ABSTRACT
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.
Subject(s)
White Matter , Animals , Humans , White Matter/diagnostic imaging , Brain , Corpus Callosum/diagnostic imaging , Corpus Callosum/physiology , Thalamus/diagnostic imaging , Macaca mulatta , MammalsABSTRACT
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.
Subject(s)
Callithrix , Wakefulness , Access to Information , Animals , Brain/physiology , Callithrix/physiology , Humans , Magnetic Resonance Imaging/methods , Mice , RatsABSTRACT
Curiosity is a fundamental nature of animals for adapting to changing environments, but its underlying brain circuits and mechanisms remain poorly understood. One main barrier is that existing studies use rewards to train animals and motivate their engagement in behavioral tasks. As such, the rewards become significant confounders in interpreting curiosity. Here, we overcame this problem by studying research-naïve and naturally curious marmosets that can proactively and persistently participate in a visual choice task without external rewards. When performing the task, the marmosets manifested a strong innate preference towards acquiring new information, associated with faster behavioral responses. Longitudinally functional magnetic resonance imaging revealed behavior-relevant brain states that reflected choice preferences and engaged several brain regions, including the cerebellum, the hippocampus, and cortical areas 19DI, 25, and 46D, with the cerebellum being the most prominent. These results unveil the essential brain circuits and dynamics underlying curiosity-driven activity.
Subject(s)
Brain/diagnostic imaging , Brain/physiology , Exploratory Behavior/physiology , Nerve Net/diagnostic imaging , Nerve Net/physiology , Animals , Callithrix , Choice Behavior/physiology , Female , Magnetic Resonance Imaging/methods , Male , Motivation/physiologyABSTRACT
The standard anatomical brain template provides a common space and coordinate system for visualizing and analyzing neuroimaging data from large cohorts of subjects. Previous templates and atlases for the common marmoset brain were either based on data from a single individual or lacked essential functionalities for neuroimaging analysis. Here, we present new population-based in-vivo standard templates and tools derived from multi-modal data of 27 marmosets, including multiple types of T1w and T2w contrast images, DTI contrasts, and large field-of-view MRI and CT images. We performed multi-atlas labeling of anatomical structures on the new templates and constructed highly accurate tissue-type segmentation maps to facilitate volumetric studies. We built fully featured brain surfaces and cortical flat maps to facilitate 3D visualization and surface-based analyses, which are compatible with most surface analyzing tools, including FreeSurfer, AFNI/SUMA, and the Connectome Workbench. Analysis of the MRI and CT datasets revealed significant variations in brain shapes, sizes, and regional volumes of brain structures, highlighting substantial individual variabilities in the marmoset population. Thus, our population-based template and associated tools provide a versatile analysis platform and standard coordinate system for a wide range of MRI and connectome studies of common marmosets. These new template tools comprise version 3 of our Marmoset Brain Mapping Project and are publicly available via marmosetbrainmapping.org/v3.html.
Subject(s)
Atlases as Topic , Brain Mapping/methods , Brain/anatomy & histology , Callithrix/anatomy & histology , Animals , Female , Male , Reference StandardsABSTRACT
The primate superior colliculus (SC) has recently been shown to possess both a large foveal representation as well as a varied visual processing repertoire. This structure is also known to contribute to eye movement generation. Here, we describe our current understanding of how SC visual and movement-related signals interact within the realm of small eye movements associated with the foveal scale of visuomotor behavior. Within the SC's foveal representation, there is a full spectrum of visual, visual-motor, and motor-related discharge for fixational eye movements. Moreover, a substantial number of neurons only emit movement-related discharge when microsaccades are visually guided, but not when similar movements are generated toward a blank. This represents a particularly striking example of integrating vision and action at the foveal scale. Beyond that, SC visual responses themselves are strongly modulated, and in multiple ways, by the occurrence of small eye movements. Intriguingly, this impact can extend to eccentricities well beyond the fovea, causing both sensitivity enhancement and suppression in the periphery. Because of large foveal magnification of neural tissue, such long-range eccentricity effects are neurally warped into smaller differences in anatomical space, providing a structural means for linking peripheral and foveal visual modulations around fixational eye movements. Finally, even the retinal-image visual flows associated with tiny fixational eye movements are signaled fairly faithfully by peripheral SC neurons with relatively large receptive fields. These results demonstrate how studying active vision at the foveal scale represents an opportunity for understanding primate vision during natural behaviors involving ever-present foveating eye movements.NEW & NOTEWORTHY The primate superior colliculus (SC) is ideally suited for active vision at the foveal scale: it enables detailed foveal visual analysis by accurately driving small eye movements, and it also possesses a visual processing machinery that is sensitive to active eye movement behavior. Studying active vision at the foveal scale in the primate SC is informative for broader aspects of active perception, including the overt and covert processing of peripheral extra-foveal visual scene locations.
Subject(s)
Behavior, Animal/physiology , Eye Movements/physiology , Fovea Centralis/physiology , Motor Activity/physiology , Primates/physiology , Psychomotor Performance/physiology , Superior Colliculi/physiology , Visual Perception/physiology , AnimalsABSTRACT
Microsaccades are systematically modulated by peripheral spatial cues, and these eye movements have been implicated in perceptual and motor performance changes in cueing tasks. However, an additional oculomotor factor that may also influence performance in these tasks, fixational eye position itself, has been largely neglected so far. Using precise eye tracking and real-time retinal-image stabilization, we carefully analyzed fixational eye position dynamics and related them to microsaccade generation during spatial cueing. As expected, during baseline fixation, microsaccades corrected for a foveal motor error away from the preferred retinal locus of fixation (the so-called ocular position "set point" of the oculomotor system). However, we found that this relationship was violated during a short period immediately after cue onset; a subset of cue-directed "express microsaccades" that were highly precise in time and direction, and that were larger than regular microsaccades, occurred. These movements, having <100-ms latencies from cue onset, were triggered when fixational eye position was already at the oculomotor set point when the cue appeared; they were thus error-increasing rather than error-decreasing. Critically, even when no microsaccades occurred, fixational eye position itself was systematically deviated toward the cue, again with ~100-ms latency, suggesting that the oculomotor system establishes a new set point at different postcue times. This new set point later switched to being away from the cue after ~200-300 ms. Because eye position alters the location of retinal images, our results suggest that both eye position and microsaccades can be associated with performance changes in spatial cueing tasks. NEW & NOTEWORTHY Covert spatial cueing tasks are a workhorse for studying cognitive processing in humans and monkeys, but gaze is not perfectly stable during these tasks. We found that minute fixational eye position changes, independent of the more studied microsaccades, are not random in cueing tasks and are thus not "averaged out" in analyses. These changes can additionally dictate microsaccade times. Thus, in addition to microsaccadic influences, retinal image changes associated with fixational eye position are relevant for performance in cueing tasks.
Subject(s)
Cues , Fixation, Ocular/physiology , Saccades/physiology , Space Perception/physiology , Visual Perception/physiology , Animals , Behavior, Animal/physiology , Eye Movement Measurements , Macaca mulatta , MaleABSTRACT
Microsaccades occur during gaze fixation to correct for miniscule foveal motor errors. The mechanisms governing such fine oculomotor control are still not fully understood. In this study, we explored microsaccade control by analyzing the impacts of transient visual stimuli on these movements' kinematics. We found that such kinematics can be altered in systematic ways depending on the timing and spatial geometry of visual transients relative to the movement goals. In two male rhesus macaques, we presented peripheral or foveal visual transients during an otherwise stable period of fixation. Such transients resulted in well-known reductions in microsaccade frequency, and our goal was to investigate whether microsaccade kinematics would additionally be altered. We found that both microsaccade timing and amplitude were modulated by the visual transients, and in predictable manners by these transients' timing and geometry. Interestingly, modulations in the peak velocity of the same movements were not proportional to the observed amplitude modulations, suggesting a violation of the well-known "main sequence" relationship between microsaccade amplitude and peak velocity. We hypothesize that visual stimulation during movement preparation affects not only the saccadic "Go" system driving eye movements but also a "Pause" system inhibiting them. If the Pause system happens to be already turned off despite the new visual input, movement kinematics can be altered by the readout of additional visually evoked spikes in the Go system coding for the flash location. Our results demonstrate precise control over individual microscopic saccades and provide testable hypotheses for mechanisms of saccade control in general.NEW & NOTEWORTHY Microsaccadic eye movements play an important role in several aspects of visual perception and cognition. However, the mechanisms for microsaccade control are still not fully understood. We found that microsaccade kinematics can be altered in a systematic manner by visual transients, revealing a previously unappreciated and exquisite level of control by the oculomotor system of even the smallest saccades. Our results suggest precise temporal interaction between visual, motor, and inhibitory signals in microsaccade control.
Subject(s)
Evoked Potentials, Visual , Saccades , Animals , Biomechanical Phenomena , Fixation, Ocular , Macaca mulatta , Male , Models, Neurological , Visual PerceptionABSTRACT
Early brain development is a complex and rapid process, the disturbance of which may cause the onset of brain disorders. Based on longitudinal imaging data acquired from 6 to 16 months postnatal, we describe a systematic trajectory of monkey brain development during late infancy, and demonstrate the influence of phencyclidine (PCP) on this trajectory. Although the general developmental trajectory of the monkey brain was close to that of the human brain, the development in monkeys was faster and regionally specific. Gray matter volume began to decrease during late infancy in monkeys, much earlier than in humans in whom it occurs in adolescence. Additionally, the decrease of gray matter volume in higher-order association regions (the frontal, parietal and temporal lobes) occurred later than in regions for primary functions (the occipital lobe and cerebellum). White matter volume displayed an increasing trend in most brain regions, but not in the occipital lobe, which had a stable volume. In addition, based on diffusion tensor imaging, we found an increase in fractional anisotropy and a decrease in diffusivity, which may be associated with myelination and axonal changes in white matter tracts. Meanwhile, we tested the influence of 14-day PCP treatment on the developmental trajectories. Such treatment tended to accelerated brain maturation during late infancy, although not statistically significant. These findings provide comparative information for the understanding of primate brain maturation and neurodevelopmental disorders.
Subject(s)
Brain/drug effects , Brain/growth & development , Excitatory Amino Acid Antagonists/pharmacology , Phencyclidine/pharmacology , Animals , Brain/anatomy & histology , Diffusion Tensor Imaging , Gray Matter/anatomy & histology , Gray Matter/drug effects , Gray Matter/growth & development , Macaca mulatta , Magnetic Resonance Imaging , Male , Neural Pathways/drug effects , Neural Pathways/growth & development , White Matter/anatomy & histology , White Matter/drug effects , White Matter/growth & developmentABSTRACT
Background: Patent foramen ovale (PFO) has been associated with migraine, cryptogenic stroke (CS), and hypoxemia. However, which examination method is most reliable remains controversial. This study sought to investigate the diagnostic value of contrast-enhanced ultrasonography (cU), including contrast-enhanced transcranial Doppler (cTCD), contrast transthoracic echocardiography (cTTE), and contrast transesophageal echocardiography (cTEE), for PFO; and to determine the best diagnostic strategy. Methods: This retrospective observational study included a total of 147 consecutive patients suspected PFO at The First Hospital of Shanxi Medical University between October 2019 and January 2022. The patients also underwent cTCD, cTTE, and cTEE examinations. The standard for the diagnosis of PFO was confirmation of the presence of PFO by color Doppler flow signals or contrast microbubbles (MBs) passing through the foramen ovale. Results: A total of 123 patients were diagnosed with PFO and 24 patients without PFO during the study period. The detectable rates of cTCD, cTTE, and cTEE were 120 (97.56%), 110 (89.43%), and 121 (98.37%), respectively. The sensitivity between cTCD and cTEE for PFO were comparable [97.56%, 95% confidence interval (CI): 92.5% to 99.4% vs. 98.37%, 95% CI: 93.7% to 99.7%; P>0.99], and the sensitivity of both were higher than that of cTTE (89.43%, 95% CI: 82.3% to 94.0%; P=0.02 and P=0.001, respectively). In addition, the specificity of cTEE for PFO was significantly higher than that of cTCD (100%, 95% CI: 82.3% to 100.0% vs. 75.00%, 95% CI: 53.0% to 89.4%; P<0.001) and cTTE (100%, 95% CI: 82.3% to 100.0% vs. 75.00%, 95% CI: 53.0% to 89.4%; P<0.001). Further, the semi-quantitative classification ability of cTCD for PFO with right-to-left shunt (RLS) was significantly higher than that of cTTE and cTEE (P=0.02 and P<0.001, respectively), and that of cTTE was significantly higher than that of cTEE (P=0.01). The Spearman analysis showed that the degree of RLS was positively correlated with the inner diameter of the PFO (r=0.695, P<0.001). Conclusions: The combination of cTCD and cTEE may provide a favorable strategy for the diagnosis of PFO.
ABSTRACT
BACKGROUND: Bisphenol A (BPA) is an endocrine disruptor that in animal studies can bind to the thyroid hormone receptor and affect thyroid function. Relevant epidemiologic studies are limited and results are inconsistent. We explored the relationship between urinary BPA and thyroid function in a Chinese population. METHODS: The study population included 3394 subjects age 40 years or older who were enrolled in a population-based study from Songnan Community, Baoshan District, Shanghai, China, from June through August 2009. We analyzed the association between urinary BPA and thyroid function using multivariate linear regression. Participants were further divided according to thyroid function status, and logistic regression was applied to determine the relationship between urinary BPA and thyroid function. RESULTS: Each one-quartile increase in BPA was related to an increase of 0.068 pmol/l (95% confidence interval = 0.065- 0.071) in free triiodothyronine and a 0.084 µIU/ml decline (-0.099 to -0.069) in thyroid-stimulating hormone (TSH) in men. For women, there was a 0.10 pmol/l (0.09 to 0.11) increase in free triiodothyronine and a 0.13 µIU/ml decline (-0.14 to -0.11) in TSH. High urinary BPA level was associated with increased thyroid function (adjusted odds ratio= 1.71 [1.26 to 2.32]). CONCLUSIONS: Our results support previous reports of associations between BPA exposure and altered thyroid hormones in animal models and epidemiologic studies. Because our study is cross-sectional, no causal relationships can be established.
Subject(s)
Benzhydryl Compounds/urine , Estrogens, Non-Steroidal/urine , Phenols/urine , Thyroid Gland/metabolism , Thyrotropin/blood , Triiodothyronine/blood , Aged , Benzhydryl Compounds/adverse effects , Benzhydryl Compounds/metabolism , China , Environmental Exposure/statistics & numerical data , Estrogens, Non-Steroidal/adverse effects , Estrogens, Non-Steroidal/metabolism , Female , Humans , Linear Models , Logistic Models , Male , Middle Aged , Phenols/adverse effects , Phenols/metabolismABSTRACT
INTRODUCTION: The purposes of this research were to investigate the long-term responses of mandibular condylar cartilage to experimentally induced disordered occlusion and to evaluate changes in the expression of the SDF-1/CXCR4 axis. METHODS: Experimentally induced disordered occlusions were created in 8-week-old female Sprague-Dawley rats by orthodontic methods. After 24 weeks, remodeling of the mandibular condylar cartilage was assessed by hematoxylin and eosin staining. Protein and mRNA expression of SDF-1, CXCR4, MMP9, IL6, OPG, and RANKL were investigated by means of immunohistochemical staining and real-time polymerase chain reaction. RESULTS: Obvious cartilage degenerative remodeling responses were observed; they appeared as uneven distributions of cellular disposition, loss of cartilage surface integrity, and cell-free areas. Regenerative responses presenting as thickening of the whole and the calcified cartilage layers in the experimental group were also observed. Compared with the age-matched controls, the protein and mRNA levels of SDF-1, CXCR4, MMP9, IL6, and OPG, but not RANKL, were increased in the experimental group (all, P <0.05). In addition, the mRNA level of RANKL/OPG showed a decreasing trend in the experimental group compared with the age-matched controls (P = 0.052). CONCLUSIONS: This study demonstrated that long-term experimentally induced disordered occlusion leads to a combined response in degeneration and regeneration of mandibular cartilage, accompanied by active interaction of the SDF-1/CXCR4 axis and local upregulation of MMP9, IL6, and OPG.
Subject(s)
Cartilage, Articular/metabolism , Cartilage, Articular/pathology , Malocclusion/complications , Mandibular Condyle/physiopathology , Osteoarthritis/pathology , Temporomandibular Joint Disorders/pathology , Animals , Bone Remodeling , Chemokine CXCL12/metabolism , Female , Interleukin-6/metabolism , Matrix Metalloproteinase 9/metabolism , Osteoarthritis/etiology , Osteoprotegerin/metabolism , RANK Ligand/metabolism , Rats , Rats, Sprague-Dawley , Receptors, CXCR4/metabolism , Regeneration , Temporomandibular Joint Disorders/etiologyABSTRACT
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 an additional commissural pathway in rodents, termed the thalamic commissures (TCs), as another interhemispheric axonal fiber pathway that connects cortex to the contralateral thalamus. Here, we demonstrate that TCs also exist in primates and characterize the connectivity of these pathways with high-resolution diffusion-weighted magnetic resonance imaging, viral axonal tracing, and functional MRI. 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 an important 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.
ABSTRACT
Comprehensive integration of structural and functional connectivity data is required to model brain functions accurately. While resources for studying the structural connectivity of non-human primate brains already exist, their integration with functional connectivity data has remained unavailable. Here we present a comprehensive resource that integrates the most extensive awake marmoset resting-state fMRI data available to date (39 marmoset monkeys, 710 runs, 12117 mins) with previously published cellular-level neuronal tracing data (52 marmoset monkeys, 143 injections) and multi-resolution diffusion MRI datasets. The combination of these data allowed us to (1) map the fine-detailed functional brain networks and cortical parcellations, (2) develop a deep-learning-based parcellation generator that preserves the topographical organization of functional connectivity and reflects individual variabilities, and (3) investigate the structural basis underlying functional connectivity by computational modeling. This resource will enable modeling structure-function relationships and facilitate future comparative and translational studies of primate brains.
Subject(s)
Brain , Callithrix , Animals , Brain/diagnostic imaging , Diffusion Magnetic Resonance Imaging , Computer SimulationABSTRACT
At any moment in time, new information is sampled from the environment and interacts with ongoing brain state. Often, such interaction takes place within individual circuits that are capable of both mediating the internally ongoing plan as well as representing exogenous sensory events. Here, we investigated how sensory-driven neural activity can be integrated, very often in the same neuron types, into ongoing saccade motor commands. Despite the ballistic nature of saccades, visually induced action potentials in the rhesus macaque superior colliculus (SC), a structure known to drive eye movements, not only occurred intra-saccadically, but they were also associated with highly predictable modifications of ongoing eye movements. Such predictable modifications reflected a simultaneity of movement-related discharge at one SC site and visually induced activity at another. Our results suggest instantaneous readout of the SC during movement generation, irrespective of activity source, and they explain a significant component of kinematic variability of motor outputs.
Subject(s)
Eye Movements/physiology , Mesencephalon/physiology , Superior Colliculi/physiology , Action Potentials , Animals , Electrophysiological Phenomena , Longitudinal Studies , Macaca mulatta , Male , Specimen HandlingABSTRACT
Visual selection in primates is intricately linked to eye movements, which are generated by a network of cortical and subcortical neural circuits. When visual selection is performed covertly, without foveating eye movements toward the selected targets, a class of fixational eye movements, called microsaccades, is still involved. Microsaccades are small saccades that occur when maintaining precise gaze fixation on a stationary point, and they exhibit robust modulations in peripheral cueing paradigms used to investigate covert visual selection mechanisms. These modulations consist of changes in both microsaccade directions and frequencies after cue onsets. Over the past two decades, the properties and functional implications of these modulations have been heavily studied, revealing a potentially important role for microsaccades in mediating covert visual selection effects. However, the neural mechanisms underlying cueing effects on microsaccades are only beginning to be investigated. Here we review the available causal manipulation evidence for these effects' cortical and subcortical substrates. In the superior colliculus (SC), activity representing peripheral visual cues strongly influences microsaccade direction, but not frequency, modulations. In the cortical frontal eye fields (FEF), activity only compensates for early reflexive effects of cues on microsaccades. Using evidence from behavior, theoretical modeling, and preliminary lesion data from the primary visual cortex and microstimulation data from the lower brainstem, we argue that the early reflexive microsaccade effects arise subcortically, downstream of the SC. Overall, studying cueing effects on microsaccades in primates represents an important opportunity to link perception, cognition, and action through unaddressed cortical-subcortical neural interactions. These interactions are also likely relevant in other sensory and motor modalities during other active behaviors.
Subject(s)
Cues , Eye Movements , Animals , Primary Visual Cortex , Saccades , Visual PerceptionABSTRACT
Product affinity segmentation discovers groups of customers with similar purchase preferences for cross-selling opportunities to increase sales and customer loyalty. However, this concept can be challenging to implement efficiently and effectively for actionable strategies. First, the nature of skewed and sparse product-level data in the clustering process results in less meaningful solutions. Second, customer segmentation becomes challenging on massive data sets due to the computational complexity of traditional clustering methods. Third, market basket analysis may suffer from association rules too general to be relevant for important segments. In this article, we propose to partition customers into groups with their product purchase similarity maximized by detecting communities in the customer-product bipartite graph using the Louvain algorithm. Through a case study using data from a large U.S. retailer, we demonstrate that the proposed method generates interpretable clustering results with distinct product purchase patterns. Comprehensive characteristics of customers and products in each cluster can be inferred with statistical significance since they are essentially driven by products purchased by customers. Compared with the conventional RFM (recency, frequency, monetary) model, the proposed approach leads to higher response rates in the recommendation of products to customers in the same cluster. Our analysis provides greater insights into customer purchase behaviors, improves product recommendation effectiveness, and addresses computational complexity in the context of skewed and sparse big data.
Subject(s)
Commerce , Consumer Behavior , Health ServicesABSTRACT
The corpus callosum, the principal structural avenue for interhemispheric neuronal communication, controls the brain's lateralization. Developmental malformations of the corpus callosum (CCD) can lead to learning and intellectual disabilities. Currently, there is no clear explanation for these symptoms. Here, we used resting-state functional MRI (rsfMRI) to evaluate the dynamic resting-state functional connectivity (rsFC) in both the cingulate cortex (CG) and the sensory areas (S1, S2, A1) in three marmosets (Callithrix jacchus) with spontaneous CCD. We also performed rsfMRI in 10 CCD human subjects (six hypoplasic and four agenesic). We observed no differences in the strength of rsFC between homotopic CG and sensory areas in both species when comparing them to healthy controls. However, in CCD marmosets, we found lower strength of quasi-periodic patterns (QPP) correlation in the posterior interhemispheric sensory areas. We also found a significant lag of interhemispheric communication in the medial CG, suggesting asynchrony between the two hemispheres. Correspondingly, in human subjects, we found that the CG of acallosal subjects had a higher QPP correlation than controls. In comparison, hypoplasic subjects had a lower QPP correlation and a delay of 1.6 s in the sensory regions. These results show that CCD affects the interhemispheric synchrony of both CG and sensory areas and that, in both species, its impact on cortical communication varies along the CC development gradient. Our study shines a light on how CCD misconnects homotopic regions and opens a line of research to explain the causes of the symptoms exhibited by CCD patients and how to mitigate them.
Subject(s)
Brain Diseases/physiopathology , Callithrix/physiology , Corpus Callosum/physiology , Neural Pathways/physiology , Adult , Animals , Child , Child, Preschool , Corpus Callosum/physiopathology , Female , Gyrus Cinguli/physiopathology , Humans , Magnetic Resonance Imaging/methods , Male , Neocortex/physiology , Neocortex/physiopathology , Young AdultABSTRACT
BACKGROUND: The casein kinase 2-interacting protein-1 (CKIP-1) is important in the development of osteoblasts and cardiomyocytes. However, the effects of CKIP-1 on osteoblast precursor mesenchymal stem cells (MSCs) remain unclear. This study aimed to determine whether CKIP-1 affects osteogenic differentiation in MSCs and explore the relationship of CKIP-1 and inflammation. METHODS: Bone marrow MSCs of CKIP-1 wild type (WT) and knockout (KO) mice were cultivated in vitro. Cell phenotype was analyzed by flow cytometry, colony formation was detected to study the proliferative ability. Osteogenic and adipogenic induction were performed. The osteogenic ability was explored by alizarin red staining, alkaline phosphatase (ALP) staining and ALP activity detection. Quantitative real-time polymerase chain reaction (qRT-PCR) was carried out to determine the mRNA expression levels of osteoblast marker genes. The adipogenic ability was detected by oil red O staining. Content of the bone was analyzed to observe the differences of bone imaging parameters including trabecular bone volume/tissue volume (BV/TV), bone surface area fraction/trabecular BV, trabecular number (Tb.N), and trabecular spacing (Tb.sp). Interleukin (IL)-1ß was injected on WT mice of 2 months old and 18 months old, respectively. Difference in CKIP-1 expression was detected by RT-PCR and western blot. The relationship between CKIP-1 and inflammation was explored by RT-PCR and western blot. RESULTS: ALP assays, alizarin red staining, and qRT-PCR showed that MSCs derived from CKIP-1 KO mice exhibited a stronger capability for osteogenesis. Micro-computed tomography detection showed that among 18-month-old mice, CKIP-1 KO mice presented significantly higher bone mass compared with WT mice (Pâ=â0.02). No significant difference was observed in 2-month-old mice. In vivo data showed that expression of CKIP-1 was higher in the bone marrow of aging mice than in young mice (4.3-fold increase at the mRNA level, Pâ=â0.04). Finally, the expression levels of CKIP-1 in bone marrow (3.2-fold increase at the mRNA level, Pâ=â0.03) and cultured MSCs were up-regulated on chronic inflammatory stimulation by IL-1ß. CONCLUSIONS: CKIP-1 is responsible for negative regulation of MSC osteogenesis with age-dependent effects. Increasing levels of inflammation with aging may be the primary factor responsible for higher expression levels of CKIP-1 but may not necessarily affect MSC aging.
Subject(s)
Mesenchymal Stem Cells , Osteogenesis , Animals , Carrier Proteins , Casein Kinase II , Cell Differentiation , Cells, Cultured , Inflammation , Mice , Osteogenesis/genetics , X-Ray MicrotomographyABSTRACT
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.