Dog brains are sensitive to infant- and dog-directed prosody.

When addressing preverbal infants and family dogs, people tend to use specific speech styles. While recent studies suggest acoustic parallels between infant- and dog-directed speech, it is unclear whether dogs, like infants, show enhanced neural sensitivity to prosodic aspects of speech directed to them. Using functional magnetic resonance imaging on awake unrestrained dogs we identify two non-primary auditory regions, one that involve the ventralmost part of the left caudal Sylvian gyrus and the temporal pole and the other at the transition of the left caudal and rostral Sylvian gyrus, which respond more to naturalistic dog- and/or infant-directed speech than to adult-directed speech, especially when speak by female speakers. This activity increase is driven by sensitivity to fundamental frequency mean and variance resulting in positive modulatory effects of these acoustic parameters in both aforementioned non-primary auditory regions. These findings show that the dog auditory cortex, similarly to that of human infants, is sensitive to the acoustic properties of speech directed to non-speaking partners. This increased neuronal responsiveness to exaggerated prosody may be one reason why dogs outperform other animals when processing speech.

Evolution of relative brain size in dogs-no effects of selection for breed function, litter size, or longevity.

Domestication is a well-known example of the relaxation of environmentally based cognitive selection that leads to reductions in brain size. However, little is known about how brain size evolves after domestication and whether subsequent directional/artificial selection can compensate for domestication effects. The first animal to be domesticated was the dog, and recent directional breeding generated the extensive phenotypic variation among breeds we observe today. Here we use a novel endocranial dataset based on high-resolution CT scans to estimate brain size in 159 dog breeds and analyze how relative brain size varies across breeds in relation to functional selection, longevity, and litter size. In our analyses, we controlled for potential confounding factors such as common descent, gene flow, body size, and skull shape. We found that dogs have consistently smaller relative brain size than wolves supporting the domestication effect, but breeds that are more distantly related to wolves have relatively larger brains than breeds that are more closely related to wolves. Neither functional category, skull shape, longevity, nor litter size was associated with relative brain size, which implies that selection for performing specific tasks, morphology, and life history does not necessarily influence brain size evolution in domesticated species.

Central nodes of canine functional brain networks are concentrated in the cingulate gyrus.

Compared to the field of human fMRI, knowledge about functional networks in dogs is scarce. In this paper, we present the first anatomically-defined ROI (region of interest) based functional network map of the companion dog brain. We scanned 33 awake dogs in a "task-free condition". Our trained subjects, similarly to humans, remain willingly motionless during scanning. Our goal is to provide a reference map with a current best estimate for the organisation of the cerebral cortex as measured by functional connectivity. The findings extend a previous spatial ICA (independent component analysis) study (Szabo et al. in Sci Rep 9(1):1.25. https://doi.org/10.1038/s41598-019-51752-2 , 2019), with the current study including (1) more subjects and (2) improved scanning protocol to avoid asymmetric lateral distortions. In dogs, similarly to humans (Sacca et al. in J Neurosci Methods. https://doi.org/10.1016/j.jneumeth.2021.109084 , 2021), ageing resulted in increasing framewise displacement (i.e. head motion) in the scanner. Despite the inherently different approaches between model-free ICA and model-based ROI, the resulting functional networks show a remarkable similarity. However, in the present study, we did not detect a designated auditory network. Instead, we identified two highly connected, lateralised multi-region networks extending to non-homotropic regions (Sylvian L, Sylvian R), including the respective auditory regions, together with the associative and sensorimotor cortices and the insular cortex. The attention and control networks were not split into two fully separated, dedicated networks. Overall, in dogs, fronto-parietal networks and hubs were less dominant than in humans, with the cingulate gyrus playing a central role. The current manuscript provides the first attempt to map whole-brain functional networks in dogs via a model-based approach.

Vascular supply of the metacarpophalangeal joint.

Objective: To describe in detail the arterial vasculature of metacarpophalangeal joints 2-5 on cadaver specimens and to compare it to ultrasound imaging of healthy subjects. Methods: Eighteen hands of donated human cadavers were arterially injected and investigated with either corrosion casting or cryosectioning. Each layer of cryosectioned specimens was photographed in high-resolution. Images were then segmented for arterial vessels of the metacarpophalangeal (MCP) joints 2-5. The arterial pattern of the joints was reconstructed from the segmented images and from the corrosion cast specimens. Both hands of ten adult healthy volunteers were scanned focusing on the vasculature of the same joints with high-end ultrasound imaging, including color Doppler. Measurements were made on both cryosectioned arteries and Doppler images. Results: The arterial supply of MCP joints 2-5 divides into a metacarpal and a phalangeal territory, respectively. The metacarpal half receives arteries from the palmar metacarpal arteries or proper palmar digital arteries, while the phalangeal half is supplied by both proper and common palmar digital arteries. Comparing anatomical and ultrasonographic results, we determined the exact anatomic location of normal vessels using Doppler images acquired of healthy joints. All, except three branches, were found with less than 50% frequency using ultrasound. Doppler signals were identified significantly more frequently in MCP joints 2-3 than on 4-5 (p < 0.0001). Similarly, Doppler signals differed in the number of detectable small, intraarticular vessels (p < 0.009), but not that of the large extraarticular ones (p < 0.1373). When comparing measurements acquired by ultrasound and on cadaver vessels, measurements using the former technique were found to be larger in all joints (p < 0.0001). Conclusion: Using morphological and ultrasonographic techniques, our study provides a high-resolution anatomical maps and an essential reference data set on the entire arterial vasculature of healthy human MCP 2-5 joints. We found that Doppler signal could be detected in less than 50% of the vessels of healthy volunteers except three locations. Intraarticular branches were detected with ultrasound imaging significantly more frequently on healthy MCP 2-3 joints, which should be taken into account when inflammatory and normal Doppler signals are evaluated. Our study also provides reference data for future, higher-resolution imaging techniques.

Poly(A) RNA sequencing reveals age-related differences in the prefrontal cortex of dogs.

Dogs may possess a unique translational potential to investigate neural aging and dementia because they are prone to age-related cognitive decline, including an Alzheimer's disease-like pathological condition. Yet very little is known about the molecular mechanisms underlying canine cognitive decline. The goal of the current study was to explore the transcriptomic differences between young and old dogs' frontal cortex, which is a brain region often affected by various forms of age-related dementia in humans. RNA isolates from the frontal cortical brain area of 13 pet dogs, which represented 7 different breeds and crossbreds, were analyzed. The dogs were euthanized for medical reasons, and their bodies had been donated by their owners for scientific purposes. The poly(A) tail RNA subfraction of the total transcriptome was targeted in the sequencing analysis. Cluster analyses, differential gene expression analyses, and gene ontology analyses were carried out to assess which genes and genetic regulatory mechanisms were mostly affected by aging. Age was the most prominent factor in the clustering of the animals, indicating the presence of distinct gene expression patterns related to aging in a genetically variable population. A total of 3436 genes were found to be differentially expressed between the age groups, many of which were linked to neural function, immune system, and protein synthesis. These findings are in accordance with previous human brain aging RNA sequencing studies. Some genes were found to behave more similarly to humans than to rodents, further supporting the applicability of dogs in translational aging research.

Canine Cognitive Dysfunction (CCD) scores correlate with amyloid beta 42 levels in dog brain tissue.

Alzheimer's disease (AD) is a significant burden for human health that is increasing in prevalence as the global population ages. There is growing recognition that current preclinical models of AD are insufficient to recapitulate key aspects of the disease. Laboratory models for AD include mice, which do not naturally develop AD-like pathology during aging, and laboratory Beagle dogs, which do not share the human environment. In contrast, the companion dog shares the human environment and presents a genetically heterogeneous population of animals that might spontaneously develop age-associated AD-like pathology and cognitive dysfunction. Here, we quantitatively measured amyloid beta (Aß42 or Abeta-42) levels in three areas of the companion dog brain (prefrontal cortex, temporal cortex, hippocampus/entorhinal cortex) and cerebrospinal fluid (CSF) using a newly developed Luminex assay. We found significant positive correlations between Aß42 and age in all three brain regions. Brain Aß42 abundance in all three brain regions was also correlated with Canine Cognitive Dysfunction Scale score in a multivariate analysis. This latter effect remained significant when correcting for age, except in the temporal cortex. There was no correlation between Aß42 in CSF and cognitive scores; however, we found a significant positive correlation between Aß42 in CSF and body weight, as well as a significant negative correlation between Aß42 in CSF and age. Our results support the suitability of the companion dog as a model for AD and illustrate the utility of veterinary biobanking to make biospecimens available to researchers for analysis.

Social relationship-dependent neural response to speech in dogs.

In humans, social relationship with the speaker affects neural processing of speech, as exemplified by children's auditory and reward responses to their mother's utterances. Family dogs show human analogue attachment behavior towards the owner, and neuroimaging revealed auditory cortex and reward center sensitivity to verbal praises in dog brains. Combining behavioral and non-invasive fMRI data, we investigated the effect of dogs' social relationship with the speaker on speech processing. Dogs listened to praising and neutral speech from their owners and a control person. We found positive correlation between dogs' behaviorally measured attachment scores towards their owners and neural activity increase for the owner's voice in the caudate nucleus; and activity increase in the secondary auditory caudal ectosylvian gyrus and the caudate nucleus for the owner's praise. Through identifying social relationship-dependent neural reward responses, our study reveals similarities in neural mechanisms modulated by infant-mother and dog-owner attachment.

Man's best friend in life and death: scientific perspectives and challenges of dog brain banking.

Biobanking refers to the systematic collection, storage, and distribution of pre- or post-mortem biological samples derived from volunteer donors. The demand for high-quality human specimens is clearly demonstrated by the number of newly emerging biobanking facilities and large international collaborative networks. Several animal species are relevant today in medical research; therefore, similar initiatives in comparative physiology could be fruitful. Dogs, in particular, are gaining increasing attention in translational research on complex phenomena, like aging, cancer, and neurodegenerative diseases. Therefore, biobanks gathering and storing dog biological materials together with related data could play a vital role in translational and veterinary research projects. To achieve these aims, a canine biobank should meet the same standards in sample quality and data management as human biobanks and should rely on well-designed collaborative networks between different professionals and dog owners. While efforts to create dog biobanks could face similar financial and technical challenges as their human counterparts, they can widen the spectrum of successful collaborative initiatives towards a better picture of dogs' physiology, disease, evolution, and translational potential. In this review, we provide an overview about the current state of dog biobanking and introduce the "Canine Brain and Tissue Bank" (CBTB)-a new, large-scale collaborative endeavor in the field.

CDKN2A Gene Expression as a Potential Aging Biomarker in Dogs.

Describing evolutionary conserved physiological or molecular patterns, which can reliably mark the age of both model organisms and humans or predict the onset of age-related pathologies has become a priority in aging research. The age-related gene-expression changes of the Cyclin Dependent Kinase Inhibitor 2A (CDKN2A) gene have been well-documented in humans and rodents. However, data is lacking from other relevant species, including dogs. Therefore, we quantified the CDKN2A mRNA abundance in dogs of different ages, in four tissue types: the frontal cortex of the brain, temporal muscle, skin, and blood. We found a significant, positive correlation between CDKN2A relative expression values and age in the brain, muscle, and blood; however, no correlation was detected in the skin. The strongest correlation was detected in the brain tissue (CDKN2A/GAPDH: r = 0.757, p < 0.001), similarly to human findings, while the muscle and blood showed weaker, but significant correlation. Our results suggest that CDKN2A might be a potential blood-borne biomarker of aging in dogs, although the validation and optimization will require further, more focused research. Our current results also clearly demonstrate that the role of CDKN2A in aging is conserved in dogs, regarding both tissue specificity and a pivotal role of CDKN2A in brain aging.

Creating a cross-sectional, CT and MR atlas of the Pannon minipig.

PURPOSE: The purpose of this study was to create a detailed cross-sectional anatomical reference atlas of the Pannon minipig by correlating good resolution CT and MR images with high quality cross-sectional anatomical images. According to the authors knowledge, no detailed anatomical atlas is available for the minipig. MATERIAL AND METHOD: An adult female minipig was utilized for this purpose. The animal was placed in a PVC half tube, and CT generated images of 0.6 mm slice thickness and MR images of 1.41 mm slice thickness were obtained. The images covered the whole body from the most rostral portion of the snout to the tip of the tail. The CT and MR scans were aligned with frozen anatomical sections prepared with an anatomical band saw from the same animal and significant structures were identified and labelled. The terminology employed has been referenced from the Nomina Anatomica Veterinaria 6th edition-2017. FINDINGS AND CONCLUSIONS: The resulting atlas consists of 109 anatomical slices and the corresponding 109 CT and 109 MR scans (altogether 327 images) and the nomenclature list for each image. Although this publication contains limited images of the resulted atlas, it is a reference source for anatomy education and clinical sciences. We are of the opinion that more comprehensive and especially online available interactive atlases should be prepared using similar methodology.

Transcallosal Removal of a Choroid Plexus Tumor From the Lateral Ventricle in a Dog. Case Report.

A 6-years-old female Staffordshire terrier was referred for periodic generalized seizures and asymmetric visual deficits. Magnetic resonance imaging revealed a 23.2 × 19.3 × 23.0 mm soft tissue mass within the right lateral ventricle and consequential dilatation of the lateral ventricles. Surgically, an interhemispheric approach was performed next to the marginal gyrus after a right parieto-parasagittal craniotomy, and a large choroid plexus tumor was transcallosally removed. After 3 days, the dog was discharged to home, and supportive treatment was continued. Histology revealed a choroid plexus papilloma, which was also confirmed by immunohistochemistry. One month after surgery, a control MRI showed that the ventricles were still dilated, but there was no sign of recurrent tumor. The dog had two additional seizures at home during the month following the intervention and one more grand mal episode was observed 4 months after the surgery. Nine months after the surgery, the dog showed no seizure activity, but her vision had not yet returned.

Digital Endocasting in Comparative Canine Brain Morphology.

Computed tomography (CT) is one of the most useful techniques for digitizing bone structures and making endocranial models from the neurocranium. The resulting digital endocasts reflect the morphology of the brain and the associated structures. Our first aim was to document the methodology behind creating detailed digital endocasts of canine skulls. We created digital endocasts of the skulls of 24 different dog breeds and 4 wild canids for visualization and teaching purposes. We used CT scanning with 0.323 mm × 0.322 mm × 0.6 mm resolution. The imaging data were segmented with 3D Slicer software and refined with Autodesk Meshmixer. Images were visualized in 3D Slicer and surface models were converted to 3D PDFs to provide easier interactive access, and 3D prints were also generated for visualization purposes. Our second aim was to analyze how skull length and width relate to the surface areas of the prepiriform rhinencephalic, prefrontal, and non-prefrontal cerebral convexity areas of the endocasts. The rhinencephalic area ratio decreased with a larger skull index. Our results open the possibility to analyze the relationship between the skull and brain morphology, and to link certain features to behavior, and cognition in dogs.

Longitudinal Volumetric Assessment of Ventricular Enlargement in Pet Dogs Trained for Functional Magnetic Resonance Imaging (fMRI) Studies.

BACKGROUND: Recent studies suggest that clinically sound ventriculomegaly in dogs could be a preliminary form of the clinically significant hydrocephalus. We evaluated changes of ventricular volumes in awake functional magnetic resonance imaging (fMRI) trained dogs with indirectly assessed cognitive abilities over time (thus avoiding the use of anaesthetics, which can alter the pressure). Our research question was whether ventricular enlargement developing over time would have any detrimental effect on staying still while being scanned; which can be extrapolated to the ability to pay attention and to exert inhibition. METHODS: Seven healthy dogs, 2-8 years old at the baseline scan and 4 years older at rescan, participated in a rigorous and gradual training for staying motionless (<2 mm) in the magnetic resonance (MR) scanner without any sedation during 6 minute-long structural MR sequences. On T1 structural images, volumetric analyses of the lateral ventricles were completed by software guided semi-automated tissue-type segmentations performed with FMRIB Software Library (FSL, Analysis Group, Oxford, UK). RESULTS AND CONCLUSION: We report significant enlargement for both ventricles (left: 47.46 %, right: 46.07 %) over time while dogs retained high levels of attention and inhibition. The results suggest that even considerable ventricular enlargement arising during normal aging does not necessarily reflect observable pathological changes in behavior.

Two different indications of ventriculoperitoneal and cystoperitoneal shunting in six dogs.

In this study we described two different indications of ventriculo- and cystoperitoneal shunting (VPS, CPS) procedures in six dogs, including their clinical data and magnetic resonance imaging (MRI) examinations. One dog had moderate and two dogs had severe congenital hydrocephalus, one was presented with intracranial pressure elevation due to meningoencephalitis of unknown origin (MUO) associated with congenital hydrocephalus, and two with quadrigeminal cysts (QC). VPS procedures were done in four and CPS in two dogs, using low-pressure valve systems. The follow-up period ranged from 1 to 6 months and control MRI scans were also made. Significant improvement was detected in five cases during the short-term follow-up period (1 month) and in four cases in the medium-term follow-up (2-6 months). Major complications were found in two cases: one dog with acute-hypertensive hydrocephalus died one week after surgery, and in another case development of a chronic subdural haematoma and hygroma caused death 3 months after the surgery. Minor complications (e.g. subdural hygroma) were found in two cases. In cases of severe hydrocephalus or intracranial cysts, higher-pressure valve systems are recommended in order to prevent subdural hygroma. Transient postoperative clinical signs usually resolve within one week after the surgery.

Dogs can sense weak thermal radiation.

The dog rhinarium (naked and often moist skin on the nose-tip) is prominent and richly innervated, suggesting a sensory function. Compared to nose-tips of herbivorous artio- and perissodactyla, carnivoran rhinaria are considerably colder. We hypothesized that this coldness makes the dog rhinarium particularly sensitive to radiating heat. We trained three dogs to distinguish between two distant objects based on radiating heat; the neutral object was about ambient temperature, the warm object was about the same surface temperature as a furry mammal. In addition, we employed functional magnetic resonance imaging on 13 awake dogs, comparing the responses to heat stimuli of about the same temperatures as in the behavioural experiment. The warm stimulus elicited increased neural response in the left somatosensory association cortex. Our results demonstrate a hitherto undiscovered sensory modality in a carnivoran species.

Resting-state fMRI data of awake dogs (Canis familiaris) via group-level independent component analysis reveal multiple, spatially distributed resting-state networks.

Resting-state networks are spatially distributed, functionally connected brain regions. Studying these networks gives us information about the large-scale functional organization of the brain and alternations in these networks are considered to play a role in a wide range of neurological conditions and aging. To describe resting-state networks in dogs, we measured 22 awake, unrestrained individuals of both sexes and carried out group-level spatial independent component analysis to explore whole-brain connectivity patterns. In this exploratory study, using resting-state functional magnetic resonance imaging (rs-fMRI), we found several such networks: a network involving prefrontal, anterior cingulate, posterior cingulate and hippocampal regions; sensorimotor (SMN), auditory (AUD), frontal (FRO), cerebellar (CER) and striatal networks. The network containing posterior cingulate regions, similarly to Primates, but unlike previous studies in dogs, showed antero-posterior connectedness with involvement of hippocampal and lateral temporal regions. The results give insight into the resting-state networks of awake animals from a taxon beyond rodents through a non-invasive method.

A Recurrent Suprapituitary Ependymal Cyst Managed by Endoscopy-Assisted Transsphenoidal Surgery in a Canine: A Case Report.

A 9-years-old spayed female mixed-breed dog was referred for the evaluation of intermittent head tremors, obtundation, long-standing blindness, and a tendency to seek confined spaces. The dog lost its vision 6 months before the current presentation. A menace response was absent on ophthalmological examination. Neurological examination did not show any abnormalities. A cyst measuring 16 × 18 × 14 mm was observed above the pituitary gland on magnetic resonance imaging. It extended toward the frontal area and compressed the optic chiasm and hypothalamic regions. A minimum preoperative database, including the findings of other required blood tests, was prepared. No abnormal laboratory findings were observed. Endoscopy-assisted transsphenoidal hypophysectomy was performed to remove the pituitary gland, drain the cyst, and partially excise the cyst wall. Normal pituitary gland tissue was observed on histopathology, and the mass was found to have a neuroendocrine or ependymal origin on cytology. Strict post-operative laboratory tests were performed at 1-h intervals for 24 h. An empty sella turcica region, and a collapsed and empty cyst wall was observed on follow-up magnetic resonance imaging. After 3 days of observation, the dog was discharged with a prescription of substitution therapy. However, the dog presented with the same signs and symptoms 73 days after the surgery. Cyst recurrence was apparent on magnetic resonance imaging. The owner requested euthanasia, and an ependymal cyst was observed on necropsy. To the best of our knowledge, we present the first case of an intra- and suprasellar ependymal cyst, and its surgical management in a canine. The findings from this case suggest that endoscopic transsphenoidal drainage and hypophysectomy could be a good surgical approach in cases where involvement of the pituitary gland is confirmed or strongly suspected on the basis of cytological and imaging findings.

MRI, CT and high resolution macro-anatomical images with cryosectioning of a Beagle brain: Creating the base of a multimodal imaging atlas.

Most common methods that directly show macro- or microscopic anatomy of the brain usually require the removal of the organ from the neurocranium. However, the brain can be revealed in situ by using proper sectioning techniques. Our aim was to both improve the cryosectioning method, test its limits and create a high-resolution macro-anatomical image series of a Beagle brain, which at the time of the study did not exist. A two-year-old female Beagle has been scanned with CT and MRI ante and post mortem, then the arteries of the head were filled with red resin. After freezing to -80°C, a neurocranium block was created and was embedded into a water-gelatin mix. Using a special milling device and a DSLR camera, 1112 consecutive RGB-color cryosections were made with a 100 µm layer thickness and captured in high resolution (300 dpi, 24-bit color, and pixel size was 19.5 x 19.5 µm). Image post-processing was done with Adobe Photoshop CS3 and Thermo Scientific Amira 6.0 softwares, and as a result of the proper alignment and coregistration, visualization and comparing was possible with all the applied imaging modalities (CT, MRI, cryosectioning) in any arbitrary plane. Surface models from the arteries, veins, brain and skull were also generated after segmentation in the same coordinate system, giving a unique opportunity for comparing the two-dimensional and three-dimensional anatomy. This is the first study which focuses directly to this high-definition multimodal visualization of the canine brain, and it provides the most accurate results compared to previous cryosectioning studies, as using an improved method, higher image quality, more detailed image, proper color fidelity and lower artefact formation were achieved. Based on the methodology we described, it can serve as a base for future multimodal (CT, MR, augmented- or virtual reality) imaging atlases for medical, educational and scientific purposes.

A detailed canine brain label map for neuroimaging analysis.

BACKGROUND AND AIMS: Dogs have recently become an important model species for comparative social and cognitive neuroscience. Brain template-related label maps are essential for functional magnetic resonance imaging (fMRI) data analysis, to localize neural responses. In this study, we present a detailed, individual-based, T1-weighted MRI-based brain label map used in dog neuroimaging analysis. METHODS: A typical, medium-headed dog (a 7.5-year-old male Golden Retriever) was selected from a cohort of 22 dogs, based on brain morphology (shape, size, and gyral pattern), to serve as the template for a label map. RESULTS: Eighty-six 3-dimensional labels were created to highlight the main cortical (cerebral gyri on the lateral and medial side) and subcortical (thalamus, caudate nucleus, amygdala, and hippocampus) structures of the prosencephalon and diencephalon, and further main parts of brainstem (mesencephalon and rhombencephalon). DISCUSSION: Importantly, this label map is (a) considerably more detailed than any available dog brain template; (b) it is easy to use with freeware and commercial neuroimaging software for MRI and fMRI analysis; and (c) it can be registered to other existing templates, including a recent average-based dog brain template. Using the coordinate system and label map proposed here can enhance precision and standard localization during future canine neuroimaging studies.