scholarly journals Hippocampal subfields revealed through unfolding and unsupervised clustering of laminar and morphological features in 3D BigBrain

2019 ◽  
Author(s):  
J. DeKraker ◽  
J.C. Lau ◽  
K.M. Ferko ◽  
A.R. Khan ◽  
S. Köhler
Keyword(s):  
Internal Structure ◽  
Ground Truth ◽  
Longitudinal Axis ◽  
Unsupervised Clustering ◽  
Morphological Features ◽  
Unique Combination ◽  
Hippocampal Subfields ◽  
Human Hippocampus ◽  
Hippocampal Structure

AbstractThe internal structure of the human hippocampus is challenging to map using histology or neuroimaging due to its complex archicortical folding. Here, we aimed to overcome this challenge using a unique combination of three methods. First, we leveraged a histological dataset with unprecedented 3D coverage, 3D BigBrain. Second, we imposed a computational unfolding framework that respects the topological continuity of hippocampal subfields, which are traditionally defined by laminar composition. Third, we adapted neocortical parcellation techniques to map the hippocampus with respect to not only laminar but also morphological features. Unsupervised clustering of these features revealed subdivisions that closely resemble ground-truth manual subfield segmentations. Critically, we also show that morphological features alone are sufficient to derive most hippocampal subfield boundaries. Moreover, some features showed differences within subfields along the hippocampal longitudinal axis. Our findings highlight new characteristics of internal hippocampal structure, and offer new avenues for its characterization with in-vivo neuroimaging.

scholarly journals Anatomical and microstructural determinants of hippocampal subfield functional connectome embedding

2018 ◽  
Vol 115 (40) ◽  
pp. 10154-10159 ◽  
Author(s):  
Reinder Vos de Wael ◽  
Sara Larivière ◽  
Benoît Caldairou ◽  
Seok-Jun Hong ◽  
Daniel S. Margulies ◽  
...  
Keyword(s):  
Resting State ◽  
State Of The Art ◽  
Model System ◽  
Hippocampal Subfields ◽  
Functional Connectome ◽  
Human Hippocampus ◽  
Complex Anatomy ◽  
Robust Evidence ◽  
Anterior Posterior

The hippocampus plays key roles in cognition and affect and serves as a model system for structure/function studies in animals. So far, its complex anatomy has challenged investigations targeting its substructural organization in humans. State-of-the-art MRI offers the resolution and versatility to identify hippocampal subfields, assess its microstructure, and study topographical principles of its connectivity in vivo. We developed an approach to unfold the human hippocampus and examine spatial variations of intrinsic functional connectivity in a large cohort of healthy adults. In addition to mapping common and unique connections across subfields, we identified two main axes of subregional connectivity transitions. An anterior/posterior gradient followed long-axis landmarks and metaanalytical findings from task-based functional MRI, while a medial/lateral gradient followed hippocampal infolding and correlated with proxies of cortical myelin. Findings were consistent in an independent sample and highly stable across resting-state scans. Our results provide robust evidence for long-axis specialization in the resting human hippocampus and suggest an intriguing interplay between connectivity and microstructure.

scholarly journals Brainwide functional networks associated with anatomically- and functionally-defined hippocampal subfields using ultrahigh-resolution fMRI

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wei-Tang Chang ◽  
Stephanie K. Langella ◽  
Yichuan Tang ◽  
Sahar Ahmad ◽  
Han Zhang ◽  
...  
Keyword(s):  
Resting State ◽  
Functional Organization ◽  
A Priori ◽  
Longitudinal Axis ◽  
Functional Networks ◽  
Resting State Functional Connectivity ◽  
Underlying Assumption ◽  
Isotropic Resolution ◽  
Hippocampal Subfields ◽  
Fine Grained

AbstractThe hippocampus is critical for learning and memory and may be separated into anatomically-defined hippocampal subfields (aHPSFs). Hippocampal functional networks, particularly during resting state, are generally analyzed using aHPSFs as seed regions, with the underlying assumption that the function within a subfield is homogeneous, yet heterogeneous between subfields. However, several prior studies have observed similar resting-state functional connectivity (FC) profiles between aHPSFs. Alternatively, data-driven approaches investigate hippocampal functional organization without a priori assumptions. However, insufficient spatial resolution may result in a number of caveats concerning the reliability of the results. Hence, we developed a functional Magnetic Resonance Imaging (fMRI) sequence on a 7 T MR scanner achieving 0.94 mm isotropic resolution with a TR of 2 s and brain-wide coverage to (1) investigate the functional organization within hippocampus at rest, and (2) compare the brain-wide FC associated with fine-grained aHPSFs and functionally-defined hippocampal subfields (fHPSFs). This study showed that fHPSFs were arranged along the longitudinal axis that were not comparable to the lamellar structures of aHPSFs. For brain-wide FC, the fHPSFs rather than aHPSFs revealed that a number of fHPSFs connected specifically with some of the functional networks. Different functional networks also showed preferential connections with different portions of hippocampal subfields.

scholarly journals Simulating a Ground Truth for Transit Time Analysis of Indicator Dilution Curves

2020 ◽  
Vol 6 (3) ◽  
pp. 268-271
Author(s):  
Michael Reiß ◽  
Ady Naber ◽  
Werner Nahm
Keyword(s):  
Transit Time ◽  
Sampling Rate ◽  
Ground Truth ◽  
Indicator Dilution ◽  
Cross Sectional ◽  
In Vivo Measurements ◽  
Multiple Indicator Dilution ◽  
Transit Times ◽  
Dilution Curves

AbstractTransit times of a bolus through an organ can provide valuable information for researchers, technicians and clinicians. Therefore, an indicator is injected and the temporal propagation is monitored at two distinct locations. The transit time extracted from two indicator dilution curves can be used to calculate for example blood flow and thus provide the surgeon with important diagnostic information. However, the performance of methods to determine the transit time Δt cannot be assessed quantitatively due to the lack of a sufficient and trustworthy ground truth derived from in vivo measurements. Therefore, we propose a method to obtain an in silico generated dataset of differently subsampled indicator dilution curves with a ground truth of the transit time. This method allows variations on shape, sampling rate and noise while being accurate and easily configurable. COMSOL Multiphysics is used to simulate a laminar flow through a pipe containing blood analogue. The indicator is modelled as a rectangular function of concentration in a segment of the pipe. Afterwards, a flow is applied and the rectangular function will be diluted. Shape varying dilution curves are obtained by discrete-time measurement of the average dye concentration over different cross-sectional areas of the pipe. One dataset is obtained by duplicating one curve followed by subsampling, delaying and applying noise. Multiple indicator dilution curves were simulated, which are qualitatively matching in vivo measurements. The curves temporal resolution, delay and noise level can be chosen according to the requirements of the field of research. Various datasets, each containing two corresponding dilution curves with an existing ground truth transit time, are now available. With additional knowledge or assumptions regarding the detection-specific transfer function, realistic signal characteristics can be simulated. The accuracy of methods for the assessment of Δt can now be quantitatively compared and their sensitivity to noise evaluated.

scholarly journals Tau isoforms are differentially expressed across the hippocampus in chronic traumatic encephalopathy and Alzheimer’s disease

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Jonathan D. Cherry ◽  
Camille D. Esnault ◽  
Zachary H. Baucom ◽  
Yorghos Tripodis ◽  
Bertrand R. Huber ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Chronic Traumatic Encephalopathy ◽  
Temporal Cortex ◽  
Head Impacts ◽  
Hippocampal Subfields ◽  
Mild Disease ◽  
Tau Isoforms ◽  
Ghost Tangles

AbstractChronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease, characterized by hyperphosphorylated tau, found in individuals with a history of exposure to repetitive head impacts. While the neuropathologic hallmark of CTE is found in the cortex, hippocampal tau has proven to be an important neuropathologic feature to examine the extent of disease severity. However, the hippocampus is also heavily affected in many other tauopathies, such as Alzheimer’s disease (AD). How CTE and AD differentially affect the hippocampus is unclear. Using immunofluorescent analysis, a detailed histologic characterization of 3R and 4R tau isoforms and their differential accumulation in the temporal cortex in CTE and AD was performed. CTE and AD were both observed to contain mixed 3R and 4R tau isoforms, with 4R predominating in mild disease and 3R increasing proportionally as pathological severity increased. CTE demonstrated high levels of tau in hippocampal subfields CA2 and CA3 compared to CA1. There were also low levels of tau in the subiculum compared to CA1 in CTE. In contrast, AD had higher levels of tau in CA1 and subiculum compared to CA2/3. Direct comparison of the tau burden between AD and CTE demonstrated that CTE had higher tau densities in CA4 and CA2/3, while AD had elevated tau in the subiculum. Amyloid beta pathology did not contribute to tau isoform levels. Finally, it was demonstrated that higher levels of 3R tau correlated to more severe extracellular tau (ghost tangles) pathology. These findings suggest that mixed 3R/4R tauopathies begin as 4R predominant then transition to 3R predominant as pathological severity increases and ghost tangles develop. Overall, this work demonstrates that the relative deposition of tau isoforms among hippocampal subfields can aid in differential diagnosis of AD and CTE, and might help improve specificity of biomarkers for in vivo diagnosis.

scholarly journals The freshwater crabs of Danum Valley Conservation Area in Sabah, East Malaysia, with a description of a new species of Thelphusula Bott, 1969 (Crustacea, Brachyura, Gecarcinucidae, Potamidae, Sesarmidae)

ZooKeys ◽  
2018 ◽  
Vol 760 ◽  
pp. 89-112 ◽  
Author(s):  
Peter K. L. Ng ◽  
Paul Y. C. Ng
Keyword(s):  
New Species ◽  
Adult Male ◽  
New Record ◽  
Morphological Features ◽  
Unique Combination ◽  
Conservation Area ◽  
Freshwater Crabs ◽  
East Malaysia ◽  
A New Species ◽  
Malaysian Borneo

Seven species of freshwater crabs from three families are recorded from and around the Danum Valley Conservation Area in Sabah, Malaysian Borneo: Thelphusulacapillodigitus sp. n., Thelphusuladicerophilus Ng & Stuebing, 1990, Arachnothelphusaterrapes Ng, 1991, Terrathelphusasecula Ng & Tan, 2015, Parathelphusavalida Ng & Goh, 1987 (new record) (Gecarcinucidae); Isolapotamoningeri Ng & Tan, 1998 (Potamidae); and Geosesarmadanumense Ng, 2002 (Sesarmidae). The new species of Thelphusula Bott, 1979, can be distinguished from all congeners by a unique combination of morphological features, most notably the presence of dense patches of short setae on the fingers of the adult male chelipeds, as well as the structure of the male first gonopod. Arachnothelphusaterrapes is confirmed to be a phytotelm species. A key to all species in the conservation area is provided.

The human hippocampus at 7 T-In vivo MRI

Hippocampus ◽  
2009 ◽  
Vol 19 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Jens M. Theysohn ◽  
O. Kraff ◽  
S. Maderwald ◽  
M.U. Schlamann ◽  
A. de Greiff ◽  
...  
Keyword(s):  
Human Hippocampus

scholarly journals R51Q SNX10 induces osteopetrosis by promoting uncontrolled fusion of monocytes to form giant, non-functional osteoclasts

2018 ◽  
Author(s):  
Maayan Barnea ◽  
Merle Stein ◽  
Sabina Winograd-Katz ◽  
Moran Shalev ◽  
Esther Arman ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Mouse Model ◽  
Autosomal Recessive ◽  
Molecular Mechanisms ◽  
Precursor Cell ◽  
Unique Combination ◽  
Sorting Nexin ◽  
Autosomal Recessive Osteopetrosis

SummaryThe molecular mechanisms that regulate fusion of monocytes into functional osteoclasts are virtually unknown. We describe a knock-in mouse model for the R51Q mutation in sorting nexin 10 (SNX10) that exhibits osteopetrosis and related symptoms of patients of autosomal recessive osteopetrosis linked to this mutation. Osteopetrosis arises in homozygous R51Q SNX10 mice due to a unique combination of reduced numbers of osteoclasts that are non-functional. Fusion of mutant monocytes is deregulated and occurs rapidly and continuously to form giant, non-functional osteoclasts. Mutant osteoclasts mature quickly and survive poorly in vitro, possibly accounting for their scarcity in vivo. These cells also exhibit impaired ruffled borders, which are required for bone resorption, providing an additional basis for the osteopetrotic phenotype. More broadly, we propose that the maximal size of osteoclasts is actively determined by a genetically-regulated, cell-autonomous mechanism that limits precursor cell fusion, and for which SNX10 is required.

scholarly journals Reduced GluN1 in mouse dentate gyrus is associated with CA3 hyperactivity and psychosis-like behaviors

2018 ◽  
Vol 25 (11) ◽  
pp. 2832-2843 ◽  
Author(s):  
Amir Segev ◽  
Masaya Yanagi ◽  
Daniel Scott ◽  
Sarah A. Southcott ◽  
Jacob M. Lister ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Basolateral Amygdala ◽  
Pyramidal Neurons ◽  
Mossy Fibers ◽  
Model Systems ◽  
Memory Processing ◽  
Hippocampal Subfields ◽  
Whole Cell Patch Clamp ◽  
Hippocampal Activity

Abstract Recent findings from in vivo-imaging and human post-mortem tissue studies in schizophrenic psychosis (SzP), have demonstrated functional and molecular changes in hippocampal subfields that can be associated with hippocampal hyperexcitability. In this study, we used a subfield-specific GluN1 knockout mouse with a disease-like molecular perturbation expressed only in hippocampal dentate gyrus (DG) and assessed its association with hippocampal physiology and psychosis-like behaviors. First, we used whole-cell patch-clamp recordings to measure the physiological changes in hippocampal subfields and cFos immunohistochemistry to examine cellular excitability. DG-GluN1 KO mice show CA3 cellular hyperactivity, detected using two approaches: (1) increased excitatory glutamate transmission at mossy fibers (MF)-CA3 synapses, and (2) an increased number of cFos-activated pyramidal neurons in CA3, an outcome that appears to project downstream to CA1 and basolateral amygdala (BLA). Furthermore, we examined psychosis-like behaviors and pathological memory processing; these show an increase in fear conditioning (FC), a reduction in prepulse inhibition (PPI) in the KO animal, along with a deterioration in memory accuracy with Morris Water Maze (MWM) and reduced social memory (SM). Moreover, with DREADD vectors, we demonstrate a remarkably similar behavioral profile when we induce CA3 hyperactivity. These hippocampal subfield changes could provide the basis for the observed increase in human hippocampal activity in SzP, based on the shared DG-specific GluN1 reduction. With further characterization, these animal model systems may serve as targets to test psychosis mechanisms related to hippocampus and assess potential hippocampus-directed treatments.

scholarly journals Toward Development of a Vocal Fold Contact Pressure Probe: Sensor Characterization and Validation Using Synthetic Vocal Fold Models

2019 ◽  
Vol 9 (15) ◽  
pp. 3002 ◽  
Author(s):  
Mohsen Motie-Shirazi ◽  
Matías Zañartu ◽  
Sean D. Peterson ◽  
Daryush D. Mehta ◽  
James B. Kobler ◽  
...  
Keyword(s):  
Contact Pressure ◽  
Vocal Fold ◽  
Ground Truth ◽  
Pressure Probe ◽  
Primary Role ◽  
Novel Approach ◽  
Sensor Position ◽  
Probe Sensor ◽  
Contact Pressures

Excessive vocal fold collision pressures during phonation are considered to play a primary role in the formation of benign vocal fold lesions, such as nodules. The ability to accurately and reliably acquire intraglottal pressure has the potential to provide unique insights into the pathophysiology of phonotrauma. Difficulties arise, however, in directly measuring vocal fold contact pressures due to physical intrusion from the sensor that may disrupt the contact mechanics, as well as difficulty in determining probe/sensor position relative to the contact location. These issues are quantified and addressed through the implementation of a novel approach for identifying the timing and location of vocal fold contact, and measuring intraglottal and vocal fold contact pressures via a pressure probe embedded in the wall of a hemi-laryngeal flow facility. The accuracy and sensitivity of the pressure measurements are validated against ground truth values. Application to in vivo approaches are assessed by acquiring intraglottal and VF contact pressures using a synthetic, self-oscillating vocal fold model in a hemi-laryngeal configuration, where the sensitivity of the measured intraglottal and vocal fold contact pressure relative to the sensor position is explored.

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