Direct interhemispheric cortical communication via thalamic commissures: a new white matter pathway in the primate brain.

Cortical neurons of eutherian mammals project to the contralateral hemisphere, crossing the midline primarily via the corpus callosum and the anterior, posterior, and hippocampal commissures. We recently reported and named the thalamic commissures (TCs) as an additional interhemispheric axonal fiber pathway connecting the cortex to the contralateral thalamus in the rodent brain. Here, we demonstrate that TCs also exist in primates and characterize the connectivity of these pathways with high-resolution diffusion-weighted MRI, viral axonal tracing, and fMRI. We present evidence of TCs in both New World (Callithrix jacchus and Cebus apella) and Old World primates (Macaca mulatta). Further, like rodents, we show that the TCs in primates develop during the embryonic period, forming anatomical and functionally active connections of the cortex with the contralateral thalamus. We also searched for TCs in the human brain, showing their presence in humans with brain malformations, although we could not identify TCs in healthy subjects. These results pose the TCs as a vital fiber pathway in the primate brain, allowing for more robust interhemispheric connectivity and synchrony and serving as an alternative commissural route in developmental brain malformations.

Interspecies activation correlations reveal functional correspondences between marmoset and human brain areas.

The common marmoset has enormous promise as a nonhuman primate model of human brain functions. While resting-state functional MRI (fMRI) has provided evidence for a similar organization of marmoset and human cortices, the technique cannot be used to map the functional correspondences of brain regions between species. This limitation can be overcome by movie-driven fMRI (md-fMRI), which has become a popular tool for noninvasively mapping the neural patterns generated by rich and naturalistic stimulation. Here, we used md-fMRI in marmosets and humans to identify whole-brain functional correspondences between the two primate species. In particular, we describe functional correlates for the well-known human face, body, and scene patches in marmosets. We find that these networks have a similar organization in both species, suggesting a largely conserved organization of higher-order visual areas between New World marmoset monkeys and humans. However, while face patches in humans and marmosets were activated by marmoset faces, only human face patches responded to the faces of other animals. Together, the results demonstrate that higher-order visual processing might be a conserved feature between humans and New World marmoset monkeys but that small, potentially important functional differences exist.

Early molecular events of autosomal-dominant Alzheimer's disease in marmosets with PSEN1 mutations.

INTRODUCTION: Fundamental questions remain about the key mechanisms that initiate Alzheimer's disease (AD) and the factors that promote its progression. Here we report the successful generation of the first genetically engineered marmosets that carry knock-in (KI) point mutations in the presenilin 1 (PSEN1) gene that can be studied from birth throughout lifespan. METHODS: CRISPR/Cas9 was used to generate marmosets with C410Y or A426P point mutations in PSEN1. Founders and their germline offspring are comprehensively studied longitudinally using non-invasive measures including behavior, biomarkers, neuroimaging, and multiomics signatures. RESULTS: Prior to adulthood, increases in plasma amyloid beta were observed in PSEN1 mutation carriers relative to non-carriers. Analysis of brain revealed alterations in several enzyme-substrate interactions within the gamma secretase complex prior to adulthood. DISCUSSION: Marmosets carrying KI point mutations in PSEN1 provide the opportunity to study the earliest primate-specific mechanisms that contribute to the molecular and cellular root causes of AD onset and progression. HIGHLIGHTS: We report the successful generation of genetically engineered marmosets harboring knock-in point mutations in the PSEN1 gene. PSEN1 marmosets and their germline offspring recapitulate the early emergence of AD-related biomarkers. Studies as early in life as possible in PSEN1 marmosets will enable the identification of primate-specific mechanisms that drive disease progression.

Ex vivo comparison of pin placement with patient-specific drill guides or freehand technique in canine cadaveric spines.

OBJECTIVE: To compare vertebral implant placement in the canine thoracolumbar spine between 3D-printed patient-specific drill guides (3DPG) and the conventional freehand technique (FH). STUDY DESIGN: Ex vivo study. ANIMALS: Cadaveric canine spines (n = 24). METHODS: Implant trajectories were established for the left and right sides of the T10 through L6 vertebrae based on computed tomography (CT) imaging. Customized drill guides were created for each vertebra of interest. Each cadaver was randomly assigned to one of six veterinarians with varying levels of experience placing vertebral implants. Vertebrae were randomly assigned a surgical order and technique (3DPG or FH) for both sides. Postoperative CT images were acquired. A single, blinded observer assessed pin placement using a modified Zdichavsky classification. RESULTS: A total of 480 implants were placed in 240 vertebrae. Three sites were excluded from the analysis; therefore, a total of 238 implants were evaluated using the FH technique and 239 implants using 3DPG. When evaluating implant placement, 152/239 (63.6%) of 3DPG implants were considered to have an acceptable placement in comparison with 115/248 (48.32%) with FH. Overall, pin placement using 3DPG was more likely to provide acceptable pin placement (p < .001) in comparison with the FH technique for surgeons at all levels of experience. CONCLUSION: The use of 3DPG was shown to be better than the conventional freehand technique regarding acceptable placement of implants in the thoracolumbar spine of canine cadavers. CLINICAL SIGNIFICANCE: Utilizing 3DPG can be considered better than the traditional FH technique when placing implants in the canine thoracolumbar spine.

Functional Organization of Frontoparietal Cortex in the Marmoset Investigated with Awake Resting-State fMRI.

Frontoparietal networks contribute to complex cognitive functions in humans and macaques, such as working memory, attention, task-switching, response suppression, grasping, reaching, and eye movement control. However, there has been no comprehensive examination of the functional organization of frontoparietal networks using functional magnetic resonance imaging in the New World common marmoset monkey (Callithrix jacchus), which is now widely recognized as a powerful nonhuman primate experimental animal. In this study, we employed hierarchical clustering of interareal blood oxygen level-dependent signals to investigate the hypothesis that the organization of the frontoparietal cortex in the marmoset follows the organizational principles of the macaque frontoparietal system. We found that the posterior part of the lateral frontal cortex (premotor regions) was functionally connected to the anterior parietal areas, while more anterior frontal regions (frontal eye field [FEF]) were connected to more posterior parietal areas (the region around the lateral intraparietal area [LIP]). These overarching patterns of interareal organization are consistent with a recent macaque study. These findings demonstrate parallel frontoparietal processing streams in marmosets and support the functional similarities of FEF-LIP and premotor-anterior parietal pathways between marmoset and macaque.

Divergence of rodent and primate medial frontal cortex functional connectivity.

With the medial frontal cortex (MFC) centrally implicated in several major neuropsychiatric disorders, it is critical to understand the extent to which MFC organization is comparable between humans and animals commonly used in preclinical research (namely rodents and nonhuman primates). Although the cytoarchitectonic structure of the rodent MFC has mostly been conserved in humans, it is a long-standing question whether the structural analogies translate to functional analogies. Here, we probed this question using ultra high field fMRI data to compare rat, marmoset, and human MFC functional connectivity. First, we applied hierarchical clustering to intrinsically define the functional boundaries of the MFC in all three species, independent of cytoarchitectonic definitions. Then, we mapped the functional connectivity "fingerprints" of these regions with a number of different brain areas. Because rats do not share cytoarchitectonically defined regions of the lateral frontal cortex (LFC) with primates, the fingerprinting method also afforded the unique ability to compare the rat MFC and marmoset LFC, which have often been suggested to be functional analogs. The results demonstrated remarkably similar intrinsic functional organization of the MFC across the species, but clear differences between rodent and primate MFC whole-brain connectivity. Rat MFC patterns of connectivity showed greatest similarity with premotor regions in the marmoset, rather than dorsolateral prefrontal regions, which are often suggested to be functionally comparable. These results corroborate the viability of the marmoset as a preclinical model of human MFC dysfunction, and suggest divergence of functional connectivity between rats and primates in both the MFC and LFC.

An open access resource for functional brain connectivity from fully awake marmosets.

The common marmoset (Callithrix jacchus) is quickly gaining traction as a premier neuroscientific model. However, considerable progress is still needed in understanding the functional and structural organization of the marmoset brain to rival that documented in longstanding preclinical model species, like mice, rats, and Old World primates. To accelerate such progress, we present the Marmoset Functional Brain Connectivity Resource (marmosetbrainconnectome.org), currently consisting of over 70 h of resting-state fMRI (RS-fMRI) data acquired at 500 µm isotropic resolution from 31 fully awake marmosets in a common stereotactic space. Three-dimensional functional connectivity (FC) maps for every cortical and subcortical gray matter voxel are stored online. Users can instantaneously view, manipulate, and download any whole-brain functional connectivity (FC) topology (at the subject- or group-level) along with the raw datasets and preprocessing code. Importantly, researchers can use this resource to test hypotheses about FC directly - with no additional analyses required - yielding whole-brain correlations for any gray matter voxel on demand. We demonstrate the resource's utility for presurgical planning and comparison with tracer-based neuronal connectivity as proof of concept. Complementing existing structural connectivity resources for the marmoset brain, the Marmoset Functional Brain Connectivity Resource affords users the distinct advantage of exploring the connectivity of any voxel in the marmoset brain, not limited to injection sites nor constrained by regional atlases. With the entire raw database (RS-fMRI and structural images) and preprocessing code openly available for download and use, we expect this resource to be broadly valuable to test novel hypotheses about the functional organization of the marmoset brain.

The effect of repeated freezing and thawing on the suture pull-out strength in equine arytenoid and cricoid cartilages.

OBJECTIVE: To assess the effect of repeated freezing and thawing on the suture pull-out strength in arytenoid and cricoid cartilages subjected to the laryngoplasty (LP) procedure. STUDY DESIGN: Ex vivo experimental study. SAMPLE POPULATION: Ten grossly normal equine cadaveric larynges. METHODS: Bilateral LP constructs were created using a standard LP technique. One hemilarynx was randomly allocated to the single freeze and thaw group and the other allocated to the repeated freeze and thaw (3 complete cycles) group. The suture ends of each LP construct were attached to a load frame and subjected to monotonic loading until construct failure. Mean load (N) and displacement (mm) at LP construct failure were compared between groups. RESULTS: All LP constructs failed by suture pull through the arytenoid cartilage. The mean load at failure was similar between groups (118.9 ± 25.5 N in the single freeze and thaw group and 113.4 ± 20.5 N in the repeated freeze and thaw group, P = .62). The mean displacement at failure was similar between groups (54.4 ± 15.1 mm in the single freeze and thaw group and 54.4 ± 15.4 mm in the repeated freeze and thaw group, P = .99). CONCLUSION: Repeated freezing and thawing did not affect the suture pullout strength of the arytenoid and cricoid cartilages. CLINICAL SIGNIFICANCE: Laryngeal specimens that have been subjected to repeated freezing and thawing can be utilized in the experimental evaluation of LP procedures because there is no alteration of the suture pull-out strength of the relevant cartilages.

Cortico-Subcortical Functional Connectivity Profiles of Resting-State Networks in Marmosets and Humans.

Understanding the similarity of cortico-subcortical networks topologies between humans and nonhuman primate species is critical to study the origin of network alternations underlying human neurologic and neuropsychiatric diseases. The New World common marmoset (Callithrix jacchus) has become popular as a nonhuman primate model for human brain function. Most marmoset connectomic research, however, has exclusively focused on cortical areas, with connectivity to subcortical networks less extensively explored. Here, we aimed to first isolate patterns of subcortical connectivity with cortical resting-state networks in awake marmosets using resting-state fMRI, then to compare these networks with those in humans using connectivity fingerprinting. In this study, we used 5 marmosets (4 males, 1 female). While we could match several marmoset and human resting-state networks based on their functional fingerprints, we also found a few striking differences, for example, strong functional connectivity of the default mode network with the superior colliculus in marmosets that was much weaker in humans. Together, these findings demonstrate that many of the core cortico-subcortical networks in humans are also present in marmosets, but that small, potentially functionally relevant differences exist.SIGNIFICANCE STATEMENT The common marmoset is becoming increasingly popular as an additional preclinical nonhuman primate model for human brain function. Here we compared the functional organization of cortico-subcortical networks in marmosets and humans using ultra-high field fMRI. We isolated the patterns of subcortical connectivity with cortical resting-state networks (RSNs) in awake marmosets using resting-state fMRI and then compared these networks with those in humans using connectivity fingerprinting. While we could match several marmoset and human RSNs based on their functional fingerprints, we also found several striking differences. Together, these findings demonstrate that many of the core cortico-subcortical RSNs in humans are also present in marmosets, but that small, potentially functionally relevant differences exist.

Intrinsic functional clustering of ventral premotor F5 in the macaque brain.

Neurophysiological and anatomical data suggest the existence of several functionally distinct regions in the lower arcuate sulcus and adjacent postarcuate convexity of the macaque monkey. Ventral premotor F5c lies on the postarcuate convexity and consists of a dorsal hand-related and ventral mouth-related field. The posterior bank of the lower arcuate contains two additional premotor F5 subfields at different anterior-posterior levels, F5a and F5p. Anterior to F5a, area 44 has been described as a dysgranular zone occupying the deepest part of the fundus of the inferior arcuate. Finally, area GrFO occupies the most rostral portion of the fundus and posterior bank of inferior arcuate and extends ventrally onto the frontal operculum. Recently, data-driven exploratory approaches using resting-state fMRI data have been suggested as a promising non-invasive method for examining the functional organization of the primate brain. Here, we examined to what extent partitioning schemes derived from data-driven clustering analysis of resting-state fMRI data correspond with the proposed organization of the fundus and posterior bank of the macaque arcuate sulcus, as suggested by invasive architectonical, connectional and functional investigations. Using a hierarchical clustering analysis, we could retrieve clusters corresponding to the dorsal and ventral portions of F5c on the postarcuate convexity, F5a and F5p at different antero-posterior locations on the posterior bank of the lower arcuate, area 44 in the fundus, as well as part of area GrFO in the most anterior portion of the fundus. Additionally, each of these clusters displayed distinct whole-brain functional connectivity, in line with previous anatomical tracer and seed-based functional connectivity investigations of F5/44 subdivisions. Overall, our data suggests that hierarchical clustering analysis of resting-state fMRI data can retrieve a fine-grained level of cortical organization that resembles detailed parcellation schemes derived from invasive functional and anatomical investigations.

Structural alterations in cortical and thalamocortical white matter tracts after recovery from prefrontal cortex lesions in macaques.

Unilateral damage to the frontoparietal network typically impairs saccade target selection within the contralesional visual hemifield. Severity of deficits and the degree of recovery have been associated with widespread network dysfunction, yet it is not clear how these behavioural and functional brain changes relate with the underlying structural white matter tracts. Here, we investigated whether recovery after unilateral prefrontal cortex (PFC) lesions was associated with changes in white matter microstructure across large-scale frontoparietal cortical and thalamocortical networks. Diffusion-weighted imaging was acquired in four male rhesus macaques at pre-lesion, week 1, and week 8-16 post-lesion when target selection deficits largely recovered. Probabilistic tractography was used to reconstruct cortical frontoparietal fiber tracts, including the superior longitudinal fasciculus (SLF) and transcallosal fibers connecting the PFC or posterior parietal cortex (PPC), as well as thalamocortical fiber tracts connecting the PFC and PPC to thalamic nuclei. We found that the two animals with small PFC lesions showed increased fractional anisotropy in both cortical and thalamocortical fiber tracts when behaviour had recovered. However, we found that fractional anisotropy decreased in cortical frontoparietal tracts after larger PFC lesions yet increased in some thalamocortical tracts at the time of behavioural recovery. These findings indicate that behavioural recovery after small PFC lesions may be supported by both cortical and subcortical areas, whereas larger PFC lesions may have induced widespread structural damage and hindered compensatory remodeling in the cortical frontoparietal network.

Altered Resting-State Functional Connectivity Between Awake and Isoflurane Anesthetized Marmosets.

The common marmoset (Callithrix jacchus) is a New World primate that is becoming increasingly popular as a preclinical model. To assess functional connectivity (FC) across the marmoset brain, resting-state functional MRI (RS-fMRI) is often performed under isoflurane anesthesia to avoid the effects of motion, physiological stress, and training requirements. In marmosets, however, it remains unclear how isoflurane anesthesia affects patterns of FC. Here, we investigated the effects of isoflurane on FC when delivered with either medical air or 100% pure oxygen, two canonical methods of inhalant isoflurane anesthesia delivery. The results demonstrated that when delivered with either medical air or 100% oxygen, isoflurane globally decreased FC across resting-state networks that were identified in awake marmosets. Generally, although isoflurane globally decreased FC in resting-state networks, the spatial structure of the networks was preserved. Outside of the context of RS networks, we indexed pair-wise functional connectivity between regions across the brain and found that isoflurane substantially altered interhemispheric and thalamic FC. Taken together, these findings indicate that RS-fMRI under isoflurane anesthesia is useful to evaluate the global structure of functional networks, but may obfuscate important nodes of some network components when compared to data acquired in fully awake marmosets.

Evaluation of the airway mechanics of modified toggle laryngoplasty constructs using a vacuum chamber airflow model.

OBJECTIVE: To evaluate the airway mechanics of modified toggle LP constructs in an airflow chamber model and compare these to the airway mechanics of standard LP constructs. STUDY DESIGN: Ex-vivo experimental study. SAMPLE POPULATION: Fifty-one equine cadaveric larynges. METHODS: Bilateral LP constructs were performed using a modified toggle (n = 23) or a standard (n = 21) LP technique. Constructs were tested in an airflow model before and after cyclic loading which was designed to mimic postoperative swallowing. The cross-sectional area (CSA), peak translaryngeal airflow (L/s), and impedance (cmH2 0/L/s) were determined and compared between LP constructs before and after cycling. RESULTS: The mean CSA of the rima glottidis of the modified toggle LP constructs was 15.2 ± 2.6 cm2 before and 14.7 ± 2.6 cm2 after cyclic loading, and the mean CSA of the rima glottidis of the standard LP constructs was 16.4 ± 2.9 cm2 before and 15.7 ± 2.8 cm2 after cyclic loading. The modified toggle LP constructs had similar peak translaryngeal impedance before and after cyclic loading (p = .13); however, the standard LP constructs had higher peak translaryngeal impedance after cyclic loading (p = .02). CONCLUSION: The modified toggle and standard LP constructs had comparable airway mechanics in an ex-vivo model. CLINICAL SIGNIFICANCE: Further investigation is warranted to determine the extent to which the modified toggle LP technique restores normal airway function in horses with RLN.

Functional Localization of the Frontal Eye Fields in the Common Marmoset Using Microstimulation.

The frontal eye field (FEF) is a critical region for the deployment of overt and covert spatial attention. Although investigations in the macaque continue to provide insight into the neural underpinnings of the FEF, due to its location within a sulcus, the macaque FEF is virtually inaccessible to electrophysiological techniques such as high-density and laminar recordings. With a largely lissencephalic cortex, the common marmoset (Callithrix jacchus) is a promising alternative primate model for studying FEF microcircuitry. Putative homologies have been established with the macaque FEF on the basis of cytoarchitecture and connectivity; however, physiological investigation in awake, behaving marmosets is necessary to physiologically locate this area. Here, we addressed this gap using intracortical microstimulation in a broad range of frontal cortical areas in three adult marmosets (two males, one female). We implanted marmosets with 96-channel Utah arrays and applied microstimulation trains while they freely viewed video clips. We evoked short-latency fixed vector saccades at low currents (<50 µA) in areas 45, 8aV, 8C, and 6DR. We observed a topography of saccade direction and amplitude consistent with findings in macaques and humans: small saccades in ventrolateral FEF and large saccades combined with contralateral neck and shoulder movements encoded in dorsomedial FEF. Our data provide compelling evidence supporting homology between marmoset and macaque FEF and suggest that the marmoset is a useful primate model for investigating FEF microcircuitry and its contributions to oculomotor and cognitive functions.SIGNIFICANCE STATEMENT The frontal eye field (FEF) is a critical cortical region for overt and covert spatial attention. The microcircuitry of this area remains poorly understood because in the macaque, the most commonly used model, it is embedded within a sulcus and is inaccessible to modern electrophysiological and imaging techniques. The common marmoset is a promising alternative primate model due to its lissencephalic cortex and potential for genetic manipulation. However, evidence for homologous cortical areas in this model remains limited and unclear. Here, we applied microstimulation in frontal cortical areas in marmosets to physiologically identify FEF. Our results provide compelling evidence for an FEF in the marmoset and suggest that the marmoset is a useful model for investigating FEF microcircuitry.

Intrinsic Functional Boundaries of Lateral Frontal Cortex in the Common Marmoset Monkey.

The common marmoset (Callithrix jacchus) is a small New World primate species that has been recently targeted as a potentially powerful preclinical model of human prefrontal cortex dysfunction. Although the structural boundaries of frontal cortex were described in marmosets at the start of the 20th century (Brodmann, 1909) and refined more recently (Paxinos et al., 2012), the broad functional boundaries of marmoset frontal cortex have yet to be established. In this study, we sought to functionally derive boundaries of the marmoset lateral frontal cortex (LFC) using ultra-high field (9.4 T) resting-state functional magnetic resonance imaging (RS-fMRI). We collected RS-fMRI data in seven (four females, three males) lightly anesthetized marmosets and used a data-driven hierarchical clustering approach to derive subdivisions of the LFC based on intrinsic functional connectivity. We then conducted seed-based analyses to assess the functional connectivity between these clusters and the rest of the brain. The results demonstrated seven distinct functional clusters within the LFC. The functional connectivity patterns of these clusters with the rest of the brain were also found to be distinct and organized along a rostrocaudal gradient, consonant with those found in humans and macaques. Overall, these results support the view that marmosets are a promising preclinical modeling species for studying LFC dysfunction related to neuropsychiatric or neurodegenerative human brain diseases.SIGNIFICANCE STATEMENT The common marmoset is a New World primate that has garnered recent attention as a powerful complement to canonical Old World primate (e.g., macaques) and rodent models (e.g., rats, mice) for preclinical modeling of the human brain in healthy and diseased states. A critical step in the development of marmosets for such models is to characterize functional network topologies of frontal cortex in healthy, normally functioning marmosets, that is, how these circuitries are functionally divided and how those topologies compare to human circuitry. To our knowledge, this is the first study to demonstrate functional boundaries of the lateral frontal cortex and the corresponding network topologies in marmoset monkeys.

Looming and receding visual networks in awake marmosets investigated with fMRI.

An object that is looming toward a subject or receding away contains important information for determining if this object is dangerous, beneficial or harmless. This information (motion, direction, identity, time-to-collision, size, velocity) is analyzed by the brain in order to execute the appropriate behavioral responses depending on the context: fleeing, freezing, grasping, eating, exploring. In the current study, we performed ultra-high-field functional MRI (fMRI) at 9.4T in awake marmosets to explore the patterns of brain activation elicited by visual stimuli looming toward or receding away from the monkey. We found that looming and receding visual stimuli activated a large cortical network in frontal, parietal, temporal and occipital cortex in areas involved in the analysis of motion, shape, identity and features of the objects. Looming stimuli strongly activated a network composed of portions of the pulvinar, superior colliculus, putamen, parietal, prefrontal and temporal cortical areas. These activations suggest the existence of a network that processes visual stimuli looming toward peripersonal space to predict the consequence of these stimuli. Together with previous studies in macaque monkeys, these findings indicate that this network is preserved across Old and New World primates.

Comparison of resting-state functional connectivity in marmosets with tracer-based cellular connectivity.

Resting-state functional MRI (RS-fMRI) is widely used to assess how strongly different brain areas are connected. However, this connection obtained by RS-fMRI, which is called functional connectivity (FC), simply refers to the correlation of blood oxygen level-dependent (BOLD) signals across time it has yet to be quantified how accurately FC reflects cellular connectivity (CC). In this study, we elucidated this relationship using RS-fMRI and quantitative tracer data in marmosets. In addition, we also elucidated the effects of distance between two brain regions on the relationship between FC and CC across seed region. To calculate FC, we used full correlation approach that is considered to reflect not only direct (monosynaptic connections) but also indirect pathways (polysynaptic connections). Our main findings are that: (1) overall FC obtained by RS-fMRI was highly correlated with tracer-based CC, but correlation coefficients varied remarkably across seed regions; (2) the strength of FC decreased with increase in the distance between two regions; (3) correlation coefficients between FC and CC after regressing out the effects of the distance between two regions still varied across seed regions, but some regions have strong correlations. These findings suggest that although FC reflects the strength of monosynaptic pathways, it is strongly affected by the distance between regions.

Whole brain mapping of somatosensory responses in awake marmosets investigated with ultra-high-field fMRI.

The common marmoset (Callithrix jacchus) is a small-bodied New World primate that is becoming an important model to study brain functions. Despite several studies exploring the somatosensory system of marmosets, all results have come from anesthetized animals using invasive techniques and postmortem analyses. Here, we demonstrate the feasibility for getting high-quality and reproducible somatosensory mapping in awake marmosets with functional magnetic resonance imaging (fMRI). We acquired fMRI sequences in four animals, while they received tactile stimulation (via air-puffs), delivered to the face, arm, or leg. We found a topographic body representation with the leg representation in the most medial part, the face representation in the most lateral part, and the arm representation between leg and face representation within areas 3a, 3b, and 1/2. A similar sequence from leg to face from caudal to rostral sites was identified in areas S2 and PV. By generating functional connectivity maps of seeds defined in the primary and second somatosensory regions, we identified two clusters of tactile representation within the posterior and midcingulate cortex. However, unlike humans and macaques, no clear somatotopic maps were observed. At the subcortical level, we found a somatotopic body representation in the thalamus and, for the first time in marmosets, in the putamen. These maps have similar organizations, as those previously found in Old World macaque monkeys and humans, suggesting that these subcortical somatotopic organizations were already established before Old and New World primates diverged. Our results show the first whole brain mapping of somatosensory responses acquired in a noninvasive way in awake marmosets.NEW & NOTEWORTHY We used somatosensory stimulation combined with functional MRI (fMRI) in awake marmosets to reveal the topographic body representation in areas S1, S2, thalamus, and putamen. We showed the existence of a body representation organization within the thalamus and the cingulate cortex by computing functional connectivity maps from seeds defined in S1/S2, using resting-state fMRI data. This noninvasive approach will be essential for chronic studies by guiding invasive recording and manipulation techniques.

Pharmacokinetics of platinum and safety evaluation of carboplatin-impregnated calcium sulfate hemihydrate beads after implantation in healthy cats.

OBJECTIVE: To evaluate the pharmacokinetics (PK) of platinum (Pt) and safety of carboplatin-impregnated calcium sulfate hemihydrate (C-I CSH) beads after implantation in healthy cats. STUDY DESIGN: In vivo experimental study. ANIMALS: Six healthy adult cats. METHODS: Three C-I CSH beads were implanted in muscle pockets over the right and left hemithoraces of each cat (~3.9 mg/kg of Pt; 60.4 mg/m2 of calculated carboplatin). Hematology and blood chemistry were tested at baseline and 3, 7, 14, and 21 days postimplantation. Serum was analyzed for Pt at specific times from 1 hour to 21 days. Tissue was obtained for histopathology and analysis of Pt at 3, 7, 14, and 21 days at standardized distances from implantation sites. RESULTS: Platinum was detected in tissues at all times and distances (range, 0.1-4.19 µg/g). Serum Pt increased up to 2.6 hours (3.25 µg/mL) then decreased sharply. Samples containing muscle had higher Pt compared with samples without muscle (P = .004). Mild hypercalcemia was noted in four cats, and mild inflammatory reaction was noted on histopathology of all samples. CONCLUSION: Platinum was released from C-I CSH beads differentially into surrounding tissues over 21 days. Systemic absorption of Pt was minimal, but mild hypercalcemia occurred. CLINICAL SIGNIFICANCE: Implantation was well tolerated by healthy adult cats. Securing beads within muscle may limit Pt diffusion to targeted tissue. Although Pt concentrations did not achieve levels reported to be cytotoxic for feline sarcoma cells in culture, results provide evidence to support evaluation of efficacy in the tumor microenvironment of cats with locally invasive cancers.

Pharmacokinetics and pharmacodynamics of hydromorphone hydrochloride in healthy horses.

OBJECTIVES: To determine the physiologic and behavioral effects and pharmacokinetic profile of hydromorphone administered intravenously (IV) to horses. STUDY DESIGN: Prospective, randomized, crossover study. ANIMALS: A group of six adult healthy horses weighing 585.2 ± 58.7 kg. METHODS: Each horse was administered IV hydromorphone (0.025 mg kg-1; treatment H0.025), hydromorphone (0.05 mg kg-1; treatment H0.05) or 0.9% saline in random order with a 7 day washout period. For each treatment, physiologic, hematologic, abdominal borborygmi scores and behavioral data were recorded over 5 hours and fecal output was totaled over 24 hours. Data were analyzed using repeated measures anova with significance at p < 0.05. Blood samples were collected in treatment H0.05 for quantification of plasma hydromorphone and hydromorphone-3-glucuronide and subsequent pharmacokinetic parameter calculation. RESULTS: Hydromorphone administration resulted in a dose-dependent increase in heart rate (HR) and systolic arterial pressure (SAP). HR and SAP were 59 ± 17 beats minute-1 and 230 ± 27 mmHg, respectively, in treatment H0.05 at 5 minutes after administration. No clinically relevant changes in respiratory rate, arterial gases or temperature were observed. The borborygmi scores in both hydromorphone treatments were lower than baseline values for 2 hours. Fecal output did not differ among treatments and no evidence of abdominal discomfort was observed. Recorded behaviors did not differ among treatments. For hydromorphone, mean ± standard deviation for volume of distribution at steady state, total systemic clearance and area under the curve until the last measured concentration were 1.00 ± 0.29 L kg-1, 106 ± 21 mL minute-1 kg-1 and 8.0 ± 1.5 ng hour mL-1, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Hydromorphone administered IV to healthy horses increased HR and SAP, decreased abdominal borborygmi and did not affect fecal output.