A digital 3D atlas of the marmoset brain based on multi-modal MRI.

The common marmoset (Callithrix jacchus) is a New-World monkey of growing interest in neuroscience. Magnetic resonance imaging (MRI) is an essential tool to unveil the anatomical and functional organization of the marmoset brain. To facilitate identification of regions of interest, it is desirable to register MR images to an atlas of the brain. However, currently available atlases of the marmoset brain are mainly based on 2D histological data, which are difficult to apply to 3D imaging techniques. Here, we constructed a 3D digital atlas based on high-resolution ex-vivo MRI images, including magnetization transfer ratio (a T1-like contrast), T2w images, and multi-shell diffusion MRI. Based on the multi-modal MRI images, we manually delineated 54 cortical areas and 16 subcortical regions on one hemisphere of the brain (the core version). The 54 cortical areas were merged into 13 larger cortical regions according to their locations to yield a coarse version of the atlas, and also parcellated into 106 sub-regions using a connectivity-based parcellation method to produce a refined atlas. Finally, we compared the new atlas set with existing histology atlases and demonstrated its applications in connectome studies, and in resting state and stimulus-based fMRI. The atlas set has been integrated into the widely-distributed neuroimaging data analysis software AFNI and SUMA, providing a readily usable multi-modal template space with multi-level anatomical labels (including labels from the Paxinos atlas) that can facilitate various neuroimaging studies of marmosets.

Vocal coordination and vocal imitation: a role for mirror neurons?

Some birds and mammals have vocal communication systems in which coordination between individuals is important. Examples would include duetting or antiphonal calling in some birds and mammals, rapid exchanges of the same vocalization, and vocal exchanges between paired individuals and other nearby pairs. Mirror neurons may play a role in such systems but become functional only after experience.

A resource for the detailed 3D mapping of white matter pathways in the marmoset brain.

While the fundamental importance of the white matter in supporting neuronal communication is well known, existing publications of primate brains do not feature a detailed description of its complex anatomy. The main barrier to achieving this is that existing primate neuroimaging data have insufficient spatial resolution to resolve white matter pathways fully. Here we present a resource that allows detailed descriptions of white matter structures and trajectories of fiber pathways in the marmoset brain. The resource includes: (1) the highest-resolution diffusion-weighted MRI data available to date, which reveal white matter features not previously described; (2) a comprehensive three-dimensional white matter atlas depicting fiber pathways that were either omitted or misidentified in previous atlases; and (3) comprehensive fiber pathway maps of cortical connections combining diffusion-weighted MRI tractography and neuronal tracing data. The resource, which can be downloaded from marmosetbrainmapping.org, will facilitate studies of brain connectivity and the development of tractography algorithms in the primate brain.

The scientific contributions of Paul D. MacLean (1913-2007).

Paul D. MacLean, a leading brain scientist of the 20th century, died on December 26, 2007. We review his life as a scientist and highlight some of his most important research contributions.

Cerebrospinal fluid to brain transport of manganese in a non-human primate revealed by MRI.

Manganese overexposure in non-human primates and humans causes a neurodegenerative disorder called manganism thought to be related to an accumulation of the metal in the basal ganglia. Here, we assess changes in the concentration of manganese in regions of the brain of a non-human primate (the common marmoset, Callithrix jacchus) following four systemic injections of 30 mg/kg MnCl2 H2O in the tail vein using T1-weighted magnetic resonance imaging (MRI) and compare these to changes in the rat following the same exposure route and dose. The doses were spaced 48 h apart and we imaged the animals 48 h after the final dose. We find that marmosets have significantly larger T1-weighted image enhancements in regions of the brain compared to rats, notably in the basal ganglia and the visual cortex. To confirm this difference across species reflects actual differences in manganese concentrations and not variations in the MRI properties of manganese, we measured the longitudinal relaxivity of manganese (chi1) in the in vivo brain and found no significant species' difference. The high manganese uptake in the marmoset basal ganglia and visual cortex can be explained by CSF-brain transport from the large lateral ventricles and we confirm this route of uptake with time-course MRI during a tail-vein infusion of manganese. There is also high uptake in the substructures of the hippocampus that are adjacent to the ventricles. The large manganese accumulation in these structures on overexposure may be common to all primates, including humans.

Neural circuits underlying crying and cry responding in mammals.

Crying is a universal vocalization in human infants, as well as in the infants of other mammals. Little is known about the neural structures underlying cry production, or the circuitry that mediates a caregiver's response to cry sounds. In this review, the specific structures known or suspected to be involved in this circuit are identified, along with neurochemical systems and hormones for which evidence suggests a role in responding to infants and infant cries. In addition, evidence that crying elicits parental responses in different mammals is presented. An argument is made for including 'crying' as a functional category in the vocal repertoire of all mammalian infants (and the adults of some species). The prevailing neural model for crying production considers forebrain structures to be dispensable. However, evidence for the anterior cingulate gyrus in cry production, and this structure along with the amygdala and some other forebrain areas in responding to cries is presented.

Urinary prolactin is correlated with mothering and allo-mothering in squirrel monkeys.

The hormone prolactin is implicated in infant care-giving by parents and allo-parents in a variety of species. Adult female squirrel monkeys (Saimiri spp.) engage in allo-mothering behavior, which includes carrying and nursing infants, but communal care of offspring has not been investigated from an endocrine standpoint in this taxon. We attempted to fill this gap by examining prolactin levels in squirrel monkeys (Saimiri sciureus) as a function of parental responsiveness. Subjects were housed at the National Institutes of Health Animal Center and assays were performed at the Wisconsin National Primate Research Center. To test for the presence of prolactin in squirrel monkey, saliva, blood and saliva were simultaneously collected from anesthetized subjects during routine health examinations. Prolactin was detectable in serum but not in saliva samples. In the core investigation, behavioral data were collected by focal animal sampling on three 1-male multi-female groups, and individually identified urine was collected non-invasively from foil containers underneath group cages on a daily basis throughout the behavioral study. Changes in urinary prolactin over time reflected changes in the reproductive state of a female who was pregnant, gave birth and lactated during the study. Mean urinary prolactin levels in non-lactating females and a male housed with infants in one group were higher than in adults from 2 groups without infants. In the group with infants, mean urinary prolactin levels in adults increased with the amount of infant contact and care-giving. The squirrel monkey may represent a new primate model for investigating the endocrinology of infant care-giving.

A potential role for thalamocingulate circuitry in human maternal behavior.

BACKGROUND: Little is known about the regional brain basis of human maternal behavior. To understand this better, we have been examining brain activity in mothers listening to infant cries. METHODS: We measured functional Magnetic Resonance Imaging brain activity in healthy, breastfeeding first-time mothers with young infants while they listened to infant cries, white noise control sounds, and a rest condition. Based on the thalamocingulate theory of maternal behavior and pilot work, we hypothesized that the cingulate, medial thalamus, medial prefrontal cortex, and right orbitofrontal cortex would display more activity with infant cries than with white noise (comparison 1) and would uniquely activate with the cries, meaning that these regions would display activity with cry minus rest but not with white noise minus rest (comparison 2). RESULTS: In hypothesized regions, the group displayed more activity in the medial thalamus, medial prefrontal and right orbitofrontal cortices with both comparisons. The anterior and posterior cingulate cortex displayed more activity only with comparison 1. In non-hypothesized brain regions, several other structures thought important in rodent maternal behavior displayed activity with both comparisons including the midbrain, hypothalamus, dorsal and ventral striatum, and vicinity of the lateral septal region. CONCLUSIONS: Our results partially support our hypotheses and are generally consistent with neuroanatomical studies of rodent maternal behavior.

Vocal communication and the triune brain.

This paper tests the 'fit' between Paul MacLean's triune brain scheme of brain organization and existing knowledge about the pathways mediating vocal communication in mammals. One component of MacLean's limbic system ('paleomammalian brain'), the 'thalamocingulate circuit,' is found to have an important role in expression of vocalizations, particularly the 'isolation call' (such as are given by mammalian infants when distressed or separated from their caregivers). Recent evidence suggests that this circuit may also have a role in perception of infant cries in humans. Outside of this circuit, the triune brain model has little to offer in the way of insights into how the brain is organized to mediate vocal communication. There is little evidence that the striatal complex ('R-complex' or 'protoreptilian formation') is involved in any major way in vocal communication, although it appears to be involved in some visual displays in both reptiles and nonhuman primates. Interestingly, components of the reptilian brain may be involved in human speech production, and avian homologues involved in birdsong. The neocortex ('neomammalian formation') has well-known importance in speech production and perception, but little evidence exists for a role in vocal production in nonhuman mammals. However, cortical mechanisms do play a role in perception of vocalizations, at least in nonhuman primates. It is concluded that a set of neural structures termed the 'communication brain' mediate vocal communication in mammals, and that this model does not fit well into the triune brain scheme of brain organization.

Adult cortisol response to immature offspring play in captive squirrel monkeys.

Variable environmental and social conditions influence hypothalamic-pituitary-adrenal activity in captive animals. Socially separated and individually housed animals generally experience increased cortisol secretion compared to animals housed with conspecifics, and social companionship can buffer the stress response when exposed to challenges such as introduction to novel environments. Nevertheless, the presence of conspecifics may also be the cause of stress because social dynamics impact individuals. Squirrel monkeys (Saimiri spp.) readily form same-sex affiliative social relationships, but in captivity, the presence of immature offspring severely disrupts affiliative associations among adults. We examined behavioral and physiological effects of the presence of immature offspring on adults by comparing two groups of adults with immature offspring to an all-adult group. We conducted behavioral observations and collected urine from adult members, and urine was assayed for cortisol at the Wisconsin National Primate Research Center. Adults in groups with immature offspring received an average of 18 play attempts per hour from the offspring, experienced a fivefold decrease in adult affiliation, and showed higher urinary cortisol levels compared to the all-adult group. A principal components analysis showed that adults characterized by receiving play attempts, rejecting play attempts, and lacking affiliative contact with other adults showed the highest mean urinary cortisol levels. Further analyses demonstrated that the persistent play attempts by immature offspring, not the resulting lack of adult huddling, were primarily responsible for the observed increase in urinary cortisol levels. Taken together, these data suggest that the disruptive effect of immature offspring produces a chronic cortisol increase in captive adult squirrel monkeys.

Puzzle Feeders and Gum Feeders as Environmental Enrichment for Common Marmosets.

Common marmosets (Callithrix jacchus jacchus) are highly social New World monkeys that consume a principally gummivorous and insectivorous diet. We examined the efficacy of two types of foraging devices, Puzzle-Feeders(tm) and gum feeders, as environmental enrichment for marmosets housed singly (n = 16) or in sibling (n = 4) and heterosexual (n = 8) pairs. In experiment 1, marmosets were exposed to each of the two types of foraging devices for three hours, once per week for two weeks. Thirty-minute observations were conducted at the beginning and end of each exposure period. Marmosets in all housing conditions experienced significant reductions in the frequency of stereotyped pacing and significantly less time sitting still while exposed to the foraging devices. Marmosets experienced significantly lower levels of feeder use and significantly more time sitting still at the end of the three-hour exposure than at the beginning. Marmosets that were singly or sibling housed used the devices the most and had the largest reductions in time spent sitting still during enrichment. In experiment 2, singly housed marmosets were given two types of gum feeders, a wooden and a Gumabone(tm) gum feeder, each for a week-long period. Thirty-minute observations were conducted three times per week immediately after loading the feeders with fresh gum. The wooden gum feeders were heavily gouged during the week-long exposure, although significantly less use of both types of gum feeders was observed on the third and fifth days. These results indicated that marmosets in variable social housing conditions can benefit from environmental enrichment additional to social housing, and that foraging enrichment promotes increased non-stereotyped movement and decreased pacing in this species.

A combined histological and MRI brain atlas of the common marmoset monkey, Callithrix jacchus.

The common marmoset, Callithrix jacchus, is of growing importance for research in neuroscience and related fields. In the present work, we describe a combined histological and magnetic resonance imaging (MRI) atlas constructed from the brains of two adult female marmosets. Histological sections were processed from Nissl staining and digitized to produce an atlas in a large format that facilitates visualization of structures with significant detail. Naming of identifiable brain structures was performed utilizing current terminology. The histological sections and a simplified schematic atlas are available online at http://udn.nichd.nih.gov/brainatlas_home.html.

Squirrel monkey chuck call: vocal response to playback chucks based on acoustic structure and affiliative relationship with the caller.

Adult female squirrel monkeys (genus Saimiri) that are socially familiar often exchange the chuck vocalization, which differs acoustically across individuals. We used behavioral observations, vocalization playback experiments, and analysis of the acoustic properties of vocalizations to investigate the effect of caller identity and acoustic structure on vocal response to playback chucks in two all-female social groups (n=10 females). Females were most likely to respond with a chuck to the playback chucks of their closely affiliated partners compared to those of nonaffiliated group members. This shows for the first time that the chuck stimulus alone is sufficient to elicit a chuck response from a female's affiliated partner. Additionally, females responded with a chuck mostly to familiar playback chucks from their own group and least to playbacks of silent controls. Unfamiliar playback chucks from the same species and a different squirrel monkey species elicited chuck responses intermediate between familiar chucks and silent controls. Post-hoc discriminant function analyses provide preliminary evidence that females are most likely to respond to unfamiliar chucks when those chucks are close in acoustic structure to familiar chucks from their own social group. These results provide a provisional explanation for error in the squirrel monkey signal processing system, in which unfamiliar chucks never heard before nevertheless elicit a chuck response if they are similar in acoustic structure to familiar group chucks.

Morphine administration selectively facilitates social play in common marmosets.

Common marmosets (Callithrix jacchus) form extended families, and several cohorts of young may reside together. Play is shown extensively among the offspring. We hypothesized that opiate activity modulates social play, and predicted that administration of morphine (0.5 mg/kg) would facilitate social play, whereas pretreatment with naloxone (0.5 mg/kg) would block morphine's effects. Morphine administration was associated with significantly increased social play, and the effect of morphine was attributable to the focal subject, since play initiated by others was unaffected by treatment. Non-social categories of play, such as object manipulation and locomotor play, and affiliative behaviors, such as time spent huddled, were unaffected by treatment. Twittering and play face, behaviors used by young during play, also increased after morphine administration. Pretreatment with naloxone blocked morphine's effects. Total activity was significantly increased by morphine administration. We conclude that social play is specifically facilitated by opiate activation, whereas other categories of play behavior and social behavior were unaffected by morphine. Thus, social play represents a distinct category of social behavior in juvenile common marmosets with regulatory processes that are unique from other types of social behavior.

Acoustic properties of vocally disruptive behaviors in the nursing home.

BACKGROUND: Disruptive vocalizations are among the most common behavior problems in the nursing home. However, their acoustic properties have not been previously investigated. OBJECTIVE: This paper examines the acoustic properties of disruptive vocalizations and attempts to link them to resident and verbalization characteristics. METHODS: This study characterizes the sounds emitted by 26 nursing home residents who manifested disruptive vocalizations. Verbalizations were audiotaped and then used in a sonographic evaluation and an acoustic analysis. RESULTS: Vocalizations of verbally agitated nursing home residents were characterized by their relatively short duration. Consistent positive correlations were found between seemingly disturbing types of vocalizations, such as yelling and howling, and higher levels of several parameters of the fundamental frequency. A similar positive correlation was also found between acoustic parameters and medical disease indicators. With the exception of the length of stream of utterances, the indicators did not differentiate between types of dementia. CONCLUSIONS: Because of the large number of comparisons undertaken, it is difficult to conclude which associations between acoustic properties and resident or vocalization characteristics are attributable to real underlying trends and which are due to chance and error. Consistencies that deserve further research pertain to the perceptions of the types of vocalizations the person tends to emit and to the physical health of the person.