DHARANI: A 3D Developing Human-Brain Atlas Resource to Advance Neuroscience Internationally Integrated Multimodal Imaging and High-Resolution Histology of the Second Trimester.

We introduce DHARANI, the first online platform with three-dimensional (3D) histological reconstructions of the developing human brain from 14 to 24 gestational weeks (GW) across the five fetal brains. DHARANI features 5132 Nissl, hematoxylin and eosin stained, 20 µm coronal and sagittal sections, postmortem MRI, and a neuroanatomical atlas with 466 annotated sections covering ∼500 brain structures. It is accessible online at https://brainportal.

Establishing neuroanatomical correspondences across mouse and marmoset brain structures.

Interest in the common marmoset is growing due to evolutionarily proximity to humans compared to laboratory mice, necessitating a comparison of mouse and marmoset brain architectures, including connectivity and cell type distributions. Creating an actionable comparative platform is challenging since these brains have distinct spatial organizations and expert neuroanatomists disagree. We propose a general theoretical framework to relate named atlas compartments across taxa and use it to establish a detailed correspondence between marmoset and mice brains.

Histological characterization and development of mesial surface sulci in the human brain at 13-15 gestational weeks through high-resolution histology.

Cellular-level anatomical data from early fetal brain are sparse yet critical to the understanding of neurodevelopmental disorders. We characterize the organization of the human cerebral cortex between 13 and 15 gestational weeks using high-resolution whole-brain histological data sets complimented with multimodal imaging. We observed the heretofore underrecognized, reproducible presence of infolds on the mesial surface of the cerebral hemispheres.

A Standardized Protocol for the Safe Retrieval of Infectious Postmortem Human Brain for Studying Whole-Brain Pathology.

We describe a safe and standardized perfusion protocol for studying brain pathology in high-risk autopsies using a custom-designed low-cost infection containment chamber and high-resolution histology. The output quality was studied using the histological data from the whole cerebellum and brain stem processed using a high-resolution cryohistology pipeline at 0.5 μm per pixel, in-plane resolution with serial sections at 20-μm thickness.

A guide to the BRAIN Initiative Cell Census Network data ecosystem.

Characterizing cellular diversity at different levels of biological organization and across data modalities is a prerequisite to understanding the function of cell types in the brain. Classification of neurons is also essential to manipulate cell types in controlled ways and to understand their variation and vulnerability in brain disorders. The BRAIN Initiative Cell Census Network (BICCN) is an integrated network of data-generating centers, data archives, and data standards developers, with the goal of systematic multimodal brain cell type profiling and characterization.

Cellular anatomy of the mouse primary motor cortex.

An essential step toward understanding brain function is to establish a structural framework with cellular resolution on which multi-scale datasets spanning molecules, cells, circuits and systems can be integrated and interpreted. Here, as part of the collaborative Brain Initiative Cell Census Network (BICCN), we derive a comprehensive cell type-based anatomical description of one exemplar brain structure, the mouse primary motor cortex, upper limb area (MOp-ul). Using genetic and viral labelling, barcoded anatomy resolved by sequencing, single-neuron reconstruction, whole-brain imaging and cloud-based neuroinformatics tools, we delineated the MOp-ul in 3D and refined its sublaminar organization.

Genetic dissection of the glutamatergic neuron system in cerebral cortex.

Diverse types of glutamatergic pyramidal neurons mediate the myriad processing streams and output channels of the cerebral cortex, yet all derive from neural progenitors of the embryonic dorsal telencephalon. Here we establish genetic strategies and tools for dissecting and fate-mapping subpopulations of pyramidal neurons on the basis of their developmental and molecular programs. We leverage key transcription factors and effector genes to systematically target temporal patterning programs in progenitors and differentiation programs in postmitotic neurons.

Semantic segmentation of microscopic neuroanatomical data by combining topological priors with encoder-decoder deep networks.

Understanding of neuronal circuitry at cellular resolution within the brain has relied on neuron tracing methods which involve careful observation and interpretation by experienced neuroscientists. With recent developments in imaging and digitization, this approach is no longer feasible with the large scale (terabyte to petabyte range) images. Machine learning based techniques, using deep networks, provide an efficient alternative to the problem.

Application of Supervised Machine Learning to Extract Brain Connectivity Information from Neuroscience Research Articles.

Understanding the complex connectivity structure of the brain is a major challenge in neuroscience. Vast and ever-expanding literature about neuronal connectivity between brain regions already exists in published research articles and databases. However, with the ever-expanding increase in published articles and repositories, it becomes difficult for a neuroscientist to engage with the breadth and depth of any given field within neuroscience.

Rapid Emergence of SARS-CoV-2 in the Greater New York Metropolitan Area: Geolocation, Demographics, Positivity Rates, and Hospitalization for 46 793 Persons Tested by Northwell Health.

Background: In March 2020, the greater New York metropolitan area became an epicenter for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The initial evolution of case incidence has not been well characterized.

Methods: Northwell Health Laboratories tested 46 793 persons for SARS-CoV-2 from 4 March through 10 April.

Multimodal cross-registration and quantification of metric distortions in marmoset whole brain histology using diffeomorphic mappings.

Whole brain neuroanatomy using tera-voxel light-microscopic data sets is of much current interest. A fundamental problem in this field is the mapping of individual brain data sets to a reference space. Previous work has not rigorously quantified in-vivo to ex-vivo distortions in brain geometry from tissue processing.

Open access resource for cellular-resolution analyses of corticocortical connectivity in the marmoset monkey.

Understanding the principles of neuronal connectivity requires tools for efficient quantification and visualization of large datasets. The primate cortex is particularly challenging due to its complex mosaic of areas, which in many cases lack clear boundaries. Here, we introduce a resource that allows exploration of results of 143 retrograde tracer injections in the marmoset neocortex.

ZEBrA: Zebra finch Expression Brain Atlas-A resource for comparative molecular neuroanatomy and brain evolution studies.

An in-depth understanding of the genetics and evolution of brain function and behavior requires a detailed mapping of gene expression in functional brain circuits across major vertebrate clades. Here we present the Zebra finch Expression Brain Atlas (ZEBrA; www.zebrafinchatlas.

ESTIMATING DIFFEOMORPHIC MAPPINGS BETWEEN TEMPLATES AND NOISY DATA: VARIANCE BOUNDS ON THE ESTIMATED CANONICAL VOLUME FORM.

Anatomy is undergoing a renaissance driven by the availability of large digital data sets generated by light microscopy. A central computational task is to map individual data volumes to standardized templates. This is accomplished by regularized estimation of a diffeomorphic transformation between the coordinate systems of the individual data and the template, building the transformation incrementally by integrating a smooth flow field.

Traumatic microbleeds suggest vascular injury and predict disability in traumatic brain injury.

Traumatic microbleeds are small foci of hypointensity seen on T2*-weighted MRI in patients following head trauma that have previously been considered a marker of axonal injury. The linear appearance and location of some traumatic microbleeds suggests a vascular origin. The aims of this study were to: (i) identify and characterize traumatic microbleeds in patients with acute traumatic brain injury; (ii) determine whether appearance of traumatic microbleeds predict clinical outcome; and (iii) describe the pathology underlying traumatic microbleeds in an index patient.

Can One Concurrently Record Electrical Spikes from Every Neuron in a Mammalian Brain?

The classic approach to measure the spiking response of neurons involves the use of metal electrodes to record extracellular potentials. Starting over 60 years ago with a single recording site, this technology now extends to ever larger numbers and densities of sites. We argue, based on the mechanical and electrical properties of existing materials, estimates of signal-to-noise ratios, assumptions regarding extracellular space in the brain, and estimates of heat generation by the electronic interface, that it should be possible to fabricate rigid electrodes to concurrently record from essentially every neuron in the cortical mantle.

Relation of koniocellular layers of dorsal lateral geniculate to inferior pulvinar nuclei in common marmosets.

Traditionally, the dorsal lateral geniculate nucleus (LGN) and the inferior pulvinar (IPul) nucleus are considered as anatomically and functionally distinct thalamic nuclei. However, in several primate species it has also been established that the koniocellular (K) layers of LGN and parts of the IPul have a shared pattern of immunoreactivity for the calcium-binding protein calbindin. These calbindin-rich cells constitute a thalamic matrix system which is implicated in thalamocortical synchronisation.

An active texture-based digital atlas enables automated mapping of structures and markers across brains.

Brain atlases enable the mapping of labeled cells and projections from different brains onto a standard coordinate system. We address two issues in the construction and use of atlases. First, expert neuroanatomists ascertain the fine-scale pattern of brain tissue, the 'texture' formed by cellular organization, to define cytoarchitectural borders.

On variational solutions for whole brain serial-section histology using a Sobolev prior in the computational anatomy random orbit model.

This paper presents a variational framework for dense diffeomorphic atlas-mapping onto high-throughput histology stacks at the 20 μm meso-scale. The observed sections are modelled as Gaussian random fields conditioned on a sequence of unknown section by section rigid motions and unknown diffeomorphic transformation of a three-dimensional atlas. To regularize over the high-dimensionality of our parameter space (which is a product space of the rigid motion dimensions and the diffeomorphism dimensions), the histology stacks are modelled as arising from a first order Sobolev space smoothness prior.

Towards a comprehensive atlas of cortical connections in a primate brain: Mapping tracer injection studies of the common marmoset into a reference digital template.

The marmoset is an emerging animal model for large-scale attempts to understand primate brain connectivity, but achieving this aim requires the development and validation of procedures for normalization and integration of results from many neuroanatomical experiments. Here we describe a computational pipeline for coregistration of retrograde tracing data on connections of cortical areas into a 3D marmoset brain template, generated from Nissl-stained sections. The procedure results in a series of spatial transformations that are applied to the coordinates of labeled neurons in the different cases, bringing them into common stereotaxic space.

Comparative three-dimensional connectome map of motor cortical projections in the mouse brain.

The motor cortex orchestrates simple to complex motor behaviors through its output projections to target areas. The primary (MOp) and secondary (MOs) motor cortices are known to produce specific output projections that are targeted to both similar and different target areas. These projections are further divided into layer 5 and 6 neuronal outputs, thereby producing four cortical outputs that may target other areas in a combinatorial manner.