fast specific changes in activity in the auditory brain regions that were stimulus-specific, varying over different seasons, and in several instances lateralized to the left side of the brain. This set of results illustrates the unique features of fMRI that provides opportunities to localize and quantify the brain responses to rapid changes in hormonal status. fMRI offers a new image-guided research strategy in which the spatio-temporal profile of fast neuromodulations can be identified and linked to specific behavioral inputs or outputs. This approach can also be combined with more localized invasive methods to investigate the mechanisms underlying the observed neural changes.

Distribution of endomorphin-like-immunoreactive neurones in the brain of the cichlid fish Oreochromis mossambicus.

Endomorphins (EMs) are tetrapeptides involved in pain and neuroendocrine responses with a high affinity for µ-opioid receptors in mammals. In the present study, we investigated the distribution of EM-like-immunoreactive (EM-L-IR) neurones in the brain of the cichlid fish Oreochromis mossambicus. Application of antisera against EM-1 and 2 (EM-1-2) revealed the presence of EM-L-IR somata and fibres throughout the different subdivisions of the olfactory bulb, such as the olfactory nerve layer and the granule cell layer. Although the extensions of EM-L-IR fibres were seen along the medial olfactory tract, intensely labelled EM-L-IR somata were found in different subdivisions of the telencephalon. In the diencephalon, intensely stained EM-L-IR neurones were noted in the preoptic area, the nucleus preopticus pars magnocellularis, the suprachiasmatic nucleus, the nucleus lateralis tuberis pars lateralis and the nucleus lateralis tuberis pars medialis regions, whereas projections of EM-L-IR fibres were also seen along the hypothalamic-hypophyseal tract, suggesting a possible hypophysiotrophic role for these neurones. Intense to moderately stained EM-L-IR neurones were noted in different subdivisions of thalamic nucleus, such as the dorsal posterior thalamic nucleus, commissura posterior, ventromedial thalamic nucleus, nucleus posterior tuberis, ventrolateral thalamic nucleus and medial preglomerular nucleus. Numerous intensely stained perikarya and axonal fibres were also noted throughout the inferior lobe, along the periventricular margin of the reccessus lateralis and in the nucleus recesus lateralis regions. In addition, numerous moderately labelled EM-like neuronal populations were found in the secondary gustatory nucleus and rostral spinal cord. The widespread distribution of EM-L-IR neurones throughout the brain and spinal cord indicates the diverse roles for these cells in neuroendocrine and neuromodulatory responses for the first time in fish. The present study provides further insights into the possible existence of EM-like peptides in early vertebrate lines and suggests that these peptides might have been well-conserved during the course of evolution.

Design and implementation of embedded 8-channel receive-only arrays for whole-brain MRI and fMRI of conscious awake marmosets.

PURPOSE: The common marmoset (Callithrix jacchus) is a New World primate of increasing interest to neuroscience and in translational brain research. The present work describes the design and implementation of individualized 8-channel receive-only radiofrequency (RF) coil arrays that provide whole-brain coverage and allow anatomical and functional MRI experiments in conscious, awake marmosets. METHODS: The coil arrays were designed with their elements embedded inside individualized restraint helmets. The size, geometry, and arrangement of the coil elements were optimized to allow whole-brain coverage. Coil-to-coil decoupling was achieved by a combination of geometric decoupling and low input impedance preamplifiers. The performance of the embedded arrays was compared against that of one 8-channel receive-only array built to fit the external surface of the helmets. RESULTS: Three individualized helmets with embedded coil arrays were built for three marmosets. Whole-brain coverage was achieved with high sensitivity extending over the entire cortex. Visual stimulation of conscious awake marmosets elicited robust BOLD fMRI responses in both primary and higher order visual areas of the occipitotemporal cortex. CONCLUSION: The high sensitivity provided by embedded receive-only coil arrays allows both anatomical and functional MRI data to be obtained with high spatial resolution in conscious, awake marmosets. Magn Reson Med 78:387-398, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Representation of Afferent Signals from Forearm Muscle and Cutaneous Nerves in the Primary Somatosensory Cortex of the Macaque Monkey.

Proprioception is one's overall sense of the relative positions and movements of the various parts of one's body. The primary somatosensory cortex (SI) is involved in generating the proprioception by receiving peripheral sensory inputs from both cutaneous and muscle afferents. In particular, area 3a receives input from muscle afferents and areas 3b and 1 from cutaneous afferents. However, segregation of two sensory inputs to these cortical areas has not been evaluated quantitatively because of methodological difficulties in distinguishing the incoming signals. To overcome this, we applied electrical stimulation separately to two forearm nerves innervating muscle (deep radial nerve) and skin (superficial radial nerve), and examined the spatiotemporal distribution of sensory evoked potentials (SEPs) in SI of anaesthetized macaques. The SEPs arising from the deep radial nerve were observed exclusively at the bottom of central sulcus (CS), which was identified as area 3a using histological reconstruction. In contrast, SEPs evoked by stimulation of the superficial radial nerve were observed in the superficial part of SI, identified as areas 3b and 1. In addition to these earlier, larger potentials, we also found small and slightly delayed SEPs evoked by cutaneous nerve stimulation in area 3a. Coexistence of the SEPs from both deep and superficial radial nerves suggests that area 3a could integrate muscle and cutaneous signals to shape proprioception.

Development and Implementation of a Corriedale Ovine Brain Atlas for Use in Atlas-Based Segmentation.

Segmentation is the process of partitioning an image into subdivisions and can be applied to medical images to isolate anatomical or pathological areas for further analysis. This process can be done manually or automated by the use of image processing computer packages. Atlas-based segmentation automates this process by the use of a pre-labelled template and a registration algorithm. We developed an ovine brain atlas that can be used as a model for neurological conditions such as Parkinson's disease and focal epilepsy. 17 female Corriedale ovine brains were imaged in-vivo in a 1.5T (low-resolution) MRI scanner. 13 of the low-resolution images were combined using a template construction algorithm to form a low-resolution template. The template was labelled to form an atlas and tested by comparing manual with atlas-based segmentations against the remaining four low-resolution images. The comparisons were in the form of similarity metrics used in previous segmentation research. Dice Similarity Coefficients were utilised to determine the degree of overlap between eight independent, manual and atlas-based segmentations, with values ranging from 0 (no overlap) to 1 (complete overlap). For 7 of these 8 segmented areas, we achieved a Dice Similarity Coefficient of 0.5-0.8. The amygdala was difficult to segment due to its variable location and similar intensity to surrounding tissues resulting in Dice Coefficients of 0.0-0.2. We developed a low resolution ovine brain atlas with eight clinically relevant areas labelled. This brain atlas performed comparably to prior human atlases described in the literature and to intra-observer error providing an atlas that can be used to guide further research using ovine brains as a model and is hosted online for public access.

Behavioral evidence of heterospecific bonding between the lamb and the human caregiver and mapping of associated brain network.

While behavioral mechanisms of bonding between young mammals and humans have been explored, brain structures involved in the establishment of such processes are still unknown. The aim of the study was to identify brain regions activated by the presence of the caregiver. Since human positive interaction plays an important role in the bonding process, activation of specific brain structures by stroking was also examined. Twenty-four female lambs reared in groups of three were fed and stroked daily by a female caregiver between birth and 5-7 weeks of age. At 4 weeks, an isolation-reunion-separation test and a choice test revealed that lambs developed a strong bond with their caregiver. At 5-7 weeks of age, lambs were socially isolated for 90min. They either remained isolated or met their caregiver who stroked them, or not, at regular intervals over a 90-min period. Neuronal activation was investigated at the end of the period for maximum c-Fos expression. Reunion with the caregiver appeased similarly the lambs whether stroking was provided or not. Stroking did not activate a specific brain network compared to no stroking. In both cases, brain regions associated with olfactory, visual and tactile cue processing were activated in the presence of the caregiver, suggesting a multisensory process involved. In addition, activation of the oxytocinergic system in the hypothalamic paraventricular nucleus induced by the presence of the caregiver suggests similar neuroendocrine mechanisms involved in inter-conspecific and animal-human bonding.