What is the Human Cortex?

The cerebral cortex is the thin surface layer of the brain found in vertebrate animals that has evolved most recently, showing the greatest variation in size among different mammals (it is especially large in humans). Each part of the cerebral cortex is six layered (e.g., L2), with different kinds of nerve cells (e.g., spiny stellate) in each layer. The cerebral cortex plays a crucial role in most higher level cognitive functions, such as thinking, memory, planning, perception, language, and attention. Although there has been some progress in understanding the macroscopic organization of this very complicated tissue, its organization at the level of individual nerve cells and their interconnecting synapses is largely unknown.

Petabyte connectomic reconstruction of a volume of human neocortex. Left: Small subvolume of the dataset. Right: A subgraph of 5000 neurons and excitatory (green) and inhibitory (red) connections in the dataset. The full graph (connectome) would be far too dense to visualize.

Mapping the structure of the brain at the resolution of individual synapses requires high-resolution microscopy techniques that can image biochemically stabilized (fixed) tissue. We collaborated with brain surgeons at Massachusetts General Hospital in Boston (MGH) who sometimes remove pieces of normal human cerebral cortex when performing a surgery to cure epilepsy in order to gain access to a site in the deeper brain where an epileptic seizure is being initiated. Patients anonymously donated this tissue, which is normally discarded, to our colleagues in the Lichtman lab. The Harvard researchers cut the tissue into ~5300 individual 30 nanometer sections using an automated tape collecting ultra-microtome, mounted those sections onto silicon wafers, and then imaged the brain tissue at 4 nm resolution in a customized 61-beam parallelized scanning electron microscope for rapid image acquisition.

Imaging the ~5300 physical sections produced 225 million individual 2D images. The team then computationally stitched and aligned this data to produce a single 3D volume. While the quality of the data was generally excellent, these alignment pipelines had to robustly handle a number of challenges, including imaging artifacts, missing sections, variation in microscope parameters, and physical stretching and compression of the tissue. Once aligned, a multiscale flood-filling network pipeline was applied (using thousands of Google Cloud TPUs) to produce a 3D segmentation of each individual cell in the tissue. Additional machine learning pipelines were applied to identify and characterize 130 million synapses, classify each 3D fragment into various “subcompartments” (e.g., axon, dendrite, or cell body), and identify other structures of interest such as myelin and cilia. Automated reconstruction results were imperfect, so manual efforts were used to “proofread” roughly one hundred cells in the data. Over time, the scientists expect to add additional cells to this verified set through additional manual efforts and further advances in automation.

Source: https://ai.googleblog.com/

Nanospheres Dissolve Clots In A Few Minutes

Researchers from North Carolina State University and the University of North Carolina at Chapel Hill have developed a drug-delivery system that allows rapid response to heart attacks without surgical intervention. In laboratory and animal testing, the system proved to be effective at dissolving clots, limiting long-term scarring to heart tissue and preserving more of the heart’s normal function.

Our approach would allow health-care providers to begin treating heart attacks before a patient reaches a surgical suite, hopefully improving patient outcomes,” says Ashley Brown, corresponding author of a paper on the work and an assistant professor in the Joint Biomedical Engineering Program (BME) at NC State and UNC. “And because we are able to target the blockage, we are able to use powerful drugs that may pose threats to other parts of the body; the targeting reduces the risk of unintended harms.”

Heart attacks, or myocardial infarctions, occur when a thrombus – or clotblocks a blood vessel in the heart. In order to treat heart attacks, doctors often perform surgery to introduce a catheter to the blood vessel, allowing them to physically break up or remove the thrombus. But not all patients have quick access to surgical care. And more damage can occur even after the blockage has been removed. That’s because the return of fresh blood to tissues that had been blocked off can cause damage of its own, called reperfusion injury. Reperfusion injury can cause scarring, stiffening cardiac tissue and limiting the heart’s normal functionality.

To address these problems, researchers have developed a solution that relies on porous nanogel spheres, about 250 nanometers in diameter, which target a thrombus and deliver a cocktail of two drugs: tPA and Y-27632.

In in vitro testing, the researchers found that the targeted tPA/Y-27632 cocktail dissolved clots in a matter of minutes. While this has yet to be tested in trials, it may work more quickly than surgical interventions, which require time to prep the patient and get the catheter in place. In tests using laboratory rats, the researchers also found that their technique limited scarring and preserved heart function after heart attack better than targeted tPA or Y-27632 by themselves – and far better than a control group in which animals received neither drug.

The paper was recently published in the journal ACS Nano. Trials on larger animals are now being planned.

Source: https://news.ncsu.edu/