Showing posts with label brain connectivity. Show all posts
Showing posts with label brain connectivity. Show all posts

Thursday, July 21, 2016

Mapping the Human Connectome

reposted from The Scientist


Mapping the Human Connectome

A new map of human cortex combines data from multiple imaging modalities and comprises 180 distinct regions.
By  | July 20, 2016
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A multimodal map of human cortex: areas connected to hearing (red), touch (green) vision (blue) and opposing cognitive systems (light and dark)WASHINGTON UNIVERSITY; MATTHEW GLASSER, DAVID VAN ESSENSince the turn of the 20th century, neuroscientists have been trying to map the human brain. Now, using data from the Human Connectome Project, researchers from Washington University School of Medicine in St. Louis have created a multimodal map of the human cortex that combines data from cortical architecture, function, connectivity, and topography. The map, detailed today (July 20) inNature, identifies 180 brain areas, 97 of which are new to neuroscience.
“It’s really a breakthrough in mapping the living human brain using [magnetic resonance imaging-based] methods,” neuroscientist Katrin Amunts at the University of Düsseldorf, Germany, who was not involved in the work, told The Scientist. “It’s methodically beautiful because it’s a multimodal approach, so it integrates different aspects of brain organization,” she added.
The gold standard for brain mapping is still based on Brodmann’s map, developed in 1909, which divided the cerebral cortex into 50 different areas based on its cellular architecture. But this was based on the study of just a single postmortem human brain. Subsequent maps have improved upon Brodmann’s, but they typically represented only a single modality of brain structure or function and were based on a small number of individuals. Washington University’s Matthew GlasserDavid Van Essen, and colleagues decided to create a map that combines these properties to produce a more comprehensive atlas of the human cortex.
“You can look at a map of Earth and see mountains, valleys, and undulations—which are analogous to the folds of the cerebral cortex—but that doesn’t tell us directly about brain function,” Van Essen told The Scientist. “We want to look at the ‘political subdivisions,’” he added.
To generate the map, Glasser’s team used magnetic resonance imaging (MRI) data from the Human Connectome Project, a five-year National Institutes of Health-funded effort to map the anatomical and functional connectivity of the human brain. The researchers surveyed brain architecture based on structural MRI of cortical myelin content and thickness; cortical function, as measured by functional MRI (fMRI) scans of participants completing seven tasks, ranging from listening comprehension to math problems; and functional connectivity and topography, as measured with resting-state fMRI.
“It’s particularly important to find places where you have multiple independent measures changing in the same location,” Glasser told The Scientist. “Up until this point, people were looking at only single modalities.”
Using a combination of algorithms and human interpretation to analyze the MRI data from 210 healthy young adults, Glasser’s team separated the brain into 180 regions per hemisphere. Eighty-three of these regions had previously been reported in the literature, but 97 of them were new. One surprise was the rediscovery of a language-associated region called area 55b, which was first identified in 1956.
The researchers then used this map to train a machine-learning algorithm to identify the “fingerprints” of these brain areas in a group of another 210 people. The algorithm correctly identified more than 96 percent of the same cortical areas in the new group, and was able to identify how these maps differed between individuals, the researchers reported.
“There are many billions of brains, and each one is like a planet unto itself, with different geography and different political terrain,” Van Essen said. It’s these differences that could explain what makes a healthy brain different from one with schizophrenia or Alzheimer’s disease, for example. 
The new brain map gives researchers a standardized tool for identifying specific brain regions, and could be used by neurosurgeons to home in on their targets with greater accuracy, Glasser and colleagues suggested.
In addition, the map could also expand scientists’ understanding of human evolution, by allowing for better comparisons with the brains of other nonhuman primates and other animals.
“The results of this new approach [provide] a remarkable new map of the cortex that informs about the fundamental functional and structural organization of the cortex and will be a new standard to map functional imaging studies to in the future,” Ed Lein, an investigator at the Allen Institute for Brain Science in Seattle who was not involved in the study, wrote in an email to The Scientist.
Because the map is based on neuroimaging, it has relatively low spatial resolution and provides indirect measurements of brain connectivity, Lein noted. “There are still many questions about how this parcellation based on neuroimaging . . .  relates to the physical connectivity of the neocortex and its cellular, molecular and synaptic organization.”  
Glasser said his team will continue to refine the map. “We consider this a version 1.0 brain map,” he said, adding, “we’re hoping it will be able to grow and improve as new information becomes available.”
M. Glasser et al, “A multi-modal parcellation of human cerebral cortex,” Nature,doi:10.1038/nature18933, 2016.
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Tuesday, February 11, 2014

New evidence that chronic stress predisposes brain to mental illness


New evidence that chronic stress predisposes brain to mental illness

BERKELEY —
University of California, Berkeley, researchers have shown that chronic stress generates long-term changes in the brain that may explain why people suffering chronic stress are prone to mental problems such as anxiety and mood disorders later in life.
myelin stained blue
Myelin is stained blue in this cross section of a rat hippocampus. Myelin, which speeds electrical signals flowing through axons, is produced by oligodendrocytes, which increase in number as a result of chronic stress. New oligodendrocytes are shown in yellow. Image by Aaron Friedman and Daniela Kaufer.
Their findings could lead to new therapies to reduce the risk of developing mental illness after stressful events.
Doctors know that people with stress-related illnesses, such as post-traumatic stress disorder (PTSD), have abnormalities in the brain, including differences in the amount of gray matter versus white matter. Gray matter consists mostly of cells – neurons, which store and process information, and support cells called glia – while white matter is comprised of axons, which create a network of fibers that interconnect neurons. White matter gets its name from the white, fatty myelin sheath that surrounds the axons and speeds the flow of electrical signals from cell to cell.
How chronic stress creates these long-lasting changes in brain structure is a mystery that researchers are only now beginning to unravel.
In a series of experiments, Daniela Kaufer, UC Berkeley associate professor of integrative biology, and her colleagues, including graduate students Sundari Chetty and Aaron Freidman, discovered that chronic stress generates more myelin-producing cells and fewer neurons than normal. This results in an excess of myelin – and thus, white matter – in some areas of the brain, which disrupts the delicate balance and timing of communication within the brain.
“We studied only one part of the brain, the hippocampus, but our findings could provide insight into how white matter is changing in conditions such as schizophrenia, autism, depression, suicide, ADHD and PTSD,” she said.
The hippocampus regulates memory and emotions, and plays a role in various emotional disorders.
Kaufer and her colleagues published their findings in the Feb. 11 issue of the journal Molecular Psychiatry.
Does stress affect brain connectivity?
Kaufer’s findings suggest a mechanism that may explain some changes in brain connectivity in people with PTSD, for example. One can imagine, she said, that PTSD patients could develop a stronger connectivity between the hippocampus and the amygdala – the seat of the brain’s fight or flight response – and lower than normal connectivity between the hippocampus and prefrontal cortex, which moderates our responses.
“You can imagine that if your amygdala and hippocampus are better connected, that could mean that your fear responses are much quicker, which is something you see in stress survivors,” she said. “On the other hand, if your connections are not so good to the prefrontal cortex, your ability to shut down responses is impaired. So, when you are in a stressful situation, the inhibitory pathways from the prefrontal cortex telling you not to get stressed don’t work as well as the amygdala shouting to the hippocampus, ‘This is terrible!’ You have a much bigger response than you should.”
white matter fibers in human brain
White matter fiber architecture of the brain. Human Connectome Project.
She is involved in a study to test this hypothesis in PTSD patients, and continues to study brain changes in rodents subjected to chronic stress or to adverse environments in early life.
Stress tweaks stem cells
Kaufer’s lab, which conducts research on the molecular and cellular effects of acute and chronic stress, focused in this study on neural stem cells in the hippocampus of the brains of adult rats. These stem cells were previously thought to mature only into neurons or a type of glial cell called an astrocyte. The researchers found, however, that chronic stress also made stem cells in the hippocampus mature into another type of glial cell called an oligodendrocyte, which produces the myelin that sheaths nerve cells.
The finding, which they demonstrated in rats and cultured rat brain cells, suggests a key role for oligodendrocytes in long-term and perhaps permanent changes in the brain that could set the stage for later mental problems. Oligodendrocytes also help form synapses – sites where one cell talks to another – and help control the growth pathway of axons, which make those synapse connections.
The fact that chronic stress also decreases the number of stem cells that mature into neurons could provide an explanation for how chronic stress also affects learning and memory, she said.
Kaufer is now conducting experiments to determine how stress in infancy affects the brain’s white matter, and whether chronic early-life stress decreases resilience later in life. She also is looking at the effects of therapies, ranging from exercise to antidepressant drugs, that reduce the impact of stress and stress hormones.
Kaufer’s coauthors include Chetty, formerly from UC Berkeley’s Helen Wills Neuroscience Institute and now at Harvard University; Friedman and K. Taravosh-Lahn at UC Berkeley’s Department of Integrative Biology; additional colleagues from UC Berkeley and others from Stanford University and UC Davis.
The work was supported by a BRAINS (Biobehavioral Research Awards for Innovative New Scientists) award from the National Institute of Mental Health of the National Institutes of Health (R01 MH087495), a Berkeley Stem Cell Center Seed Grant, the Hellman Family Foundation and the National Alliance for Research on Schizophrenia and Depression.

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